Monthly Archives: July 2008

Juniorprof is swamped

Lot’s of great stuff happening in the lab these days, lots of grants in various stages of readiness and a whole slew of trips upcoming. All of which means very little time for blogging. We’ll try to get something new up here in the next few days but for now the nose needs to stay on the proverbial grind-stone…

Book meme, while we’re memeing

I’m a bit confused on exactly which tags DrdrA has passed onto me but I’ll follow on uncertain Chad and Bikemonkey either way… Continue reading

Your ipod’s lame music meme

DrdrA tagged me so I’ll play along. For consideration are the lamest songs on your ipod. I am a real music junkie and I have too much stuff to do songs so I will do a slight variation on the meme, lamest artists/bands/groups on my ipod: Here goes…

1) Air Supply. I have ’em all. Making love out of nothing at all is a pure classic.
2) Rick Astley. One word: awesome
3) Erasure. Still great after all these years. Seen ’em twice live, they should be on Broadway (propably are).
4) Celion Dion. Hey I lived in Quebec for 3 years (yeah I know she’s a traitor).
5) Evanescence. I don’t know but I think they are widely considered lame now, but I don’t care… great stuff for the gym.

Well that does it. I guess we’ll get to the new book one next.

Pain is the 5th vital sign, problem for opiate abuse?

Drugmonkey points out that the graphic I linked to in the Las Vegas Sun last week was part of a series of articles on growing rates of narcotic abuse in Nevada. In part one of that series Marshall Allen and Alex Richards take issue with the American Pain Society and the Veteran’s Affairs campaign called “Pain is the 5th vital sign”:

The use of narcotics to treat pain got a tremendous boost in 1995 from the American Pain Society. Its corporate members include the pharmaceutical companies Purdue, maker of OxyContin; Abbott, maker of Vicodin and UCB, and Watson, maker of the hydrocodone drugs Lortab and Norco.

The society set guidelines saying proper pain management includes urging patients to report unrelieved pain. At the time studies had shown that cancer patients were suffering needlessly because they were not being given enough painkillers.

In January 1999, the Veterans Affairs Department, citing the American Pain Society’s statement that pain is one of the main reasons people consult a doctor, launched a campaign known as “Pain is the Fifth Vital Sign.”

The initiative encouraged health care providers to monitor a patient’s reported level of pain — a subjective symptom — as they did the four measurable vital signs: blood pressure, breathing rate, pulse and temperature. Health care providers asked patients to rank pain on a scale of 1 to 10, and were then urged to treat it.

Dr. Mel Pohl, a Las Vegas addiction recovery specialist, criticizes the pharmaceutical industry’s role in making pain the fifth vital sign.

“The rationale was that we don’t want people to suffer,” Pohl said. “In the best case that’s what it was about. In the worst case, somebody was working this out with the (financial) bottom line in mind. Probably both factors are part of it.”

Soon after, the methods advocated by Veterans Affairs were endorsed by the Joint Commission, the agency that monitors and regulates hospitals. Every hospital is now expected to measure pain in a similar manner.

What is the problem here? Continue reading

NIH Transformative R01 Program: Pain Focus

So NIH has released an intention to begin a new funding opportunity for “Transformative” R01s. Included in the focus is the transition from acute to chronic pain. This “transition” is a mysterious one and the fact of the matter is that we know very little about how or why this happens. It appears that NIH has been persuaded that we need to know more about this and that such knowledge may help us design more effective analgesics or even compounds that can prevent such a transition.

A few quick-hit points:
1) I am familiar with the back story on the work to get such a directive into the NIH roadmap and it has been a long, hard fought process. Kudos to those who put this proposal together and saw it through.
2) This is a big step for the field. As I have mentioned before, pain research has been struggling for funding and general NIH attention of late despite the obvious clinical importance (more people see docs for pain treatment than any other reason).
3) Hopefully this will be a stepping stone to ramp up the NIH pain consortium. Once upon a time there was a huge pain research presence at NIH. Although increasing the number of pain-oriented labs at NIH may never happen (and may not be the best way to go), I see no down side to utilizing the pain consortium to increase the NIH focus on pain research (and to get into some congressional offices to talk about the importance of pain research).

The google search terms are telling me something

Just a quick note to the people clicking through here looking for info on hyperalgesia and allodynia and/or central sensitization. I am happy to see that people are coming here as a result of these search terms and it is worth noting that we are right below wikipedia on the google search terms. If you’re reading through and happen to see this post, please know that I am more than happy to field some questions. Mind you, I am not the world expert but I can try my best to be helpful. Moreover, I have several ideas for some pain-related posts in the coming weeks but none of them are set in stone and I’d love to hear any suggestions. Remember, I am doing this in an effort to compile some reliable and free info (including links to freely available lit) so any suggestions on how this series should go forward are most welcome.

I don’t find this helpful

The cracker wars, that is. You know what I’m talking about. I won’t be linking anything here cause I don’t want that kind of traffic. However, I would like to get a few thoughts off my chest. At first I thought it was a tad amusing but it is escalating into a mess that I find utterly despicable and childish. At some point I followed the evo-devo / religious right flame wars on SB with some amusement but then the whole framing thing happened and somewhere along the line I realized that there is the very real issue of educational integrity (which I care deeply about) and, on the other hand, a bunch of people with too much time on their hands going bonkers over issues that they know nothing about (philosophizing aside).

Let’s face it, there are a whole lot of people in this world that live in a world of shit. Almost none of us do and we don’t know what its like. By any measure we are lucky to have this privilege. For those not lucky enough to be born in the right place at the right time, many of them find respite in their religious belief. Some of them will survive horrendous conditions and unbelievable hardships and then credit their still beating heart to their faith. I may not agree with their conclusion but I do say you are a stronger one than I. It is one thing to point out ridiculous behavior on the part of the often silly (and frequently malicious – see birth control policies) Catholic League. It is another to openly ridicule a tradition that gives some people strength when such ridicule serves no real purpose other than to call another human an idiot (in some many words).

When I see such childish and uncalled-for behavior I often think back to stories of my grandfather in WWII. To this day he credits his continued existence to his faith. I would argue that it was something else but I cannot argue with the fact that he was driven at times to survive if for no other reason than to take communion one more time. That faith has been lost on me but it is easy to recognize that it is a lack of necessity as I have not been called upon to live through the great depression, drop out of school prior to my teens or watch thousands of good men die right in front of me. Limitless opportunity has dropped into my lap as a product of the hard work and sacrifice of others and often times I feel my success has been no more than an ability to keep my nose clean and show up on time.

So, PZ and your ilk, I think you would be well served to recall such privilege (although you may not reflect on it in such a way that I do) when you ridicule your fellow man and the beliefs that help him get through a day that you might not endure. There is the real issue of addressing political forces in this nation that would continue to take advantage of those that are less fortunate and there are the beliefs of many of those same people that deserve a modicum of respect (or at least to be left well enough alone).

PI suckitudes?

Drugmonkey has a post up about a colleague potentially bailing on PIdom for another career path. I’ve recently posted on the same topic and expressed some of the same sentiments. In DM’s discussion of this topic he raises the following point on the suckitudes of PIdom and how they weigh against the positives:

I don’t think I ever really understood where PIs who express disappointment with non-PI career path choices are coming from until recently. No, not one of my trainees, even worse. One of my science homies is thinking very seriously about taking an alternative path. I’m trying to be supportive. I know deep down that this person will make the best decision for himself and his goals/aspirations in life. Academic PIdom has copious suckitudes that can be magically relieved by taking another path. I know this.

Still. He’s been toiling on the edge along with many of us for years, trying to make it as a grant funded research-focused PI. From many measures and appearances he’s finally won! Things are looking like the PI / research path is going to work, if not just fine, at least as well as anyone else has it. He’s poised to really take off, scientifically. Apparently it isn’t enough.

This little passage can be especially pertinent for the junior PI who is currently starting up a lab and experiencing the suckitudes that come along with the current funding problems. While I’ve addressed how life changes from postdoc-hood to PIdom before, it is worth revisiting some of these issues from a fresh perspective. Continue reading

Opiate abuse on the rise, a problem for pain management?

Drugmonkey, via Kevin Z, points out a map of the US showing rates of prescription narcotic use in the US by state and rather alarming trends in increases in narcotic use nearly across the board (from the Las Vegas Sun). Anyone with any medical knowledge can look at the list of drugs assessed by the Las Vegas Sun reporters and recognize that the compounds under scrutiny are pain medications. All of them are opiates. As we all know opiates are commonly used to treat acute and chronic pain and they are generally the first class of compounds (with the possible of exception of NSAIDs) that a doctor will consider to control pain.

The data presented in the interactive map show that there are wide variations in specific opiate use across the US but the general trend is a large increase in opiate use in nearly every state. This can generally be interpreted as an increase in opiate abuse nation-wide. I see no reason to dispute this point as it is well supported by media reports and population-based clinical studies. My reason for bringing this up is that beyond (and likely connected to) the increase in opiate abuse is a looming problem for pain management connected to opiate over-use.

Let us begin with an example of why this is a problem. Migraine. Migraine is one of the most common forms of chronic pain affliction and it is commonly treated by NSAIDs, triptans and/or opiates. Recent evidence suggests that medication use can exacerbate migraine frequency and intensity and opiates appear to be a major contributor to this problem. For instance, Rami Burstein’s group has shown that I.V. NSAIDs (ketorolac, specifically) can be effective in reducing the intensity of migraine and in reducing the body-wide allodynia that often accompanies a migraine attack. However, in their study they noted that there was a subset of patients that did not respond to ketorolac and whose headaches (and allodynia) were very difficult to treat: patients with a history of opiate use. Subsequent studies (some of which are circling the meetings and not published yet) have shown that opiate use can exacerbate migraine frequency and intensity and that opiates are likely to be the strong contributers to medication over-use headache. Opiates are analgesics, why would this happen. Continue reading

What is Central Sensitization?

In the previous post on allodynia and hyperalgesia, I mentioned that sensitization of nociceptive neurons in the dorsal horn of the spinal cord were crucial for the development of allodynia and likely contribute strongly to hyperalgesia. When pain scientist and clinicians talk about this type of sensitization they often refer to it as “central sensitization”. What, exactly does this mean?

Central sensitization is loosely defined as an increased response to stimulation that is mediated by amplification of signaling in the central nervous system (CNS). While the stimulation does not necessarily need to be of noxious intensity, for central sensitization to be present it should recruit mechanisms that would signal a noxious response. An example of this is the case of allodynia. Under normal conditions a non-noxious stimuli may not recruit electrophysiological activity in nociceptive neurons in the dorsal horn. On the other hand, following an injury, this same innocuous stimulation may recruit activity in these same central neurons. This would be an example of central sensitization and, in this case, the sensitization would provide a mechanism for allodynia. Central sensitization was first described by Clifford Woolf. In a Nature paper in 1983 he showed that a thermal injury in the periphery caused an amplification of painful stimuli evoked activity coupled to an augmentation of the flexion reflex response (recorded by EMG). Because this reflex is mediated by a dorsal horn – ventral horn reflex arc this gave evidence that amplification of pain signaling was occurring in the CNS. Importantly, he also noted that the injury (to only one paw) stimulated an increase in the reflex arc on the contralateral side of the body. Because this occurred on the side opposite the injury, it could not have been mediated by peripheral mechanisms and must have involved amplification of signaling in the CNS. He termed this phenomena “central sensitization” and realized that such mechanisms could give rise to pain amplification similar to what is seen in humans following an injury or in chronic pain conditions. Continue reading