31 December 2009

TENS confusion

Given that TENS was part of the discovery of the gate-control theory 40 years ago, it really would be nice if its implications for the distinction between nociception and pain had seeped in. This is from a press release on Science Daily:
Widely used device for pain therapy not recommended for chronic low back pain A new guideline issued by the American Academy of Neurology finds that transcutaneous electric nerve stimulation (TENS), a widely used pain therapy involving a portable device, is not recommended to treat chronic low-back pain that has persisted for three months or longer because research shows it is not effective.... TENS can be effective in treating diabetic nerve pain, also called diabetic neuropathy, but more and better research is needed to compare TENS to other treatments for this type of pain. Research on TENS for chronic low-back pain has produced conflicting results. For the guideline, the authors reviewed all of the evidence for low-back pain lasting three months or longer. Acute low-back pain was not studied. The studies to date show that TENS does not help with chronic low-back pain.


So far so good. But then in the nickel summary of what TENS is they write:
With TENS, a portable, pocket-sized unit applies a mild electrical current to the nerves through electrodes. TENS has been used for pain relief in various disorders for years. Researchers do not know how TENS may provide relief for pain. One theory is that nerves can only carry one signal at a time. The TENS stimulation may confuse the brain and block the real pain signal from getting through.

How about:
Neural signals reporting injury have to pass through a gate in the spine in order to be transmitted to the brain and cause pain. The electric impulse from TENS closes the gate.

That's still inaccurate. But it at least avoids framing the phenomenon as the system stopping the pain before it gets to the brain. Getting people used to distinguishing between nociception and pain is a small but important step in a better public understanding of analgesia and chronic pain conditions.

11 December 2009

Acetaminophen-Related Liver Damage May Be Prevented By Common Herbal Medicine

Perhaps I can slacken my anti-acetaminopen stance* a bit....

Acetaminophen-Related Liver Damage May Be Prevented By Common Herbal Medicine: "Acetaminophen-Related Liver Damage May Be Prevented By Common Herbal Medicine

A well-known Eastern medicine supplement may help avoid the most common cause of liver transplantation, according to a study by researchers at the Stanford University School of Medicine. The finding came as a surprise to the scientists, who used a number of advanced genetic and genomic techniques in mice to identify a molecular pathway that counters acetaminophen toxicity, which leads to liver failure.

'I didn't know anything about the substance that was necessary for the pathway's function, so I had to look it up,' said Gary Peltz, MD, PhD, professor of anesthesiology. 'My postdoctoral fellow, whose parents and other family members in Asia were taking this compound in their supplements, started laughing. He recognized it immediately.'

The molecule was S-methylmethionine, which had been marketed as an herbal medicine known as Vitamin U for treatment of the digestive system. It is highly abundant in many plants, including cabbage and wheat, and is routinely ingested by people. [...]

Peltz is the senior author of the research, which will be published online Nov. 18 in Genome Research. The experiments were conducted in Peltz's laboratory at Roche Palo Alto in Palo Alto, Calif., where Peltz worked before coming to Stanford in July 2008. He is continuing the research at Stanford. The first author of the paper, Hong-Hsing Liu, MD, PhD, is now a postdoctoral scholar in Peltz's Stanford lab.

Acetaminophen is a pain reliever present in many over-the-counter cold and flu medicines. It is broken down, or metabolized, in the body into byproducts - one of which can be very toxic to the liver. At normal, therapeutic levels, this byproduct is easily deactivated when it binds to a naturally occurring, protective molecule called glutathione. But the body's glutathione stores are finite, and are quickly depleted when the recommended doses of acetaminophen are exceeded.

Unfortunately, the prevalence of acetaminophen makes it easy to accidentally exceed the recommended levels, which can occur by dosing more frequently than indicated or by combining two or more acetaminophen-containing products. However, severe liver damage can occur at even two to three times the recommended dose (the maximum adult dose is 4 grams per day; toxic daily levels range from 7 to 10 grams).

'It's a huge public health problem,' said Peltz. 'It's particularly difficult for parents, who may not realize that acetaminophen is in so many pediatric medicines.' Acetaminophen overdose is the most common cause of liver transplantation in this country. The only effective antidote is an unpalatable compound called NAC that can induce nausea and vomiting, and must be administered as soon as possible after the overdose.

Peltz and his colleagues used 16 inbred strains of laboratory mice for their investigations. Most strains are susceptible to acetaminophen toxicity, but one is resistant. They compared how the drug is metabolized by the different strains and looked for variations in gene expression and changes in endogenous metabolites in response to acetaminophen administration. They identified 224 candidate genes that might explain the resistant strain's ability to ward off liver damage, and then plumbed computer databases to identify those involved in metabolizing acetaminophen's dangerous byproducts.

One, an enzyme called Bhmt2, fit the bill: It helped generate more glutathione, and its sequence varied between the resistant and non-resistant strains of mice. Bhmt2 works by converting the diet-derived molecule S-methylmethionine, or SMM, into methionine, which is subsequently converted in a series of steps into glutathione. The researchers confirmed the importance of the pathway by showing that SMM conferred protection against acetaminophen-induced liver toxicity only in strains of mice in which the Bhmt2 pathway was functional.

'By administering SMM, which is found in every flowering plant and vegetable, we were able to prevent a lot of the drug's toxic effect,' said Peltz. He and his colleagues are now working to set up clinical trials at Stanford to see whether it will have a similar effect in humans. In the meantime, though, he cautions against assuming that dosing oneself with SMM will protect against acetaminophen overdose.

'There are many pathways involved in the metabolism of this drug, and individuals' genetic backgrounds are tremendously variable. This is just one piece of the puzzle; we don't have the full answer,' he said. However, if subsequent studies are promising, Peltz envisions possibly a co-formulated drug containing both acetaminophen and SMM or using SMM as a routine dietary supplement."



*I don't doubt its usefulness for many conditions. What I don't like is how it's seen/promoted/prescribed as something benign by consumers/companies and drug stores/doctors.

Antidepressants, CYP2D6, and opioid metabolism

Awhile back I posted this bleg for more information about the interaction between antidepressants and codeine. Peter Nelson emailed me asking whether I had found out anything else. I hadn't, so he did some research of his own which he has kindly agreed to allow me to share.

Take it away, Peter:

[Usual disclaimer: Neither he nor I are medical professionals. Don't take this as medical advice, et cetera.]

Since emailing you I’ve been studying the research literature and it’s crystal clear that codeine will not have any analgesic properties for people either genetically lacking CYP2D6 (6-10% of caucasians, other %’s for other ethnic groups) or who are taking a drug that blocks it.
Many antidepressants, including fluoxetine, paroxetine and bupropion are strong inhibitors of it, as are many other drugs including various antiarrhythmics, antifungals, cancer drugs, etc.

The story on the other synthetic opioids doesn’t look too good either. CYP2D6 plays a critical role in the metabolism of hydrocodone, oxycodone, and tramadol but they have more complex metabolic pathways and even now there are details that remain to be elucidated.

Hydrocodone itself has little affinity for the μ opioid (pain) receptors so it has to get metabolized the main clinically-active metabolite is assumed to be hydromorphone because it’s a known painkiller with a high affinity for the μ opioid receptors. And lack of CYP2D6 blocks that process. That part is clear, but there are unanswered questions.

For example in Kaplan et al, (Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability J Pharmacol Exp Ther. 1997 Apr;281(1):103-8) subjects’ subjective perception of the effects of hydrocodone were unrelated to hydromorphone conversion. Heiskanen et al, (Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone. Clin Pharmacol Ther. 1998 Dec;64(6):603-11. ) performed a similar experiment involving oxycodone with similar results.
But critically, neither experiment looked at pain tolerance. Also Otton et al, (CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone - SV - Clin Pharmacol Ther - 01-NOV-1993; 54(5):) performed an experiment similar to Kaplan’s but did find that subjects responded in ways consisten with hydromorphone conversion (again, no pain test).

Based on what we think we know about hydrocodone (i.e., that the active metabolite is hydromorphone), Otton’s results make more sense. But both hydrocodone and oxycodone still have work left to do elucidating the effects of some of the other metabolites that are currently thought to be inactive.

And Heiskanen’s results also make sense because oxycodone – the parent compound - actually appears to have a nontrivial affinity for μ receptors itself, and furthermore some of its other metabolites such as noroxycodone, which may be mediated by a different enzyme – CYP2C19 - may also have high binding affinity. (Lalovic et al, Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Dispos. 2004 Apr;32(4):447-54. )
In other words oxycodone may work fine as an analgesic for CYP2D6 impaired patients. BUT that doesn’t mean oxycodone gets us off the hook - instead it appears to have a nastier hook: The oxymorhone is far more readily cleared than the parent compound oxycodone. So without CYP2D6 oxycodone accumulates, potentially becoming toxic or fatal.
Two studies underscore that risk: Jannetto, et al, Pharmacogenomics as molecular autopsy for postmortem forensic toxicology; genotyping cytochrome P450 2D6 for oxycodone cases. J Anal Toxicol 2002; 26:438–447 and Drummer et al, A study of deaths involving oxycodone. J Forensic Sci 1994; 39:1069–1075.

The real bottom lines are these:
1. Work remains to be done in elucidating both the pharmacokinetics and clinical effects of various metabolites for all of the synthetic opioids.

2. As far as I could tell, there seem to be no human studies evaluating analgesic properties of synthetic opioids for patients who either lack the gene for CYP2D6 or for whom CYP2D6 is blocked by a drug-drug interaction.

3. Drug-drug interactions of this type will become more common as the population becomes older and as we use a greater variety of drugs. As it is, bupropion. paroxetine and fluoxetine (all potent CYP2D6 blockers) accounted for roughly 50 million prescriptions in the US alone last year. Other CYP2D6 blockers account for millions more.

4. I’ve spoken to several physicians about this and they all expressed worry and concern that they feel unsure how to do pain management for CYP2D6-impaired patients, especially in postoperative or fracture cases where OTC drugs aren’t enough and the “nuclear options” like fentanyl or methadone (both of which work regardless of CYP2D6) would be overkill and dangerous.

Visit Peter's blog at http://blog.pnart.com/. Thanks again!

12 November 2009

What's bad about masochistic pain?

Here's the video from the talk I gave back in April about whether masochistic pain is good:
http://www.adamswenson.net/HSG/HSG1.html
But since it's just me reading the paper aloud, you'll probably want to skip ahead and just watch the discussion:
Part 1 http://www.adamswenson.net/HSG/HSG2.html
Part 2 http://www.adamswenson.net/HSG/HSG3.html
The paper and powerpoint slides are available on the website.

Warning: This is totally unsafe for work, and most definitely not for the squeamish. The talk proper may cause mild reactions in those allergic to analytic philosophy. Such reactions are less common with the discussion alone.

08 November 2009

List of Hospice & Palliative Medicine Blogs (Current & Inactive)

Some of you may find this useful:

Pallimed: A Hospice & Palliative Medicine Blog: *Updated* List of Hospice & Palliative Medicine Blogs (Current & Inactive): "

Children Can Greatly Reduce Abdominal Pain By Using Their Imagination: UNC Study

Children Can Greatly Reduce Abdominal Pain By Using Their Imagination: UNC Study: "
Children with functional abdominal pain who used audio recordings of guided imagery at home in addition to standard medical treatment were almost three times as likely to improve their pain problem, compared to children who received standard treatment alone.

And those benefits were maintained six months after treatment ended
[....]

The study focused on functional abdominal pain, defined as persistent pain with no identifiable underlying disease that interferes with activities. It is very common, affecting up to 20 percent of children. Prior studies have found that behavioral therapy and guided imagery (a treatment method similar to self-hypnosis) are effective, when combined with regular medical care, to reduce pain and improve quality of life.
[....]
In the group that used guided imagery, the children reported that the CDs were easy and enjoyable to use. In that group, 73.3 percent reported that their abdominal pain was reduced by half or more by the end of the treatment course. Only 26.7 percent in the standard medical care only group achieved the same level of improvement. This increased to 58.3 percent when guided imagery treatment was offered later to the standard medical care only group. In both groups combined, these benefits persisted for six months in 62.5 percent of the children.
"


Acetaminophen May Be Linked To Asthma In Children And Adults

More reason to stay away as much as possible....

Acetaminophen May Be Linked To Asthma In Children And Adults: "New research shows that the widely used pain reliever acetaminophen may be associated with an increased risk of asthma and wheezing in both children and adults exposed to the drug. Researchers from the University of British Columbia, Vancouver, BC, Canada, conducted a systematic review and metaanalysis of 19 clinical studies (total subjects=425,140) that compared the risk of asthma or wheezing with acetaminophen exposure.

The analysis showed that the pooled odds ratio (odds ratio for all studies combined) for asthma among users of acetaminophen was 1.63. The risk of asthma in children who used acetaminophen in the year prior to asthma diagnosis or in the first year of life was elevated to 1.60 and 1.47, respectively.

Furthermore, results showed a slight increase in the risk of asthma and wheezing with prenatal use of acetaminophen by mothers. Researchers speculate that acetaminophen's lack of inhibition of cyclooxygenase, the key enzyme involved in the inflammatory response of asthma, may be one explanation for the potential link between acetaminophen use and asthma. "


22 October 2009

Bandolier Evidence-Based guides

Turns out my favorite Little Book of Pain (no joke: that's the title) has a bunch of evidence-based reviews of all sorts of pain-related topics. The main site is here:

Here are some examples

Migraine


Pain in general


Other general pain control stuff

Palliative and supportive care

Pain care before, during, and after operations

Dysmenorrhoea (menstrual cramps)

18 September 2009

Why papercuts hurt so damn much

During my bimonthly rereading of Price's Psychological Mechanisms of Pain and Analgesia, I ran across this in the middle of a discussion of the relationship between tissue damage and pain intensity:

the rate of tissue damage is a direct function of protein in activation that, in turn, is a function of temperature. However, the amount of tissue damage is a function of both skin temperature and duration of stimulation. Since heat-induced pain depends only on the temperature attained by the cells of the skin and on duration of stimulation, pain intensity follows the rate of tissue damage and not its total amount. One consequence of this phenomenon is that some extensive wounds may be less painful than slight wounds. Pain from tissues that have suddenly become inflamed, such as a toothache, is an example." [Page 11; italics original]

A role for glial cell-targeting treatments for pain?

The Psychology of Pain blog links to an interesting new study from CU-Boulder. I don't want to steal too much of his post, so here's a tease:
Under normal circumstances glial cells are thought to be like housekeepers, said Watkins. They essentially clean up debris and provide support for neurons.

But, like Gremlins, they have a nasty side too
[the researchers] believe they have figured out how morphine affects glial cells and neurons. 'We've found that different receptors are involved in how morphine suppresses pain through its actions on neurons versus how morphine activates glial cells,' Watkins said. 'What this means is that you should be able to separate the suppressive effects of morphine -- its pain-reducing effects through its action on neurons -- from all of its bad effects when it excites glial cells.'


(Via Psychology of Pain.)

19 August 2009

More sting connoisseurship

Here's a nice little interview vignette with Justin Schmidt whose 'Justin O. Schmidt's 'Sting Pain Index' I've mentioned before.

On reflection, it is quite funny how much power a drop of venom gives a little tiny bug over us:

Oh, Sting, Where Is Thy Death? - Happy Days Blog - NYTimes.com: The pain index came into being, he said, because he wanted to understand the two ways stinging can be of defensive value to an insect. ‘One is that it can actually do serious damage, to kill the target or make it impaired. The other is the whammy, the pain.’ He could quantify the amount of venom injected and its toxicity, but he had no way to measure pain other than through direct experience. So the pain index gave him a tool for interpreting an insect’s overall defensive strategy.

In fact, most insect stings do no damage at all, except to the two percent of people who suffer an allergic reaction. They just scare the wits out of us. And this is why they fascinate Schmidt: We typically outweigh any insect tormentor by a million times or more. We can outthink it. ‘And yet it wins,’ said Schmidt, ‘and the evidence that it has won is that people flap their arms, run around screaming, and do all kinds of carrying on.’ It wins ‘by making us hurt far more than any animal that size ought to be able to do. It deceives us into thinking serious damage is being done.’ And that’s generally enough to deliver the insect’s message, which is: Stay away from me and my nest."


At least, its funny when a harvester ant whose sting “felt like somebody was putting a knife in and twisting it” makes the point. Less so, when it comes from sterner teachers
A wasp known in the American Southwest as the “tarantula hawk” made him lie down and scream: “The good news is that by three minutes, it’s gone. If you really use your imagination you can get it to last five.” On the other hand, the sting of a bullet ant in Brazil (4-plus on the pain index) had him “still quivering and screaming from these peristaltic waves of pain” twelve hours later, despite the effects of ice compresses and beer.

Redheads need more drugs

Huh.

The Pain of Being a Redhead - Well Blog - NYTimes.com:
A growing body of research shows that people with red hair need larger doses of anesthesia and often are resistant to local pain blockers like Novocaine. As a result, redheads tend to be particularly nervous about dental procedures and are twice as likely to avoid going to the dentist as people with other hair colors, according to new research published in The Journal of the American Dental Association.

Researchers believe redheads are more sensitive to pain because of a mutation in a gene that affects hair color. In people with brown, black and blond hair, the gene, for the melanocortin-1 receptor, produces melanin. But a mutation in the MC1R gene results in the production of a substance called pheomelanin that results in red hair and fair skin.

The MC1R gene belongs to a family of receptors that include pain receptors in the brain, and as a result, a mutation in the gene appears to influence the body’s sensitivity to pain. A 2004 study showed that redheads require, on average, about 20 percent more general anesthesia than people with dark hair or blond coloring. And in 2005, researchers found that redheads are more resistant to the effects of local anesthesia, such as the numbing drugs used by dentists.
[....]


It's also nice to hear that the research came from taking this sort of common experience seriously, rather than simply dismissing it:
Dr. Daniel I. Sessler, an anesthesiologist and chairman of the department of outcomes research at the Cleveland Clinic, said he began studying hair color after hearing so many colleagues speculate about redheads requiring more anesthesia.

‘The reason we studied redheads in the beginning, it was essentially an urban legend in the anesthesia community saying redheads were difficult to anesthetize,’ Dr. Sessler said. ‘This was so intriguing we went ahead and studied it. Redheads really do require more anesthesia, and by a clinically important amount.’


If I had red hair, I would bring a copy of the paper with me to the dentist/doctor to help them take my needs seriously.*

*Just as I would, for example, show literature on the usefulness of pre-incision lidocaine in lowering post-surgicial pain to my surgeon.

I might also post articles on the problems with using morphine in patients with kidney problems on the wall by an elderly relative's hospital bed.

Methadone prescribers' network

The astonishing recent rise in opioid overdoses (many involving methadone) has finally forced me to agree that our (at least in the US) opioid policies and practices need some revision. Thus this expansion of a program available to buprenorphine prescribers seems welcome.

A New Service For Health Care Providers Who Prescribe Methadone To Treat Chronic Pain Or Opioid Addiction: "
A new service for health care providers prescribing methadone to treat chronic pain or opioid addiction -- the Physician Clinical Support System for Methadone (PCCS-M) -- opens this week with a mechanism to connect prescribers of methadone with experienced clinicians for one-to-one mentoring regarding the use of this medication.

Methadone is an inexpensive opioid medication that has several unique properties that make it particularly well suited to the treatment of chronic pain or opioid addiction, but it also has side effects and the potential for overdose and requires specific information for its proper use.

The new service is one in a number of federally-funded projects that address the need within the nation's health care system to provide safe and effective care of patients with chronic pain and opioid addiction while, at the same time, protecting the public from prescription drug abuse and diversion of medications. Using this new service, prescribers can contact a mentor, a knowledgeable colleague, by phone or e-mail with specific questions about the use of methadone for treating chronic pain or opioid addiction.

Source: American Society of Addiction Medicine "



As a general rule, I think drug policy should (strongly) promote the responsible clinician's ability to prescribe opioids as she sees fit . So, insofar as this sort of program can help stem diversion and accidental overdose, I'd much rather see more of these than more restrictive drug policies.

15 August 2009

Coral for neuropathic pain

Not as cool as sea-snail venom, but still worth filing under 'cool things from the sea'

New Hope Of Relief For Neuropathic Pain: "New Hope Of Relief For Neuropathic Pain

A compound initially isolated from a soft coral (Capnella imbricata) collected at Green Island off Taiwan, could lead scientists to develop a new set of treatments for neuropathic pain - chronic pain that sometimes follows damage to the nervous system.
[....]

Recent research suggests inflammation in the nervous system is a major causative factor for this condition. Inflammation activates supporting cells, such as microglia and astrocytes, that surround the nerve cells. These activated cells release compounds called cytokines that can excite nerves carrying pain sensation (nociceptive pathways) and cause the person to experience mildly uncomfortable stimuli as very painful (hyperalgesia), or stimuli that would normally induce no discomfort at all as painful (allodynia). Thus, cold drafts or lightly brushing the skin can produce intense pain, severely affecting the person's quality of life.

[....]

Although the chemical they studied, capnellene, was originally isolated in 1974, it is only recently that scientists have started to appreciate its potential. Capnellene is interesting because its structure is very different from pain-relieving drugs currently in use. Initial experiments suggested that it may have pain-relieving properties. Working with Yen-Hsuan Jean MD, PhD and other colleagues, Dr Wen tested capnellene and a second very similar compound, in isolated microglial cells and in experimental models of the condition in rats.

They found that the compounds significantly reduced pain-related activities in isolated microglia, and that these compounds also significantly reversed hyperalgesic behaviour in the experimental rats.
"


14 July 2009

Mindfulness in cancer treatment

Go read Mindy Greenstein's WaPo piece:

Aided by a Proponent of Mindfulness, Cancer Patient Focuses on Joys of Today - washingtonpost.com



Why are you still here?

It's awesome. Trust me.

Okay fine. Don't believe me. Here's a small bit of its awesomeness to entice you:
Sanderson realized that this was what she was doing with her needle and, ultimately, with her illness: letting her experience of the present moment be overtaken by her fears for the future. Every hour she spent ruminating about the pain that was awaiting her was another hour she wasn't fully engaged with her life, another hour she couldn't enjoy. She couldn't pretend she didn't know her prognosis. So she chose a different route.

"I realized," she told us, "that the moments of pain -- even if the pain was excruciating -- were actually very short compared with the pain I put myself through by thinking about it ahead of time." If she could stay focused on the present moment no matter what she was doing -- washing dishes, talking to a colleague, even chatting with the doctor just before her treatment -- up until the moment the needle actually pierced her skin, she could cope. Even more, if she could keep that same focus from meandering to thoughts about what lay ahead in the future in general, she could continue to make the most of every moment that was not painful.

Some people think being positive means being certain of a cure. For others, it means enjoying the kindness of a friend or the mischief of a child or a rerun of "Battlestar Galactica" today, and leaving tomorrow's sorrows for tomorrow. For me, it meant.....

Oh you want to know how it ends don't you?

Now do you believe me?

Go read it. I'll still be here when you get back.

H/T: LB

Confusing 'ameliorating' with 'obliterating'

I've seen several authors make this point, but in an email to me, reader SV put it in a very nice way:
"We physicians are called upon to "ameliorate" pain, which often is considered synonymous with "obliterating" pain."

This is a very important flip-side to the incredible advances that have been made in pain medicine and public expectations about treatment.


The way 'ameliorate' and 'obliterate' have gotten run together in the public's (and even in many physicians') expectations has a significant downside: In addition to being annoying and disappointing to all involved, there's a case to be made that this sometimes (often?) leads to worse treatment outcomes.

For example, if a patient expects complete relief from her pain, partial relief might leave her depressed, frustrated, and resigned. Attitudes like those can be some of the biggest factors in determining how bad a pain is.* This is especially the case with many chronic pain conditions.

Of course, we've come a long way from seeing pain as an inevitable concomitant of disease and treatment, and thus not a direct concern for the physician.

And, we've to a large degree gotten over the invidious tendency to heap moral condemnation upon those who don't suffer in silence, and to see all pains, including medical pains, as deserved (the words 'pain' and 'punishment' both have their roots in 'poena').

On that note, this story in the Boston Globe is important: The Day Pain Died: What Really Happened During the Most Famous Moment in Boston Medicine

So, I suppose its worth keeping some perspective on how much attitudes and expectations have come in a very short amount of time. Still, there's still a long way left to go.

--

*As always: These attitudes are not merely responses to the pain, they can become part of the pain itself.

It is a serious conceptual mistake to think of a patient who feels helpless and resigned in the face of her pain as (necessarily) being in two bad states:
(a) Her pain is bad to degree x
and
(b) Feeling helpless and resigned is bad to degree y.

Rather, these feelings are themselves parts of the pain. Their treatment is just as much a treatment of the pain itself as is the administration of morphine.

01 July 2009

Percocet and Vicodin be gone (hopefully)

In light of my long-running antipathy toward the way acetominophen is currently used and regulated, this makes me very happy:

Panel Recommends Ban on 2 Popular Painkillers - NYTimes.com

By GARDINER HARRIS
Published: June 30, 2009

ADELPHI, Md. — A federal advisory panel voted narrowly on Tuesday to recommend a ban on Percocet and Vicodin, two of the most popular prescription painkillers in the world, because of their effects on the liver.
[....]

The agency is not required to [....] follow the recommendations of its advisory panels, but it usually does.


Unfortunately
But they voted 20 to 17 against limiting the number of pills allowed in each bottle, with members saying such a limit would probably have little effect and could hurt rural and poor patients. Bottles of 1,000 pills are often sold at discount chains.

‘We have no data to show that people who overdose shop at Costco,’ said Dr. Edward Covington, a panel member from the Cleveland Clinic Foundation.

IIRC, the problem is that their parents do. The patients who intentionally take handfuls of acetaminophen are usually teenage girls in initial and not-fully-serious suicide attempts. Few other countries allow the sort of bulk packaging we do.

Finally, I find this very hard to bellieve:
Still, some doctors predicted that the recommendation would put extra burdens on physicians and patients.

‘More people will be suffering from pain,’ said Dr. Sean Mackey, chief of pain management at Stanford University Medical School. ‘More people will be seeing their doctors more frequently and running up health care costs.’

The recommendation doesn't attempt to ban acetominophen. And, the 1,000 pill bottles are relatively cheap, so its hard to see too much of an increase in marginal cost if a patient will also have to buy the acetominophen OTC.

Moreover, why would more people go to the doctor because they have to get their oxycodone and acetominophen separately? Why would they go more frequently?

Indeed,
“It ties the doctor’s hands when you put the two drugs together,” said Dr. Scott M. Fishman, a professor of anesthesiology at the University of California, Davis, and a former president of the American Academy of Pain Medicine. “There’s no reason you can’t get the same effect by using them separately.” Dr. Fisher said the combinations were prescribed so often for the sake of convenience, but added, “When you’re using controlled substances, you want to err on the side of safety rather than convenience.”



Fingers crossed that the FDA will follow the recommendation....


25 June 2009

Whose problem is the diversion of opioids?

Okay. In the last post I mentioned that I get annoyed when concerns about opioids being diverted pop up in discussions about when opioids are indicated treatments. It's not that I don't think diversion is an important concern in drug policy. It's just that I feel like it shouldn't be part of discussions of when opioids are good treatments.

Anyway, I was annoyed by not knowing I feel this way.* So, the following is some off-the-cuff noodling about when concerns are relevant in decisions about the use of opioid drugs. I'm not at all sure about how much of it I want to stand behind. But hopefully it might be useful for sparking some discussion.

*I remember someone once telling me that philosophy starts with a sense of wonder. I have since found that, for me, it usually starts with annoyance; it ends in wonder.

-------------

In general, I tend to think that the dangers of opioid diversion --opioids ending up outside of the patient's hands-- get too much weight in discussions of drug policy (although some recent statistics on overdose and death rates involving opioids are giving me some pause in my beliefs about the severity of diversion's harms).

But in addition to questions about how severe the consequences of diversion are, we also need to know whose problem it is. A comprehensive drug policy spans many different areas including, inter alia, the law in its criminal, civil, and regulatory forms; professional determinations of best clinical practices; and individual clinicians' decisions about how to treat individual patients. Thus we need to know whether preventing diversion should have the same importance for everyone involved in the prescription drug arena.

I'm going to suggest that preventing diversion can be a legitimate concern at the more general levels. And they may inform doctors practices in a general way. But, I suspect, the potential harms resulting from diversion should not factor into a doctor's decisions about what medications to prescribe a patient.

My claims here will rest on the supposition that a clinician's ethical responsibilities arise from her patient's individual welfare. Her professional obligation is not the promotion of the general welfare via her interactions with a certain individual. The clinician's responsibility is to alleviate her patient's suffering in the safest and most effective way available.

A rough analogy may help bring out this distinction between duties based in the promotion of the general welfare and duties based in the promotion of an individual's welfare. In an adversarial system of criminal justice like we have in the United States, the role of a defense attorney is to advocate for her clients interests as best she can. Even if she recognized that her client's conviction may benefit the public at large, she is obligated to ignore that fact in doing her job. This doesn't mean that the job of defense attorney is entirely removed from the enterprise of promoting the public good. It's that a system in which a party is assigned to look out only for the interests of the defendant is more likely to be better overall. (One major disanalogy here is that my supposition about the source of the doctor's duties need not appeal to claims about what would best promote the general welfare.)

If we a clinician's duties as tied her patient's welfare in this way, concerns about the welfare of others are thus (nearly always) irrelevant to decisions about what substances to prescribe her patient. This suggests that even though the clinician may foresee that others may be harmed through diversion if she prescribes an opioid to a patient, this possibility should have no weight in her decision about what to prescribe. Her duty arises from and is directed at the health of her patients, not the health of people in general.

Obviously, this has its limits. Massive harms to others may trump this obligation. And it may be that if two treatments were exactly equal in their efficacy and safety, then considerations of the general good or other effects on others may break the tie.

Nor does this mean that the doctor must completely ignore the possibility that the drug will be diverted. Other public entities' interests in preventing diversion are based in their obligation to protect public health overall. But given the source of her professional obligations, the clinician's concerns about diversion should be limited to its effects on her patient's health.

Clearly, a responsible clinician must be attuned to the possibility that the patient herself will divert the drug. But her vigilance is not demanded by the need to prevent harms to the recipients of the diversion. It comes from her responsibilities to the patient. The clinician's treatment decisions must be based on the supposition that the patient will comply with the prescribed regime. She cannot aim to promote an individual's welfare by prescribing her a substance that she believes that the patient will not take. Therefore, the belief that the patient will take the drug as prescribed is a necessary condition of justifiably prescribing an opioid.

Suppose that a patient is accompanied by a stoned adolescent whose T-shirt reads "I love drugs!" Does this necessary condition imply that she ought to take into consideration the likelihood that the son will divert the drugs?

The answer seems to be yes. She cannot prescribe a medication to benefit her patient if she believes that the patient won't take the drug because someone else will steal it. Of course, it's unlikely that the suspicion in this case would justify her refusing to prescribe an otherwise indicated opioid Much will hang on the strength of her conviction that the drug will be diverted. In the drug diverting adolescent case, the clinician may be required to put special emphasis on the need to keep control of the medication in counseling the patient. But as long as she can be satisfied that the patient will be reasonably vigilant, she will be justified in writing the prescription. Her uncertainty about the likelihood of diversion combined with the need to respect the patient's autonomy will set the bar for reasonable vigilance pretty low.

Cases in which she should altogether refuse to prescribe on these grounds will likely be rare. But they are easy to imagine. Suppose that a disabled patient is completely dependent on her caretaker for all of her medications. If the clinician was convinced that the caretaker would divert a significant portion of the prescribed opioid, then she should not write the prescription. Indeed, doing so would be tantamount to writing the prescription for the caretaker. Though, she may have some obligation to seek other ways of getting the indicated treatment to the patient (e.g., recommending at home nursing visits, and patient treatment).

What's important is the way concerns about diversion are figuring in here. A clinician should be cautious of diversion insofar as it would interfere with her patient's treatment. Her responsibilities do not depend on how the recipients of the diverted substance may be affected. Those dangers of diversion give her reason to, for example, keep her cabinets locked. But they should be irrelevant to her decisions about patients' treatments.

This is not to say that a comprehensive drug policy should not be concerned about the harms to non-patients who gain access to opioids through diversion. It is a fact that the availability of opioids in legitimate channels will involve some diversion and some non- patients will be harmed. While the clinician's responsibility is based in her individual patient's welfare, government policies are properly attuned to protecting welfare across the board. Thus entities (in the US) like the FDA, the Department of Justice and the DEA are justified in creating policies and enforcement practices which will minimize the amount of diversion.

But this picture of the clinician's obligations does create tension between the government's proper aims creating drug policy and the duties of clinicians. We should thus want a principled way of resolving these kinds of inevitable conflict. One possibility is that one set of considerations will always trump the other (that is, the first set is lexically prior to the other).

To see the implications of a lexical ordering of these considerations suppose that the paramount consideration in shaping drug policy was ensuring clinicians' abilities to carry out their duties to their patients. This would have implications for how we decide conflicts. Such a partial lexical ordering would entail that the protection of access to safe and effective drugs cannot be trumped by considerations about diversion. More generally, this might mean that any proposed policy that would promote the general good could be vetoed if it unreasonably affected the ability of clinicians to treat their patients.

This ordering of concerns would be unlikely to undermine reasonable restrictions on the use and prescription of opioids. For example, this is compatible with a well regulated and organized system for inventory control in the manufacturing, shipping, and distribution of opioids. The same is true for methods of verifying the legitimacy of prescriptions and the identity of patients. But some apparently relatively mild restrictions on prescribing ability may not be compatible with this set of drug policy priorities.

For example, the FDA is presently considering requiring all clinicians who prescribe powerful long-acting opioids to have a special certification. Many general practice clinicians who currently prescribe such medications may be unwilling to go through the hassle of obtaining and maintaining the certification. If the certification process was unduly difficult, many clinicians would be unable to prescribe the medications that they thought were best indicated for their patients conditions. Such a regulation would likely decrease the number of deaths from diversion. But no matter how many diversion related deaths would be prevented, it should be rejected if we believe that the clinician's abilities to treat their patients should always trump any other consideration.

So, in sum, here's what I've suggested: If we think about the source and nature of clinicians' professional obligations in a particular way, then concerns about diversion should not play a role in determining whether to prescribe an opioid (outside of diversion undermining the treatment regime). Direct focus on preventing diversion is instead the job of regulatory agencies whose mission is the common public good.

I haven't given any argument in favor of the further idea that concerns about diversion should always be subordinated to clinicians ability to prescribe opioids as they see fit. Though I am definitely attracted to this view. We can leave that a subject for another post.

Opioids often preferable to NSAID's in the elderly

This is important.

The NYT reports that in light of findings that
[in elderly patients] The risks of Nsaids include ulcers and gastrointestinal bleeding and, with some drugs, an increased risk of heart attacks or strokes. The drugs do not interact well with medicines for heart failure and other conditions, and may increase high blood pressure and affect kidney function, experts said.

The American Geriatrics Society
removed those everyday medicines, called Nsaids, for nonsteroidal anti-inflammatory drugs, from the list of drugs recommended for frail elderly adults with persistent pain. The panel said the painkillers should be used “rarely” in that population, “with extreme caution” and only in “highly selected individuals.”
[....]
“We’ve come out a little strong at this point in time about the risks of Nsaids in older people,” said Dr. Bruce Ferrell, a professor of geriatrics at U.C.L.A. who is chairman of the panel. “We hate to throw the baby out with the bathwater — they do work for some people — but it is fairly high risk when these drugs are given in moderate to high doses, especially when given over time.

“It looks like patients would be safer on opioids than on high doses of Nsaids for long periods of time,” he continued

Link (My italics; I've interpolated the order of the paragraphs)


Editorial comment: I'm unhappy that the reporter chose to use this quote in emphasizing that opioids have their own dangers:
“We’re seeing huge increases nationwide of reports about the misuse and diversion of prescription drugs and related deaths,” said Dr. Roger Chou, a pain expert who was not involved in writing the guidelines for the elderly but directed the clinical guidelines program for the American Pain Society. “The concerns about opioids are very real.”

Diversion of opioids is a real problem. But it really annoys me to see it used as a counterpoint in discussions of their clinical usefulness.

I almost feel like these claims are saying something like: Advil might kill Grandma, but we might not want to give her a safer treatment because her grandson might steal it and kill himself.' (I don't think the reporter or Dr. Chou intended it this way --that's just how I take it)

Update: I was bothered by not knowing why the stuff about diversion annoys me so much. So I've posted some very rough thoughts here.

16 June 2009

Resources for Causalgia (CRPS/RSD)

Here's a helpful guide to resources on Complex Regional Pain Syndrome/Reflex Sympathetic Dystrophy (CRPS/RSD/Causalgia)

Resources and Relief for Reflex Sympathetic Dystrophy



For those of you who don't know, Causalgia (CRPS/RSD) should rank high on the list of 'Things-You-Don't-Want'.

On the IASP definition:


Causalgia
A syndrome of sustained burning pain, allodynia, and hyperpathia after a traumatic nerve lesion, often combined with vasomotor and sudomotor dysfunction and later trophic changes.


Or as it was first described by Silas Weir Mitchell in 1872 after the Civil War

"We have some doubt as to whether this form of pain ever originates at the moment of the wounding. . . Of the special cause which provokes it, we know nothing, except that it has sometimes followed the transfer of pathological changes from a wounded nerve to unwounded nerves, and has then been felt in their distribution, so that we do not need a direct wound to bring it about. The seat of the burning pain is very various; but it never attacks the trunk, rarely the arm or thigh, and not often the forearm or leg. Its favorite site is the foot or hand. . . Its intensity varies from the most trivial burning to a state of torture, which can hardly be credited, but reacts on the whole economy, until the general health is seriously affected....The part itself is not alone subject to an intense burning sensation, but becomes exquisitely hyperanesthetic, so that a touch or tap of the finger increases the pain." quoted in UCLA pain exhibit


In other words, in causalgia part of your body feels like it's constantly on fire.

Online introduction to pain processes

The-New-Science-of-Pain-Relief has a nice introductory walkthrough of the basic neurology of pain here.

Philosophers will, of course, carefully take note the role of C nociceptive afferents.

Art

Check out this collection of pain sufferers' art:

Main page

Galleries by theme

11 June 2009

ABC story on FDA Acetaminophen overdose report

With every changing of the seasons comes a new set of cautions about acetaminophen use.

Like the changing of the leaves, experts call for better public education and packaging practices.

And, like the migration of the butterflies^, the pharmaceutical industry tells them to go f*** themselves:
McNeil Consumer Healthcare, a Johnson & Johnson subsidiary and the manufacturer of Tylenol, said in a statement Thursday that they fear the [FDA report's] recommendations could have the effect of steering consumers away from an appropriate and safe drug.

"While we share the FDA's mutual goal of preventing and decreasing the misuse and overdose of acetaminophen, we have concerns that some of the FDA recommendations could discourage appropriate use and are not necessary to addressing the root causes of acetaminophen overdose," the statement reads. Link


See this show again in a few months and a couple thousand more deaths.

^Sorry for the bad simile

Pain in animal slaughter

Newsflash!

Cutting calves throats hurts, study says...

A re-evaluation of the need to stun calves prior to slaughter by ventral-neck incision : An introductory review.: "

N Z Vet J. 2009 Apr; 57(2): 74-6
Mellor DJ, Gibson TJ, Johnson CB

Commercial slaughter of farm livestock usually employs an extensive incision that severs the soft tissues of the neck including the major blood vessels supplying and draining the brain. It is intended to cause a catastrophic decrease in cerebral blood flow with rapid onset of unconsciousness or insensibility. The tissues of the neck are innervated with nociceptive nerve fibres and their transection will cause a barrage of sensory impulses. Consciousness, and therefore the ability of the animal to feel pain and experience distress after the incision, may persist for 60 seconds or longer in cattle. These observations suggest that livestock may experience pain and distress during the period before they become unconscious (insensible). Psychological shock and fear may also be associated with the extensive tissue damage and blood loss. Pre-incision stunning has been adopted as a precautionary measure to prevent suffering. However, the question remains: How intense and noxious are these experiences? Recent methodological developments related to quantitative analysis of the electroencephalogram (EEG) allow the experience of pain to be assessed more directly than has hitherto been possible. This methodology has now been applied to the question of the slaughter of calves by ventral-neck incision. The new information demonstrates clearly for the first time that the act of slaughter by ventral-neck incision is associated with noxious stimulation that would be expected to be perceived as painful in the period between the incision and loss of consciousness. These data provide further support for the value of stunning in preventing pain and distress in animals subjected to this procedure."



(Via HubMed - pain.)

Obstetric anesthesia: Past present and future.

And yet another addition to my never ending reading list.

Obstetric anesthesia: Past present and future.: "

J Matern Fetal Neonatal Med. 2009 Jun 1; 1-4
Kuczkowski KM

Obstetric anesthesia is science and art combined, and obstetric anesthesiologists must be concerned simultaneously with the lives of (at least two) intricately interwoven patients - the mother and her baby (ies). Obstetric anesthesia, by definition, is a subspecialty of anesthesia devoted to peripartum, perioperatvie, pain and anesthetic management of women during pregnancy and the puerperium. Perhaps no other subspecialty of anesthesiology provides more personal gratification than the practice of obstetric anesthesia. An obstetric anesthesiologist has become an essential member of the peripartum care team, who closely works with the obstetrician, perinatologist, midwife, neonatologist and labor and delivery nurse to ensure the highest quality care for the pregnant woman and her baby. Exchange on information and communication skills in ever changing environment of labor and delivery is essential for perfect outcome, which is always expected when providing safe passage for both the mother and her fetus from antepartum to postpartum period. Changes in maternal-fetal and neonatal medicine and obstetric anesthesia have continued to develop rapidly during the recent years. The purpose of this article is to explore a number of important issues in modern practice of obstetric anesthesia."



(Via HubMed - pain.)

Effect of mental stress on cold pain in chronic tension-type headache sufferers.

Here's a little bit about headache and stress.

Effect of mental stress on cold pain in chronic tension-type headache sufferers.: "

J Headache Pain. 2009 Jun 5;
Cathcart S, Winefield AH, Lushington K, Rolan P

Mental stress is a noted contributing factor in chronic tension-type headache (CTH), however the mechanisms underlying this are not clearly understood. One proposition is that stress aggravates already increased pain sensitivity in CTH sufferers. This hypothesis could be partially tested by examining effects of mental stress on threshold and supra-threshold experimental pain processing in CTH sufferers. Such studies have not been reported to date. The present study measured pain detection and tolerance thresholds and ratings of supra-threshold pain stimulation from cold pressor test in CTH sufferers (CTH-S) and healthy Control (CNT) subjects exposed to a 60-min stressful mental task, and in CTH sufferers exposed to a 60-min neutral condition (CTH-N). Headache sufferers had lower pain tolerance thresholds and increased pain intensity ratings compared to controls. Pain detection and tolerance thresholds decreased and pain intensity ratings increased during the stress task, with a greater reduction in pain detection threshold and increase in pain intensity ratings in the CTH-S compared to CNT group. The results support the hypothesis that mental stress contributes to CTH through aggravating already increased pain sensitivity in CTH sufferers."



(Via HubMed - pain.)

Acupuncture And Pain

In answer to a reader's question, How To Cope With Pain digs up some conclusions about the efficacy of acupuncture.

Acupuncture And Pain: "An excellent review article by Edzard Ernst, M.D.,  reports that the conditions that are most solidly backed up by evidence showing acupuncture helps are:

  • chemotherapy-induced nausea/vomiting

  • postoperative nausea/vomiting

  • idiopathic headache (headache of unknown cause)

Many other diseases, both pain-related and not, were not helped by acupuncture.  Ernst concludes that studies ‘do not suggest that this treatment is effective for a wide range of conditions.’"


[Read the rest for some limitations in the current literature]

The original article is Acupuncture: What does the most reliable evidence tell us?, in the Journal of Pain and Symptom Management 2009, Vol 37, pages 709-714.

(Via How To Cope With Pain Blog.)

Palliative care for a patient with anorexia nervosa

Pallimed brings up a very hard case. I'm honestly not sure what I think about much of this:

Palliative care & eating disorders: "The International Journal of Eating Disorders has a case report and discussion of a patient with refractory anorexia nervosa who died receiving hospice care. This is one fascinating case report. The case, to summarize briefly, involved a young woman with a long history of anorexia nervosa, refractory to all attempts at treatment (including involuntary/forced treatment) who apparently also was not deemed a candidate for forced guardianship (the hospital's legal counsel advised she would not meet requirements to be declared incompetent).

This is how they describe the ethics committee's response to the case:

The committee’s members struggled to understand how one could die from a psychiatric illness (other than by suicide or unintentional overdose) and were not sure how to proceed. Although they could delineate the differences between acute mental health risks such as suicide, drug overdoses, psychosis or self-neglect, they had no points of reference regarding how to manage a patient who was chronically a danger to herself, unwilling to engage in further treatments, and unresponsive to all prior attempts to treat her involuntarily. The only examples the committee raised for comparison concerned drug users who received heart valve replacements, yet continued to use, knowing that such ongoing use would kill them. In such cases, if a high risk of ongoing subsequent IV drug use was suspected ahead of time, the decision was often made not to provide valve replacements, but there was no forced treatment.
This is how they presented what palliative care for anorexia nervosa would look like to the patient (italics mine):
If she chose to pursue treatment she would be assisted, but the staff would not force her into any involuntary placements or impose any treatment she did not want. There would be no weigh-ins, no calorie or exercise monitoring, no IM medications and no required therapy sessions. She would be offered outpatient therapy only as she felt desirable and necessary. Psychiatric medications would be prescribed as the patient deemed necessary to help manage depression, anxiety and insomnia. The patient would receive weekly visits from a palliative care nurse, who would work with her to manage her symptoms and keep her comfortable. The patient agreed to no further hospitalizations, but did not fully agree with the plan for ‘‘palliative care’’ since she did not believe she was going to die.
The patient basically continued her illness behaviors, got weaker/sicker, and was eventually enrolled in an inpatient hospice where she died.

Some observations.
  1. AN is clearly at times a terminal illness, refractory to all attempts to reverse it.
  2. In this case it was clear that the patient's life could have been prolonged although only with forced treatment. It was the opinion of her physicians that such forced treatment, while life-prolonging, would not 'cure' her AN (for some patients a trial, or many trials, of forced nutritional treatment along with psychiatric care gets them to the point at which they are willing to continue with voluntary treatment and can have a durable response; it was felt this would never happen with this patient). Thus the decision came down to trying to force further involuntary treatment vs. letting the disease run its natural course with her inevitably dying.
  3. I found it interesting that they did not feel there was enough of a chance she'd be considered incompetent that they didn't even put her through the court process. Her statement that she did not think she would die (and it seems she continued that belief until the end, and persisted at least until she was enrolled in hospice in saying that she in fact wanted to live) seems to me to indicate such a fundamental lack of insight into her condition that I'm not sure I believe that. Granted, I'm not too familiar with criteria for declaring someone incompetent on psychiatric grounds, but I assume it has something to do with one's mental illness being such that one cannot even take in basic medical information.
  4. That said, and even if she was legally stripped of her decision-making rights, for situations in which even involuntary treatment would not work long-term, is it right to force patients to do that? In this situation they concluded No, and made plans accordingly, which seemed to work as well as could be expected under the circumstances.

[A very interesting discussion follows in the rest. Definitely give it a read]


(Via Pallimed: A Hospice & Palliative Medicine Blog.)

Treating Psychiatric Symptoms

From the How To Cope With Pain Blog, here's a bit about the role of a psychiatrist in comprehensive pain management:

Treating Psychiatric Symptoms: "

Welcome to the continuing series Why You Should See a Pain Management Psychiatrist.  Last week we learned that psychiatric symptoms - such as depression, anxiety, etc. - often accompany chronic pain.  This week we’ll look at how to treat psychiatric diseases.


As we saw, depression (8-50% of patients with pain), anxiety (19-50%), PTSD (10%), sleep disturbance (50% or more), drug and alcohol problems (3-19%) are common in patients with pain.  Let’s look at some important issues related to treating these problems.


1. Identifying symptoms


To be able to treat psychiatric symptoms, they first have to be identified.  Your doctor should be asking about these common symptoms and referring you if appropriate.  You should also report if you’re having such symptoms.  Don’t be embarrassed or feel like you’re complaining.  Getting help is important!


2. Taking symptoms seriously


If you’re having significant depression, anxiety or other symptoms, it’s important to report these to start to get treatment for them.  These symptoms should not be dismissed as, ‘of course you have depression - it’s because of your pain.’  Chronic pain does not automatically  mean depression, anxiety and disturbed sleep.  There’s treatment for these symptoms.!  And they should be treated!


3. Treat all the disorders that are present.


We know that if psychiatric problems are present along with pain, it’s crucial to treat both.  Treating just 1 doesn’t make the other go away.  For example, if someone has depression and pain, treating just pain doesn’t necessarily mean the depression will go away.  And sometimes neither gets better unless you treat both.


4. Treatment


There are both therapies and medications to treat nearly all psychiatric diseases.  Medication should be used only along with therapy.  I strongly recommend trying therapy first, before medication, to see if just therapy alone can work.  There are times, when psychiatric symptoms are severe, that both will be started at once, but that’s less common.  Most people with pain disorders are already on several medications and sometimes already tolerating side effects, so trying non-medication treatment first makes sense.


Other articles in the series:



  1. Why comprehensive treatment works better

  2. Benefits of a psychiatric evaluation

  3. Treatment of psychiatric symptoms

  4. Using psychiatric medications for pain

  5. Learning psychological skills

  6. Making positive behavioral changes

  7. Making positive psychological changes

  8. Benefits of supportive therapy

  9. Benefits of a pain support group

  10. New brain-based treatments

"



(Via How To Cope With Pain Blog.)

Refusal to torture in Milgram experiments

Oh well. From Brain Blogger, a new experiment which deflates some of the hope for humanity I had held out in the face of the Milgram experiments on torture and obedience to authority:

For the first time in over 30 years, a scientist named Dr. Jerry Burger managed to obtain approval for a study partially reproducing the Milgram experiment, and in 2009 he published his findings in the journal American Psychologist....Dr. Burger also had some subjects witness a planted tester who refused to administer the test. He hypothesized that seeing a prior refusal might embolden test subjects to also refuse. Nevertheless, Dr. Burger’s results were comparable to Dr. Milgram’s results, and having a witnessed refusal did not significantly change [the willingness of subjects to continue increasing the voltage of the shocks].

References

Burger, J. (2009). Replicating Milgram: Would people still obey today? American Psychologist, 64 (1), 1-11 DOI: 10.1037/a0010932

Though I think Dr. Surve is reaching quite a bit in concluding that
Whatever moral compass human beings claim to possess, this research suggests that when presented with a perceived authority figure, the majority will override that compass in favor of obedience. The only possible conclusion, then, is that most human beings are in fact hard-wired to torture.

The first sentence gets some support from the experiment. I don't see why the second would.

Not that that's much consolation.

Sphenopalatine ganglioneuralgia (aka Brain Freeze)

Brain Blogger has a primer here.

It's based on this article:
Kaczorowski, M. (2002). Ice cream evoked headaches (ICE-H) study: randomised trial of accelerated versus cautious ice cream eating regimen. BMJ, 325(7378), 1445-1446. DOI: 10.1136/bmj.325.7378.1445

Sigh. I must be in the wrong field. Not much ice cream related research in philosophy.

Migraines

From Brain Blogger Dr. Shaheen Lakhan's interview with headache expert Dr. Roger K Cady, a bit about the current understanding of what migraines are:

Shaheen Lakhan: To start off, what sets a migraine apart from a tension-type headache?

Roger Cody: ...tension headache is a headache without the presence of other symptoms. The headache is generally mild to moderate in intensity, more likely to be on both sides of the head and with a steady and pressure quality to the pain. It is not associated with nausea or sensitivity to light or sound.

Migraine is the most common headache causing people to seek medical attention. Migraine is always more than just a headache. The headache can be on one or both sides of the head and more likely to have a throbbing quality or to be made worse by daily activity or things like bending over. Associated with the headache are symptoms like nausea and sensitivity to light, sound, and other sensory stimuli.
[....]
In people with migraine, many experts suggest that migraine and tension headaches exist on the same spectrum and arise out of the same pathophysiological process (big and little migraines).

SL: I recall the vascular theory of migraine from decades past which held that migraine symptoms were a function of ischemia and hyperemia. How far have we advanced in understanding the pathogenesis of migraine?

RC: The pathophysiology of migraine has changed dramatically over the last 2 decades. Today migraine is understood as a neurological disease with a genetic predisposition. Sufferers inherit a nervous system that is more vigilant of its surroundings than the brain of a non-migraineur, and this nervous system has an enduring predisposition to recurrent attacks of migraine triggered by events that do not produce migraine in the general population. This tendency spans decades of life for most migraineurs. Migraine is the quintessential example of how the genetic makeup of the individual and their environment can interact to produce an attack of migraine and over time the disease of migraine.

An attack of migraine occurs when the nervous system encounters triggering events that overwhelm the brain’s capacity to adjust. The first phase of a migraine is called the premonitory period or prodrome. This period is characterized by non-headache symptoms such as fatigue, cognitive change, sensory sensitivity, nasal congestion, muscle pain, yawning. This can be a warning for many people that an attack of disabling migraine is inevitable.

The second phase is called the aura and occurs in approximately 30% of attacks. This represents an electrical event in the brain called spreading cortical depression and produces a period of neurological changes that can last up to one hour but the symptoms are fully reversible. Symptoms generally are visual such as flashing lights or sensory such as numbness in the face or upper extremity.

The third phase is the headache phase. It usually begins with a mild headache that progresses sometimes very rapidly into a moderate to severe headache that is associated with nausea, sometimes vomiting and sensory sensitivity to light, sound, touch, and smell. Also there is frequently muscle pain in the head, neck, and shoulders and nasal congestion or “sinus” symptoms. However, large studies consistently show that what most physicians or patients consider sinus headache is actually migraine. This generally causes a person to seek refuge in a dark quiet place and generally lasts from 4-72 hours.

The final phase is called the postdrome. Sometimes it is referred to as the migraine hangover and consists of muscle aches and pain, slowed cognition, fatigue, and general malaise that can last up to another 24 hours. More rarely, some people experience a boost in energy and elation.

Read the whole thing here

06 June 2009

Guide to torture justifications

Having trouble keeping up with the lines of justification for the US torture regime? Digby brings you a handy chart:


Go here for a larger version.

06 May 2009

The day after the day after

Question: When I haven't been to judo in a few weeks, I'm more sore 48 hours after practice than I am 24 hours afterward. But after getting back in shape the soreness seems to constantly decrease with time. Other people tell me similar things with other new exercise regimes. So I don't think I'm idiosyncratic. Why does this happen?

My initial thought --and here I reveal the depth of my ignorance-- was that since the tissues have been healing, the worsening allodynia isn't due to increased prostaglandins, bradykinin, leukotrienes, etc, released by the damaged muscle. Rather it's from dorsal horn wind-up, and neurogenic inflammatory factors like substance p and neurokinins A and B. It makes sense that those would continue to increase over time.

But that wouldn't explain why this doesn't seem to happen when I'm already in shape, even when a workout is much harder than usual.

Or is it just the obvious answer that the difference between relative inactivity and a moderate workout is less than the difference between a moderate workout and a really hard one?

Ideas?

05 May 2009

Regional blocks better for Cesarean sections

Medical News Today
For Cesarean Section, Regional Blocks Prove Superior To General Anesthesia
30 Apr 2009

General anesthesia (GA) is associated with an increased risk of infant intubation and low Apgar scores, relative to regional anesthesia. An analysis of 50,806 cesarean deliveries, published in the open access journal BMC Medicine, strongly supports guidelines that regional anesthesia is to be preferred over GA for most cesarean sections.

Charles Algert, from the Kolling Institute at the Royal North Shore Hospital, Sydney, was part of a team of researchers who studied births in the state of New South Wales, Australia, between 1998 and 2004. He said, "We have shown that general anesthesia poses significant risks to the neonate of both resuscitation requiring intubation and of a poor Apgar score at 5 minutes. The greatest relative risk of both adverse outcomes occurred in low-risk, planned, repeat cesarean deliveries under GA, but the greatest excess in risk attributable to GA was for emergency deliveries for fetal distress where the infant would already have been compromised to some extent".

Although current guidelines recommend regional blocks, GA was still used for 12.6% of cesareans across NSW in 2006. According to the NHS Maternity Statistics, 8.7% of cesarean sections in England in 2006-2007 were performed using GA. It is generally presumed that any harm caused by GA is short-lasting, with most studies focusing on resuscitation and the Apgar score at one minute. According to Algert, however, this may not be the case, "The increased rates of neonatal intubation after GA shown in this study represent harm in and of itself, and the persistence of low 5-minute Apgar scores suggests that deleterious effects may last longer than the immediate aftermath of delivery".

The authors conclude, "Clinicians considering the use of GA for a cesarean delivery should be aware of these possible consequences for the infant, for both planned and emergency sections".

Regional block versus general anaesthesia for caesarean section and neonatal outcomes: a population-based study
Charles S Algert, Jennifer R Bowen, Warwick B Giles, Greg E Knoblanche, Samantha L Lain and Christine L Roberts
BMC Medicine (in press)
Article available at journal website: http://www.biomedcentral.com/bmcmed/

Source:
Graeme Baldwin
BioMed Central

Article URL: http://www.medicalnewstoday.com/articles/148091.php

02 May 2009

New warning labels on NASIDs

Medical News Today News Article: "FDA Requires Additional Labeling For Over-the-Counter Pain Relievers And Fever Reducers To Help Consumers Use Products Safely

29 Apr 2009   

The Food and Drug Administration issued a final rule today that requires manufacturers of over-the-counter (OTC) pain relievers and fever reducers to revise their labeling to include warnings about potential safety risks, such as internal bleeding and liver damage, associated with the use of these popular drugs.

Products covered by the FDA action include acetaminophen, and a class of drugs known as the nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs include aspirin, ibuprofen, naproxen, and ketoprofen. Acetaminophen is in a class by itself. The revised labeling applies to all OTC pain relievers and fever reducers, including those that contain one of these ingredients in combination with other ingredients, such as in cold medicines containing pain relievers or fever reducers.

'Acetaminophen and NSAIDs are commonly used drugs for both children and adults because they are effective in reducing fevers and relieving minor aches and pain, such as headaches and muscle aches, ' said Charles Ganley, M.D., director, FDA's Office of Nonprescription Drugs in the Center for Drug Evaluation and Research. 'However, the risks associated with their use, need to be clearly identified on the label so that consumers taking these drugs are fully aware of the potential harm they can cause. It is important that they know how to take these medications safely to reduce their risk.'

Under the final rule, manufacturers must ensure that the active ingredients of these drugs are prominently displayed on the drug labels on both the packages and bottles. The labeling also must warn of the risks of stomach bleeding for NSAIDs and severe liver damage for acetaminophen.

Since 2006, some manufacturers have voluntarily revised their product labeling to identify these potential safety concerns. However, the voluntary changes to labeling do not address all of the labeling requirements in the new rule. For example, the new rule includes a warning on products containing acetaminophen that instructs consumers to ask a doctor before they are taking the blood thinning drug warfarin. The new rule requires all manufacturers to relabel their products within one year of today's date.

Safety data reported in medical literature indicate that people sometimes take more acetaminophen than the labeling recommends. Others unknowingly take multiple products containing acetaminophen at the same time. Exceeding the recommended dosage of acetaminophen may increase the risks for severe liver damage. Alcohol use can also increase the risk of liver damage with acetaminophen.

The risk for stomach bleeding may increase in people who use NSAIDs and who are taking blood-thinning drugs (anticoagulants) or steroids. Stomach bleeding risks also increase for people who take multiple NSAIDs at the same time, or in people who take them longer than directed. Alcohol use can increase the risk for stomach bleeding with NSAIDs use.

An FDA Advisory Committee meeting will be convened on June 29 & 30, 2009, to discuss further steps the FDA could take to reduce the risk of liver damage associated with acetaminophen overdoses.

To read the final rule on the relabeling of OTC pain relievers and fever reducers, go here.

To read the FR Notice announcing the FDA Advisory Committee meeting, see link.

Source
Food and Drug Administration
Article URL: http://www.medicalnewstoday.com/articles/148085.php"



Medical News Today News Article


Medical News Today News Article: "Stroking The Skin Sends Signals Direct To The Brain, Deadens Pain Impulses

16 Apr 2009   

The specialised nerve fibres in the skin are called CT nerves (C-tactile) and they travel directly to the areas in the brain that are important in the emergence of feelings.

'Basically the signals that tell the brain that we are being stroked on the skin have their own direct route to the brain, and are not blocked even if the brain is receiving pain impulses from the same area. In fact it's more the opposite, that the stroking impulses are able to deaden the pain impulses,' says Line Löken, postgraduate student in neurophysiology at the Sahlgrenska Academy.
[....]
Each individual nerve fibre is responsible for touch signals from roughly a square centimetre of skin. The research team used a specially-designed robot, which brushed over the exact area of skin for which a particular nerve fibre is responsible. The subjects were also asked to rate how pleasant or unpleasant they found the brushing.

'As the nerve signals that were sent in the CT nerves became more frequent, the subjects reported the experience as being increasingly pleasant. Of the skin nerves that we studied, it was only the CT nerves that had this strong link between the frequency of the signals and how pleasant it felt,' says researcher Johan Wessberg.

Notes:

Journal: Nature Neuroscience
Title of the article: Coding of pleasant touch by unmyelinated afferents in humans
Authors: Line S. Löken, Johan Wessberg, India Morrisson, Francis McGlone, Håkan Olausson
The full text article is available on Nature Neuroscience's web page: http://www.nature.com/neuro/journal/vaop/ncurrent/abs/nn.2312.html

By: Elin Lindström Claessen
"



A Trance of Pleasure

And now for something completely different:

A Trance of Pleasure:

A 2003 study in Epilepsy and Behavior has some descriptions of the ecstatic seizures experienced by some patients with epilepsy.



They include intense erotic and spiritual experiences, feelings of become close to and blending with other people, and some sensations that couldn't be fully captured in words.



I've put some of the descriptions below because they sound absolutely wonderful:





Patient 1

The first seizure occurred during a concert when he was a teenager. He remembers perceiving short moments of an indefinable feeling. Such episodes recurred and a few months later evolved into a GTC [generalized tonic–clonic seizure]. He characterizes these sensations as ‘a trance of pleasure.’ ‘It is like an emotional wave striking me again and again. I feel compelled to obey a sort of phenomenon. These sensations are outside the spectrum of what I ever have experienced outside a seizure.’ He also describes cold shivering, increased muscle tension, and a delicious taste, and he swallows repeatedly. He enjoys the sensations and is absorbed in them in a way that he can barely hear when spoken to. When in a particular, relaxed mood, he can sometimes induce seizures by ‘opening up mentally’ and contracting muscles. He denies any religious aspects of the symptoms. ‘It’s the phenomenon, the feeling, the fit taking control.’ It lasts a few minutes and afterward he is tired with difficulties expressing himself for about 1 hour.



Patient 6

This man has a multifaceted symptomatology and a tendency to interpret bodily sensations as supernatural phenomena. Nevertheless, from the beginning of his forties, he experienced distinct, stereotypical attacks with a ‘change of concept of the surrounding world.’ He reports an ‘oscillating erotic sensation, like twinkling polar light’ in his pelvic region and down the inside of his thighs. This is described as different from sexual excitement, more like ‘an erogenous charge of the skin.’ He may also have a clairvoyant feeling of a ‘telepathic contact with a divine power.’ These sensations are of short duration and may be accompanied by faintness and followed by drowsiness. With carbamazepine treatment, the frequency of these attacks has been considerably reduced.



Patient 11

The attacks started in his first school year. The experiences are beyond what can be described in words. ‘I can sense the colours red and orange without seeing them. The feeling has an erotic aspect. It starts in the stomach and spreads upwards. It is pleasant, but not similar to ordinary joy. It is like an explosion.’ In the close presence of another person, he can feel a sort of peculiar unification. An intense déjà vu sensation, a queer taste, and ‘gooseflesh’ are also components of the seizures. As a child he was surprised that his friends denied having similar feelings, and he learned to keep them to himself. Sometimes these attacks evolved into CPSs with reduced consciousness and complex automatisms and afterward he had transient difficulties speaking. Before the diagnosis of epilepsy was made in his late teens, he was referred to a psychiatrist. A right-sided temporal lobe calcification was diagnosed by computed tomography at about 30 years, but he refused surgery. At 42, an expansion in the same region was found by MRI, and he was operated for an anaplastic oligodendroglioma. He was seizure-free for 6 years until recurrence of the tumor.



One of the striking things about epilepsy is how different each person's experience of having a seizure can be.



While it is stereotypically assumed to be a negative experience, some aspects can be remarkably beautiful.



The Russian author Dostoyevsky famously said of his epilepsy 'I would experience such joy as would be inconceivable in ordinary life - such joy that no one else could have any notion of. I would feel the most complete harmony in myself and in the whole world and this feeling was so strong and sweet that for a few seconds of such bliss I would give ten or more years of my life, even my whole life perhaps.'



There are several more case descriptions in the article, all of which have some aspect which touch at least the edge of ecstasy, if not the very heart of the experience.





Link to article.

Link to PubMed entry for same.

"



(Via Mind Hacks.)

Another new paper by me: Privation Theories of Pain

Yep. More from me. This time in a philosophy of religion journal --guess I'm branching out.

Privation Theories of Pain

Most modern writers accept that a privation theory of evil should explicitly account for the evil of pain. But pains are quintessentially real. The evil of pain does not seem to lie in an absence of good. Though many directly take on the challenges this raises, the metaphysics and axiology of their answers is often obscure. In this paper I try to straighten things out. By clarifying and categorizing the possible types of privation views, I explore the ways in which privationists about evil are—or should or could be—privationists about pain’s evil.

International Journal for Philosophy of Religion (2009)
DOI: 10.1007/s11153-009-9202-4
http://www.springerlink.com/content/644751l635n21r71/

Super awesome paper: Pain's Evils

Okay. I'm lying. It isn't really super awesome. But it is a new paper by me in the latest issue of the journal Utilitas:

Pain's Evils


The traditional accounts of pain’s intrinsic badness assume a false view of what pains are. Insofar as they are normatively significant, pains are not just painful sensations. A pain is a composite of a painful sensation and a set of beliefs, desires, emotions, and other mental states. A pain’s intrinsic properties can include inter alia depression, anxiety, fear, desires, feelings of helplessness, and the pain’s meaning. This undermines the traditional accounts of pain’s intrinsic badness. Pain is intrinsically bad in two distinct and historically unnoticed ways. First, most writers hold that pain’s intrinsic badness lies either in its unpleasantness or in its being disliked. Given my wider conception of pain, I believe it is both. Pain’s first intrinsic evil lies in a conjunction of all the traditional candidates for its source. Pain’s second intrinsic evil lies in the way it necessarily undermines the self-control necessary for intrinsic goods like autonomy.

Utilitas Vol. 21 No. 2 June 2009
doi:10.1017/S0953820809003550

More drugs, please: Italian edition

May I have your attention please?


Ahem.


STOP DENYING CANCER PATIENTS THE MEDICINE THEY NEED.


Thank you for your attention


Pattern and quality of care of cancer pain management. Results from the Cancer Pain Outcome Research Study Group.: "

Br J Cancer. 2009 Apr 28;
Apolone G, Corli O, Caraceni A, Negri E, Deandrea S, Montanari M, Greco MT

Most patients with advanced or metastatic cancer experience pain and despite several guidelines, undertreatment is well documented. A multicenter, open-label, prospective, non-randomised study was launched in Italy in 2006 to evaluate the epidemiology, patterns and quality of pain care of cancer patients. To assess the adequacy of analgesic care, we used a standardised measure, the pain management index (PMI), that compares the most potent analgesic prescribed for a patient with the reported level of the worst pain of that patient together with a selected list of clinical indicators. A total of 110 centres recruited 1801 valid cases. 61% of cases were received a WHO-level III opioid; 25.3% were classified as potentially undertreated, with wide variation (9.8-55.3%) according to the variables describing patients, centres and pattern of care. After adjustment with a multivariable logistic regression model, type of recruiting centre, receiving adjuvant therapy or not and type of patient recruited (new or already on follow-up) had a significant association with undertreatment. Non-compliance with the predefined set of clinical indicators was generally high, ranging from 41 to 76%. Despite intrinsic limitations of the PMI that may be considered as an indicator of the poor quality of cancer pain care, results suggest that the recourse to WHO third-level drugs still seems delayed in a substantial percentage of patients. This delay is probably related to several factors affecting practice in participating centres and suggests that the quality of cancer pain management in Italy deserves specific attention and interventions aimed at improving patients' outcomes.British Journal of Cancer advance online publication, 28 April 2009; doi:10.1038/sj.bjc.6605053 www.bjcancer.com."



(Via HubMed - pain.)

Translating nociceptive processing into human pain models.

Limits on pain models:

Translating nociceptive processing into human pain models.: "

Exp Brain Res. 2009 Apr 29;
Schmelz M

As volunteers can easily communicate quality and intensity of painful stimuli, human pain models appear to be ideally suited to test analgesic compounds, but also to study pain mechanisms. Acute stimulation of nociceptors under physiologic conditions has proven not to be of particular use as an experimental pain model. In contrast, if the experimental models include sensitization of the peripheral or central pain processing they may indeed mimic certain aspects of chronic pain conditions. Peripheral inflammatory conditions can be induced experimentally with sensitization patterns correlating to clinical inflammatory pain. There are also well-characterized models of central sensitization, which mimic aspects of neuropathic pain patients such as touch evoked allodynia and punctate hyperalgesia. The main complaint of chronic pain patients, however, is spontaneous pain, but currently there is no human model available that would mimic chronic inflammatory or neuropathic pain. Thus, although being helpful for proof of concept studies and dose finding, current human pain models cannot replace patient studies for testing efficacy of analgesic compounds."



(Via HubMed - pain.)