More on NSAID and cox-2 dangers

Old, 'safe' painkillers found to cause same heart ills as new

ANDRÉ PICARD

From Wednesday's Globe and Mail

Some older, "safe" painkillers appear to cause the same heart problems as the much-scrutinized and discredited painkiller Vioxx, according to new research, which raises new concerns about the safety of treatments for chronic painful conditions such as arthritis.

At the same time, Vioxx itself appears to have even more side effects than previously believed, according to research published on-line yesterday by the Journal of the American Medical Association.

Three articles in JAMA feature some striking conclusions, including:

Older painkillers such as diclofenac sharply increase the risk of heart attacks in regular users.

Other traditional painkillers including meloxicam, indomethacin and perhaps even over-the-counter products such as ibuprofen may also increase the risk of heart disease.

Rofecobix (brand name Vioxx) -- already pulled from the market because it increased the risk of heart attacks and stroke -- may also cause kidney damage and heart arrhythmia (abnormal heart rhythm).

Celecoxib (brand name Celebrex) -- which is still available -- may cause heart problems, but only when taken at relatively high doses of 200 milligrams or more daily.

The painkiller naproxen does not reduce the risk of cardiovascular problems, as previous research has suggested, but it does not cause additional risk, either.

More than 30 million people worldwide take these medications, known as non-steroidal anti-inflammatory drugs, for the daily treatment of pain and inflammation. So, the potential repercussions of the findings are widespread.

NSAIDs are already known to cause gastrointestinal problems, and adding heart problems to the mix could deter patients from their use.

"It's important not to get too alarmed by these findings," said David Juurlink, a scientist at the Toronto-based Institute for Clinical Evaluative Sciences.

He said the news that taking diclofenac can increase risk by 40 per cent may alarm some users, but that they need to bear in mind that individual risk depends on dose and cardiovascular risk factors.

"All drugs have risks and benefits and data like this force us to scrutinize our behaviour," Dr. Juurlink said.

One study, led by Jingjung Zhang of Harvard Medical School in Boston, looked at the safety of cyclooxygenase 2 (cox-2) inhibitors such as Vioxx, Celebrex and valdecoxib (brand name Bextra, it has also been withdrawn from the market). The researchers combined the findings of 114 studies involving more than 115,000 patients and found that those taking Vioxx had markedly higher rates of kidney problems and arrhythmia.

Patients taking the other drugs did not have the same problems, leading Dr. Zhang to conclude that there is "no cox-2 inhibitor class effect."

The second study, led by Patricia McGettigan of the University of Newcastle in New South Wales, Australia, examined the cardiovascular risks associated with a broad range of painkillers, new and old. The review of 17 studies included more than 75,000 patients taking cox-2 inhibitors and 375,000 taking traditional NSAIDs.

Patients taking Vioxx saw their risk of heart attack double, while those taking diclofenac saw their risk increase 40 per cent. Ibuprofen increased risk by 7 per cent, a virtually negligible effect.

David Graham of the U.S. Food and Drug Administration (but who has clashed publicly with his employer about its policies), said in an editorial published by JAMA that, for patients with arthritis and other chronic conditions that require pain relief "naproxen appears to be the safest NSAID choice."

He said that while the data on Celebrex look relatively good, it is no better than traditional NSAIDs, so its use is not justified.
© Copyright 2006 Bell Globemedia Publishing Inc.

Link

The effect of dread on pain preferences

Straight from the neuroeconomists to you:

Research Shows Anticipating Pain Hurts
By LAURAN NEERGAARD AP Medical Writer

May 04,2006 | WASHINGTON -- Anyone who's ever taken a preschooler to the doctor knows they often cry more before the shot than afterward. Now researchers using brain scans to unravel the biology of dread have an explanation: For some people, anticipating pain is truly as bad as experiencing it.

How bad? Among people who volunteered to receive electric shocks, almost a third opted for a stronger zap if they could just get it over with, instead of having to wait.

More importantly, the research found that how much attention the brain pays to expected pain determines whether someone is an "extreme dreader" -- suggesting that simple diversions could alleviate the misery.

[....]

Standard economic theory says that people should postpone bad outcomes for as long as possible, because something might happen in the interim to change improve the outlook.

In real life, the "just get it over with" reaction is more likely, said Berns, a professor of psychiatry and behavioral sciences. He offers a personal example: He usually pays credit card bills as soon as they arrive instead of waiting until they're due, even though "it doesn't make any sense economically."

So Berns designed a study to trace dread inside the brain. He put 32 volunteers into an MRI machine while giving them a series of 96 electric shocks to the foot. The shocks varied in intensity, from barely detectable to the pain of a needle jab.

Participants were told one was coming, how strong it would be, and how long the wait for it would be, from 1 to 27 seconds.

Later, participants were given choices: Would they prefer a medium jolt in 5 seconds or 27 seconds? What about a mild jolt in 20 seconds vs. a sharp one in 3 seconds?

When the voltage was identical, the volunteers almost always chose the shortest wait. But those Berns dubbed "extreme dreaders" picked the worst shock if it meant not having to wait as long.

The MRI scans showed that a brain network that governs how much pain people feel became active even before they were shocked, particularly the parts of this "pain matrix" that are linked to attention -- but not brain regions involving fear and anxiety. The more dread bothered someone, the more attention the pain-sensing parts of the brain were paying to the wait.

In other words, the mere information that you're about to feel pain "seems to be a source of misery," George Lowenstein, a specialist in economics and psychology at Carnegie Mellon University, wrote in an accompanying review of the work.

"These findings support the idea that the decision to delay or expedite an outcome depends critically on how a person feels while waiting," Lowenstein added.

© 2006 The Associated Press.
Link

Categories: Attention, Anticipation

Milimeter wave therapy

A Soviet technology developed during the Cold War to keep short-range military communications secure may someday provide relief from hard-to-treat conditions such as nerve pain, intense itching, and nausea caused by chemotherapy. And, with the support of a $4 million grant from the National Institutes of Health, Temple University School of Medicine scientists are the only group in the United States now investigating this alternative therapy.
[....]
Millimeter wave therapy, which directs a low-intensity electromagnetic beam to the skin, has been used for more than 25 years in Eastern Europe, where it is credited with alleviating more than 50 different conditions, ranging from heart disease to skin wounds and even cancer. Doctors there believe that the waves boost the immune system, act as an anti-inflammatory, and provide sedation and pain relief, all with virtually no side effects.

While the therapy remains largely unknown in the West, Marvin Ziskin, M.D., professor of radiology and medical physics at Temple, first encountered it in the early 1990s on a trip to the former Soviet Union.
[....]
"We found that millimeter waves reduce pain in laboratory animals, stimulate the immune system and slow the progression of skin melanomas, without damage to the skin or other harmful side effects. It's a painless, non-invasive, easily tolerated therapy," said Ziskin.
[....]
Eastern European doctors directly apply millimeter waves to skin lesions and acupuncture points. It's also common to beam them onto a diseased organ or a troublesome joint.

Absorbed very rapidly by the skin, millimeter waves appear to initiate a response in peripheral nerve endings. Ziskin's working hypothesis is that as waves reach these nerve endings, a signal is conveyed to the nervous system to modulate neural activity, in the process activating various biological effects. In one possible scenario, millimeter waves trigger the release of opioids that are known to be involved in sedation, pain relief and modulation of the immune system.

"Applying the waves to points on the skin with the highest density of nerves appears to work best. Using this approach, under strict double-blind conditions, we've produced evidence of pain relief in experimental animal models as well as in a small group of human volunteers," said Ziskin.
LInk

Categories: Analgesics, Chronic_pain

Obese people more sensitive to pain?

COLUMBUS , Ohio – Obese people may be more sensitive to pain than people who aren't obese, a new study suggests.

All of the older adults who completed the study had osteoarthritis of the knee, a disease that causes inflammation and extreme pain in the knees.

Participants were given a mild electrical stimulation on their left ankle to measure their pain reflex. The stimulus was given before and after the participants took part in a 45-minute coping skills training session that included a progressive muscle relaxation exercise.

The obese patients showed a greater physical response to the electrical stimulation than did the non-obese people, both before and after the training session. This indicates they had a lower tolerance for the painful stimulation despite reporting, in questionnaires, that they felt no more pain than non-obese people.

"The relaxation procedure helped both groups cope with pain," said Charles Emery, the study's lead author and a professor of psychology at Ohio State University. "Additionally, our tests showed both groups had higher physical pain thresholds after the relaxation session. But the obese participants still had a lower threshold for tolerating the pain."

"This is important because if an obese person begins an exercise program, he may not cognitively experience pain when in fact it is hurting the body on some level," Emery said. "That could lead to severe pain down the road."
[....]
But they were particularly interested in seeing how the obese group responded to pain; according to Emery, a small number of studies have looked at pain sensitivity in obese people, but many of these studies report conflicting results.

"Some studies say that obese people are more tolerant of pain, while other studies say they are less tolerant," Emery said.

About a third of the study's 62 participants were obese. Researchers determined who was obese based on participants' body mass index (BMI) scores, which relates height to weight. Obese patients in this study had a BMI greater than 30 but less than 35. (Scores higher than 35 are considered morbidly obese.)

The participants underwent two rounds of electrical stimulation – once before, and once after a 45-minute training session where they learned different ways of coping with pain, including instruction in progressive muscle relaxation therapy.
Link

Categories: Pain_tolerance

Another acetaminophen warning

Wow. Acetaminophen overdose causes 40-50% of acute liver failure cases.

Medical News Today
Expert Warns Of Overuse Of Over-the-Counter Pain Medication
13 Mar 2006

Acetaminophen is generally a safe and effective medication, one that is used by millions of people every day to treat minor aches and pains and to diminish fevers. It might surprise many people, then, that overdoses of Tylenol and other products containing acetaminophen account for a staggering 40 percent to 50 percent of all acute liver failure cases each year in the United States.

Of those cases, nearly half are unintentional overdoses, a recent finding that many experts say is alarming. That's why people need to take extra care not to take even a little more of the medication than the recommended dose during any 24-hour period.

“My overall recommendation for people using Tylenol is that it is a safe drug,” says Robert J. Fontana, M.D., associate professor of internal medicine at the University of Michigan Medical School, member of the Gastroenterology Division and medical director of liver transplantation. “However, like most other things in life, too much of a good thing can be bad for you.”

For instance, an adult should not take more than eight Tylenol Extra Strength pills, which contains 500 milligrams per tablet, in a 24-hour period (i.e. the maximum daily dose is 4,000 milligrams per day). Exceeding that dosage, could lead to inadvertent liver or kidney damage in some people, Fontana says.

Fontana notes that damage occurs acutely rather than chronically - in other words, it isn't the dosage of the medicine a person takes over several weeks that is the problem, it is the daily dose that may lead to liver toxicity.

Here's how the problem occurs: Whenever you take a medication, your liver typically is involved with metabolizing, or eliminating, the drug from your system. When you take too much acetaminophen, you overwhelm your body's ability to eliminate the medication safely. High levels of the medication can build up in the blood, and that can damage liver cells that are trying to metabolize the drug, which can lead to liver injury, Fontana says.

A multicenter study that the U-M Health System recently participated in indicated that about half of acetaminophen overdoses that resulted in liver failure were unintentional, something the researchers refer to as “therapeutic misadventures.”

“What I mean by that is that individuals were taking acetaminophen for some type of medical problem - such as a headache, back pain or the flu - inadvertently took too much and subsequently developed liver failure,” Fontana says. “If you go to a drug store, as many as 150 products that consumers can buy without a prescription have acetaminophen in them.”

It doesn't take much for someone to consume a toxic dose of acetaminophen. For instance, consider someone who is taking an over-the-counter product that helps stop sneezing or coughing that contains 350 to 500 milligrams of acetaminophen per dose, with one or two doses every four hours. If that person also has a headache or muscle aches, he or she may take some acetaminophen and quickly go into the potentially toxic range.

In addition to the possible overuse of acetaminophen when taking non-prescription medications, another potential hazard occurs among people who take Tylenol or a similar medication in addition to a prescription pain reliever that also contains acetaminophen, such as Vicodin or Darvocet.

“We're particularly concerned that health care providers may not be aware of this, and when they prescribe these potent pain medicines, there needs to be greater education of our patients of the total dose it is safe for them to take,” Fontana says. “In addition, patients with severe or chronic pain may take increasing doses of prescription narcotics and not be aware that they contain 500 to 750 milligrams of acetaminophen in each tablet.”

This is a concern not only for adults, but also for children because there's been a shift toward using acetaminophen products for babies and children. “As parents,” Fontana says, “we need to be aware of this so that we avoid inadvertent toxicity in trying to treat our children at home when they have high fevers.”

Other factors can compound a person's likelihood of developing liver damage from overuse of acetaminophen. Information increasingly suggests that if you drink alcohol daily or on a chronic basis, that may predispose you to liver damage from acetaminophen, Fontana says. That may occur due to development of nutritional deficiencies or a reduction in the level of the detoxifying enzymes in your liver as a result of drinking, he notes.

The U-M Health System and other institutions are involved with ongoing studies of acute liver failure and drug-induced liver injury. In addition to exploring and identifying the causes and natural history of acute liver failure, researchers also are doing exploratory work on a potential genetic predisposition to acute liver failure.

A recent study also described a new blood test to help identify patients with acetaminophen liver toxicity so that treatment can be started rapidly. “This new blood test holds great promise for identifying patients early on prior to the development of life-threatening liver failure,” Fontana says.

Facts about acetaminophen and liver damage:

-- Before taking acetaminophen, experts recommend that you tell your doctor if you have ever had liver disease or if you drink alcohol daily or on a chronic basis.

-- One way to prevent acetaminophen-related liver toxicity is to carefully read the labels on all medications so you are aware of their acetaminophen content (both prescription and over-the-counter).

-- Acetaminophen is found in Tylenol-brand products, but it also is found in numerous other brand-name medications, including some varieties of Excedrin, FeverAll, Genapap, Percocet and more. It also is included in combination products, such as Midol Teen Menstrual Formula Caplets containing Acetaminophen and Pamabrom. Many prescription pain relievers also contain acetaminophen, such as Lorcet Plus, Darvocet and Vicodin.

-- In case of an overdose, call your local poison control center at 1-800-222-1222. If the victim is not breathing, call 911.

-- Remember to keep medications locked up or out of reach of children.

-- Do not take the full day's dose of acetaminophen at one time; space it out over the course of the day.

Written by Katie Gazella
Link

Categories: acetaminophen

Fentanyl

Another entry in my occasional series: Meet your analgesics (and anesthetics in this case)

Fentanyl



What it is:

First synthesized in Belgium in the late 1950s, fentanyl, with an analgesic potency of about 80 times that of morphine, was introduced into medical practice in the 1960s as an intravenous anesthetic under the trade name of Sublimaze®. Thereafter; two other fentanyl analogues were introduced; alfentanil (Alfenta®), an ultra-short (5-10 minutes) acting analgesic, and sufentanil (Sufenta®), an exceptionally potent analgesic (5 to 10 times more potent than fentanyl) for use in heart surgery. Today, fentanyls are extensively used for anesthesia and analgesia. Duragesic®, for example, is a fentanyl transdermal patch used in chronic pain management, and Actiq® is a solid formulation of fentanyl citrate on a stick that dissolves slowly in the mouth for transmucosal absorption. Actiq® is intended for opiate-tolerant individuals and is effective in treating breakthrough pain in cancer patients. Carfentanil (Wildnil®) is an analogue of fentanyl with an analgesic potency 10,000 times that of morphine and is used in veterinary practice to immobilize certain large animals. Link

Wikipedia entry

Its use in chemical warfare:
Center for Nonproliferation Studies
The Moscow Theatre Seige

Categories: Fentanyl, Analgesics

Pain measurement

Some of the various tools for measuring pain:

The McGill Pain Questionnaire (the granddaddy of them all)
The Short-Form McGill Pain Questionnaire (the nice-uncle of them all)

The Brief Pain Inventory (long-form) (short-form)

A literature review (geared toward end-of-life issues)

A list from City of Hope with links

Categories: Pain_assessment, McGill_Pain_Questionnaire

Self-indulgence

In case you've been riveted to your seats these past few months, waiting to see if I get a job, the search is over.

Come this summer, PFP's world headquarters will be moving back to the City of Angels after experiencing 7-years of actual winter. I've been hired by Cal State University Northridge's philosophy department

I'm extremely happy since this was the job I really wanted. And when this blogger is happy, you all get more (about) pain.

Now, back to the pain and suffering.

Primer on pain

Just came across this online primer on pain physiology and psychology. I didn't get a chance to read the whole thing and so I can't vouch for it, but it seems pretty accessable and non-technical.

Categories: Links

Solicitiousness and pain, or: your blogger tries some research

Another favorite topic:

Solicitousness and chronic pain: a critical review
Toby RO Newton-John
Abstract: This article offers a critical review of the literature examining spouse responses to the pain behaviour of
chronic pain patients. An overview is given of 27 studies that have explored patient–spouse interactions
in chronic pain, together with a summary of the various .ndings. It is concluded that the body of research
is broadly supportive of the operant behavioural paradigm on which it has developed. Patients’ coping
with chronic pain is signi.cantly influenced by the ways in which those closest to them respond to their
expressions of discomfort. However, it is argued that the behavioural model alone is insuf.cient when
accounting for the complexity of pain couples’ interactions. The impact of the spouse’s response is mediated
by a range of cognitive and affective variables that have yet to be fully recognized in the research
literature. It is also argued that the operationalization of the construct of solicitousness, which is central
to research on chronic pain couples, is flawed. A number of suggestions for future theoretical and empirical
developments in this area are made.
Pain Reviews 2002; 9; 7-27

Being the dedicated scholar I am, I recently decided to see if solicitiousness had a similar effect in the short-term by breaking my ribs. Unfotunately, I've been a bit too dedicated to my research in the past. My wife has had to sit through too much blabber about solicitiousnes and pain, and therefore knows better than to pay attention to every whine.. So while I get plenty of sympathy, I still have to fetch my own Advil.

And I'm better-off for it.

Categories: Solicitiousness

CIPA

A nice resource of work on that perennial favorite of philosophers everywhere: congenital insensitivity to pain and anhidrosis (CIPA):
http://www.geometry.net/health_conditions/congenital_pain_insensitivity_page_no_2.php

Categories: Congenital_insensitivity, Links

A non-drug bibliography for palliative care

Good stuff:

http://www.cityofhope.org/prc/pdf/Non-Drug%20Bibliography.pdf

Categories: Palliative_care, Bibliography,Links

Attention and distraction (and some hypnosis)

And now some material on attention and distraction:

Effects of attentional focusing on pain perception
Britton W. Brewer and Paul Karoly
Abstract Two experiments were conducted to examine the hypothesized differential effectiveness of two attentional focusing strategies in pain perception. In the first experiment, subjects (72 male college students) rated their levels of pain after being exposed to either low- or high-intensity pressure stimulation for 75 s. Subjects were instructed to use either an external or internal focus of attention during the pain induction. Results revealed that external focusing was more effective for coping than internal focusing across both levels of stimulus intensity. The second experiment was a replication of the first, and featured bolstered internal focusing and stimulus intensity manipulations. Results showed that high-intensity stimulation produced higher pain ratings than did low-intensity stimulation for subjects in the internal focusing conditions, but not for those in the external focusing conditions. The findings support the power of distraction strategies for dealing with short-term pain with a rapid onset. Theoretical implications are discussed.
Motivation and Emotion 13(3), 193-203 DOI: 10.1007/BF00995535

Laser-evoked potentials to noxious stimulation during hypnotic analgesia and distraction of attention suggest different brain mechanisms of pain control
Marc Friederich, Ralf H. Trippe, Mustafa özcan, Thomas Weiss, Holger Hecht and Wolfgang H.R. Miltner

Psychological accounts of hypnosis have hypothesized that hypnosis and attention might share similar mechanisms and that hypnosis simply represents an extensive state of reduced attention. This assumption implies that reports of pain and electrocortical brain responses to painful stimulation should be similarly reduced when subjects are exposed to suggestions of hypnotic analgesia (HA) or requested to distract their attention from painful stimuli (distraction of attention: DA) as compared to a control condition (CC). To test this hypothesis, we recorded event-related electrical brain potentials to noxious laser-heat stimuli and pain reports during HA, DA, and CC from subjects highly susceptible to hypnotic suggestions. Pain reports were significantly reduced during HA and DA as compared to CC. The amplitudes of the late laser-evoked brain potential (LEP) components N200 and P320 were also significantly smaller during DA than during CC. However, no significant difference of these late LEP amplitudes was obtained for HA as compared to CC. Results indicate that hypnotic analgesia and distraction of attention represent different mechanisms of pain control and involve different brain mechanisms. Psychophysiology
Volume 38 Page 768 - September 2001 doi:10.1111/1469-8986.3850768

A Comparison of Distraction Strategies for Venipuncture Distress in Children
MacLaren and Cohen
Objective To compare the effects of two pediatric venipuncture distress-management distraction strategies that differed in the degree to which they required children's interaction. Methods Eighty-eight 1- to 7-year-old children receiving venipuncture were randomly assigned to one of three treatment conditions: interactive toy distraction, passive movie distraction, or standard care. Distress was examined via parent, nurse, self-report (children over 4 years), and observational coding. Engagement in distraction was assessed via observational coding.ResultsChildren in the passive condition were more distracted and less distressed than children in the interactive condition. Although children in the interactive condition were more distracted than standard care children, there were no differences in distress between these groups. Conclusions Despite literature that suggests that interactive distraction should lower distress more than passive distraction, results indicate that a passive strategy might be most effective for children's venipuncture. It is possible that children's distress interfered with their ability to interact with the distractor.
J. Pediatr. Psychol..2005; 30: 387-396. doi:10.1093/jpepsy/jsi062

Parents' Positioning and Distracting Children During Venipuncture
Effects on Children's Pain, Fear, and Distress
Kim Cavender, Melinda D. Goff, Ellen C. Hollon, Cathie E. Guzzetta,
The purpose of this study was to determine the effectiveness of parental positioning and distraction on the pain, fear, and distress of pediatric patients undergoing venipuncture. An experimental-comparison group design was used to evaluate 43 patients (20 experimental and 23 comparison) who were 4 to 11 years old. Experimental participants used parental positioning and distraction. All participants rated their pain and fear; parents and child life specialists (CLS) rated the child's fear, and CLS rated the child's distress. Self-reported pain and fear were highly correlated (p < .001) but not significantly different between the two groups. Fear rated by CLS (p < .001) and parents (p = .003) was significantly lower in experimental participants. Although no difference was found in distress between the two groups, a significant time trend was discovered (p < .001). The parental positioning-distraction intervention has the potential to enhance positive clinical outcomes with a primary benefit of decreased fear. Further research is warranted.
Children's Medical Center of Dallas Journal of Holistic Nursing, Vol. 22, No. 1, 32-56 (2004)
DOI: 10.1177/0898010104263306
Link (full text)

Brief Cognitive Interventions for Burn Pain
Jennifer A. Haythornthwaite, John W. Lawrence, James A. Fauerbach
This study tested the efficacy of 2 brief cognitive interventions in supplementing regular medical treatment for pain during burn dressing change. Forty-two burn inpatients were randomly assigned to 3 groups: sensory focusing, music distraction, and usual care. Patients reported pain, pain relief, satisfaction with pain control, and pain coping strategies. The sensory focusing group reported greater pain relief compared to the music distraction group and a reduction in remembered pain compared to the usual care group, although group differences were not observed on serial pain ratings. In addition, after controlling for burn size and relevant covariates, regression analyses indicated that catastrophizing predicted pain, memory for pain, and satisfaction with pain control. Refinement of the sensory focusing intervention is warranted to reduce catastrophic thinking and improve pain relief.
Annals of Behavioral Medicine, 2001, Vol. 23, No. 1, Pages 42-49
(doi: 10.1207/S15324796ABM2301_7)

Categories: Attention, Distraction, Hypnosis

Virtual-reality-palooza

I've written here before about the use of virtual reality in treating pain during medical procedures. Here's a collection of abstracts that I've come across recently:

Use of Virtual Reality as a Distractor for Painful Procedures in a Patient with Pediatric Cancer: A Case Study
Jonathan Gershon, Elana Zimand, Rosemarie Lemos, Barbara Olasov Rothbaum, Larry Hodges
Virtual reality (VR) has been demonstrated as an effective tool to help people overcome a variety of anxiety disorders. In this case study, the use of VR as a distractor to alleviate pain and anxiety associated with an invasive medical procedure for a pediatric cancer patient was explored. An A-B-C-A design during four consecutive medical appointments in an outpatient oncology clinic compared no distraction (A), non-VR distraction on a computer screen (B), and VR distraction with a head set (C). Behavioral observations of distress by the researcher and reports of pain and anxiety by the patient, parent, and nurse were taken before and during the procedure. The child's pulse was monitored throughout the procedure. The findings from this case study suggest benefit from using VR distraction, as indicated by lower pain and anxiety ratings, reduced pulse, and fewer observed behavioral indices of distress. The need for larger scale studies and application of VR with younger children is discussed in the context of confirming effectiveness of this technique and providing more generalizable information about efficacy. CyberPsychology & Behavior. Dec 2003, Vol. 6, No. 6: 657-661

Effects of Distraction Using Virtual Reality Glasses During Lumbar Punctures in Adolescents With Cancer
Suzanne Sander Wint, RN, BSN, CPON, Debra Eshelman, RN, MSN, CPNP, Jill Steele, RN, MSN, and Cathie E. Guzzetta, RN, PhD, HNC, FAAN

Purpose/Objectives: To determine the effects of virtual reality (VR) glasses on adolescents with cancer undergoing lumbar punctures (LPs).

Design: Pilot study using an experimental, control group design.

Setting: In-hospital oncology clinic.

Sample: 30 adolescents with cancer (17 in the VR and 13 in the control group) undergoing frequent LPs.

Methods: Subjects were randomly assigned to groups. Both groups received standard intervention during the LP, but the experimental group also wore VR glasses and watched a video. Following the LP, both groups rated their pain using a visual analog scale (VAS) and were interviewed to evaluate their experience.

Main Research Variables: Pain, subjective evaluation of experience.

Findings: Although VAS pain scores were not statistically different between the two groups (p = 0.77), VAS scores tended to be lower in the VR group (median VAS of 7.0, range 0-48) than in the control group (median VAS of 9.0, range 0-59). 77% of subjects in the experimental group said the VR glasses helped to distract them from the LP.

Conclusions: VR glasses are a feasible, age-appropriate, nonpharmacologic adjunct to conventional care in managing the pain associated with LPs in adolescents.

Implications for Practice: The clinical application of various age-appropriate distracters to reduce pain in adolescents undergoing painful procedures should be explored.
Link

Immersive Virtual Reality for Reducing Experimental Ischemic Pain
Hunter G. Hoffman, Azucena Garcia-Palacios, Veronica Kapa, Jennifer Beecher, Sam R. Sharar
This study explored the novel use of immersive virtual environments as a nonpharmacologic pain control technique and whether it works for both men and women. Fourteen female and 8 male students underwent pain induced via a blood pressure cuff ischemia lasting 10 min or less. Pain ratings increased significantly every 2 min during the no distraction phase (0 to 8 min) and dropped dramatically during the last 2 min period when participants were in the virtual environment (a 59% drop for women and a 41% drop for men). Five visual analog pain scores for each treatment condition served as the primary dependent variables. All 22 participants reported a drop in pain in the virtual environment, and the magnitude of pain reduction from the virtual environment was large (a 52% drop) and statistically significant. This is the first study to show immersive virtual environment distraction is also effective for women. The results show that virtual environments can function as a strong nonpharmacologic pain reduction technique, showing the same pattern of results obtained from recent clinical studies using virtual environments with burn patients during physical therapy. Practical applications of virtual environment pain reduction, and the value of a multidisciplinary approach to studying pain are discussed. International Journal of Human-Computer Interaction, 2003, Vol. 15, No. 3, Pages 469-486 (doi: 10.1207/S15327590IJHC1503_10)
Link

Effects of distraction using virtual reality glasses during lumbar punctures in adolescents with cancer Suzanne Sander and Jill Steele
Key points:
*Virtual reality glasses are a feasible, age-appropriate, nonpharmacologic adjunct to converntional care in managing pain associated with lumbar punctures in adolescents with cancer.
*visual analogue pain scores tended to be lower in the VR group
*The majority of adolescents who received the VR glasses felt the glasses distracted them from the lumbar puncture and wanted to use them again.
*More research is needed to explore novel distraction techniques for managing pediatric pain associated with procedures
Link (full text)

Virtual Reality Pain Distraction
Hunter Hoffman, PhD, and David Patterson, PhD ABPP ABPH
Introduction
Patients commonly report experiencing excessive pain during medical procedures (Melzack, 1990), especially during severe burn wound care (Carrougher et al., 2003). Although opioid analgesics are currently essential for pain control during burn wound care, dosage amounts are limited by side effects (e.g., nausea, constipation, interference with appetite, sleep cycles) and other concerns associated with this class of medications (Cherny et al., 2001). Pain control is particularly challenging for patients with severe burn injuries. Patients treated for this form of trauma typically undergo daily wound care to clean, prevent infection, monitor the healing progress, and bandage again. Most burn patients report severe to excruciating pain during these medical procedures (Carrougher et al., 2003). APS Bulletin SPRING 2005 • VOLUME 15, NUMBER 2
Link (full text)

The effectiveness of virtual reality based pain control with multiple treatments.
Hoffman, H.G., Patterson, D.R., Carrougher, G.J., & Sharar, S. (2001).
Objective: The present study explored whether immersive virtual reality continues to reduce pain (via distraction) with repeated use.

Setting: Burn care unit at a regional trauma center.

Patients: Seven patients aged 9-32 years, mean age = 21.9 years (average of 23.7% total body surface area burned, range TBSA = 3% to 60%), performed range of motion exercises of their injured extremity under an occupational therapist’s direction on at least three separate days each.

Intervention: For each physical therapy session, each patient spent equal amounts of time in VR and in the control condition (no distraction). The mean duration of physical therapy in VR was 3.5, 4.9 and 6.4 minutes for the first, second and third session, respectively. Condition order was randomized and counterbalanced.

Outcome measures: For each of the three physical therapy sessions, five visual analog pain scores for each treatment condition served as the dependent variables.

Results: Pain ratings were statistically lower when patients were in VR, and the magnitude of VR pain reduction did not diminish with repeated use of VR. The results of this study may be examined in more detail at www.vrpain.com.

Conclusions: Although the small sample size limits generalizability, results provide converging preliminary evidence that virtual reality can function as a strong nonpharmacologic pain reduction technique for burn patients during physical therapy. Results suggest that virtual reality does not diminish in analgesic effectiveness with three (and possibly more) uses. Virtual reality may also have analgesic potential for other painful procedures or pain populations. Practical implications are discussed. Clinical Journal of Pain, 17, 229-235.
Link (full text)

And a link with even more resources: www.vrpain.com

Categories: Virtual_reality, Distraction, Attention, Burn_care, Palliative_care

Self-efficacy and the opioid system

Perceived Self-Efficacy and Pain Control: Opioid and Nonopioid Mechanisms
[Personality Processes and Individual Differences]

Bandura, Albert; O'Leary, Ann; Taylor, C Barr; Gauthier, Janel; Gossard, Denis

Abstract: In this experiment, we tested for opioid and nonopioid mechanisms of pain control through cognitive means and the relation of opioid involvement to perceived coping efficacy. Subjects were taught cognitive methods of pain control, were administered a placebo, or received no intervention. Their pain tolerance was then measured at periodic intervals after they were administered either a saline solution or naloxone, an opiate antagonist that blocks the effects of endogenous opiates. Training in cognitive control strengthened perceived self-efficacy both to withstand and to reduce pain; placebo medication enhanced perceived efficacy to withstand pain but not reductive efficacy; and neither form of perceived self-efficacy changed without any intervention. Regardless of condition, the stronger the perceived self-efficacy to withstand pain, the longer subjects endured mounting pain stimulation. The findings provide evidence that attenuation of the impact of pain stimulation through cognitive control is mediated by both opioid and nonopioid mechanisms. Cognitive copers administered naloxone were less able to tolerate pain stimulation than were their saline counterparts. The stronger the perceived self-efficacy to reduce pain, the greater was the opioid activation. Cognitive copers were also able to achieve some increase in pain tolerance even when opioid mechanisms were blocked by naloxone, which is in keeping with a nonopioid component in cognitive pain control. We found suggestive evidence that placebo medication may also activate some opioid involvement. Because placebos do not impart pain reduction skills, it was perceived self-efficacy to endure pain that predicted degree of opioid activation. Journal of Personality & Social Psychology. 53(3):563-571, September 1987.

Categories:
Attention
Self-efficacy

Fetal pain law

Just saw this:

Wisconsin Gov. Jim Doyle (D) on Friday vetoed a bill (SB 138) that would have required physicians to tell women seeking abortion at more than 20 weeks' gestation that fetuses can feel pain, the AP/St. Paul Pioneer Press reports (Richmond, AP/St. Paul Pioneer Press, 1/7). The state Senate and Assembly approved the bill in September and November 2005, respectively. Supporters of the bill say some research supports the claim that fetuses can feel pain, while the bill's opponents say the research has not been proven (Kaiser Daily Women's Health Policy Report, 11/10/05). Doyle said there is no definitive proof that fetuses can feel pain and added that the state Legislature, which has a Republican majority, should not be permitted to determine what constitutes scientific fact, the AP/Pioneer Press reports. Doyle in his veto message wrote, "It would be reckless to inject a requirement that doctors communicate unproven science to their patients during an already difficult and sometimes traumatic time," adding, "This bill intrudes on the doctor-patient relationship ... and contravenes the requirement that doctors provide objective and accurate information to their patients" (AP/St. Paul Pioneer Press, 1/7). Link

Here's what a pretty authoritative JAMA study concluded awhile back:

Conclusions Evidence regarding the capacity for fetal pain is limited but indicates that fetal perception of pain is unlikely before the third trimester. Little or no evidence addresses the effectiveness of direct fetal anesthetic or analgesic techniques. Similarly, limited or no data exist on the safety of such techniques for pregnant women in the context of abortion. Anesthetic techniques currently used during fetal surgery are not directly applicable to abortion procedures. Link

There are several serious philosophical problems here. One involves understanding under what conditions we should say a fetus is having pain. Nancy Hardcastle addresses this in the final chapter of her The Myth of Pain.

I'm more interested in what the normative significance of the findings. I believe, for example, that the painful sensation is a very minimally normatively significant property of pain. Other components like emotional responses and cognitive states like meanings, can be much more significant (i.e., weigh more heavily in how evil we adjudge the pain to be).

Suppose then that we find out that at n weeks fetuses have active nociceptive pathways which, when stimulated, evoke some rudimentary withdrawl response. Assuming that we want to say that the fetus experiences pain, it is a further question how normatively significant that pain is. Presumably the fetus's experience wouldn't contain the complex emotions and affect that our pains involve.

But what does this show? Does it mean that the fetus's pain would be only minimally morally significant? Or ought we assess the moral badness of pain for fetuses on a different scale from adult humans? How do we decide? If we have an account of what makes pain intrinsically bad for adult humans, should we assume that account will translate to an account for fetuses?

Categories: Fetal_pain, Legal, Abortion

Plotinus on pain

Ok. I believe some wierd* things about pain (e.g., pains are not just sensations; pains have two potentially conflicting intrinsic values; some painful sensations are not pains; pain is essentially and intrinsicaly bad in virtue of being the privation of that which is intrinsically good for a person, and many others). But Plotinus seriously one-ups me with this claim about how a person suffers pain.

13. The characteristic activities are not hindered by outer events
but merely adapt themselves, remaining always fine, and perhaps all
the finer for dealing with the actual. When he has to handle particular
cases and things, he may not be able to put his vision into act without
searching and thinking, but the one greatest principle is ever present
to him, like a part of his being- most of all present, should he be
even a victim in the much-talked-of Bull of Phalaris. No doubt, despite
all that has been said, it is idle to pretend that this is an agreeable
lodging; but what cries in the Bull is the thing that feels the torture;
in the Sage there is something else as well, The Self-Gathered which,
as long as it holds itself by main force within itself, can never
be robbed of the vision of the All-Good. Link

I wonder if Plotinus thought himself a Sage...

The Bull of Phalaris:

Perillos of Athens, a brass-founder, proposed to Phalaris, Tyrant of Agrigentum, the invention of a new means for executing criminals; accordingly, he cast a brazen bull, made totally of brass, hollow, with a door in the side. The victim was shut up in the bull and a fire was set under it, heating the metal until it became "red hot" and causing the victim inside to slowly roast to death. So that nothing unseemly might spoil his feasting, Phalaris commanded that the bull be designed in such a way that its smoke rose in spicy clouds of incense. The head of the ox was supplied by a complex system of tubes and stops so that the prisoner's screams were converted into sounds not unlike the bellowing of an infuriated ox. It is also said that when the bull was reopened, the victims' scorched bones shone like jewels and were made into bracelets.

Phalaris commended the invention, and ordered its horn sound system to be tested by Perillos himself. When Perillos entered, he was immediately locked in, and the fire was set, so that Phalaris could hear the sound of his screams.Link

* Since I'm presently on the job market, 'wierd' here means 'exciting, insightful, and challenging'
Categories: Plotinus, Torture, Wierd

Vioxx litigation

By JOHN CURRAN Associated Press Writer
December 26,2005 | ATLANTIC CITY, N.J. -- For someone mired in judicial purgatory, Superior Court Judge Carol Higbee is remarkably upbeat. She doesn't want pity -- many judges work as hard, she says. She doesn't want publicity -- it makes her uncomfortable, and she grants interview requests grudgingly. She just wants justice -- and she's ready to dispense it, one Vioxx case at a time, even if it takes a lifetime.

And at the current rate, it could, assuming the cases are not settled or withdrawn.

Higbee, 55, is the New Jersey judge assigned to thousands of cases brought in state court against Merck & Co. over its now-withdrawn painkiller Vioxx. The lawsuits -- all 4,333 of them -- blame the Whitehouse Station-based pharmaceutical company for heart attacks and strokes suffered by users.

Merck has acknowledged links between Vioxx and heart attacks and strokes in clinical studies, but only after 18 months' use.

If they all go to trial and take as long as a recent, seven-week case, Higbee would need 583 years to hear them all.

"I don't foresee that that's the way things will happen," she said in a recent interview with The Associated Press. "I'm going to be a judge for X many more years and during those years, I'll be trying cases. Maybe they're Vioxx cases, maybe they're others."

The way things are going, they'll be Vioxx cases. With 9,200 cases filed nationwide and former users still streaming into courthouses with new claims, the litigation shows no signs of slowing.

Merck & Co. has said it plans to fight the lawsuits, one by one. In New Jersey, the responsibility for trying them all falls to Higbee, a soft-spoken former medical malpractice attorney known for cutting through the cant without playing favorites.

Higbee says patience isn't one of her strong points. But she has shown plenty of it so far, refereeing battling lawyers in the recent trial -- which ended Nov. 3 with a Merck victory -- and meeting with lawyers for Merck and the plaintiffs to schedule the trials to come.

On Feb. 27, it's back to the courtroom for the next Vioxx trial. As in the first, Higbee will spend her days on the bench and her nights at home reviewing trial transcripts in preparation for the next day's session. And when she isn't dealing with a Vioxx issue, she'll be tending to the 375 non-Vioxx cases on her docket.

"Vioxx is important. Every other piece of litigation I have is important. Even though it's more high-profile, it's not more important than any other case," Higbee said.

A native of Mishawaka, Ind., Higbee attended Temple University and its law school before spending 17 years in private practice, working as a plaintiffs attorney on behalf of victims of slip-and-falls, bad drugs and negligent doctors. In 1993, she was appointed to the bench by then-New Jersey Gov. James Florio, a position that now pays $141,000 annually.

When it became clear that Vioxx litigation was going to tax New Jersey courts, the state Administrative Office of the Courts looked to Higbee.

"Judge Higbee was an obvious choice," spokeswoman Winnie Comfort said. "She's experienced and she can manage the incredible workload that comes with some of these mass tort cases."

When she's off the bench, Higbee spends her time at home tending to her rose bushes and tomatoes, reading mystery novels and -- with her husband, a high school English teacher and part-time actor -- raising their 5-year-old granddaughter.

For now, though, her eyes are squarely on the mountain of work ahead of her.

Will the Vioxx workload ever ease up?

"It depends on the participants," she said. "They can choose what they want to do. And what they want to do today may be different from what they want to do later. Litigation, it's just like the rest of life. You never know what's around the corner."
© 2005 The Associated Press. Link

Categories: Legal, Vioxx, Pain-killers, NSAID, Cox-2

Tylenol tragedies

I've railed about acetaminophen here before. It really is ugly: People who just need more pain-relief; attempted suicides (often first-attempts involving people who aren't really trying to kill themselves); and recreational drug users who don't know that its the acetaminophen that's more dangerous (to them) than the hydrocodone or oxycotin.

By LAURAN NEERGAARD AP Medical Writer

December 26,2005 | WASHINGTON -- Think popping extra pain pills can't hurt? Think again: Accidental poisonings from the nation's most popular pain reliever seem to be rising, making acetaminophen the leading cause of acute liver failure.

Use it correctly and acetaminophen, best known by the Tylenol brand, lives up to its reputation as one of the safest painkillers. It's taken by some 100 million people a year, and liver damage occurs in only a small fraction of users.

But it's damage that can kill or require a liver transplant, damage that frustrated liver specialists insist should be avoidable.

The problem comes when people don't follow dosing instructions -- or unwittingly take too much, not realizing acetaminophen is in hundreds of products, from the over-the-counter remedies Theraflu and Excedrin to the prescription narcotics Vicodin and Percocet.

"The argument that it's the safest sort of has overruled the idea that people cannot take any amount they feel like," says Dr. William Lee of the University of Texas Southwestern Medical Center, who laments that acetaminophen is popped like M&Ms.

Acetaminophen bottles currently recommend that adults take no more than 4,000 milligrams a day, or eight extra-strength pills.

Just a doubling of the maximum daily dose can be enough to kill, warns Dr. Anne Larson of the University of Washington Medical Center.

Yet, "if two is good, 10 is better in some patients' minds," she says with a sigh.

The Food and Drug Administration has long wrestled with the liver risk, warning two years ago that more than 56,000 emergency-room visits a year are due to acetaminophen overdoses and that 100 people die annually from unintentionally taking too much.

A study published this month by Larson and Lee has agency officials weighing whether to revisit the issue.

Over six years, researchers tracked 662 consecutive patients in acute liver failure who were treated at 22 transplant centers. (Acute liver failure is the most severe type, developing over days, unlike chronic liver failure that can simmer for years because of alcohol abuse or viral hepatitis.)

Almost half were acetaminophen-related. More remarkable was the steady increase: Acetaminophen was to blame for 28 percent of the liver poisonings in 1998, but caused 51 percent of cases in 2003.

That makes acetaminophen the most common cause of acute liver failure, the researchers report in the journal Hepatology.

While most patients pulled through with intensive care, 74 died and 23 others received a transplant.

Some 44 percent of the cases were suicide attempts.

But more, 48 percent, were unintentional overdoses, which "isn't hard to do," Larson says.

Say you take Tylenol Cold & Flu Severe for the flu's aches and stuffiness -- 1,000 mg of acetaminophen, every six hours. A headache still nags so between doses you pop some Excedrin -- 500 mg more of acetaminophen. Switch to Nyquil Cold/Flu at bedtime, another 1,000 mg.

Maybe you already use arthritis-strength acetaminophen for sore joints -- average dose 1,300 mg.

Depending on how often they're taken, the total acetaminophen can add up fast.

That's the nonprescription realm. Surprisingly, 63 percent of unintentional overdoses involved narcotics like Vicodin and Percocet that contain from 325 mg to 750 mg of acetaminophen inside each pill.

Some were chronic pain sufferers taking more and more narcotics as their bodies adjusted to the powerful painkillers, not knowing they were getting ever-higher acetaminophen at the same time. Or they added over-the-counter products for other complaints.

Just this month, Larson treated an 18-year-old whose liver crashed after using Vicodin for three or four days for car-crash injuries. "She was just taking too much because her pain was bothering her."

Led by Tylenol manufacturer McNeil Consumer & Specialty Pharmaceuticals, most over-the-counter products now voluntarily list acetaminophen on front labels.

McNeil also runs ads about the risk, saying "if you're not going to read the label, then don't buy our products," says spokeswoman Kathy Fallon.

But how strongly labels warn varies by product. A rule to standardize warnings, urged by FDA's scientific advisers in 2002, still is working its way through the agency.

While FDA runs a consumer education campaign about the liver risk, nonprescription drugs chief Dr. Charles Ganley says the new study suggests the agency may need to further target narcotic-acetaminophen combinations.

Lee wants to copy Britain, which saw a 30 percent drop in severe liver poisonings after restricting how much acetaminophen could be bought at once.

That's unlikely. Meanwhile, the advice is simple: Read drug labels and add up all your acetaminophen, avoiding more 4,000 mg a day. For extra safety, Lee advises no more than 2,000 to 3,000 mg for more vulnerable people, who regularly use alcohol or have hepatitis.Link

It's not that I think acetaminophen should be discouraged or even removed from OTC. But I do think we need some more effective education campaigns.
Categories: Acetaminophen, Legal, Tylenol

Starting off, and update

For you new readers of PFP, let me entice you with my two favorite (apparent) facts about pain:

Pain hurts less when it is inflicted by a woman, researchers have found.
Students were asked to put their fingers in a clamp which was tightened until the pain was unbearable. Researchers from the University of Westminster found that people allowed women to turn the clamp much further than men.

Dr David Williams, who led the research said the study suggested people do not expect women to inflict as much pain. He said: "This effect is likely to be a result of what participants subconsciously expect, based on socially acquired gender stereotypes - people feel that they are less likely to experience intense pain from a stimulus given by a woman rather than a man.

"This effect is less likely to be down to males trying to appear macho in front of a female - a conscious and deliberate act - as the result applied to both genders." He said the fact there were no differences in how men and women responded to the test suggested women do not actually handle pain better.

Dr Williams said people's sensitivity to pain was also shown to depend on their surroundings. In the study, people appeared to suffer more if there was a poster on the wall which might trigger negative feelings, such as a chart of wounds or a poster calling for blood donors.

Dr Williams, who carried out the research for his PhD, said: "People subconsciously evaluate their environment. "This evaluation can result in identical stimuli being perceived as more or less painful for the same participant or, in some cases, an innocuous stimulus being perceived as painful or a relatively intense stimulus perceived as innocuous."

He said the finding could have implications for how patients are given potentially painful treatments. "Individuals can be 'primed' for pain by qualities of their environment and, as a result, may suffer unnecessarily during acutely painful clinical procedures. "Awareness of these principles may be useful in developing methods of reducing suffering in those situations." Link

I originally posted about this here,
and for the past year I've been waiting for the study to show up in a peer-reviewed journal, and for some corroboration. It's time to go to the source. More soon.

Categories: Gender, Environment

Another pain blog

Here's a very, very, very good blog on pain:
www.painonline.com
Hope posting this doesn't drive me out of business.
Categories: Resources

Biofeedback and pain modulation

From Wired:

Pain can be mysterious, untreatable and debilitating, and its causes can be unknown. But if you could see the pain -- or, at least, your brain's reaction to it -- you might be able to master it.

A study from researchers at Stanford University and MRI technology company Omneuron suggests that's possible, and the results could lead to better therapies for those suffering from crippling chronic pain.

The researchers asked people in pain to try to control a pain-regulating region of the brain by watching activity in that area from inside a real-time functional magnetic resonance imaging, or fMRI, machine. Initial results showed subjects could reduce their pain, some quite dramatically.

It's the first evidence that humans can take control of a specific region of the brain, and thereby decrease pain, said Stanford professor Sean Mackey, who co-wrote the paper, which was published last week in Proceedings of the National Academy of Sciences.

"(Similar to) going to a gym and working muscle using weights, here we're using the real-time fMRI technology to exercise a certain brain region," he said.

Study co-leader and Omneuron CEO Christopher deCharms said for many people with chronic pain, available treatments like medication or surgery simply don't work. But this exercise, which researchers have termed "neuroimaging therapy," could one day help some of the millions of Americans who suffer from untreatable chronic pain.

In the study, eight healthy subjects who'd been subjected to a painful stimulus and eight chronic pain patients underwent a series of fMRIs. The images tracked activity in the brain's rostral anterior cingulate cortex -- an area deCharms said is related to pain. Subjects watched this area on a monitor in real time during the procedure. Prompted by researchers' suggestions of trying to lessen their own pain by ignoring it or imagining it as benign, they set out in a mental game of hot-and-cold to lessen their discomfort.

Twenty-eight healthy subjects and four pain patients were also put into control groups that tried to control pain by viewing other patients' brain data or using other mental strategies, but no fMRIs. These tactics didn't show a significant reduction in pain, deCharms said.

The pain patients reported that the fMRI helped them decrease their overall pain 64 percent. Healthy subjects said they saw a 23 percent increase in their ability to control the strength of their pain, and a 38 percent increase in their ability to master its unpleasantness.

"I think most people found it very exciting to be able to watch the activity in their own brain, moment by moment, as it took place," deCharms said.

Vera A. Gonzales, a pain psychologist in League City, Texas, said she thinks the study lends scientific data to what scientists already knew empirically -- that people can decrease their own pain by focusing on certain thoughts.

It probably also helped that subjects could watch their brain activity unfold on a screen, she said. For years, some therapy methods have allowed patients to monitor and try to control their biofeedback by concentrating on things like skin temperature and heart rate.

Mackey and deCharms cautioned it will be some time before such therapy could be available for commercial use. They're investigating the process of getting Food and Drug Administration approval, and right now they're focusing on a study to investigate the effects of long-term neuroimaging therapy, deCharms said. One day, patients may even be able to think away other problems like depression, anxiety and dyslexia.

"We don't yet have a good answer to what happens if you keep practicing and practicing," he said.
Link

Categories: Biofeedback, fMRI, Attention, Pain-modulation

Another resource

Just found this website on pain geared toward patients:
http://pain.healthcentersonline.com/
Haven't looked into who underwrites it so caveat lector.

Categories: resources

Merk deleted data on Vioxx

[ed: I'm going to post new stuff below the welcome post for a bit. Thus some articles will magically appear in posts before they were written.]
From Forbes.com:

Merck's Deleted Data
Robert Langreth and Matthew Herper, 12.08.05, 8:10 PM ET
A top editor of The New England Journal of Medicine says that he was stunned to find out that data linking Vioxx to cardiovascular risk was deleted from a major study his journal published five years ago--and that it appears that Merck researchers may have deleted that data.

"I was somewhere between surprised and stunned," Dr. Gregory Curfman, executive editor of The Journal, says. "They allowed us to publish an article that was just incomplete and inaccurate in some respects and was misleading and may have contributed to the detriment to the public health."
[...]
Merck recalled Vioxx after its own study linked long-term use of the drug to an increased risk of heart attacks and strokes. Now, the question is if that alarm should have been sounded much earlier.

Just days after Merck recalled Vioxx from the market, editors at The Journal discovered....early versions of the manuscript [that] contained a blank table entitled "CV events"--which is standard jargon for cardiovascular events. Time stamps in the software indicated that the table was deleted two days before the manuscript was submitted to The New England Journal on May 18, 2000. "When you hover the cursor over the editing changes, the identity of the editor pops up, and it just says 'Merck,'" Curfman says.
[...]
The editors weren't sure what to make of the finding, so they kept quiet. It wasn't clear that the information that had been in the table would have changed the conclusions of the study...."We talked internally. Should some action be taken? We did not feel we had sufficient evidence to act on it," Curfman says.
[...]
an internal Merck document dated July 5, 2000--after the VIGOR manuscript was submitted to the journal, but well before the study went to press....it indicated that two Merck authors on the VIGOR study knew of three additional heart attacks among Vioxx patients in the study, which had not been disclosed to The New England Journal of Medicine. The heart attacks occurred in the final five weeks of the trial and in patients at low risk for heart problems.
[...]
Curfman says the editors had assumed that the VIGOR manuscript only included limited data on heart attacks because that was all that was available at the time. "It turns out that they had quite a bit more already worked up," he says. He raced back to the office and spent the next few weeks analyzing all the VIGOR drafts, raw data and correspondence.
[...]
Curfman says he called lead author Claire Bombardier of the University of Toronto, on Monday, indicating that the statement [noting the potential trouble] would be published. She told him that she would begin working on a correction.....Bombardier said that the VIGOR paper appropriately disclosed the data and that the authors were working on finalizing a response to the editorial.
[...]
Hints that Vioxx might cause heart attacks had existed for years, as basic research pointed to a mechanism by which the drug might cause more clots. When VIGOR was published in The New England Journal of Medicine, there were already questions among scientists about the potential of Vioxx and related drugs
[...]
In a statement, Merck disputed The New England Journal analysis. "The VIGOR publication, which was peer-reviewed, fairly and accurately described the results of the study as of the prespecified cutoff for analysis. The additional events referred to in the editorial were events that were reported after the prespecified cutoff date and, therefore, these were not included in the primary analysis reported in the article.

"Nevertheless, the additional events were disclosed to the FDA in 2000, presented publicly to the FDA's Advisory Committee in February 2001 and included in numerous press releases subsequently issued by Merck. We also note that these additional events did not materially change any of the conclusions in the article."

Curfman responded, "We're not buying into that."
">Link

Here's a bit of hearsay: when these stories came out last year, a close friend and former Pfizer statistician told PFP that her department had been warning management for quite awhile that their studies on Celebrex and heart trouble were using the wrong endpoints and potentially distorting the conclusions.
Categories: Legal, Vioxx, Cox-2

Self-injurious behavior

A number of cases have been reported in which patients are said to have damaged or destroyed areas of body afflicted by neuropathic pain and sensory deficit (the latter being an inevitable accompaniment of the former) (see Mailis, 1996).

In 30 years of pain clinic practice with a particular emphasis on neuropathic pain, I have seen two only patients in whom ‘self-injurious behaviour’ (Mailis, 1996) has occurred. Patient 1 was one of 160 patients with central post-stroke pain (CPSP) personally seen and examined by myself; Patient 2 was one of 282 patients with postherpetic neuralgia (PHN) personally seen and examined by myself.

Patient 1 was a right-handed man who had a stroke at age 66 affecting the left side of his body, including the face. He was aphasic, and remained so for 6 weeks; he had hiccoughs which persisted for 2 or 3 months. There was severe loss of power in his left arm and leg.

Burning and shooting pain appeared in the left side of his face some 3 months later.

He was first seen in the Pain Clinic 2 years after the stroke. By this time his motor deficit was almost imperceptible. He still complained of burning and shooting pains in the left side of the face, particularly at the tip of his nose; he also had occasional pins and needles in his left arm and even less frequently in his left leg. He stated that his facial pain was exacerbated by drinking hot liquids; that the left side of his face always felt hot, and sometimes went red for 3 or 4 weeks at a time. On examination, tactile and sharpness sensations were diminished on the left side of the face, particularly on the outer lower left side of his nose, and to a lesser extent in his left arm. There was no clinically evident deficit of temperature sensation.

The ala nasae of the left nostril was absent, leaving a half-moon-shaped gap extending about 7.5 mm up the nose in comparison with the right side. He said that he had ‘picked and pulled’ at his nostril ever since the pain came on, because that was where the pain was worst. His GP confirmed that this self-inflicted mutilation had occurred since the central post-stroke pain came on. The patient averred that he still felt pain in the ‘missing part’ of his nose.

He had had a stellate ganglion block and an intravenous infusion of lignocaine in another hospital before being referred to us; neither had had any effect on his pain. We prescribed nortriptyline, rising to 75 mg nocte. This also had no effect, and the patient discharged himself after 3 months.

Patient 2 was an apparently phlegmatic male farmer born in 1912 who had herpes zoster affecting his right ophthalmic nerve (V1) in 1984, at the age of 72. When seen in the Pain Clinic 2 years later, aged 74, he had some mild backache but was otherwise an extremely healthy man, still working. He complained of a pain on the right side of his forehead which he described on his McGill Questionnaire as "Throbbing, boring, pressing, pulling, and hot". He had some mild dynamic tactile allodynia. Amitriptyline, rising to 50 mg nocte, was prescribed. When next seen in a follow-up clinic, a few months later, he stated that he felt ‘much better’. However, the following year he had a mild stroke, which resulted in him being treated with Madopar® 62.5 mg b.d.

He was next seen in the Pain Clinic 9 months later (now aged 75). There were no evident symptoms or signs of stroke; he was then taking a proprietary drug containing both an anticholinergic and a calcium channel blocker. His forehead pain was still described as ‘much better’.

Beginning 3 months later, he complained that he ‘couldn't feel the right side of his forehead’. He had begun to scratch the area, resulting in red scratchmarks. When asked why he did this, he denied that there was any pain or itching, but said that as he couldn't feel anything, he wanted ‘to make sure it was still there’. Clinical testing confirmed the absence of tactile and sharpness sensations, and severe diminution of temperature sensation; an area about 3 cm wide and 4 cm wide centred above the middle of the right eyebrow could be said to be virtually anaesthetic.

He was seen at frequent intervals over the next 4 years. Within 18 months, he had scratched his forehead down to the bone in circular area of about 1.5 cm diameter about 2.5 cm above the middle of the right eyebrow, surrounded by a rectangular area in which injury changed centripetally from down to periosteum to more superficial cutaneous layers. He prevented the process of healing by repeated scratching. He repeatedly denied that he felt any pain, but said that there was some ‘irritation’. As he was clean-shaven, he was asked whether or not he didn't think that seeing his forehead in a shaving mirror every morning confirmed that it was indeed present. He admitted this, but said it had become a habit during the day to touch and subsequently scratch, harder and harder, to see if he could elicit any sensation which would confirm its presence. Medical treatment with both external applications of benzydamine and lignocaine creams, and systemically with tricyclics, carbamazepine, baclofen, and buprenorphine had no effect; neither did transcutaneous nerve stimulation, stellate ganglion or supraorbital nerve blocks.
Discussion

Neither of our patients was assessed by a clinical psychologist. However, both appeared to be of normal intelligence; both were married men doing responsible jobs. They may well have been exogenously depressed by their illness, but showed no obvious clinical signs of endogenous depression at interview. They thus did not overtly exhibit two of the criteria listed by Mailis (1996) for self-injurious behaviour (SIB): low intelligence and depressive personality.

Many of the cases of SIB reported in the literature (which has been extensively reviewed by Mailis, 1996) were of ‘ulcers’ and ‘excoriations’. Injury of this sort is undoubtedly under-reported. However, both the cases reported here had extensive and unequivocal injuries. It is interesting, and perhaps significant, that both involve the face, for by far the greatest number of reported self-inflicted injuries are facial, in patients with anaesthesia dolorosa following destructive procedures of the trigeminal ganglion.

Prima facie, it would seem that the first patient reported herein was a genuine case of autotomy; he destroyed a painful part, in which he subsequently continued to have phantom pain.

The second patient, however, mutilated an area from which he had no apparent sensory input. This is an extreme case of a much commoner clinical phenomenon: following peripheral nerve injury resulting in an anaesthetic area of skin, most patients take no notice of it, except to remark, if directly questioned, that they have an area in which there is no feeling. A small number, however, become obsessed with a perfectly painless but anaesthetic area. The patient reported here is such a case, although the only one in our experience who has injured himself as a result.

However, another case involving a patient with HZ-PHN has been reported to me anecdotally by Dr R.W. Johnson (Bristol). This concerns an elderly man who had facial zoster, and subsequently had violent itching in his analgesic right ala nasae. Because he could feel no pain, scratching the itch eventually resulted in excavation of the lower outer border of the nose.

These cases are clearly not autotomy as commonly defined (the term is not included in either the first (Merskey, 1986) or second ( Mersky and Bogduk, 1994) edition of the IASP Classification of Chronic Pain). The term as now used in neurological/pain medicine appears to have been introduced by Wall et al. (1979), although they did not limit it to a phenomenon occurring only in supposed neuropathic pain, as now is the case.

There is an implication for experimental animal work, in which it is well-known (but rarely reported) that of animals subjected to nerve ligation and other subtotal nerve injuries, only a proportion exhibit signs of neuropathic pain, and of this proportion, only a few perform autotomy. If an animal chews off an extremity, how do we know whether it is doing so because the extremity hurts, or because it regards an anaesthetic part as a foreign body, and rids itself of it? This would appear to be the conclusion from the work of Shir et al. (2001), who found that autotomy only occurs in rats with completely denervated hindlimbs. The best argument against such an interpretation has been put forward by Blumenkopf and Lipman (1991) on the basis of animal studies, but cannot be justified by experience with human patients. The present case 2 had no pain in the mutilated area, and I do not regard it as a case of autotomy, whereas case 1 not only had pain in the mutilated area, but continued to experience such pain in the missing ala nasae after SIB, thus raising the interesting question of the relationship between pain in an area of partial sensory deficit and phantom pain.

DOI
Categories: Self-injurious behavior

Congenital insensitivity to pain

From a very nice overview of the research on the subject:

5. Congenital indifference to pain

With these insights into the basis of pain insensitivity, stoics will patiently await the unravelling of the genetic basis of the clinically less pressing, but philosophically more interesting problem of congenital indifference to pain. – John Wood, 1996

Congenital indifference to pain, also referred to as congenital universal insensitivity to pain, has been reported since the early 1930s (Dearborn; Ford; Boyd; McMurray; Ogden; Landrieu and Davis). These individuals typically have painless injuries beginning in infancy, but normal sensory responses on examination. Perception of passive movement, joint position, and vibration is normal, as are tactile thresholds and light touch perception. The ability to distinguish sharp and dull stimuli and detect differences in temperature seems to be intact ( McMurray and Ogden). Reflexes and autonomic responses are also normal.

Peripheral nerve samples were obtained from several of the earlier cases of congenital indifference to pain, and no abnormalities were observed (Ogden et al., 1959). Because of their seemingly normal neurologic examinations, these individuals were considered to have a deficit in the affective response to pain rather than in the sensory discrimination of painful stimuli. However, because morphometric analysis of nerve fiber size density had not been performed, it is unclear whether selective loss of nerve fibers was present. There have been mixed results with some biopsies reported as abnormal ( Low and Dyck) and it is possible that some cases are HSAN V. Because of the possibility of peripheral neuropathy, these cases are therefore not considered definitive examples of indifference to pain ( Dyck and Thomas).

A case of congenital indifference to pain with normal nerve morphology has been described by Landrieu et al. (1990). The patient was a 5-year-old girl with painless fractures and indifference to ‘casual injuries’. Withdrawal reflexes and grimacing were present to pinprick and hot water (43°C), but she was indifferent to prolonged or repeated application of the painful stimuli anywhere on her body. Subcutaneous injection of histamine yielded normal results. She had an otherwise normal neurological examination. She detected pinprick, heat, and cold, and responded normally to light touch, joint position, vibration, and pressure. Her reflexes were normal, no autonomic abnormalities were observed, and cortical sensory evoked potentials were normal. A sural nerve biopsy appeared normal using electron microscopy, and the size density distributions appeared normal for both myelinated and unmyelinated fibers. In addition, she was reported to have normal psychomotor development.

The normal electron microscopic nerve morphometry rules out the possibility of a selective absence of unmyelinated nociceptors, although it does not exclude the possibility of other structural or neurochemical abnormalities. This patient demonstrates that congenital indifference to pain does not require the same type of peripheral nerve abnormalities associated with the hereditary sensory neuropathies. As Thomas (1993) has suggested, such patients ‘could represent a disturbance affecting neurotransmitters that did not involve loss of nerve fibers, or … the differences could be due to an abnormality of the central sensory pathways or processing’. Additionally, the case suggests that abnormal pain responses can occur even though pain discrimination, affect, and withdrawal responses appear preserved.

Davis et al. (1998) described a subject with normal perception of pinprick, light touch, and vibration. In addition to lifelong lack of pain perception with accompanying painless injuries, she had gait disturbance and spasticity. Sural nerve biopsy and electrophysiologic studies were normal. At age 56, she had progressive decline in cognitive abilities. Autopsy conducted at age 62 showed evidence of Alzheimer's disease and thalamic gliosis at multiple levels, including both ventral and midline nuclei. The amount of gliosis exceeded that found in age-matched normal brains and in an Alzheimer's disease control brain. Other family members were reported to have similar symptoms, including a lack of response to painful stimuli. Although complicated by the presence of other neurologic symptoms, this report suggests that deficits present in hereditary pain insensitivity and indifference disorders can have central as well as peripheral origins.
6. Asymbolia for pain and related conditions

When lesions occur in the areas of the brain that subserve the processing of painful stimuli, deficits in one or more of the components of pain perception can occur, and disorders similar to congenital pain insensitivity can result. Lesions in the anterior cingulate cortex or insular cortex impact the medial pain system and, thus, might be expected to cause a loss of the affective-motivational component. Lesions in the primary and secondary somatosensory cortex affect the lateral pain system; their expected major effect would be loss of sensory-discriminative components of pain.

Loss of the affective-motivational component of pain has been called ‘asymbolia for pain’. An early report described a patient who showed a lack of responsiveness to strong electrical currents and physically threatening gestures (Schilder and Stengel, 1931). Although there was some reaction to pain, no withdrawal responses occurred, and the patient at times ‘even seemed to derive some pleasure’ from the painful stimuli. The authors described both the ‘pain reaction’ and the ‘appreciation of pain’ as inadequate, and attributed pain asymbolia to findings of parietal lobe lesions in this patient and two others who were studied.

Later authors restricted use of the term ‘asymbolia for pain’ to patients with deficits in the affective-motivational component of pain but preserved sensory discrimination. Such patients perceive painful stimuli but lack emotional responses and withdrawal movements (Berthier et al., 1988). As in the earlier descriptions, some patients reportedly smiled or laughed in response to noxious stimuli. Computed tomography demonstrated insular cortex lesions in all patients in a series of six such patients ( Berthier et al., 1988). Lesions in the secondary somatosensory cortex could have explained a lack of response to painful stimuli, but no such abnormalities were found in two of these patients.

It is also possible that central lesions could impair the sensory-discriminative components of pain while sparing affective-motivational components. Ploner et al. (1999) describe a patient with a lesion in the primary and secondary somatosensory areas subserving the left hand. He had normal heat pain thresholds in the right hand, but did not perceive pain in the left hand, even at temperatures much higher than those used on his unaffected side. He showed deficits in the assessment of both stimulus localization and quality in the left hand. When offered a list of prompts including both painful and non-painful thermal descriptors, the patient would not use any of them to describe the stimulus, nor could he locate the stimulus more specifically than ‘between fingertips and shoulder’.

However, when stimulus intensities equal to and greater than what he considered painful on the unaffected side were administered to the left hand, the patient described a ‘clearly unpleasant’ feeling that he wanted to avoid. This finding suggests that the affective-motivational component of pain was intact and is consistent with the lateral pain system, which includes the somatosensory cortex, being more involved in the sensory-discriminative component of pain than in pain affect. This case also illustrates that it is possible for pain responses to occur without an intact sensory-discriminative system.
7. Conclusions

The deficits present in the different pain insensitivity syndromes provide insight into the complex anatomical and physiological nature of pain perception. Reports of pain asymbolia and related cortical conditions illustrate that there can be losses that independently involve either the sensory-discriminative component or the affective-motivational component of pain perception, thus highlighting their different anatomical localization. The presentations of congenital indifference to pain and pain asymbolia overlap, which suggests that indifference to pain – whether congenital or acquired – may involve one or more deficits preferentially affecting the components of the medial pain system, which includes the anterior cingulate cortex.

By affecting both the lateral and medial pain systems, the peripheral nerve abnormalities observed in individuals with the various types of HSAN cause deficits in both components of pain perception. The case of Ploner et al. (1999) demonstrates that the affective-motivational component can be retained even in the absence of the sensory-discriminative component. Importantly, this suggests that the absence of affective responses in individuals with HSAN is not simply a consequence of loss of sensory discrimination but also involves loss of input to the medial pain system caused by the peripheral neuropathy.

It has been proposed that the affective component of pain is not unitary and consists of at least two stages, an immediate primary stage and a cognitively-mediated second stage (Price, 1999). In the cases reviewed, it is unclear at which stage the observed deficits originate. Careful assessment of the separate components of pain sensory intensity and unpleasantness in patients with various congenital pain insensitivity and indifference disorders will help to further clarify the pathways underlying the different components of pain perception. In addition, mapping genetic defects in HSAN patients will provide important clues about molecular mechanisms of pain, and the promise of new, more effective and selective therapies.

DOI
Categories: Congenital insensitivity to pain

Blind men and the elephant

In my dissertation I argue that the traditional account of pain's intrinsic badness --i.e., pain is bad because disliked; because unpleasant; because represents damage, et cetera-- are like the famous three blind men and the elephant. When we have the correct conception of what pain is, we can see that all of these (and other quasi-motivational states like fear) are the source of pain's intrinsic badness. For my reference, and your pleasure, here's

John Godfrey Saxe's ( 1816-1887) version of the famous Indian legend,
It was six men of Indostan
To learning much inclined,
Who went to see the Elephant
(Though all of them were blind),
That each by observation
Might satisfy his mind.

The First approached the Elephant,
And happening to fall
Against his broad and sturdy side,
At once began to bawl:
"God bless me! but the Elephant
Is very like a wall!"

The Second, feeling of the tusk
Cried, "Ho! what have we here,
So very round and smooth and sharp?
To me `tis mighty clear
This wonder of an Elephant
Is very like a spear!"

The Third approached the animal,
And happening to take
The squirming trunk within his hands,
Thus boldly up he spake:
"I see," quoth he, "the Elephant
Is very like a snake!"

The Fourth reached out an eager hand,
And felt about the knee:
"What most this wondrous beast is like
Is mighty plain," quoth he;
"'Tis clear enough the Elephant
Is very like a tree!"

The Fifth, who chanced to touch the ear,
Said: "E'en the blindest man
Can tell what this resembles most;
Deny the fact who can,
This marvel of an Elephant
Is very like a fan!"

The Sixth no sooner had begun
About the beast to grope,
Than, seizing on the swinging tail
That fell within his scope.
"I see," quoth he, "the Elephant
Is very like a rope!"

And so these men of Indostan
Disputed loud and long,
Each in his own opinion
Exceeding stiff and strong,
Though each was partly in the right,
And all were in the wrong!

Moral:

So oft in theologic wars,
The disputants, I ween,
Rail on in utter ignorance
Of what each other mean,
And prate about an Elephant
Not one of them has seen!

Source

Latency of acute pain onset

Abstract:

Features of acute pain were examined in patients at an emergency clinic. Patients who had severe, life-threatening injuries or who were agitated, drunk, or ‘in shock’ were excluded from the study. Of 138 patients who were alert, rational and coherent, 51 (37%) stated that they did not feel pain at the time of injury. The majority of these patients reported onset of pain within an hour of injury, although the delays were as long as 9 h or more in some patients. The predominant emotions of the patients were embarrassment at appearing careless or worry about loss of wages. None expressed any pleasure or indicated any prospect of gain as a result of the injury.

The occurrence of delays in pain onset was related to the nature of the injury. Of 46 patients whose injuries were limited to skin (lacerations, cuts, abrasions, burns), 53% had a pain-free period. Of 86 patients with deep-tissue injuries (fractures,next term sprains, bruises, amputation of a finger, stabs and crushes), only 28% had a pain-free period. The McGill Pain Questionnaire was administered to patients who felt pain immediately after injury or after a delay, and revealed a normal distribution of sensory scores but very low affective scores compared to patients with chronic pain. The results indicate that the relationship between injury and pain is highly variable and complex.

DOI