Pharmacology bleg

I have a request for any of you who know about the pharmacology of antidepressants. I have a friend who is taking Wellbutrin (bupropion) for smoking and codeine for chronic pain. I'm curious whether the combination may be attenuating the effect of the codeine and thus whether he should talk to his doctor about changing the codeine dose or switching medications.

Here's why: Codeine itself isn't really an analgesic. It is a substrate of a polymorphic P450 enzyme CYP2D6, and is metabolized to the more potent drug morphine. Some SSRI's like fluoxetine inhibit CYP2D6 activity. Thus combining prozac with codeine can attenuate its effects (see below).

What I'd like to know is whether bupropion might have the same effect on codeine metabolism. But I can't find anything directly on the topic.

From this chart of the various enzymes involved, it looks like that might be the case. But then I found this in the Wikipedia entry on buproprion

As bupropion is metabolized to hydroxybupropion by CYP2B6, drug interactions with CYP2B6 inhibitors (paroxetine, sertraline, fluoxetine metabolite norfluoxetine, diazepam, clopidogrel, orphenadrine and others) are possible. The expected result is the increase of bupropion and decrease of hydroxybupropion blood concentration. The reverse effect (decrease of bupropion and increase of hydroxybupropion) can be expected with CYP2B6 inducers (carbamazepine, clotrimazole, rifampicin, ritonavir, St John's Wort and others).

Hydroxybupropion (but not bupropion) inhibits CYP2D6 and is a substrate of that enzyme. Significant increase of the concentration of some drugs metabolized by CYP2D6 (venlafaxine, desipramine and dextromethorphan, but not fluoxetine or paroxetine) when taken with bupropion has been observed.

So I need your help. Can anyone point me in the direction of studies on bupropion and codeine? Or maybe just explain this in a way I can understand?

--
For your enjoyment, here are a few studies of fluoxetine and codeine that I came across in looking for an answer.

Inhibition by fluoxetine of cytochrome P450 2D6 activity.
Otton SV, Wu D, Joffe RT, Cheung SW, Sellers EM
Clin Pharmacol Ther. 1993 Apr ; 53(4): 401-9

Potent inhibition of cytochrome P450 2D6 (CYP2D6) in human liver microsomes by fluoxetine and its major metabolite norfluoxetine was confirmed (apparent inhibition constant values, 0.2 mumol/L). Several other serotonergic agents were also found to be competitive inhibitors of this genetically polymorphic enzyme. The O-demethylation ratio of dextromethorphan that expressed CYP2D6 activity in 19 patients receiving fluoxetine fell in the region of the antimode separating the O-demethylation ratio values observed in 208 extensive metabolizers from 15 poor metabolizers of a control group of healthy subjects. Inhibition of CYP2D6 activity in patients undergoing treatment with fluoxetine or other serotonin uptake inhibitors could contribute to toxicity or attenuated response from concurrent medications that are substrates of this enzyme. Other in vitro studies indicated that CYP2D6 catalyzes the O-demethylation of oxycodone to form oxymorphone. This reaction was inhibited by fluoxetine and its normetabolite in liver microsomes from both extensive and poor metabolizer individuals, indicating that these compounds are not selective inhibitors of CYP2D6 activity.

Treatment of codeine dependence with inhibitors of cytochrome P450 2D6.
Fernandes LC, Kilicarslan T, Kaplan HL, Tyndale RF, Sellers EM, Romach MK
J Clin Psychopharmacol. 2002 Jun ; 22(3): 326-9

Codeine is O-demethylated by cytochrome P450 2D6 (CYP2D6) to form the more potent drug morphine, accounting for much of codeine's analgesic and dependence-producing properties. Because morphine production can be decreased by inhibition of CYP2D6, the authors hypothesized that CYP2D6 inhibition could be used to treat codeine dependence. A randomized, double-blind, placebo-controlled trial was conducted. All patients received brief behavioral therapy. Two weeks of baseline monitoring were followed by 8 weeks of daily treatment with fluoxetine or quinidine (two potent CYP2D6 inhibitors) or placebo. Thirty patients were assessed (all white, age 40 + 12 years using 127 + 79 mg/day of codeine [mean + SD]), and 17 entered treatment. Eight patients remained in the study by treatment week 8. Quinidine > fluoxetine > placebo inhibited CYP2D6 as reflected in the change of the O-demethylation of dextromethorphan, a specific CYP2D6 probe. At treatment week 8, placebo, quinidine, and fluoxetine reduced mean daily codeine intake by 57%, 56%, and 51% of baseline intake respectively; there was no difference among treatment groups. In this small sample, CYP2D6 inhibitors did not appear to have a useful role in the treatment of codeine dependence.

The Daily Headache: Newsweek on Chronic Pain Research & Treatment

A potentially helpful blog for chronic headache sufferers :
The Daily Headache

Torture in Iraq

Do not read this excerpt from Monstering: Inside America's Policy of Secret Interrogations and Torture in the Terror War (Carroll & Graf) if you've just eaten.

Some links

A nice set of posts on pain from the blog the Transparent Eye.

And, in case I haven't linked to them before, check out the blog Psychology of Pain

Sensory deprivation torture

From Salon:

The CIA's favorite form of torture
By Mark Benjamin

Jun. 07, 2007 | According to news reports, the White House is preparing to issue an executive order that will set new ground rules for the CIA's secret program for interrogating captured al-Qaida types. Constrained by the 2006 Military Commissions Act, which contains a strict ban on abuse, it is anticipated that the order will jettison waterboarding and other brutal interrogation techniques.

[....]

The answer is most likely a measure long favored by the CIA -- sensory deprivation. The benign-sounding form of psychological coercion has been considered effective for most of the life of the agency, and its slippery definition might allow it to squeeze through loopholes in a law that seeks to ban prisoner abuse. Interviews with former CIA officials and experts on interrogation suggest that it is an obvious choice for interrogators newly constrained by law. The technique has already been employed during the "war on terror," and, Salon has learned, was apparently used on 14 high-value detainees now held at Guantánamo Bay.

A former top CIA official predicted to Salon that sensory deprivation would remain available to the agency as an interrogation tool in the future. "I'd be surprised if [sensory deprivation] came out of the toolbox," said A.B. Krongard, who was the No. 3 official at the CIA until late 2004. Alfred McCoy, a history professor at the University of Wisconsin-Madison who has written extensively about the history of CIA interrogation, agrees with Krongard that the CIA will continue to employ sensory deprivation. "Of course they will," predicted McCoy. "It is embedded in the doctrine." For the CIA to stop using sensory deprivation, McCoy says, "The leopard would have to change his spots." And he warned that a practice that may sound innocuous to some was sharpened by the agency over the years into a horrifying torture technique.

Sensory deprivation, as CIA research and other agency interrogation materials demonstrate, is a remarkably simple concept. It can be inflicted by immobilizing individuals in small, soundproof rooms and fitting them with blacked-out goggles and earmuffs. "The first thing that happens is extraordinary hallucinations akin to mescaline," explained McCoy. "I mean extreme hallucinations" of sight and sound. It is followed, in some cases within just two days, by what McCoy called a "breakdown akin to psychosis."

[....]

Just like waterboarding, Massimino said, extreme sensory deprivation techniques "push people beyond the brink of what they can bear, physically and mentally. Once you understand that, the veneer of acceptability -- the myth that 'it's not torture, it's just harsh' -- completely falls apart." But compared to the outcry over physical torture, she described a "deafening silence" about techniques like sensory deprivation.

The issue, said Massimino, is that sensory deprivation is relative -- she compared it to a "rheostat." Former CIA executive director Krongard made the same point about sensory deprivation's variability, saying that the techniques exist on a spectrum. The term could refer to anything from being left alone in a room to being subjected to complex get-ups combining goggles, earmuffs, mittens and darkened cells that quickly drive subjects into psychotic states.

On the low end, said Krongard, sensory deprivation techniques would pass muster with most observers. But he admitted that taken to extremes, some methods "would not pass anybody's muster." Sensory deprivation techniques taken to extremes would clearly violate the Geneva Conventions, according to international law experts, and would appear to be illegal under the Military Commissions Act, which bans "severe or serious mental pain and suffering." McCoy stated that based on his experience tracking down and interviewing subjects from the CIA's early research, some subjects never fully recover.

Sensory deprivation has apparently already been employed during the so-called war on terror. The prevalence of its use has been hinted at in images of alleged terror-plotter Jose Padilla and of detainees at Guantánamo shown wearing blacked-out goggles and earmuffs -- basic deprivation tools intended to soften prisoners up mentally by plunging them into a sensory void. A source familiar with the 14 high-value detainees interrogated at the CIA's so-called black sites and transferred to military custody at Guantánamo late last year, said the CIA appeared to have used some form of sensory deprivation techniques on most, if not all, of those 14 high-value detainees.

But the CIA's reliance on sensory deprivation goes all the way back to the early days of the Cold War. It is a big part of the CIA's 1963 "KUBARK" interrogation manual, obtained in 1997 by the Baltimore Sun. That agency manual describes sensory deprivation as a central tenet of coercive interrogations. For particularly rapid results, the manual endorses the use of a "cell which has no light (or weak artificial light which never varies), which is sound-proofed, in which odors are eliminated, etc." Following that plan, the manual says, "induces stress; the stress becomes unbearable for most subjects." The manual adds, "The subject has a growing need for physical and social stimuli; and some subjects progressively lose touch with reality, focus inwardly, and produce delusions, hallucinations, and other pathological effects."

As proof, the KUBARK manual refers to a raft of CIA-sponsored Cold War research on sensory deprivation, including studies at McGill University in Montreal and the National Institute of Mental Health. Subjects in that research were placed in isolated water tanks or confined to silent rooms on soft mattresses, wearing blacked-out goggles and earmuffs. In one study, subjects experienced "visual imagery somewhat resembling hallucinations" within three hours. In another study, only 6 of 17 subjects could last 36 hours on a mattress in a quiet tank that prohibited movement. The stress is described in the KUBARK manual as "unbearable."

The dark world of CIA-sponsored sensory deprivation research is plumbed in depth in the book "A Question of Torture: CIA Interrogation From the Cold War to the War on Terror," written by McCoy. "They've been doing this for 50 years," McCoy explained. His book discusses more CIA-sponsored research at McGill by Dr. Donald O. Hebb, who during the same era placed 22 college students in small, sound-proof cubicles, wearing translucent goggles, thick gloves and a U-shaped pillow around the head. Most subjects quit within two days and all experienced hallucinations and "deterioration in the capacity to think systematically."

The theory behind the CIA's fascination with sensory deprivation, McCoy said, is that subjects are so starved for stimulation that they will even crave interaction with their interrogator. "The idea is that they break down and then they cling to the interrogator, because you are hungry for stimulus," McCoy explained.

[....]

Bauer, who was the most forward-deployed Army interrogator during Operation Desert Storm, said sensory deprivation can drive people to come up with lies "based on ending the harsh treatment. That is not an effective way to conduct intelligence collection operations."

[....]

If the White House chooses to go the sensory deprivation route, it is unclear what, if anything, Congress could do to put a stop to it. There are limited tools available to the Senate Intelligence Committee, the committee with direct oversight of the agency, to step in. As one committee aide explained, "We don't have a veto over it."

-- By Mark Benjamin
Copyright ©2007 Salon Media Group, Inc.

Link

NIH Pain Consortium conference

The NIH's Pain Consortium just held a conference. Looks like lot's of interesting stuff went on.

Here's the agenda. The videocast of it is archived here. Or, if you're a nerd like me, you can grab the podcast and listen to it at the gym.

Thanks to new friend and philosopher extraordinaire J.T. for the tip.

Acupuncture and migraine

Doubt cast on needle therapy for migraine

By Nic Fleming, Health Correspondent
Last Updated: 1:05am BST 04/05/2005

Acupuncture is no better at reducing migraines than fake treatment, researchers say today.

A study involving more than 300 patients found the healing method did reduce headaches, but only by the same amount as placing needles at non-acupuncture points.

Recent studies have shown the needle treatment to be effective for relieving pain and improving function in osteoarthritis sufferers.
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The treatment is becoming increasingly mainstream and is offered on the NHS following patient demand.

Some 10 per cent of Britons - two-thirds of them women - suffer from migraines and tens of thousands are believed to have acupuncture.

Dr Klaus Linde, of the centre for complementary medicine research at the Technische Universität in Munich, reports the findings in the Journal of the American Medical Association.

Using information from patients' diaries, the researchers found the average number of days a week when patients in their acupuncture group had moderate or severe headaches dropped from 5.2 before treatment to three after.

Those in a sham acupuncture group also had 2.2 fewer days with headaches, down from five to 2.8 days. The research contradicts previous studies.

One published in the British Medical Journal last year suggested migraine patients who had acupuncture had 22 fewer days of headaches per year, made 25 per cent fewer visits to their GP and used 15 per cent less medication than those on standard NHS treatment.

George Lewith, a senior complementary medicine research fellow at Southampton University, dismissed the new research.

He said: "This is a badly conceived study that just adds more confusion to the debate because it uses non-site specific acupuncture as a control."

Link

Torture on 24

Not a good thing

U.S. Army Brigadier General Patrick] Finnegan told the producers that “24,” by suggesting that the U.S. government perpetrates myriad forms of torture, hurts the country’s image internationally. Finnegan, who is a lawyer, has for a number of years taught a course on the laws of war to West Point seniors—cadets who would soon be commanders in the battlefields of Iraq and Afghanistan. He always tries, he said, to get his students to sort out not just what is legal but what is right. However, it had become increasingly hard to convince some cadets that America had to respect the rule of law and human rights, even when terrorists did not. One reason for the growing resistance, he suggested, was misperceptions spread by “24,” which was exceptionally popular with his students. As he told me, “The kids see it, and say, ‘If torture is wrong, what about “24”?’ ” He continued, “The disturbing thing is that although torture may cause Jack Bauer some angst, it is always the patriotic thing to do.”

Gary Solis, a retired law professor who designed and taught the Law of War for Commanders curriculum at West Point, told me that he had similar arguments with his students. He said that, under both U.S. and international law, “Jack Bauer is a criminal. In real life, he would be prosecuted.” Yet the motto of many of his students was identical to Jack Bauer’s: “Whatever it takes.” His students were particularly impressed by a scene in which Bauer barges into a room where a stubborn suspect is being held, shoots him in one leg, and threatens to shoot the other if he doesn’t talk. In less than ten seconds, the suspect reveals that his associates plan to assassinate the Secretary of Defense. Solis told me, “I tried to impress on them that this technique would open the wrong doors, but it was like trying to stomp out an anthill.”

Pain's Evils

I just found out that my paper Pain's Evils will be published in Utilitas. Since this is my first major publication in a top tier journal, I'm quite a happy Adam. Once I figure out the copyright issues, I'll post a copy of the paper on my website. If you're interested in the interim, let me know and I'll send you a copy.

Meditation resources

As we've seen here before, meditation can be an effective component to treating many types of chronic pain. From a new friend, here are some nice resources:

http://www.marc.ucla.edu/ Mindful Awareness Research Center at UCLA; Podcast resources

www.mbsr.mass.edu: Mindfulness Based Stress Reduction; CD and book resources

www.contemplativeprayer: Christian Based Contemplative Prayer Information

www.contemplativemind.org: Introduction to a range of contemplative practices

Dershowitz on institutionalizing torture

Infamously:

Want to torture? Get a warrant Alan M. Dershowitz, Tuesday, January 22, 2002

AMERICAN law enforcement officers were ever to confront the law school hypothetical case of the captured terrorist who knew about an imminent attack but refused to provide the information necessary to prevent it, I have absolutely no doubt that they would try to torture the terrorists into providing the information.

Moreover, the vast majority of Americans would expect the officers to engage in that time-tested technique for loosening tongues, notwithstanding our unequivocal treaty obligation never to employ torture, no matter how exigent the circumstances. The real question is not whether torture would be used -- it would -- but whether it would be used outside of the law or within the law.

Every democracy, including our own, has employed torture outside of the law.

Throughout the years, police officers have tortured murder and rape suspects into confessing -- sometimes truthfully, sometimes not truthfully.

The "third degree" is all too common, not only on TV shows such as "NYPD Blue," but in the back rooms of real police station houses. No democracy, other than Israel, has ever employed torture within the law. Until quite recently, Israel recognized the power of its security agencies to employ what it euphemistically called "moderate physical pressure" to elicit information from terrorists about continuing threats.

This "pressure" entailed putting the suspect in a dingy cell with a smelly sack over his head and shaking him violently until he disclosed planned terrorist attacks. Israel never allowed the information elicited by these methods to be used in courts of law as confessions. But it did use the information to prevent terrorist acts.

Several attacks were prevented by this unpleasant tactic. In a courageous and controversial decision, the president of the Israeli Supreme Court wrote a majority opinion banning the use of this tactic against suspected terrorists.

The Israeli Supreme Court left open the possibility, however, that in an actual "ticking bomb" case -- a situation in which a terrorist refused to divulge information necessary to defuse a bomb that was about to kill hundreds of innocent civilians -- an agent who employed physical pressure could defend himself against criminal charges by invoking "the law of necessity."

No such case has arisen since this court decision, despite numerous instances of terrorism in that troubled part of the world. Nor has there ever been a ticking bomb case in this country.

But inevitably one will arise, and we should be prepared to confront it. It is important that a decision be made in advance of an actual ticking bomb case about how we should deal with this inevitable situation.

In my new book, "Shouting Fire: Civil Liberties in a Turbulent Age," I offer a controversial proposal designed to stimulate debate about this difficult issue. Under my proposal, no torture would be permitted without a "torture warrant" being issued by a judge.

An application for a torture warrant would have to be based on the absolute need to obtain immediate information in order to save lives coupled with probable cause that the suspect had such information and is unwilling to reveal it.

The suspect would be given immunity from prosecution based on information elicited by the torture. The warrant would limit the torture to nonlethal means, such as sterile needles, being inserted beneath the nails to cause excruciating pain without endangering life.

It may sound absurd for a distinguished judge to be issuing a warrant to do something so awful.

But consider the alternatives: Either police would torture below the radar screen of accountability, or the judge who issued the warrant would be accountable. Which would be more consistent with democratic values?

Those opposed to the idea of a torture warrant argue -- quite reasonably -- that establishing such a precedent would legitimize torture and make it easier to extend its permissible use beyond the ticking bomb case.

Those who favor the torture warrant argue that the opposite would be true: By expressly limiting the use of torture only to the ticking bomb case and by requiring a highly visible judge to approve, limit and monitor the torture, it will be far more difficult to justify its extension to other institutions.

The goal of the warrant would be to reduce and limit the amount of torture that would, in fact, be used in an emergency. This is an issue that should be discussed now, before we confront the emergency.

So, let the debate begin. . Alan M. Dershowitz is a Harvard law professor and a former member of the O.J. Simpson ""Dream Team.'' Last Sunday, he appeared on ""60 Minutes'' to make a case for legal torture. His latest book is ""Shouting Fire: Civil Liberties in a Turbulent Age'' (Little Brown, 2002).

Link

Tortured torturer

From the Washington Post, a confession by a former torturer:

An Iraq Interrogator's Nightmare

By Eric Fair
Friday, February 9, 2007; A19

A man with no face stares at me from the corner of a room. He pleads for help, but I'm afraid to move. He begins to cry. It is a pitiful sound, and it sickens me. He screams, but as I awaken, I realize the screams are mine.

That dream, along with a host of other nightmares, has plagued me since my return from Iraq in the summer of 2004. Though the man in this particular nightmare has no face, I know who he is. I assisted in his interrogation at a detention facility in Fallujah. I was one of two civilian interrogators assigned to the division interrogation facility (DIF) of the 82nd Airborne Division. The man, whose name I've long since forgotten, was a suspected associate of Khamis Sirhan al-Muhammad, the Baath Party leader in Anbar province who had been captured two months earlier.

The lead interrogator at the DIF had given me specific instructions: I was to deprive the detainee of sleep during my 12-hour shift by opening his cell every hour, forcing him to stand in a corner and stripping him of his clothes. Three years later the tables have turned. It is rare that I sleep through the night without a visit from this man. His memory harasses me as I once harassed him.

Despite my best efforts, I cannot ignore the mistakes I made at the interrogation facility in Fallujah. I failed to disobey a meritless order, I failed to protect a prisoner in my custody, and I failed to uphold the standards of human decency. Instead, I intimidated, degraded and humiliated a man who could not defend himself. I compromised my values. I will never forgive myself.

American authorities continue to insist that the abuse of Iraqi prisoners at Abu Ghraib was an isolated incident in an otherwise well-run detention system. That insistence, however, stands in sharp contrast to my own experiences as an interrogator in Iraq. I watched as detainees were forced to stand naked all night, shivering in their cold cells and pleading with their captors for help. Others were subjected to long periods of isolation in pitch-black rooms. Food and sleep deprivation were common, along with a variety of physical abuse, including punching and kicking. Aggressive, and in many ways abusive, techniques were used daily in Iraq, all in the name of acquiring the intelligence necessary to bring an end to the insurgency. The violence raging there today is evidence that those tactics never worked. My memories are evidence that those tactics were terribly wrong.

While I was appalled by the conduct of my friends and colleagues, I lacked the courage to challenge the status quo. That was a failure of character and in many ways made me complicit in what went on. I'm ashamed of that failure, but as time passes, and as the memories of what I saw in Iraq continue to infect my every thought, I'm becoming more ashamed of my silence.

Some may suggest there is no reason to revive the story of abuse in Iraq. Rehashing such mistakes will only harm our country, they will say. But history suggests we should examine such missteps carefully. Oppressive prison environments have created some of the most determined opponents. The British learned that lesson from Napoleon, the French from Ho Chi Minh, Europe from Hitler. The world is learning that lesson again from Ayman al-Zawahiri. What will be the legacy of abusive prisons in Iraq?

We have failed to properly address the abuse of Iraqi detainees. Men like me have refused to tell our stories, and our leaders have refused to own up to the myriad mistakes that have been made. But if we fail to address this problem, there can be no hope of success in Iraq. Regardless of how many young Americans we send to war, or how many militia members we kill, or how many Iraqis we train, or how much money we spend on reconstruction, we will not escape the damage we have done to the people of Iraq in our prisons.

I am desperate to get on with my life and erase my memories of my experiences in Iraq. But those memories and experiences do not belong to me. They belong to history. If we're doomed to repeat the history we forget, what will be the consequences of the history we never knew? The citizens and the leadership of this country have an obligation to revisit what took place in the interrogation booths of Iraq, unpleasant as it may be. The story of Abu Ghraib isn't over. In many ways, we have yet to open the book.

The writer served in the Army from 1995 to 2000 as an Arabic linguist and worked in Iraq as a contract interrogator in early 2004.

Link

H/T Digby

Period pain

Fyi

Ibuprofen beats acetaminophen for period pain

NEW YORK (Reuters Health) - Although both ibuprofen and acetaminophen reduce menstrual pain, ibuprofen appears to have more potent effects, according to investigators from the West Virginia University School of Medicine, Morgantown.

Although ibuprofen is accepted as an effective treatment for painful periods, or dysmenorrhea, Drs. M. Yusoff Dawood and Firyal S. Khan-Dawood note in the American Journal of Obstetrics and Gynecology, there is still controversy about the usefulness of acetaminophen. Acetaminophen, the active ingredient in Tylenol, is known as paracetamol in several countries.

To investigate further, the duo conducted a small trial involving 12 women with dysmenorrhea who were given three different treatments in random order for three different periods: 1000 milligrams of acetaminophen, 400 milligrams of ibuprofen, or an inactive placebo, four times daily for three days.

The women rated the active medications as being more effective than placebo. "However," Dr. Dawood told Reuters Health, "it appears that ibuprofen has a greater effect and patients also preferred it."

SOURCE: American Journal of Obstetrics and Gynecology, January 2007

Link

Trigeminal Neuralgia Links

Some links on Trigeminal Neuralgia (tic douloureux)

Your Complete Guide to TN
TN Support Association
Medline summary

I'm looking for information on deep brain stimulator treatments of TN. Please email me if you have any links/articles/journals that might help.

KT's Bruises

On his nerve.com photo blog, the photographer Siege published a three-week series of pictures chronicling the healing of his fiancee KT's severely bruised back after a particularly severe SM session. After being flooded with angry and concerned email, KT guest-posted the following:

My girl writes:

"The colors change like the leaves of autumn, my favorite season. It's the end and the beginning, and it's melancholy and exciting at the same time. It made me excited to see the fiery purples and reds, but this deep greenish yellow soothes me. Calms me. It's as if I've survived a wicked storm at sea and ahead is the golden sunrise on the horizon, calmly glistening on the water. When I twist my body and look into the mirror, I remember, and I smile at what I see.

I've never gotten a tattoo, but I feel this may be similar, though not permanent. Most people I know say they got theirs to mark a time in their life that they have moved on from, a reminder of what they've been through. Does it hurt while that needle was grinding away at their flesh for hours? I hear it does. But the pain is necessary, the act of enduring the pain is monumental in itself, even enjoyable at times, and the result is worth it. Though my bruises are temporary, they're far more intimate and meaningful than any markings some random tattoo artist could put on my flesh.

Some of you don't like what you saw, and that's okay by me.

I could describe to you how this act feels to me, the nurturing I felt as my man gently blindfolded me and whispered into my ear; the care I felt in the way he strapped my wrists up and hooked them to the beam above my head; how wet my pussy became during this preparation time; the release of endorphins which exploded upon the first stinging smack, and the way it faded and buzzed beneath my skin; the rush of emotions that flooded my head; how there were moments when I felt I couldn't take any more, yet still didn't want him to stop; how I went to a quiet place in my mind and allowed my body to feel physical pain, and the exercise in control and power which that requires; how scared yet safe I felt and how I allowed myself to be taken to great depths with the one I love, knowing I would come out feeling elated; how alone I felt when I sensed he had left the room, only to feel overwhelming love when he returned with a hot towel to soothe my flesh; how he looked to me, through my sensitive eyes, once the blindfold was removed; the way I collapsed into his arms afterward, feeling free and new; and why all of this is something I need every once in awhile when I get off-kilter, to steady myself, to gain perspective, to feel, to reset. But like someone commented, either you're into it or you're not. I'm not here to convince those who don't understand why it's good for me. It just is. And it's okay if you don't get it.

All you need to know is that it's more about me than about Siege. There was no rage involved. No violence. This wasn't for him. It was me needing something, bad, and he knowing just what it was, and being able to give it to me. It's something I've needed from time to time throughout my life, though past partners were not always able to scratch my itch. I would hint, and they would try, but they just didn't have the frame of mind necessary to deliver. The trust wasn't there on my part, or theirs. Instead it would become silly and giggly. We may as well have had pink fur-lined handcuffs and whipped cream.

No. I need it to be serious. This was. Now I feel peace."

Link (subscription required)

Dissertation coda

A friend liked this bit of my dissertation. So I'm sharing it with you. It's the very last section of the whole thing. It says what I've done and why I think my view isn't crazy.

§6.3

Coda

I admit that many of my conclusions in this dissertation are radical and counterintuitive. I have claimed, inter alia, that pains are not what we think, that all existing accounts of their intrinsic badness are wrong, that they have two distinct intrinsic values, that a privation theory of their intrinsic badness is correct, that this privation is found in their phenomenology, and that intrinsic value can have properties no one has thought to combine. Radical and counterintuitive are usually okay in small doses, but in this dissertation the dosage may seem lethal.

I suspect that much of what is worrisome here is due to the shadow of the kernel view. All of these conclusions flow from the rejection of the kernel view. If pain kernels [the raw sensation of pain] are not what we care about from the normative standpoint, then we can take a much more capacious view of what pains are and what we are referring to when we say that a pain ‘hurts’. That opens the door to progress and the conclusions of this dissertation.

Several years ago, in the middle of a judo match, I broke my collarbone. As is often the case with severe trauma, the immediate pain was surprisingly mild. In many parts of this dissertation I have been painting a picture of what I felt for just a few moments when I later attempted to get out of the car in the hospital parking lot. It’s true that my memories may be tainted by theory; and it has been several years since the accident. But it was not me whose body twisted and crumpled or me who shrieked.

As philosophers we must follow our arguments where they take us. But we must also be conscious of when they’ve taken us over a cliff. I, of course, believe my arguments. But it is my reflections on countless stubbed toes, headaches, and memories of pains past, as well as my research into pain science and the depictions of pain in literature, which convince me that we are still on the right side of the precipice.

Finally, even if some of my arguments have taken us astray, I hope that this dissertation’s approach has been suggestive. Working on pain, and just pain, can, I think, keep us close to the foundations of normative theory and illuminate many of their joints and fissures. Pain is both a window into and a microcosm of much of value theory. After all, if anything is intrinsically bad, pain is.

Insect stings: Tasting notes

From the entomologist and apparent connoisseur Justin O. Schmidt.

• 1.0 Sweat bee: Light, ephemeral, almost fruity. A tiny spark has singed a single hair on your arm.
• 1.2 Fire ant: Sharp, sudden, mildly alarming. Like walking across a shag carpet & reaching for the light switch.
• 1.8 Bullhorn acacia ant: A rare, piercing, elevated sort of pain. Someone has fired a staple into your cheek.
• 2.0 Bald-faced hornet: Rich, hearty, slightly crunchy. Similar to getting your hand mashed in a revolving door.
• 2.0 Yellowjacket: Hot and smoky, almost irreverent. Imagine WC Fields extinguishing a cigar on your tongue.
• 3.0 Red harvester ant: Bold and unrelenting. Somebody is using a drill to excavate your ingrown toenail.
• 3.0 Paper wasp: Caustic & burning. Distinctly bitter aftertaste. Like spilling a beaker of Hydrochloric acid on a paper cut.
• 4.0 Pepsis wasp: Blinding, fierce, shockingly electric. A running hair drier has been dropped into your bubble bath (if you get stung by one you might as well lie down and scream).
• 4.0+ Bullet ant: Pure, intense, brilliant pain. Like walking over flaming charcoal with a 3-inch nail in your heel.

Link

Bonus: Bites and stings of medically important venomous arthropods

Caffeine is good

Hmmmm. It's winter break --14 hour days finally getting some stuff written-- and I just started doing Judo again. This would've been good news for me, but for the last paragraph.

Although it's too soon to recommend dropping by Starbucks before hitting the gym, a new study suggests that caffeine can help reduce the post-workout soreness that discourages some people from exercising.

In a study to be published in the February issue of The Journal of Pain, a team of University of Georgia researchers finds that moderate doses of caffeine, roughly equivalent to two cups of coffee, cut post-workout muscle pain by up to 48 percent in a small sample of volunteers.

Lead author Victor Maridakis, a researcher in the department of kinesiology at the UGA College of Education, said the findings may be particularly relevant to people new to exercise, since they tend to experience the most soreness.

"If you can use caffeine to reduce the pain, it may make it easier to transition from that first week into a much longer exercise program," he said.

Maridakis and his colleagues studied nine female college students who were not regular caffeine users and did not engage in regular resistance training. One and two days after an exercise session that caused moderate muscle soreness, the volunteers took either caffeine or a placebo and performed two different quadriceps (thigh) exercises, one designed to produce a maximal force, the other designed to generate a sub-maximal force. Those that consumed caffeine one-hour before the maximum force test had a 48 percent reduction in pain compared to the placebo group, while those that took caffeine before the sub-maximal test reported a 26 percent reduction in pain.

Caffeine has long been known to increase alertness and endurance, and a 2003 study led by UGA professor Patrick O'Connor found that caffeine reduces thigh pain during moderate-intensity cycling. O'Connor, who along with professors Kevin McCully and the late Gary Dudley co-authored the current study, explained that caffeine likely works by blocking the body's receptors for adenosine, a chemical released in response to inflammation.

Despite the positive findings in the study, the researchers say there are some caveats. First, the results may not be applicable to regular caffeine users, since they may be less sensitive to caffeine's effect. The researchers chose to study women to get a definitive answer in at least one sex, but men may respond differently to caffeine. And the small sample size of nine volunteers means that the study will have to be replicated with a larger study.

O'Connor said that despite these limitations, caffeine appears to be more effective in relieving post-workout muscle pain than several commonly used drugs. Previous studies have found that the pain reliever naproxen (the active ingredient in Aleve) produced a 30 percent reduction in soreness. Aspirin produced a 25 percent reduction, and ibuprofen has produced inconsistent results.

"A lot of times what people use for muscle pain is aspirin or ibuprofen, but caffeine seems to work better than those drugs, at least among women whose daily caffeine consumption is low," O'Connor said.

Link

Sea snail toxins for chronic pain

Snails offer hope for pain sufferers

The humble but lethal sea snail may hold the key to a better life for thousands of chronic pain sufferers.

Researchers from the University of Queensland believe conotoxins contained in potentially deadly sea snail venom could be used to create a treatment to replace conventional pain relief drugs such as morphine.

Dr Jenny Ekberg said her research had shown the conotoxin could produce pain relief without side effects in animals.

However, the conotoxin is yet to be tested on humans and Dr Ekberg said it could be several years before the treatment was able to be produced in marketable quantities.

"It's working beautifully at the moment, we just have to learn to synthesize it properly so that we can get enough amounts to start chemical trials on humans," she said.

Dr Ekberg said the lack of side effects meant the conotoxin had the potential to completely revolutionise pain treatment for cancer patients and chronic and neuropathic pain sufferers.

"Unlike other anaesthetics, it's very specific against the pain and doesn't cause any side effects - it's the first time anyone has discovered anything like this," she said.

Conventional medicines such as morphine can cause a range of unpleasant side effects, including nausea, vision and movement defects and drowsiness.

These symptoms often rendered sufferers unable to work and could lead to depression and, in some cases, suicide, Dr Ekberg said.

"I've met people with this, it's really horrible ... neuropathic pain, which is caused by damaged nerves, not tissue, you have to live with forever," she said.

If the research proves successful Dr Ekberg hopes the treatment will allow sufferers to live normal lives and continue working.

She believed the treatment would initially be administered through hospitals but hoped patients would eventually be able to inject it themselves at home.

© 2006 AAP

Link

What this is all about

Welcome to my pain for philosophers blog. Here's a bit about what you're looking at:

I'm a philosopher working on issues involving pain. That requires knowing quite a bit about what pains are. I thus try to keep up with the pain science literature, and created this blog to collect excerpts of articles relevant to philosophy of mind, philosophical psychology, cognitive science, value-theory, and applied ethics. I'm particularly keen on studies concerning the relationships between gender and pain; the role of depression, anxiety, and other affective disorders in pain; and the ways caregivers' attitudes influence their patients' pain and recovery.

After I started the site, I noticed that many of you find your way here from Google searches on pain and palliative medicine. And several websites geared toward pain patients and their families occasionally link here. Thus I've expanded my focus to include information about advances in pain care and in the understanding of common chronic pain conditions.

I hope you'll find this material helpful, if a bit technical. Please email me if you see something you'd like translated into English. Of course, I'm neither a doctor nor a lawyer, so I'm not offering anything here as medical or legal advice.

I'd greatly appreciate your bringing anything pain-related you may happen across to my attention. Also, if there is some topic or issue which especially interests you, please let me know. I'll try to do some digging.

You can email me at doloric@gmail.com

--Adam

*You'll notice that posting here comes in fits and starts. I try to survey the journals at least once a month, but that unfortunately doesn't happen in extremely busy months. You might therefore find it useful to subscribe to the XML feed to be updated when I post.

Back to the site.

Fear and anxiety's effects on pain-thresholds

Fear and anxiety: divergent effects on human pain thresholds
Rhudy, et. al.
Abstract
Animal studies suggest that fear inhibits pain whereas anxiety enhances it; however it is unclear whether these effects generalize to
humans. The present study examined the effects of experimentally induced fear and anxiety on radiant heat pain thresholds. Sixty male and
female human subjects were randomly assigned to 1 of 3 emotion induction conditions: (1) fear, induced by exposure to three brief shocks;
(2) anxiety, elicited by the threat of shock; (3) neutral, with no intervention. Pain thresholds were tested before and after emotion induction.
Results suggest that ®ndings from animal studies extend to humans: fear resulted in decreased pain reactivity, while anxiety led to increased
reactivity. Pain rating data indicated that participants used consistent subjective criteria to indicate pain thresholds. Both subjective and
physiological indicators (skin conductance level, heart rate) con®rmed that the treatment conditions produced the targeted emotional states.
These results support the view that emotional states modulate human pain reactivity. q2000 International Association for the Study of Pain.
Published by Elsevier Science B.V.
Pain 84 (2000) 65-72
PII: S0304-3959(99)00183-9
Categories: Fear,, Anxiety,, Stress-analgesia, Pain-threshold

Capsaicin undermines the effectiveness of vaginal self-stimulation

Following on the present theme of the analgesic effects of vaginal selt-stimulation:

Inverse relationship between intensity of vaginal self-stimulation-produced analgesia and level of chronic intake of a dietary source of capsaicin
Beverly Whipple, Margarita Martinez-Gomez, Laura Oliva-Zarate, Pablo Pacheco, and Barry R. Komisaruk
Abstract: Women who chronically ingest a diet rich in capsaicin, the pungent ingredient in hot chili peppers, showed a significantly lower magnitude of analgesia in response to vaginal self-stimulation than women with relatively low or medium levels of ingestion. Vaginal self-stimulation-produced analgesia was quantified by measuring (on the hand) pain detection thresholds, pain tolerance thresholds and tactile thresholds. Whereas vaginal self-stimulation produced a 32.6–43.8% increase in pain detection and pain tolerance thresholds in the low chili diet group, it produced only a 2.3–7.3% increase in these measures in the high chili diet group. The medium chili diet group showed an intermediate effect on the pain thresholds. Tactile thresholds were not increased by the vaginal self-stimulation. Baseline (no stimulation) pain thresholds did not differ significantly among the three groups. These findings are consistent with earlier studies in laboratory rats, in which capsaicin administered neonatally abolished vaginal stimulation-produced analgesia, but did not affect baseline pain thresholds to mechanostimulation.

LInk

Categories: Analgesia, Gender, Sex_pain, Vaginal_stimulation

Analgesia produced by copulation in rats

Momentary analgesia produced by copulation in female rats
P. Gómoraa, C. Beyera, G. González-Mariscala and B. R. Komisarukb

Abstract
To assess possible changes in nociception during copulation in estrous rats, electric shocks that were 20% suprathreshold for eliciting vocalization in response to tail shock (STS), were applied to thetail before the initiation of copulation and, thereafter coincident with the onset of mounting bouts by the male (Experiment 1). Females vocalized significantly less during non-intromittive mounts (M; P 0.001), intromissions (I; P < 0.001), and ejaculation (E; P < 0.01) than before the initiation of copulation. In order to assess the importance of vaginal stimulation (VS) by penile insertion during mating, in Experiment 2 30% STS were applied 300–400 ms after the initiation of mounting to ensure that the stimulation fell within the period of penile insertion ocurring during I and E. M failed to significantly inhibit vocalizations to 30% STS. By contrast, both I and E markedly inhibited vocalizations in response to STS. This effect was transitory since subjects (Ss) vocalized to nearly all 30% STS when delivered 15 s after I or E. Copulatory analgesia (CA) was abolished by the bilateral transection of the pelvic and hypogastric nerves but not by the transection of the pudendal nerve (Experiment 3). The magnitude of CA was calibrated by determining the doses of morphine sulfate (MS) required to produce similar decrements in vocalization to STS. The analgesic effects of I and E were equivalent to more than 10 mg/kg and 15 mg/kg, respectively, of MS (Experiment 4). Pelvic-hypogastric neurectomy, but not pudendal neurectomy, also significantly reduced the effect of VS on facilitating lordosis, inducing immobilization and hind leg extension, and blocking the withdrawal reflex to foot pinch (Experiment 5). Pelvic-hypogastric neurectomy also significantly reduced sexual receptivity, as indicated by a reduction in the number of I that the females in this group received.

DOI

Categories: Gender, Pain_and_sex, Analgesia, Stress_analgesia

Vaginal stimulation and pain threshold

Elevation of pain threshold by vaginal stimulation in women.
Whipple B, Komisaruk BR.

Abstract
In 2 studies with 10 women each, vaginal self-stimulation significantly increased the threshold to detect and tolerate painful finger compression, but did not significantly affect the threshold to detect innocuous tactile stimulation. The vaginal self-stimulation was applied with a specially designed pressure transducer assembly to produce a report of pressure or pleasure. In the first study, 6 of the women perceived the vaginal stimulation as producing pleasure. During that condition, the pain tolerance threshold increased significantly by 36.8% and the pain detection threshold increased significantly by 53%. A second study utilized other types of stimuli. Vaginal self-stimulation perceived as pressure significantly increased the pain tolerance threshold by 40.3% and the pain detection threshold by 47.4%. In the second study, when the vaginal stimulation was self-applied in a manner that produced orgasm, the pain tolerance threshold and pain detection threshold increased significantly by 74.6% and 106.7% respectively, while the tactile threshold remained unaffected. A variety of control conditions, including various types of distraction, did not significantly elevate pain or tactile thresholds. We conclude that in women, vaginal self-stimulation decreases pain sensitivity, but does not affect tactile sensitivity. This effect is apparently not due to painful or non-painful distraction.

Pain. 1985 Apr;21(4):357-67
Categories: Gender, Pain_sex, Pain_threshold

Breeding season affects stress-induced analgesia in mice

Sex differences in the expression and antagonism of swim stress-induced analgesia in deer mice vary with the breeding season
Kavaliers and Galea

Summary (you might want to skip to the underlined part)
Swim stress-induced analgesia (SSIA) was examined in photoperiodically induced 'breeding'
(reproductive) and 'non-breeding' (non-reproductive) adult male and female deer mice, Perornyscus maniculatus.
Nociceptive responses (50°C, hot-plate) of breeding and non-breeding deer mice were determined after either a 1-
or 3-min swim in 20°C water. The 1-min swim induced an immediate and relatively short-lasting naloxone (1.0
mg/kg) insensitive 'non-opioid'-mediated SSIA that was antagonized by the N-methyl-D-aspartate (NMDA)
antagonist, MK-801 (0.10 mg/kg) in all of the groups of mice except the breeding (reproductive) females. Breeding
females displayed a non-opioid analgesia that was insensitive to MK-801. The 3-min swim induced a relatively more
prolonged mixed opioid and 'non-opioid' SSIA of which the initial portion was sensitive to antagonism by MK-801
in all groups of the mice except the breeding females, while the latter portion (15 min after swim) was reduced by
naloxone in all of the groups of mice. Overall, the breeding males displayed greater levels of SSIA than the breeding
females, with no consistent sex differences in the non-breeding mice. Within sexes, the breeding males displayed
greater levels of opioid and non-opioid SSIA than the non-breeding males, while the non-breeding females
displayed greater levels of SSIA than the breeding females. These results show that both sex and reproductive status
affect the expression and neurochemical mediation of non-opioid SSIA. These findings also suggest that reproductive
females may have an unique or novel hormonally (estrogen) dependent mechanism associated with the
expression of SSIA
(c) 1995 Elsevier Science

Pain 65 (1995) 327-334
Categories: Pain_and_gender, Stress-induced_analgesia

Vaginal pain during sex

Vestibular tactile and pain thresholds in pain with vulvar vestibulitis syndrome
Pukall, et al.

Abstract
Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia** in pre-menopausal women. Little is known about sensory function
in the vulvar vestibule*, despite Kinsey's assertion that it is important for sexual sensation. We examined punctate tactile and pain thresholds
to modified von Frey filaments in the genital region of women with VVS and age- and contraceptive-matched pain-free controls. Women
with VVS had lower tactile and pain thresholds around the vulvar vestibule and on the labium minus than controls, and these results were
reliable over time. Women with VVS also had lower tactile, punctate pain, and pressure-pain tolerance over the deltoid muscle on the upper
arm, suggesting that generalized systemic hypersensitivity may contribute to VVS in some women. In testing tactile thresholds, 20% of trials
were blank, and there was no group difference in the false positive rate, indicating that response bias cannot account for the lower thresholds.
Women with VVS reported significantly more catastrophizing thoughts related to intercourse pain, but there was no difference between
groups in catastrophizing for unrelated pains. Pain intensity ratings for stimuli above the pain threshold increased in a parallel fashion with
log stimulus intensity in both groups, but the ratings of distress were substantially greater in the VVS group than in controls at equivalent
levels of pain intensity. The data imply that VVS may reflect a specific pathological process in the vestibular region, superimposed on
systemic hypersensitivity to tactile and pain stimuli.
(c) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved

Pain 96 (2002) 163-175
PII: S0304-3959(01)00442-0

* The vulvar vestibule is located posterior to the glans clitoris between the labia minora, and contains the vaginal and urethral openings
and the ducts of the Bartholin’s glands.

**Dyspareunia: Painful sexual intercourse.

Categories: Pain_and_sex
.

Sexual headaches

My new favorite word of the day:

Coital Cephalalgia (headache during or after sex)

Of course, since sex has been shown to reduce regular headaches in normal people, pre-coital cephalalgia is not as serious a condition...

The cerebral hemodynamics of headache associated with sexual activity
Evers, et al.

Abstract
Headache associated with sexual activity is an idiopathic headache disorder and regarded to be a vascular headache but no pathophysiological
studies have been performed to date to elucidate the underlying mechanisms. We investigated 12 patients with the explosive type of
sexual headache according to the criteria of the International Headache Society during a headache-free state by means of acetazolamide test
and of stress Doppler sonography. Twelve age-matched migraine patients and 14 healthy subjects served as control groups. Changes of blood
pressure, cerebral blood flow velocity (CBFV), and pulsatility index (PI) were evaluated. Patients with sexual headache showed a significantly
higher increase of blood pressure during standardized physical exercise as compared to healthy subjects and migraine patients.
Changes of CBFV by physical exercise were not different between the three examination groups. After 1 g acetazolamide, CBFV showed a
significantly higher increase in patients with sexual headache (plus 66% ^ 16%) than in healthy subjects (plus 46% ^ 18%), and PI showed a
significantly lower decrease as compared to healthy subjects and migraine patients. These data suggest that in patients with sexual headache
the metabolic rather than the myogenic component of the cerebral vasoneuronal coupling is impaired.
q 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved

Pain 102 (2003) 73-78
DOI
Categories: Headache, Pain_and_sex

Pain and cocaine

Blockade of tolerance to morphine analgesia by cocaine
Misra, et al.

Abstract
Tolerance to morphine was induced in male Sprague-Dawley rats by s.c. implantation of a morphine base pellet (75 mg) on the first and second day and determining the magnitude of tolerance 72 h after the first implant by s.c. injection of a test dose of morphine (5 mg/kg). Implantation of a cocaine hydrochloride pellet (25 mg), concurrently with morphine pellets or of a cocaine hydrochloride (50 mg) pellet after the development of tolerance, blocked both the development and expression of morphine analgesic tolerance. In morphine-pelleted animals pretreatment for 3 days with desipramine or zimelidine or phenoxybenzamine but not haloperidol produced no significant morphine tolerance. Pretreatment with a combination of desipramine and zimelidine, however, was as effective as cocaine in blocking morphine tolerance. ?-Methyl-p-tyrosine methyl ester counteracted the effect of cocaine in blocking morphine tolerance and potentiated the tolerance development. Blockade of morphine tolerance by cocaine was reinforced and facilitated by pretreatment with fenfluramine or p-chlorophenylalanine ethyl ester and to a lesser extent by clonidine and haloperidol. Acute administration of fenfluramine or zimelidine or a combination of desipramine and zimelidine or ?-methyl-p-tyrosine methyl ester or p-chlorophenylalanine ethyl ester did not significantly affect morphine analgesia. The study suggests an important role of the concomitant depletion of both central noradrenaline and serotonin in the blockade of morphine tolerance by cocaine and stresses the importance of the counter-balancing functional relationship between these two neurotransmitters in the central nervous system.
(c) 1989 Elsevier Science

DOI
Categories: Morphine, Analgesia, Pain_and_cocaine

Exercise-induced stress analgesia?

Exercise-induced analgesia: fact or artifact?
Padawer and Levine

Abstract
This study critically examines the reported exercise-induced previous termanalgesianext term effect in view of the potential previous termstressnext term-induced previous termanalgesianext term of pain testing itself. Two designs were used to test whether previous findings of previous termanalgesianext term were induced by the exercise procedures or by the previous termstressnext term of the pain testing procedures themselves used in such experiments. In the first design, post-test cold pressor pain ratings were obtained from college students following exercise (bicycle ergometry) and two control tasks (minimal exercise and non-exercise). No significant differences between these groups were found. In the second design, exercise and non-exercise groups pre-exposed to cold pressor pain testing were compared to groups that were not pre-exposed to pain testing. There were no significant effects for exercise; however, significant previous termanalgesianext term effects for pain test pre-exposure were demonstrated. Therefore previous research claiming exercise-induced previous termanalgesianext term may have confounded the effects of exercise with the effects of pre-exposure to pain testing itself.
(c)1992 Elsevier Science

Pain 48 (2) 1992, 131-135
http://dx.doi.org/10.1016/0304-3959(92)90048-G
Categories: Stress-analgesia,, Pain_and_exercise

Age differences in endogenous analgesia

Age-related differences in the endogenous analgesic response to repeated cold water immersion in human volunteers
Washington, et al.

Abstract
Recent animal studies using stress-induced analgesia have suggested a general age-related decline in endogenous pain inhibitory systems.
The aim of the current study was to examine age-related differences in the magnitude of endogenous analgesia in human volunteers, using
psychophysical measures of neuroselective electrical, and thermal CO2 laser induced pain thresholds, before, immediately after and 1 h after
repeated cold water immersion of the hand. Sensory detection thresholds did not differ between age groups indicating that the functional
integrity of primary afferent sensory ®bres appears to be intact in older people. Consistent with many previous studies, older adults required a
higher intensity of noxious stimulation in order to ®rst report the presence of pain. The cold water immersion task was effective in eliciting a
powerful analgesic response, regardless of age; pain thresholds were shown to increase by up to 100% immediately after the cold pressor test.
This effect was relatively transient with thresholds returning to baseline within 1 h. The magnitude of analgesic response, however, was found
to be signi®cantly less in older people. Age differences in the ef®cacy of endogenous analgesic systems may be expected to reduce the ability
of older adults to cope with severe persistent pain states and may help explain some of the variation in the literature on pain report.
(c) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.

Pain 89 (2000) 89-96
PII: S0304-3959(00)00352-3
Categories: Pain_and_age,, Endogenous_analgesia,, Pain_threshold

Negative affect and pain

Negative affect: effects on an evaluative measure of human pain
Rhudy, et al.

Prior work indicates that exposure to fear-inducing shock inhibits finger-withdrawal to radiant heat in humans (hypoalgesia), whereas
anxiety induced by threat of shock enhances reactivity (hyperalgesia; Pain 84 (2000) 65–75). Although finger-withdrawal latencies are
thought to reflect changes in pain sensitivity, additional measures of pain are needed to determine whether pain perception is altered. The
present study examined the impact of negative affect on visual analog scale (VAS) ratings of fixed duration thermal stimuli. One hundred
twenty-seven male and female human subjects were randomly assigned to one of three emotion-induction conditions: (1) negative affect
induced by exposure to three brief shocks; (2) negative affect elicited by the threat of shock without presentation; and (3) neutral affect, with
no intervention. VAS ratings were tested before and after emotion-induction. Results suggest that both negative affect manipulations reduced
pain. Manipulation checks indicated that the emotion-induction treatments induced similar levels of fear but with different arousal levels.
Potential mechanisms for affect induced changes in pain are discussed.
(c) 2003 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.

Pain 104 (2003) 617-626
doi:10.1016/S0304-3959(03)00119-2

Categories: Fear,, Anxiety,, Stress-induced_analgesia,, Pain-modulation

Stress-induced analgesia

Cigarette smoking, stress-induced analgesia and pain perception in men and women
Girdler, et al.

Abstract
This study examined gender differences in smoking-related analgesia and stress-induced analgesia (SIA), as a function of pain modality. Forty men (20 smokers, 20 nonsmokers) and 37 women (17 smokers) were tested twice for pain sensitivity to tourniquet ischemia, thermal heat, and cold pressor tests; once following mental stress and once following rest control, counterbalancing order. Cardiovascular and neuroendocrine responses to mental stress were also examined. While expected gender differences in pain sensitivity were observed, women smokers had greater threshold and tolerance times to ischemic pain than women nonsmokers (P!0.05) when pain testing followed rest. Male smokers had greater threshold and tolerance to cold pressor pain than male nonsmokers (P!0.05) after both rest and stress Only women showed evidence for SIA, since women nonsmokers demonstrated greater ischemic pain threshold and tolerance following mental stress versus rest (P!0.05), and all women reported lower thermal heat pain unpleasantness after stress versus rest (PZ0.05). Only nonsmokers showed expected inverse relationships between sympathetic and hypothalamic–pituitary–adrenal (HPA) axis reactivity measures and sensitivity to pain. Smokers showed evidence for blunted HPA-axis function at rest and stress. These results indicate that analgesia related to both being a smoker and stress is influenced by gender and pain modality. The reduced pain perception in smokers and absence of relationships between endogenous pain regulatory mechanisms and pain sensitivity may reflect a maladaptive response to chronic smoking.
(c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Pain 114(2005) 372-385
doi:10.1016/j.pain.2004.12.035

Categories: Stress-induced, analgesia

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