FDA OKs Ecstasy study in cancer patients

Dec. 28, 2004 | Washington -- The illegal club drug Ecstasy can trigger euphoria among the dance club set, but can it ease the debilitating anxiety that cancer patients feel as they face their final days?

The Food and Drug Administration has approved a pilot study looking at whether the recreational hallucinogen can help terminally ill patients lessen their fears, quell thoughts of suicide and make it easier for them to deal with loved ones.

'End of life issues are very important and are getting more and more attention, and yet there are very few options for patients who are facing death,' Dr. John Halpern, the Harvard research psychiatrist in charge of the study, said Monday.

The small, four-month study is expected to begin early next spring. It will test the drug's effects on 12 cancer patients from the Lahey Clinic Medical Center in the Boston area. The research is being sponsored by the Multidisciplinary Association for Psychedelic Studies, a nonprofit group that plans to raise $250,000 to fund it.

MAPS, on its web site, touted the study's approval, saying 'the longest day of winter has passed, and maybe so has the decades-long era of resistance to psychedelic research.'

The FDA would not comment, but this will be the second FDA-approved study using Ecstasy this year. South Carolina researchers are studying the effects of Ecstasy on 20 patients suffering from post traumatic stress disorder.

Ecstasy, known scientifically as MDMA for methylenedioxymethamphetamine, is a chemical cousin of methamphetamine and typically induces feelings of euphoria, increased energy and sexual arousal. But it also suppresses appetite, thirst and the need to sleep, and in high doses can sharply increase body temperature, leading to kidney and heart failure, and death.

It peaked in 2001 as a trendy recreational drug used by youth at gatherings called 'raves' and dance clubs.

Halpern, who has done other research on the effects of hallucinogenic drugs, said that some, when used properly, can have medical benefits. He said that unlike LSD, Ecstasy is 'ego-friendly,' and unlike some pain medications it does not oversedate people and make them foggy and unsteady.

Instead, he said, it can reduce stress and increase empathy. There are anecdotal reports, he said, of people dying of cancer who take Ecstasy and they are able to talk to their family and friends about death and other subjects they couldn't broach before.

'I'm hoping that we can find something that can be of use for people in their remaining days of life,' he said. If there are no significant problems, he said broader studies would follow this one.

In addition to FDA approval, the study has also received review board authorization from the Lahey Clinic and Harvard Medical School's psychiatric facility, McLean Hospital. Halpern is awaiting a license from the federal Drug Enforcement Administration.

It's been more than 40 years since Harvard has been the site of psychedelic drug research -- including the infamous LSD studies of Timothy Leary in 1963 and the Good Friday Experiment in 1965, done by Leary's student Walter Pahnke, studying the effects of psilocybin mushrooms on religious people.

But 'this is not about trying to create some sensationalistic storm,' Halpern said. 'This is about trying to help these patients in a meaningful way.'"

New Pain Reliever That Blocks Nerve Channels

From the NYT:

WASHINGTON, Dec. 28 (AP) - The government approved on Tuesday a drug that offers a new way of fighting severe pain, an option for patients who no longer benefit from morphine and other traditional pain medications.

The drug, made by the Elan Corporation, is the first in a new class of drugs that selectively blocks the nerve channels responsible for transmitting pain signals. It will be marketed as Prialt and should be available by the end of January.

'When you've taken all the kinds of pain medication that there is and you still have pain, that is a very frightening situation,' said Dr. Lars Ekman, president of research and development for Elan, which is based in Dublin. 'When you have that kind of pain, there is nowhere to go.'

The drug is part of a new class known as N-type calcium channel blockers. It is known chemically as ziconotide.

The Food and Drug Administration approved the drug for patients who no longer receive relief from morphine and have moved to the next level of treatment, which involves a pump that delivers medicine directly to the area around the spine.

Prialt has been studied in patients with cancer, AIDS and other afflictions that produce chronic pain. More than 1,200 patients took part in three clinical trials.

There are side effects, and the F.D.A. said it would require its strongest warning to appear with the drug. Side effects may include dizziness, drowsiness and altered mental status, with patients confused at times.

Despite the side effects, the drug was approved because there are no other options for these patients and the benefits outweighed the risks, the agency said.

Not NSAIDs too

Mediagenic doctors, start your engines.

A new study has found that Aleve, a popular over-the-counter painkiller made by Bayer, could increase heart problems, and federal officials are warning patients not to exceed the recommended dose of two 200-milligram pills a day or continue therapy for more than 10 days without consulting a physician.

It was the fourth big-selling pain medicine in recent months to be suspected of hurting the heart, and federal drug officials said that similar drugs, like Advil, might also increase heart risks.

The study, sponsored by the National Institutes of Health, was intended to measure whether Aleve and Celebrex, made by Pfizer, might prevent Alzheimer's disease. Nearly 2,500 patients were given one of the two drugs or a placebo and were followed for three years. Those taking Aleve had a 50 percent greater rate of heart problems - including heart attacks and stroke - than those given a placebo. The Celebrex patients saw no increase in heart events.

The latest findings follow an announcement Friday that a different national study found that those given high doses of Celebrex had a 240 percent increase in heart problems, including death. Merck executives withdrew their painkiller Vioxx after a study found that it increased the risk of heart attack and stroke by more than 100 percent. Also, Pfizer announced recently that a study of Bextra found that it increased the risk of heart attacks in those who have had cardiac surgery.

"This illustrates the fundamental dynamic that all drugs have risks," said Dr. Steven Galson, acting director of the Food and Drug Administration's center for drug evaluation and research. "All should be taken carefully."

Federal drug officials said that the entire class of painkillers known as nonsteroidal anti-inflammatories - drugs that include Celebrex, Advil and Mobic - could cause worrisome effects on the heart. Sales of Celebrex, along with other anti-inflammatories like Advil and Mobic, are expected to fall as a result.

"We know that there are other phenomena that occur across these class of drugs, including gastrointestinal bleeding," said Dr. Sandra Kweder, deputy director of the F.D.A.'s office of new drugs. Heart problems "may be another class phenomenon."

Dr. Kweder said that the agency was studying the results of this latest study and "will be assessing what regulatory actions are appropriate over the next day or two." Researchers stopped the study, but patients will be monitored. Link

Seriously, did we really just learn that "All drugs have risks"? Though it is good of the FDA to do so much to quell the panic that we've all now seen on TV and Radio. Hopefully, everyone will flock to Tylenol --the only over-the-counter non-NSAID (its more properly an analgesic)-- and start killing their livers to avoid heart attacks.

These latest revelations do highlight some serious ethical issues about how the FDA tests and approves drugs (in particular how they deal with drugs taken daily for years), but the public reaction does strike me as overblown.
Categories: Legal

Depression, anxiety, and pain

Depression and anxiety associated with three pain conditions: results from a nationally representative sample
McWilliams, et. al
DOI

Numerous studies have found pain conditions to be associated with self-reports of psychological distress and psychiatric disorders. Several important clinical implications of these associations have been noted. For example, information regarding specific patterns of comorbidity could guide clinicians' efforts to detect psychiatric disorders in patients with pain. As well, psychopathology (i.e. depression) has been found to be associated with poor pain-related outcomes such as elevated pain intensity, functional limitations, and non-recovery (see Bair et al., 2003).
[....]
McWilliams et al. (2003) found significant associations between arthritis and each of the mood and anxiety disorders considered. Given the lack of attention to anxiety disorders in the pain literature, it was particularly noteworthy that the associations between arthritis and several of the anxiety disorders (i.e. panic disorder and posttraumatic stress disorder) were stronger than the association between arthritis and depression. Evidence from other epidemiological studies indicates that migraine may also be more strongly associated with anxiety disorders, particularly panic disorder (e.g. Breslau and Davis, 1993 and Swartz et al., 2000) and generalized anxiety disorder (GAD) (e.g. Merikangas et al., 1990), than with depression. The present study utilized data from another nationally representative sample, the Midlife Development in the United States Survey (MIDUS), in an attempt to replicate these earlier findings with arthritis and migraine and to extend this line of investigation to back pain. It was hypothesized that each of these pain conditions would be significantly associated with the psychiatric disorders included in the MIDUS and that each pain condition would be more strongly associated with the anxiety disorders than with depression.
[....]
Discussion
Data from the MIDUS yielded significant positive associations between three pain conditions (arthritis, migraine, and back pain) and common mood and anxiety disorders (depression, panic attacks, and GAD). Multivariate logistic regression analyses indicated that these associations remained after adjusting for a wide range of potential confounding variables including age, gender, education level, race, and the presence of another pain condition. These findings were noteworthy because previous epidemiological studies concerning psychopathology and both migraine (e.g. Merikangas et al., 1990 and Stewart et al., 1994) and arthritis (e.g. McWilliams et al., 2003) have generally not adjusted for comorbid pain conditions.

Medical or health conditions that do not primarily involve pain are also associated with psychopathology (e.g. Wells et al., 1988). A third series of analyses examined whether each pain condition could account for unique variance in the psychiatric disorders beyond that accounted for by the number of other medical/health conditions present. The majority of the associations remained statistically significant, but the association between arthritis and panic attacks and the association between back pain and GAD did not. This pattern of findings raises the possibility that the association between arthritis and panic attacks and the association between back pain and GAD found in Models 1 and 2 reflect a more general association between health problems and psychopathology rather than more specific associations between these respective pain conditions and psychiatric disorders. Several of the other medical conditions included (e.g. recurring stomach problems) likely involved pain, so it is possible that the third set of analyses also adjusted for the presence of other forms of pain. Nonetheless, this procedure was used because the focus of the study was on three types of pain (rather than pain in general) and the goal of these analyses was to adjust for other medical and health conditions regardless of whether they involved some pain.

Consistent with previous studies, depression was significantly associated with each of the pain conditions. Based on previous research demonstrating substantial comorbidity between mood and anxiety disorders (e.g. Krueger, 1999 and Vollebergh et al., 2001), it was expected that anxiety disorders would also be associated with the pain conditions. Furthermore, several studies (e.g. Breslau and Davis, 1993; McWilliams et al., 2003 and Merikangas et al., 1990) have found pain conditions to be more strongly associated with several anxiety disorders than with depression. The present study replicated this pattern of findings and extended it to back pain. The bivariate odds ratios clearly indicated that each pain condition was more strongly associated with the anxiety disorders than with depression. However, this pattern was less consistent in the analyses that adjusted for other medical/health conditions. Three additional logistic regression analyses were used to examine whether the association between multiple pain conditions and psychopathology would be greater than the associations between pure pain conditions (i.e. those with only one pain condition) and psychopathology. The overall pattern was consistent with previous research (e.g. Dworkin et al., 1990) indicating that those with multiple physical complaints have higher rates of psychopathology than those without a physical complaint or those with a single complaint.

There is a paucity of research or clinical literature concerning anxiety disorders in relation to pain conditions. The findings of this and earlier studies suggest that such attention is warranted. More sophisticated approaches to the assessment of anxiety are required in pain-related contexts. For example, a recent issue of Arthritis Care and Research focused on assessment issues included an article on depression (Smarr, 2003), but anxiety was only addressed in an article considering ‘other measures of psychological well-being’ ( Schiaffino, 2003). Furthermore, the anxiety measure selected was the State-Trait Anxiety Inventory ( Spielberger, 1983), which includes numerous depression-related items (see Bieling et al., 1998), and appears to be more accurately described as a measure of general distress. Several self-report measures designed to assess symptoms or constructs directly related to specific anxiety disorders are available. Examples include the Penn State Worry Questionnaire ( Meyer et al., 1990) for GAD and the Mobility Inventory ( Chambless et al., 1985) for agoraphobia. As well, the CIDI-SF could readily be incorporated into assessment procedures and represents a successful compromise between the need for diagnostic-specific assessment procedures and the time constraints found in many contexts.

Temporal relationships between pain conditions and depression have long been of interest (see Fishbain et al., 1997). However, the temporal relationships between pain conditions and anxiety disorders remains largely ignored. Breslau and Davis's (1993) longitudinal study of the association between migraine and psychopathology in a community sample of young adults provides a rare exception to this general rule. They found that individuals who reported having their last migraine a year or more prior to the baseline interview were at increased risk of experiencing first incidence depression and panic disorder at a 14-month follow up. These findings suggest that depression, panic, and migraine share common predispositions and that mood and anxiety disorders are not merely the psychological consequences of a pain condition. Causal relations between anxiety and most other pain conditions have not been investigated.

Theories regarding underlying factors involved in both pain and anxiety disorders have focused on neurochemical mechanisms (e.g. Merikangas et al., 1990). Asmundson et al. (2002) reviewed several potential shared psychological vulnerabilities for posttraumatic stress disorder and pain and noted hyperarousal, hypervigilance, and attentional biases towards somatic cues may be involved in both conditions. These factors have also been implicated in other anxiety disorders, particularly panic disorder, and may be responsible for the associations observed in the present study. Recent conceptualizations of GAD have suggested that worry may be used to suppress somatic anxiety or the hyperarousal associated with perceptions of threat ( Borkovec et al., 2004). It is possible that individuals with pain conditions may use worry as a strategy for reducing somatic arousal associated with pain, and as a result may become prone to developing GAD.

The treatment implications of the associations between pain and psychiatric disorders have focused on pharmacologic interventions (e.g. Stewart et al., 1994). However, in light of their possible shared psychological vulnerabilities, psychological interventions also hold potential for treating comorbid pain and psychiatric disorders. It is noteworthy that psychosocial interventions for psychiatric disorders and pain conditions share several common elements. For example, treatments for depression and pain both focus on increasing activity levels and treatments for anxiety and pain both include strategies for reducing arousal (i.e. relaxation training). It may be possible to develop integrated psychological treatments for both conditions. As well, evidence concerning the temporal relationships between disorders may provide direction in terms of prevention efforts. For example, the findings of Breslau and Davis (1993) suggest that those with a history of migraine would be an appropriate group at which to target anxiety disorder prevention efforts.

Anxiety and headaches

Anxiety sensitivity, fear, and avoidance behavior in headache pain
Norton, et.al
DOI

Abstract
Recent research has implicated anxiety sensitivity (AS), the fear of anxiety-related sensations, as a mitigating factor involved in fear and avoidance in patients with chronic back pain [Understanding and treating fear of pain (2004) 3]. Given reported similarities between individuals experiencing chronic pain and those experiencing recurrent headaches, it is theoretically plausible that AS plays a role in influencing fear of pain and avoidance behavior in people with recurrent headache. This has not been studied to date. In the current study we used structural equation modeling to examine the role of AS in fear and avoidance behavior of patients experiencing recurrent headaches. Treatment seeking patients with recurrent headaches completed measures of AS, headache pain severity, pain-related fear, and pain-related escape and avoidance behavior. Structural equation modeling supported the prediction of a direct significant loading of AS on fear of pain. Headache severity also had a direct loading on fear of pain. Results also revealed that AS and headache severity had indirect relationships to pain-related escape and avoidance via their direct loadings on fear of pain. Headache severity also had a small direct loading on escape and avoidance behavior. These results provide compelling evidence that AS may play an important role in pain-related fear and escape and avoidance behavior in patients with recurrent headaches.
[....]
Discussion
The results of the structural equation modeling provide preliminary, albeit not perfect, support for a similar model to that found by Asmundson and Taylor (1996). Our model, consistent with the Asmundson and Taylor (1996) model, identified AS as having a direct significant relationship to fear of pain in patients with recurrent headaches. Pain severity had a direct significant loading on fear of pain, albeit of a slightly smaller magnitude than AS. Again, this finding was observed by Asmundson and Taylor (1996). As predicted, our model converged with Asmundson and Taylor's in that fear of pain had a very strong direct loading on pain-related escape and avoidance behavior. Contrary to their results, however, we found that pain severity had a small but significant direct loading on pain-related escape and avoidance behavior after accounting for the indirect loading via fear of pain. This discrepancy between our model and that of Asmundson and Taylor (1996) may indicate some differences between the experiences of chronic headache and musculoskeletal pain.
[....]
In conclusion, our results generally support the Asmundson and Taylor (1996) model when employed with a sample of patients experiencing recurring headache. Pain severity and AS both significantly influenced fear of pain, and fear of pain significantly influenced headache-related escape and avoidance behavior. In addition, pain severity had a direct, albeit small, loading on escape/avoidance behavior. These results suggest that treatment strategies that directly target AS may effectively diminish escape and avoidance behaviors in patients seeking treatment for recurrent headache.

Alzheimer's and pain

Pain reactivity in Alzheimer patients with different degrees of cognitive impairment and brain electrical activity deterioration
Benedetti, et. al.
http://dx.doi.org/10.1016/j.pain.2004.05.015

Pain perception and autonomic responses to pain are known to be altered in dementia, although the mechanisms are poorly understood. We studied patients with Alzheimer's disease (AD) whose cognitive status was assessed through the Mini Mental State Examination test and whose brain electrical activity was measured by means of quantitative electroencephalography. After assessment of both cognitive impairment and brain electrical activity deterioration, these patients underwent sensory measurements in which the minimum stimulus intensity for both stimulus detection and pain sensation was determined. In addition, heart rate responses to pain threshold×1.5 were recorded. We found that neither stimulus detection nor pain threshold was correlated to cognitive status and brain electrical activity decline. By contrast, we found a correlation between heart rate responses and deterioration of both cognitive functions and brain electrical activity. In particular, the heart rate increase after pain stimulation was correlated to the presence of slow brain electrical activity (delta and theta frequencies). This correlation was also found for the anticipatory heart rate increase just before pain stimulation. These results indicate that pain anticipation and reactivity depend on both the cognitive status and the frequency bands of the electroencephalogram, whereas both stimulus detection and pain threshold are not affected by the progression of AD. These findings indicate that, whereas the sensory-discriminative components of pain are preserved even in advanced stages of AD, the cognitive and affective functions, which are related to both anticipation and autonomic reactivity, are severely affected. This sensory-affective dissociation is well correlated with the neuropathological findings in AD.

Gender, anxiety sensitivity, and chest pain

Investigating the effect of anxiety sensitivity, gender and negative interpretative bias on the perception of chest pain
Keogh, et. al
http://dx.doi.org/10.1016/j.pain.2004.06.017

Abstract: Research suggests that anxiety sensitivity may be an important component in the negative response to pain sensations, especially those with cardiopulmonary origin. Furthermore, there is experimental evidence to suggest that such effects may be stronger in women than men. The primary aim of the current investigation was to determine the relative roles that anxiety sensitivity and gender have on the pain reports of patients referred to a hospital clinic with chest pain. A total of 78 female and 76 male adults were recruited on entry to a Rapid Access Medical Clinic. All patients had been referred with chest pain, and were administered a range of pain and anxiety measures prior to diagnosis. Results indicate that males were more likely to receive a diagnosis of cardiac chest pain, whereas females were more likely to receive a diagnosis of non-cardiac chest pain. Additionally, anxiety sensitivity was related to pain in women but not men. Finally, evidence was found for the mediating effect of negative interpretative bias on the relationship between anxiety sensitivity and pain. However, this mediating effect was only found in women. These results not only confirm that anxiety sensitivity is related to greater negative pain responses in women, but that this may be due to an increased tendency to negatively interpret sensations.

Gender

Virtual reality analgesia

I've blogged about virtual reality analgesia before. This seems to confirm that it works via attention/distraction.

Manipulating presence influences the magnitude of virtual reality analgesia
Hoffman, et. al
http://dx.doi.org/10.1016/j.pain.2004.06.013

Introduction: Excessive pain during medical procedures performed in unanesthetized patients is frequently reported (Gilron and Bailey, 2003; Karling et al., 2002; Melzack, 1990; Schechter, 1989 and Shang and Gan, 2003) despite the widespread use of analgesic therapies. In clinical settings, side effects of opioid analgesia (e.g. nausea, post-procedure sedation, cognitive dysfunction, and constipation) limit dosage. In contrast, non-pharmacologic techniques typically produce minimal and short-lived side effects, and may serve as valuable adjuncts to traditional pharmacologies. One such non-pharmacologic technique is distraction, which has been shown to help reduce procedural pain in several settings ( Fernandez and Turk, 1989 and Tan, 1982).

Researchers have recently explored the use of immersive virtual reality (VR) as a pain control technique that can be used in combination with traditional pharmacologic therapies. Subjective reports of pain during a variety of painful medical procedures in the clinical setting have been shown to drop approximately 40–50% when patients are distracted by immersive VR (Hoffman et al., 2000a; Hoffman et al., 2000b; Hoffman et al., 2001a; Hoffman et al., 2001b; Hoffman et al., 2004a and Steele et al., 2003).

We theorize that VR analgesia works via an attentional mechanism. Humans have a limited amount of conscious attention available (Kahneman, 1973). Pain requires conscious attention ( Chapman and Nakamura, 1999 and Eccleston and Crombez, 1999). VR systems provide computer-generated multi-sensory input (sight, sound, and more rarely touch, taste and/or smell). Such converging sensory input, and the interactive nature of the experience help give patients the illusion of going into the virtual environment, which can make the virtual world presented difficult for the user's brain to ignore. We theorize that the more intense the patient's illusion of going inside the virtual environment, the more his/her attention will be drawn into the virtual world ( Hoffman, 1998 and Hoffman et al., 2003a), leaving less attention available to focus on pain.

In the present study, some subjects (High Tech VR) used VR hardware (VR helmet, headphones and headtracking system) designed to elicit a strong illusion of VR presence. Others (Low Tech VR) used VR hardware designed to elicit a less compelling illusion of VR presence (see-through VR glasses, no headphones, no headtracking). Regardless of the mechanism of VR analgesia, we predicted that (1) subjects' illusion of ‘going into’ the 3D virtual world (i.e. VR presence) would be greater for the High Tech VR group, and (2) the High Tech VR group would experience more pain reduction than the Low Tech VR group. And we predicted (3) the amount of VR presence reported would be positively and significantly correlated with the amount of pain reduction in VR. In essence, we predicted a measurable dose (increasing VR presence) response (pain reduction) relationship.
[....]
Discussion:
In the current study, we compared the relative effectiveness of Low Tech VR vs. High Tech VR distraction on pain ratings during brief thermal pain stimuli. Subjects showed the predicted dose–response relationship: higher VR presence and more pain reduction in the High Tech VR group than in the Low Tech VR group, and a significant positive correlation between subjective presence ratings and amount of VR pain reduction. The results of the present study and preliminary clinical results (Hoffman et al., 2000b and Hoffman et al., 2001a) are consistent with the notion that pain and VR compete for attention. Although the present study does not specifically identify the mechanism of VR analgesia, we speculate that the more attention is directed towards VR, the less attentional resources are available to process incoming nociceptive signals, and the less pain is consciously experienced.

To date, research exploring VR analgesia has used a within-subjects design (Hoffman et al., 2000a; Hoffman et al., 2000b; Hoffman et al., 2001a; Hoffman et al., 2001b; Hoffman et al., 2004a and Hoffman et al., 2004b), such as comparing pain during 3 min of physical therapy without VR to pain during 3 min of physical therapy with VR within the same physical therapy session ( Hoffman et al., 2000b). Potential nuisance variables such as plasma opioid level or how much sleep the patient had the night prior to the study were all controlled using such a within-subject design. One potential limitation of the within-subjects design is that subjects receive (and are thus aware of) both the experimental and control conditions. In the current study a double-blind, between-groups design was used to help reduce demand characteristics.

Eccelston and Crombez (1999) claim that pain is unusually attention grabbing, making it difficult to distract attention away from pain. Similarly, McCaul and Malott (1984) have proposed that distraction works for mild to moderate pain, but is much less likely to reduce extreme pain. In contrast, preliminary clinical results show that VR is able to distract severe burn patients experiencing extreme pain during wound care ( Hoffman et al., 2000a) suggesting that in comparison to VR, pain does not appear to have privileged access to attentional resources. Why VR is able to compete with extreme pain for attentional resources is an important research question. The present results suggest that the illusion of going into the virtual environment may help explain why VR is so effective for reducing various components of the pain experience.

In a previous VR study not involving pain, Hoffman et al. (2003a) tested the fundamental assumption that VR requires conscious attention. Healthy volunteers monitored a string of numbers from a tape recorder for three odd numbers in a row while in VR (helmet worn and turned on) and without VR (helmet worn but turned off). Participants showed a significant reduction in performance on a divided attention task (accuracy in identifying the consecutive odd numbers) while in VR (74% correct) compared to the control condition (95% correct), and they also estimated that the amount of time they were able to attend to the task of monitoring the numbers was significantly higher with no VR than with VR (96 vs. 65%, respectively).

In the present study, compared to the Low Tech VR group, subjects in the High Tech VR group reported a significant increase in how much fun they had during VR. Pain reduction in VR was correlated with how much fun subjects reported having, and is consistent with severe burn patients who report having fun during wound care and physical therapy in High Tech VR (e.g. Hoffman et al., 2004a). In the present study, increasing the ‘immersiveness’ of the VR hardware also led to higher VR presence ratings and was correlated with pain reduction. Studies exploring medical applications of VR exposure therapy for treating anxiety disorders have also described manipulations of the immersiveness of the VR hardware that increased the illusion of presence and increased treatment effectiveness/clinical outcome ( Hoffman et al., 2003b). We predict that further increasing the immersiveness of VR systems in future studies will further increase the participant's illusion of presence in VR, and may increase the magnitude of VR analgesia. Future laboratory and clinical studies should systematically explore (1) the addition of converging sensory input from visual, sound, tactile, smell and vibrotactile (e.g. surround sound) stimulation, (2) increased interactivity between the participants and the virtual world, and (3) which components of the VR environment (including both hardware and software, and individual differences) contribute to the sense of presence and analgesia. Some manipulations that increase presence may also increase simulator sickness (e.g. going faster through the virtual canyon). Care should be taken to minimize simulator sickness in these more immersive VR systems, especially when used adjunctively in clinical studies in patients at risk for nausea from pharmacologic (opioid) analgesics.

[....]

VR is a promising non-pharmacologic analgesic, especially for patients who must undergo brief painful procedures. Results from the current study suggest design guidelines for VR analgesia systems. Specifically, highly immersive combinations of VR hardware and software that maximize the user's illusion of presence in the VR environment will likely enhance the effectiveness of virtual reality as a non-pharmacologic analgesic. Selecting participants who have a pre-disposition to feel high presence in VR may also be possible in some applications. Furthermore, we speculate that patients may respond better to some virtual worlds than others. Since excessive procedural pain is a widespread problem for the medical community, and these preliminary results provide additional support for the notion that VR might prove valuable for pain control, additional research on this topic is warranted.

Chronic pain and frequent use of health care

Chronic pain and frequent use of health care
Blyth, et. al
http://dx.doi.org/10.1016/j.pain.2004.05.020

Abstract: Little is known about the relationship between chronic pain status and overall use of healthcare. We examined whether disabling chronic pain was associated with more frequent use of healthcare in three settings: primary care, emergency departments, and hospital admissions. We used data from Computer-Assisted Telephone Interviews (CATI) of 17,543 residents in New South Wales, Australia aged 16 and over who were randomly sampled using a population-based two-stage stratified sample and random digit dialling methods. The overall response rate was 70.8%. Compared to chronic pain respondents with no or limited pain-related disability, those with most pain-related disability reported more: primary care visits in the last 2 weeks and last 12 months (adjusted mean number of visits 0.59 vs 0.40 and 10.72 vs 4.81, both P<0.005); hospital admissions (0.46 vs 0.18, P<0.005); and emergency department visits (0.85 vs 0.17, P>0.005). In modelling, having chronic pain per se, or having chronic pain with any level of activity interference predicted health care use after adjusting for age, gender, self-rated health, psychological distress, comorbidity and access to care. Higher levels of pain-related disability predicted health care use more than other pain status variables. There was a strong association between pain-related disability and greater use of services. Further work is needed to understand the nature of this association. Given the fluctuating course of chronic pain over time, there is a significant segment of the population that may be at risk of developing higher levels of disability associated with increased use of services.

Effects of exposure on perception of pain expression

Effects of exposure on perception of pain expression
Prkachin, et. al
http://dx.doi.org/10.1016/j.pain.2004.03.027

I don't normally quote this much from an article, but this one is interesting. Take note my simulation friends.

When a sufferer displays pain, the responses of others can vary. Common affective responses may be sympathy and empathy, but they can include fear, or even pleasure in the other's suffering. Behaviorally, observers often provide assistance or seek ways to soothe the other's suffering; however, they may also criticize, note the evidence of suffering but say nothing or not notice at all. All but the last alternative presupposes that the observer has engaged in some perceptual processing of the event (Prkachin and Craig, 1994). Differences in these responses may affect the sufferer. For example, there is evidence that health-care practitioners underestimate the suffering of pain patients ( Marquié et al., 2003). Such ‘miscalibration’ can affect treatment decisions, thereby influencing the individual's quality of life. Likewise, operant theorists suggest that the manner in which others respond to evidence of pain can set the stage for chronic pain or stoicism ( Fordyce, 1976).

The study of judgments of facial expressions of pain offers a way to understand the perception of the suffering of others. Facial expressions provide evidence about pain that is valid (Craig et al., 2001) and graded in intensity ( Prkachin, 1992 and Prkachin and Mercer, 1989). Observers are sensitive to the information contained in the display ( Prkachin and Craig, 1985 and Prkachin et al., 1994); however, there are marked individual differences in their judgments. Some of these differences may be attributable to experience. For example, Prkachin et al. (2001) studied how people with different experience perceived shoulder-pain patients' facial expressions. Observers generally underestimated pain (relative to the ratings of the sufferers themselves). Compared with people who had little experience with pain patients, health-care workers showed greater underestimation. Relatives of pain patients showed less.

[....]

There is also evidence that certain types of experience alter participants' decisional biases about pain expression. Prkachin et al. (1983) showed that providing observers with information that others should be hypersensitive to pain increased their general tendency to impute pain. Lundquist et al. (2002) showed that information that a person being judged was behaving in accordance with medical advice led judges to impute greater pain.

In the present study, we were interested in whether we could adduce evidence for selective adaptation to pain expression. We hypothesized that increasing exposure to pain expression would be associated with reduced sensitivity. Signal detection methodology was employed in order to map effects on perceptual sensitivity and decisional bias.

[....]

Results
The expectation that selective adaptation to pain expression by overexposure would result in diminished sensitivity to pain expression was not supported. Instead, high levels of exposure were associated with significant alterations in observers' criteria for indicating that a particular expression showed pain. With increasing exposure to displays of strong pain, false alarm and hit probabilities decreased in a parallel fashion, indicating that observers became more conservative in their pain judgments. To our knowledge, this is the first experimental demonstration of a quantitative shift in criteria for judging pain expression. The findings provide evidence of an adaptation-level effect (Helson, 1964 and Rollman, 1979) in the judgment of pain expression. Adaptation-level refers to the observation that, in psychophysical judgment tasks, the evaluation that an observer makes of a stimulus may depend on the context in which judgments are made. Rollman (1979), for example, demonstrated that judgments of the amount of pain induced by electric shocks were influenced by the level of comparative shocks presented at the same time. When a relatively weak stimulus was judged in the presence of a weaker stimulus, participants gave higher ratings than they gave to stronger stimuli judged in the context of even stronger stimuli. In the present study, participants were less willing to judge moderately painful expressions as painful when they had been exposed to a large number of even more painful expressions than when they had been exposed to a relatively smaller number. The significant linear reduction in false alarm and hit rates was suggestive of a ‘dose-dependent’ relationship.

This unexpected finding may bear on the observation that, relative to people with little experience with pain sufferers, health practitioners who routinely deal with pain patients provide lower judgments of the magnitude of pain when relying on the same behavioral information (Prkachin et al., 2001). There are a variety of possible interpretations of this difference, including divided attention, cognitive differences attendant on training and differential experience. The present findings suggest a relatively parsimonious interpretation of the effect. If one is exposed to evidence of considerable pain in relatively large amounts and if an adaptation-level effect is operative, then high-intensity expression may become the standard against which pain in others is evaluated, and other expressions will be ‘downgraded’ accordingly.

The second finding of note was that female observers were better able to detect the presence of pain expression than men. Though novel to the pain expression field, there is a literature that documents female superiority in decoding nonverbal cues (Brody, 1985 and Hall, 1978). The present study is consistent with that literature, which notes a particular advantage for females in decoding cues of negative emotional states. Though significant, the implications of the difference documented in the present study may be limited due to the fact that the effect size was quite small. Nevertheless, in circumstances in which it may be desirable to select individuals who decode pain expression well, such as in decoding studies or pain assessment, there may be an advantage in selecting females.

A third finding that warrants emphasis is the high level of acuity displayed by participants, regardless of experimental condition. Average values of the discriminability measure varied from 0.91 to 0.94 on an index on which a value of 1.0 indicates perfect performance. These levels of performance appear quite impressive when considered in relation to the facts that the test stimuli displayed facial behavior categorized as moderate in intensity and they were displayed for only 1 s. Clearly, under the conditions maintained in the present study, people are highly sensitive to changes in facial behavior indicative of pain. This degree of acuity appears likely to reflect the kind of non-conscious automatic activation of evaluative processes (such as trait judgments) that characterizes the perception of complex social behaviors, (Bargh and Ferguson, 2000). No doubt this speaks to the adaptive nature of sensitivity to pain expression, an ability that is likely to contribute to the fitness of both the sufferer and the observer ( Fridlund, 1994 and Williams, 2002)

Pain shrinks the brain

Curious. But until they say something about the effects of the brain-shrink, not all that useful.

Pain causes an unexpected brain drain, according to a new study in which the brains of people with chronic backaches were up to 11 percent smaller than those of non-sufferers.

People afflicted with other long-term pain and stress might face similar brain shrinkage, said study leader A. Vania Apkarian of Northwestern University.

The results suggest those with constant pain lose gray matter equal to an oversized pea for each year of pain. Gray matter is an outer layer of the brain rich in nerve cells and crucial to information and memory processing.

The results don't reveal why the brain shrinks, but it might involve degradation of neurons, which are the signal transmitters of the mind and body.

"It is possible it's just the stress of having to live with the condition," Apkarian told LiveScience. "The neurons become overactive or tired of the activity."

Another possibility is that people born with smaller numbers of neurons are predisposed to suffering chronic pain. But some of the differences measured "must be directly related to the condition," Apkarian said.

The research involved a one-time brain scan of 26 people who'd had unrelenting back pain for at least a year (and in one case for up to 35 years), along with a pain-free control group. Pain sufferers had lost 5 to 11 percent of gray matter over and above what normal aging would take away.

"People who have had pain for longer times have had more brain atrophy," Apkarian said.

No attempt was made to correlate brain size to brain function. It is possible that some of the shrinkage involves relatively noncrucial tissue -- other than neurons -- and that some of the effects are reversible if the pain is eliminated, Apkarian and colleagues write in the Nov. 23 issue of the Journal of Neuroscience.

Apkarian said other varieties of pain might cause a similar atrophy of gray matter, and he plans to study that possibility in future studies.

"Suffering of pain is fundamentally an emotional condition," Apkarian said. "Different types of pain will have different types of emotional parameters, which will probably result in different types of atrophy -- different amounts and in different brain regions." Link

Living with pain

Another great bit from the UCLA online exhibit (and apologies to my readers whom this bores --as you well know, until fame, I use this blog to record tidbits that interest me for further use).

Since 1973, the multidisciplinary pain clinic has come into its own. Many clinics now offer a variety of therapeutic approaches to effective pain management, including physical therapy, acupuncture, TENS (transcutaneous electronic nerve stimulation), hypnosis, and behavioral modification based on the methods pioneered by Bonica's colleague, Wilbert Fordyce. However, not all patients have access to good pain clinics and, in the US, many pain therapies are not covered by insurance.

Richard Sternbach, of the Pain Treatment Center at Scripps Clinic and Research Foundation in La Jolla, offered 7 steps on how to live despite pain in his 1977 pamphlet (How Can I Learn to Live With Pain When It Hurts So Much?, revised in 1983):

1. Accept the fact of your pain
2. Set specific goals of work, hobbies and social acitivities towards which you will work
3. Let yourself get angry at your pain if it seems to be getting the best of you
4. Pace your activities
* Get in shape, and keep fit
* Learn to relax, and practice it
5. Time your medications, then taper off them
6. Have family and friends support only your healthy behavior, not your invalidism
7. Be open and reasonable with your doctor

Pain and suffering

Check out this online exhibit from the UCLA pain library.

Opiates: oxycodone

My friend broke his wrist the other day. In talking to him, I realized that I don't know how the various opiate drugs stack up against each other: i.e., which are stronger and by how much, which last longer, and how they differ in their indications. So I'm on the hunt. First up: oxycodone

He was prescribed Percocet which turns out to be oxycodone and acetaminophen (Tylenol). According to the DOJ,

Oxycodone is an effective analgesic for mild to moderate pain control, chronic pain syndromes, and for the treatment of terminal cancer pain. Five mg of oxycodone is equivalent to 30 mg of codeine when administered orally. Oxycodone and morphine are equipotent for pain control in the normal population; 10 mg of orally-administered oxycodone is equivalent to 10 mg of subcutaneously administered morphine. Oxycodone is considered to be similar to morphine, in all respects, including its abuse & dependence liabilties. Oxycodone in dosages of 5 to 10 mg in combination with acetaminophen or aspirin are abused orally. High dose single entity sustained release formulations containing 10 to 80 mg of oxycodone are abused by crushing or chewing the tablet and then swallowing, snorting or injecting the drug.

Chemistry/Pharmacology

Oxycodone [4,5a-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one, dihydrohydroxycodeinone] is a semisynthetic opioid structurally related to codeine and is approximately equipotent to morphine in producing opiate-like effects. The first report that oxycodone, sold under the brand name Eukodal, produced a "striking euphoria" and habituation symptoms was published in Germany in the 1920's. While oxycodone is metabolized by the liver to oxymorphone, the physiological and behavioral effects are not related to, nor dependent on, the formation of this metabolic by-product. Link

and it looks like this:

Oxycodone comes from thebaine, a minor constituent of opium. Unlike codine and morphine, thebaine produces stimulatory instead of depressant effects.

Pictures

I've been looking for some good pain images, particularly older paintings and sculptures. I'd appreciate any suggestions.

Nagel and the objectivity of pain's badness

After several months of intermittent banging of my head against this point from Nagel, I still can't decide whether I think he's deeply right, or deeply wrong. Anyway, its worth drawing attention to because it is extremely important for how we understand impersonal (agent-neutral) reasons for alleviating pain and the source of the reasons each has to alleviate her own pains.

When the objective self contemplates pain, it has to do so through the perspective of the sufferer, and the sufferer's reaction is very clear. Of course he wants to be rid of this pain unreflectively -not because he thinks it would be good to reduce the amount of pain in the world. But at the same time his awareness of how bad it is doesn't essentially involve the thought of it as his. The desire to be rid of the pain has only the pain as its object. This is shown by the fact that it doesn't even require the idea of oneself in order to make sense: if I lacked or lost the conception of myself as distinct from other possible or actual persons, I could still apprehend the badness of pain immediately. So when I consider it from an objective standpoint, the ego doesn't get between the pain and the objective self. My objective attitude toward pain is rightly taken over from the immediate attitude of the subject, and naturally takes the form of an evaluation of the pain itself, rather than merely a judgment of what would be reasonable for its victim to want: "This experience ought not to go on, whoever is having it." To regard pain as impersonally bad from the objective standpoint does not involve the illegitimate suppression of an essential reference to the identity of its victim. In its most primitive form, the fact that it is mine -the concept of myself- doesn't come into my perception of the badness of my pain. View from Nowhere, p.161

Precis II

I finally submitted the fellowship application I've been sweating over for the past month and a half. When I returned to the precis I thought I had finished (the precis I had posted here), I realize it needed to me sexier. Here's the new version. Again, I'm curious what you think (for long comments, try using the twin site at www.dolor.blog-city.com or emailing me).

Pain is a fundamental evil. Understanding pain and its place in human life is a fundamental religious and ethical concern. From Pandora, to Job, to the Buddhists' first Noble Truth that all life is suffering, to modern secular questions about the value of life, all philosophical and religious traditions have struggled with pain's evil. From the source of our moral obligations and our understanding of what makes life good, to the role of suffering in redemption and the idea of a just god, making sense of pain is making sense of humanity. Yet, despite its central place in our understanding of ourselves and of what matters most, virtually everyone has misunderstood what pains are and therefore wherein their evil lies. I shall give a new account of both.

This is a dissertation on pain's intrinsic badness. It is also a dissertation on the nature and sources of value. The account I shall give yields insights into perennial philosophical questions including, inter alia, the ubiquity of reasons to alleviate other's pains; the nature of rationality; the role of subjective desire in ethics; the possibility of reducing value to natural properties; the value of autonomy; the nature of torture; and the normative significance of animals' pain.

Hedonism

Some online resources on hedonism:
The Cyrenaics and the Origin of Hedonism

A summary of Sidgwick's Method of Ethics

Stanford encyclopedia entry

Pain history archive

I suspect I'm going to be spending a lot of time here: http://www.library.ucla.edu/libraries/biomed/his/pain.html

The goal of the UCLA History of Pain Project is to promote and ensure the study of the history of pain research and pain therapy in the post-World War II era, in particular, the origins, growth, and development of the international, interdisciplinary pain field. Its major initiatives to achieve this goal are the creation of the John C. Liebeskind History of Pain Collection at the Louise M. Darling Biomedical Library at UCLA and the active dissemination of information about the Collection and the history of pain to appropriate audiences.

The Liebeskind History of Pain Collection includes:

* Oral histories with scientists, physicians, and other health professionals in the field of pain, and with chronic pain patients. Forty have been completed of the core collection of sixty interviews. These include interviews with leading pain scholars and clinicians such as John Bonica, Kathleen Foley, Ainsley Iggo, Ronald Melzack, Cicely Saunders, Richard Sternbach, and Patrick Wall. Master copies of the tapes and transcripts are available in the Biomedical Library after final review by the oral authors.

*Personal papers of pain pioneers and selected leaders in the pain field such as John J. Bonica (1917-1994), William K. Livingston (1892-1966) and William Noordenbos (1910-1990).
*Archival records of major pain organizations, including the American Pain Society (APS), the International Association for the Study of Pain (IASP), and the American Academy of Pain Management (APPM). Document collections are processed according to archival standards at the Biomedical Library and finding aids are developed to aid scholar access.

* Group interviews with leaders in the pain field, recorded on videotape for deposit in the Library. Three group interviews have been completed: "Perspectives on Pain" (1993), "The Bonicas: Passion is the Fuel of Life" (1994), and "Current Issues in Pain Management" (1995)

* Bibliographies of books, journals, and other materials relating to pain in the UCLA Biomedical Library; and listings of source materials available at other libraries and archives.


The Collection is supported by the extensive holdings of the Biomedical Library, which are regularly augmented with accessions of recent publications and classic works on pain.

War on drugs; war on pain

From the NYT:

In February 1999, Dr. Frank Fisher, a general practitioner in Shasta County, Calif., was arrested by agents from the California state attorney general's office and charged with drug trafficking and murder.

The arrest was based on records indicating that Dr. Fisher had been prescribing high doses of narcotic pain relievers to his patients, five of whom died. He lost his home and his medical practice and served five months in jail before it was discovered that the patients had died from accidents or from medical illnesses, not from the narcotics he prescribed.

All charges were dropped last year, and Dr. Fisher now has his medical license back. Yet his ordeal lingers as a cautionary tale of what can happen to doctors who treat pain aggressively.
....
No one questions that abuse of opiate painkillers is a problem. But federal and state law enforcement agents, who wield considerable power in deciding whether to initiate investigations, as well as the prosecutors and jurors who determine a doctor's fate if the case goes to trial, are often misled by obsolete ideas about the practice of pain medicine and the effects of opiate drugs.

Pain treatment itself is an area ripe for misinterpretation. Many patients who seek doctors' help have already tried nonsteroid anti-inflammatory drugs, conventional opiates like codeine and even surgery, yet they are still in severe pain from cancer, degenerative arthritis, nerve damage or other conditions. Large doses of medicines like hydrocodone (Vicodin), oxycodone (OxyContin), morphine or methadone may be required.
....
The red flags that rightly alert regulators to potential misconduct by doctors are, paradoxically, the very features that can also mark responsible care for intractable pain. These include prescribing high volumes of narcotic painkillers for extended periods, prescribing potentially lethal doses or prescribing several different drugs. In some regions, patients use several different pharmacies, at their doctor's instruction, because some pharmacists are reluctant to dispense large quantities of the medications.

To complicate matters further, doctor shopping can also be a sign of what is called pseudo-addiction: the efforts to obtain drugs look on the surface like drug addiction, but in fact represent the patient's attempt to attain an adequate level of pain control. Once that is achieved, the patient no longer presses for more narcotics.
....
We are unable to refer patients to doctors who will treat pain, if only because once a name gets out there, patients understandably flock, and then the doctor is targeted," said Siobhan Reynolds of Pain Relief Network, a patient advocacy group based in New York. The Association of American Physicians and Surgeons, based in Tucson and dedicated to the concerns of private practitioners, has gone so far as to warn doctors against managing chronic pain, lest they face of years of harassment and legal fees, even prison. "If you do," the association enjoins, "first discuss the risks with your family."

Scattered evidence confirms these impressions. A 1998 survey of more than 1,300 physicians by the New York State Medical Society found that 60 percent were moderately or very concerned about the possibility of being investigated by regulatory authorities for prescribing opiates for noncancer pain.

A third said they prescribed lower quantities of pills and lower dosages "frequently" because of the possibility of eliciting an investigation. When asked how often they avoided prescribing a preferred drug for noncancer pain, because doing so required triplicate forms, half said "frequently." Link

Categories: Legal

Precis

I've been trying to write a 200 word summary of my eight-million chapter dissertation. I'm having trouble writing anything that is at all informative and coherent. At risk of embarrassment, I'd like to know what you think.

Pain is a fundamental evil. It is also a topic on which all extant views of intrinsic value are intuitively inadequate. The badness of agony doesn't seem to lie just in your not liking it; claiming that its badness lies in its unpleasantness seems pleonastic. These views are incomplete, but not wholly implausible. Your dislike of a pain, the way it impels you to escape, and the way it feels, all seem to be part of its intrinsic badness.

I believe the intrinsic badness of pain lies in the way it usurps a sufferer's control over herself. All creatures capable of purposeful action properly have a particular kind of control over aspects of their mind and body. By usurping this control, a pain undermines the dominion necessary for a being's well-functioning.

This accounts for what was plausible in the extant views. In disliking a pain we rebel from the foreign invader; we are passive in its impelling us to escape; and part of the usurpation is the way a pain feels as though it consumes one's mind.

Along with practical implications for the ethics of palliative care, my view has deep implications for our understanding of the nature and sources of value. It yields, inter alia, insights into the reality and strength of our reasons to alleviate other's pains; the role of subjective desire in value-theory; the nature of torture; animal's pain; and the structure of pleasure. [237 words]

Gastrointestinal pain in children

The NYT has an article up on unexplained chronic gastrointestinal pain in children. It is, of course, non-technical enough that it probably isn't really useful, but underscores again one of my hobbyhorses: Things like anxiety, depression, and broader psychological responses, aren't as easily separable from pain as most think. As you all now know, I believe that many such factors ought to be regarded as intrinsic properties of the pain.

Nothing in this article argues for that point, but it does raise one (admittedly philosophically lame) consideration for it: Part of the stigma of receiving psychological/pscyhatric treatment for pain may lie in the thought that the sufferer is somehow deficient or abnormal in her response to pain. If we take such responses to partially constitute the pain (that is, to be part of what the pain is), then the perceived deficiency is incoherent.* It plausibly assumes that we cannot be criticized for our pains --like kidneys they are parts of us but not under our control. But if the 'response' partially constitutes the pain, then the response cannot be open to criticism.

Anyway, enough about me, here's a bit of the article

New approaches to treating pain - including cognitive behavioral therapy; alternative treatments like relaxation techniques and massage therapy; and antidepressants - are already being used in adults, but they have not been widely adopted for children, in part because only a handful of small studies support such use.

In recent years, however, experts have begun to understand more about the connections between the brain and the gut, a relationship that is reflected in popular expressions like "a gut-wrenching experience" or "having butterflies in your stomach."

The gastrointestinal tract is awash in nerve cells and neurotransmitters. About 95 percent of the body's neurotransmitter serotonin is in the intestinal tract. Stress, nervousness, fear and other emotions often play out their own drama in the gut. In children with abdominal pain, the intestinal tract becomes hypersensitive to stimuli, with the slightest bit of gas, for instance, sending a flood of pain signals to the brain

The problem appears to be a mismatch in signaling between the brain and the gut, said Dr. Lonnie Zeltzer, director of the Pediatric Pain Program at the David Geffen School of Medicine at the University of California, Los Angeles. "If you have ongoing pain, you can develop abnormal pain pathways, so that the volume of pain signaling is being turned up and up," Dr. Zeltzer said.

What causes the hypersensitivity is not completely understood, but experts believe that it is often set off by a stomach virus or an infection

"It's not uncommon that a family will get viral gastroenteritis, the whole family gets better except the child," said Dr. Zeltzer, whose book, "Conquering Your Child's Chronic Pain: A Pediatrician's Guide for Reclaiming a Normal Childhood," will be published by HarperResource in January. "The pain system is turned on and stays on."

"It's not uncommon that a family will get viral gastroenteritis, the whole family gets better except the child," said Dr. Zeltzer, whose book, "Conquering Your Child's Chronic Pain: A Pediatrician's Guide for Reclaiming a Normal Childhood," will be published by HarperResource in January. "The pain system is turned on and stays on."....

As an understanding of the brain-gut connection grows, however, some centers have begun to use techniques like cognitive behavioral therapy, relaxation training, massage therapy and other alternative approaches as a first line of treatment.

The effectiveness of these therapies is still debated, and the number of studies examining their effectiveness in children is very small, experts say. In one study published in the August issue of The Journal of Pediatric Gastroenterology and Nutrition, 18 children ages 8 through 17 who had pain for about a year were taught guided imagery and progressive relaxation.

In four to seven sessions, 89 percent of the children reported a reduction in pain, to an average of two episodes a week, from six, said Dr. Youssef, the lead author of the study. The children had fewer missed school days, and their quality-of-life scores rose significantly.

"Our goal is to help them relax about the pain," Dr. Youssef said. "If you don't worry about the pain, you don't get pain." Link

Btw: I think Dr. Youssef should have said 'If you don't worry about the pain, there is no pain'. Picky, picky, picky.

*I'm overstating the metaphysical point here. Constitution may be too strong a relation for what I have in mind. But that is a subject for another post.

Not dead...

Neither I nor this blog are dead.

With the semester starting and scrambling to get applications for fellowships/post docs together, I've been neglecting you, gentle reader.

Please stay. Its not you: you're great. Its been me. I've been inattentive to your needs. I'm sorry, and if you can just give me another chance (and a couple of more weeks), I promise I'll make it up to you. I'll give you more philosophy than ever before. Both from my dissertation, and some material on simulation theories that isn't even in press yet. Yes, I'll be good to you from now on. Please stay.

Please...

Moving...

I'm in the process of moving this blog to http://www.dolor.blog-city.com/. I like the new site's interface better, and they allow posts to be categorized (something I think will be useful for this blog).

Until I've got that site up and running, I'll continue to post new stuff on both blogs, before phasing over to the new one.

Pain in children

I just came across this online article on assessing pain in children with cancer. Both sad and interesting.

While the whole article is worth reading, here's something I was unaware of:

The first question on the Pain Experience History [ed:see next quote]addresses whether the child understands the word pain. This question evolved from two studies (42,43) documenting that hospitalized children often do not understand what pain is. The preferred word for many children under 12 years is hurt (49). The child's response to ``Tell me what pain is'' provides the health care provider with the word to use when discussing pain with the child. For example, a 12-year-old boy with Burkitt's lymphoma said pain was ``real hard throbbing'' (52). This child seemed to understand the word pain. In contrast, a 7-year-old boy with more than 20 previous surgeries denied knowing what the word pain meant (42). He did, however, understand the word hurt.

This seems to be another phenomenon which points to the fact that we must learn what pains are and their place in our lives (i.e., they are evils to be avoided). This conclusion is important for understanding what pains are.*

For just one example, simple hedonic theories of value are traditionally threatened by the fact that pleasures and pains come in myriad forms. This makes it unclear why some things are pains and others are not. Such theories therefore verge on trivial. The fact that we must learn our conceptions of pain thus suggests that the class of pains has few natural boundaries. Losing pain as a fundamental or innate concept twists the knife for these views.

Whether you buy this connection or not, the material here is at least thought provoking.

Here's a bit of the Pain Experience History questionairre

Child form (C) Parent Form (P)
(C1) Tell me what pain is.
(P1)What word(s) does your child use in regard to pain?
(C2)Tell me about the hurt you have had before.
(P2)Describe the pain experiences your child has had before.

C3)Do you tell others when you hurt? If yes, who?
P3)Does your child tell you or others when he or she is hurting?

(C4)What do you do for yourself when you are hurting?
(P4)How do you know when your child is in pain?

(C5) What do you want others to do for you when you hurt?
(P5)How does your child usually react to pain?

(C6)What don't you want others to do for you when you hurt?
(P6)What do you do for your child when he or she is hurting?

(C7)What helps the most to take your hurt away?
(P7)What does your child do for him- or herself when he or she is hurting?

(C8)Is there anything special that you want me to know about you when you hurt? (If yes, have child describe.)
(P9)What works best to decrease or take away your child's pain? Is there anything special that you would like me to know about your child and pain? (If yes, describe.)

And two, depressing but philosophically interesting, cases

Other questions focus on the child's prior pain experiences, how the child communicates about pain, and the child's preferences for management. A 5-year-old boy with Burkitt's lymphoma said ``spinal taps'' in response to the inquiry about prior pain experiences; he described his bone marrow aspiration as ``bow and arrow'' (52). A response like this provides the health care professional with important information about the child's understanding of a bone marrow aspiration. The child placed the concept of the bone marrow aspiration into the context of something more familiar-a bow and arrow.

A 9-year-old girl with osteosarcoma and severe mucositis said she told others when she hurt, but with the mucositis, she had to communicate by writing (52). She wanted to hold her mother's hand when she hurt and described back rubs, conversation, quiet distraction, and a quiet room as helpful in relieving her pain. She did not want others to surprise her by ``moving her sore leg.'' This child's responses would be extremely helpful in planning care to identify, prevent, and treat pain.

I suppose I'm alone in being impressed by the fact that the boy describes how his pain felt via an inference about what it would feel like to be shot with an arrow (though he might mean that the pain is both sharp and tight; I'm drawing my reading from the fact that the cause is having his bones drilled).

*There's a bunch of literature on how we learn pain. The references for this article are here. And you must know the classic McGill dog study if you are to impress your friends and intimidate your enemies is. I can scrounge up more references on request.

Ergonomic pain

This might interest those of the legal persuasion.
Ergonomic Pain Part 2: Differential Diagnosis and Management Considerations.

Abstract: Work-related musculoskeletal disorders (MSDs) can produce ergonomic pain in several different regions of the body, including the shoulder, elbow, wrist and hand, lumbar spine, knee, and ankle/foot. Each family of disorders is distinctive in presentation and requires diagnosis-specific interventions. Because of the complex nature of these disorders, management approaches may not always eliminate symptoms and or completely restore patient function to a level found prior to symptom onset. As a consequence, ergonomic measures should be implemented to reduce the overload on tissue and contribute to patient recovery. However, functional limits may persist and the clinician must make further decisions regarding a person's functional status in the chronic stages of the patient's care. [ABSTRACT FROM AUTHOR]

Pain Practice, Jun2004, Vol. 4 Issue 2, p136, 27p
DOI: 10.1111/j.1533-2500.2004.04209.x; (AN 13229319)

Which reminds me, why can't Rutgers give a poor grad student an office chair which doesn't force him into some obscure yogic pose for office hours? Help, OSHA?

Botox

Nothing philosophically significant here.* Just another way in which Botox --one of the most potent poisons around-- is useful for more than just destroying the expressiveness of people in LA's faces.

Abstract: Botulinum toxin type A (BoNT-A) shows significant promise in the management of a variety of headache types including migraine, chronic daily headache, tension-type headache, and other head and neck pains. Confirmation of efficacy still awaits the report of well-controlled double-blind placebo-controlled trials; however, a mounting body of evidence suggests that BoNT-A is effective, well-tolerated and safe for the management of many headache disorders. In this paper, I review recent evidence on the efficacy of BoNT-A, and also report my personal experience with the treatment in over 600 headache patients.

Author: B. Todd Troost

DOI: 10.1007/s10194-004-0063-z

Seriously though, since the etiologies of many headaches are so mysterious, any widely effective management technique will lessen a lot of suffering (N.b., people with some headache disorders --e.g., cluster-headaches-- are particularly prone to suicide).

* Okay, one small philosophical note. Its worth thinking hard about why headaches are often so much worse than many sharp and acute pains (e.g., a badly stubbed toe). Two hints:

(1) It is very difficult to disassociate from a mildly severe headache since we usually experience ourselves as being 'in our heads'.** It is comparatively easy to disassociate from a badly stubbed toe or a hammer-smashed finger.

(2) At a fairly low level of intensity, headaches can have a huge negative impact on our lives and well-being. A migraine makes it hard to carry on a civil conversation and can (temporarily) destroy one's capacity for the pursuit of long-term projects and close personal relations.(This becomes more interesting when one believes, as I do, that such effects on one's life can be intrinsic properties of a pain)

**Pace Aristotle, who seems to have believed that the heart is the seat of the soul and (so I've been told) experience.

Pain research

Yesterday, when the steel door of our department unexpectedly slammed shut on my finger, I was fortunate to be able to conduct some research and empirical testing of my philosophical views on pain.

I'm pleased to say that things turned out well. One consequence of my view is that by relaxing and accepting a pain --in particular, by letting go of the urge to fight it (see: Nagel, Korsgaard) and trying to associate with it as part of one's self (see: me)-- the pain becomes much less bad.* Importantly, that's not to say that the sensory qualities of the pain change (much). In terms of phenomenology, the pain still felt pretty much the same, but there was a substantial change in its badness.

Unfortunately, I wasn't able to reconfirm my claim --arrived at mainly through broken fingers in the past**-- that certain pains have a distinctive character indicative of the injury. That is, broken fingers have a certain feeling to them. Its been awhile since I last broke a finger and thus I was curious whether I would recognize the alleged distinctive character again.***


*N.b., this is very different from trying to ignore the pain. Actively trying to put it out of your mind, I think, tends to make it worse.

**No, I'm neither a masochist nor particularly clumsy. All the broken bones resulted from martial arts injuries in my teenage years (when I viewed such injuries as a source of pride and badge of honor --now that I have arthritis at 27 and can reliably tell you when a storm's a comin', I'm a bit less proud).

***One must, I think, learn such pain identification through experience. Many traumas probably feel like broken bones to the naive injured patient; but many broken bones have a distinctive character to those of us with experience.

Where migraines come from

I've mentioned the complexity of headaches several times. Don't believe me? A quick skim of this article covering just one of the potential etiologies should suffice to convince.

The pathogenesis of migraine headache is poorly understood but the trigeminovascular system seems to play an important role in it. The trigeminal nucleus caudalis is sensitised by noxious sensory stimuli, often from convergent afferents originating from a variety of tissues. In this paper, we review evidence to support the view that the cervical muscles play a role in the pathogenesis of the migraine headache as well by facilitating the mechanism of central sensitisation

By:Elliot Shevel1 and Egilius H. Spierings

DOI: 10.1007/s10194-004-0062-0

DOI links

I'm going to start linking to science articles using the DOI system. Here's a description of how the system works.

The digital object identifier (DOI) may be used to cite and link to
electronic documents. The DOI consists of a unique alpha-numeric
character string which is assigned to a document by the publisher upon
the initial electronic publication. The DOI will never change.
Therefore, it is an ideal medium for citing a document, particularly
Articles in Press because they have not yet received their full
bibliographic information.

The correct format for citing a DOI is shown as follows:

doi:10.1016/j.physletb.2003.10.071

When you use the DOI to create URL hyperlinks to documents on the web, they are guaranteed never to change.

Complete the following steps to resolve a DOI:

1. Open the following DOI site with your browser:
   

   http://dx.doi.org

2. Enter the entire DOI citation in the text box provided, and then click Go.
   

   The article that matches the DOI citation appears in your browser window.

The DOI scheme is administered by the International DOI Foundation. Many of the world's leading learned publishers have come together to build a DOI-based article linking scheme known as CrossRef.

Here's how we'll use it here. At the bottom of each post there will be a link that refers to an article with a DOI number. Copy the link target (it will be the DOI number). Then toward the top of this blog's sidebar, click on the DOI link to be taken to the DOI lookup page. Finally, paste the link target into the box and press enter. (This makes it seem harder than it actually is).

[update: Damn, I can't get blogger to list just the DOI number, so you need to delete the 'DOI' in the link target when you paste it in. Ugh, let me know if this is more trouble than its worth.]

ScienceDirect - Pain : Gender differences in post-operative pain and patient controlled analgesia use among adolescent surgical patients

ScienceDirect - Pain : Gender differences in post-operative pain and patient controlled analgesia use among adolescent surgical patients: "Gender differences in post-operative pain and patient controlled analgesia use among adolescent surgical patients

Deirdre E. Logan, , a and John B. Rosea, b

a The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA
b University of Pennsylvania School of Medicine, Philadelphia, PA, USA

Received 13 October 2003; Revised 12 February 2004; accepted 23 February 2004 AIB-16500 Available online 21 April 2004.


Abstract

The aim of this study was to explore gender differences in anticipatory emotional distress, coping strategies, post-operative pain perception, and patient-controlled analgesia (PCA) use among adolescent surgical patients. One hundred and two 12–18-year-old adolescents undergoing surgeries with overnight hospital stay were recruited. Participants completed pre-operative measures of anxiety and anticipated pain. Post-operatively, they reported on coping skills, post-operative anxiety, and pain. Data on PCA use were recorded from medical records. Girls reported higher levels of pre-operative state anxiety and anticipated more pain. After surgery, girls and boys differed on their lowest daily pain ratings and average daily pain ratings, with girls reporting more pain in both cases. Reports of highest daily pain were similar across genders. Gender was found to moderate the relationship between anticipatory distress and post-operative pain, such that higher anticipatory distress before surgery predicted more post-operative pain for girls, but not for boys. Patterns of PCA use did not vary by gender on post-operative days 0 or 1. Findings suggest that adolescent boys' and girls' pain experiences are different in several important respects, although somewhat less divergent than has been reported in samples of adult males and females. Results have implications for the development of targeted intervention strategies to help adolescents cope effectively with acute post-operative pain."
Gender

Alcoholic parents and chronic back pain

Chronic back pain is often weird in its sources. This may point to an interesting new variable.

Female Children of

Alcoholics and Chronic Back Pain. By: Pecukonis, Edward V.. Pain
Medicine, Jun2004, Vol. 5 Issue 2, p196, 6p;
Abstract: . A case-controlled retrospective design was used in the present
investigation with adult women to explore the relationship between chronic and
persistent back pain and a history of being raised by an alcoholic caretaker. .
A sample of 112 females was obtained from a large university primary care
health center. Fifty-nine back pain patients served as cases, while 53 females
without histories of chronic pain served as controls. . Outcome measures
consisted of a seven-question physician back pain checklist. The independent
variable, being raised by an alcoholic caretaker, was measured by the Children
of Alcoholics Screening Test (CAST). . Chronic back pain patients scored significantly
higher than the nonpain group on the CAST. . The results suggest that
additional research should explore and further define the relationship between
a childhood history of being raised by an alcoholic parent and the development
of chronic back pain as an adult. [ABSTRACT FROM AUTHOR]; DOI:
10.1111/j.1526-4637.2004.04024.x; (AN 13355886)

This
makes me curious about what the source might be. Some sort of
psychological stress? Being more likely to be beaten or engage in
activities which harm their spines and muscles when young? A genetic
predisposition to back pain and alcoholism? Interesting.

Journals

Here's a (probably incomplete) of the pain science journals I try to check over every month.

The most important

Pain

Pain Reviews

The others (in no particular order)

Journal of Headache and Pain

Journal of Pain and Symptom Managment

Pain and Central Nervous System Week

Pain Medicine

Pain Practice

Internet Journal of Pain, Symptom Control, and Palliative Care

Journal of Pain and Palliative Care Pharmacotherapy

Practical Pain Management

Admin

To my (5) loyal readers. My apologies for the spotty posting. As may be obvious from the distribution of posts, I do a survey of the recent pain science literature once a month for my own research. The fruits of that survey then trickle down here throughout the rest of the month, but mainly at the beginning.

I've been thinking about making a posting policy/schedule to keep myself on track and so readers know when to expect posts. I may end up just enshrining the current state of affairs (i.e., updating at the start of every month), or be more regular (e.g., every Monday). I'll decide and make an announcement soon.

Thanks for your continued patience as I work out some of the growing pains.

Pain websites

Here are some websources for the study of pain:
International Association for the study of Pain
Anesthesiology & Pain Management Journals
Medline Plus: Pain

And some websites:
A guide for helping children deal with pain

Examples of pain measurement scales

A guide for helping children deal with pain

Sleep and pain

Here's a bit of the abstract from Levigne et. al. "Experimental pain perception remains equally active over all sleep stages" in press at Pain

The literature on sensory perception during sleep suggests that light sleep (Stage 2) is more responsive to external sensory stimulation (e.g. sound, electrical shock) than deep sleep (Stages 3 and 4) and REM sleep. The main objective of this study was to characterize the specificity of nociceptive stimulation to trigger sleep arousal–awakening over all sleep stages....Compared to the baseline night, sleep quality was lower following the night with noxious stimulation (90.1±2.7 and 73.3±7.4 mm, respectively; P<0.03). These data suggest that pain during sleep could trigger a sleep awaking response over all sleep stages and not only in light sleep.

There are several interesting results from this study. One is the seemingly fine-grained way in which we are set up to process pains while asleep.

In the cat, during active REM sleep the sensory information arising from hair mechanoreceptors is enhanced whereas information arising from tooth pulp afferents is suppressed.... In humans, during deep sleep Stages 3 and 4, cortical EEG arousal responses induced by muscle, joint and cutaneous pain stimulations were significantly different ( Drewes et al., 1997). These findings, taken with the current results, indicate that the influence of neuronal responses, transmitted rostrally from the periphery to the thalamus and to the cortex to evoke arousal or awakening, depend on the nature of the peripheral stimuli, e.g. if relevant or potentially noxious/harmful, and on the behavioral state, e.g. awake, attentive or distracted, drowsy or asleep.

And something which conforms to our naive expectations about pain and sleep.

In addition, with longer pain stimulations, as used in the present study to mimic deep clinical muscular pain, the importance or relevance of the stimulation may override the brainstem neurons responsible for sleep maintenance and, consequently, activate the ascending arousal system to drive an awakening ( Mignot et al., 2002). Moreover, sleep awakening is probably a key reaction that prepares the sleeping person to react to a potentially threatening stimuli during an altered state of consciousness

Sleep is a evolutionarily costly activity (you're easier prey, you're using resources without gathering new ones, etc). Thus one might expect that the sleep cycle wouldn't leave one especially vulnerable to the causes of pain.

Low level representation

Interested in low level sensory representation? Non-conceptual content? Well, then this article "Rapid deterioration of pain sensory-discriminative information in short-term memory" by Rainville et. al in press at Pain (Science Direct link here) might be of interest to you.

These results are consistent with the possibility that short-term memory for pain and temperature sensation intensity relies on a transient analog representation that is quickly degraded and transformed into a more resistant but less precise categorical format. This implies that retrospective pain ratings obtained even after very short delays may be rather inaccurate but relatively reliable.

Ed. note: I don't know much about these cog sci/philosophy issues so no guarantees on relevance.

Thoughts about 'C-fibers firing'

I get irritated when philosophers talk about C-fibers firing as the neural substrate of pain experience, but not because of the factual wrongness of the claim --C-fibers and A(delta) fibers are nociceptive afferent axons which (I believe) are not even present in the brain. Clearly, they are using 'C-fibers' as shorthand for 'whatever neural mechanism science discovers about pain-processing in the brain' (Kripke explictly makes this qualification in Naming and Necessity). I have no objection to such shorthand; in fact, I like it when philosophers remember their place vis-a-vis scientists.

Instead, I worry that this shorthand connotes too simple of a picture of what pains are --both in terms of experience and underlying psychology/neurology. I worry that 'C-fibers firing' suggests that there is one discrete part of the brain dedicated to processing pains. Such a picture, I think, can lead to many philosophical mistakes about what pains are.
Let me loosely distinguish between two uses of 'brain-state': (1) a state of the brain such that that the brain has many discrete brain-states at any given time; and (2) a state of the brain such that the whole brain is in one state at any given time.

Many writers --at least those working in ethics and axiology-- seem to assume that pains are essentially phenomenological (where 'phenomenology' refers to the hurting of the pain) and only accidentally associated with emotions, affect, expectation, etc. I therefore worry that when such writers say 'of course, the phenomenology supervenes on/ is identical with some brain-state' they are too close to (1) in what they are imagining pains are. They assume that there is some discrete neural phenomenon corresponding to the discrete phenomenological phenomenon --the pain.

I, of course, think this picture of what pains are is a mistake. I think that pains are best understood as having certain emotional, desiderative, conative, and affective components essentially. Hence I worry that the shorthand 'C-fibers' in discussing brain-states takes us too close to (1) rather than the more distributed and complex picture of pains of (2) (of course, we don't want to be too close to (2) either).

Now, I believe --and hopefully will be in print soon arguing-- that this mistaken picture of what pains are has great importance for how we understand and answer the axiological and normative questions about pain. Indeed, I suspect this mistake of shorthand that I'm suggesting affects the moral philosopher's view of pain, may also matter to other issues in philosophy of mind and metaphysics where pain is a central example.
(see, for example, Nancy Hardcastle's book The Myth of Pain and her When a Pain is Not J Phil 1997 94 381-409. I'm being intentionally vague here as to whether she commits these mistakes or whether her arguments are especially attuned to them; I haven't thought enough about her work to decide what exactly is going on in it)

"And furthermore Susan, I wouldn't be surprised to learn that they habitually smoke marijuana cigarettes --reefer"

Check out this story on Alternet about the history of biomedical research on marijuana and its biochemical effects.

Ongoing research conducted by Mechoulam, and his counterpart at the University of Buffalo, Herbert Schuel, shows that anandamides appear to be involved in regulating and balancing the body's biochemical systems, influencing or controlling the reproductive, sleep, fight-or-flight and appetite cycles.

"It's a quirk of nature that THC works on our receptors," Mechoulam remarked. "We were lucky to be the only group in the world working on this chemical." All mammals, fish, birds and reptiles seem to have anandamide-based regulatory systems; it's even found in cacao nuts, from which chocolate is made. "It is found in substantial quantities in chocolate, and may account for the feelings of pleasure that come from chocolate," Schuel said. Other researchers have found that chocolate seems to prolong the marijuana high – as pot users have long claimed.
...
In 1988, an American research group that included Bill Devane announced they had found evidence of a cannabinoid receptor in the mammalian brain. Devane joined Mechoulam in Israel to further research this question: Did our brains evolve to receive marijuana?

"We assumed that such a receptor does not exist for the sake of a plant compound," they concluded. Other drugs, like opium, had been found to bind at the molecular level to brain receptor sites intended for endorphins, the body's natural pain reliever. Mechoulam and Devane decided to look for the natural version of THC, and in 1992 they announced finding a fatty molecule that bound naturally to the cannabinoid receptor site
...
Anandamides are produced by our brains and bodies to achieve a sort of yin-yang biochemical balance, and do not produce the extreme "high" of marijuana, Mechoulam says.
...
"They're completely different, from a chemical point of view, from THC," he said. "But they combine in the receptor sites the same way." Anandamides are quickly broken down by the body after they have served their intended purpose, and do not last as long as THC metabolites, which remain in the body for weeks.
...
Anandamides play a survival role for young mammals – their instinctive suckling behavior seems integrally tied to the presence of anandamides. "If we block the system (from receiving anandamides), there is no suckling," Mechoulam explains.

I'm not sure how exactly this fits with some of the research on cannabinoids and pain I posted about earlier. Here's two comments:

First, though this article is about a year old, the research on cannabinoids and pain seems to have been pretty well established for several years (there's a bigger body of literature than I suspected when I originally posted here). Thus its odd that the article doesn't mention the endogenous cannabinoid-mediated system. It lists many other biological-processes; why not the role in pain?

Is it because (a) the experts discussed or the reporter is unaware of this role --in big research fields, right hands often don't know what left hands are doing; (b) the focus of the article is on anandamides and the role cannabinoids play with pain involve a different set of receptors and chemicals? If so, what are the relevant differences?

Also, as far as I understand it 'cannabinoids' are defined as (roughly) 'chemicals unique to cannabus', but the pain-literature talks about 'cannabinoid-receptors' and 'endogenous cannabinoids'. Does this mean that there are two classes of chemical here --anandamindes and cannabinoids-- or am I just confused?

Second, the article mentions something I've heard in several places before --that its a mystery why THC interacts with these systems of ours-- with the implications being that we somehow evolved to smoke weed. But if all this research is correct, there's no mystery here. No more than why we evolved to have ascorbic acid from citrus interact beneficially with us. Presumably, if there is any sense to the 'mystery', it turns on the fact that cannabinoids are unique to cannabus. That raises the first set of questions.