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)