Jim Broatch of the RSDSA has just forwarded a press release about a new article by Vania Apkarian, whom older redears will recall as the author of "Chronic back pain is associated with decreased prefrontal and thalamic gray matter density," J Neurosci. 2004 Nov 17;24(46):10410-5 [free full text at http://www.jneurosci.org/cgi/content...rcetype=HWCIT]

In any event Dr. Apkarian's new research is as exciting as the last round was disturbing, and once again features our old "friends" the NMDA receptors:

CHRONIC PAIN LINKED TO OLD MEMORIES

Scientists have found that a key source of chronic pain appears to be an old memory trace stuck in the prefrontal cortex. With new understanding of the pain source, Vania Apkarian, professor of physiology, and of anesthesiology, at Northwestern University's Feinberg School of Medicine (USA), has identified a drug that controls persistent nerve pain by targeting the part of the brain that experiences the emotional suffering of pain. The drug is D-Cycloserine, which has been used to treat phobic behaviour over the past decade. In animal studies, D-Cycloserine appeared to significantly diminish the emotional suffering from pain as well as reduce the sensitivity of the formerly injured site. It also controlled nerve pain resulting from chemotherapy, noted Apkarian, who is a member of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University. The drug has long-term benefits. Animals appeared to be pain free 30 days after the last dose of a 30-day regime of D-Cycloserine. "In some ways, you can think of chronic pain as the inability to turn off the memory of the pain," Apkarian said. "What's exciting is that we now may be relieving what has clinically been the most difficult to treat - the suffering or the emotional component of pain." Scientists have always tried to understand pain from the viewpoint of sensation, Apkarian said. "To control it, they tried to stop the sensory input to the brain. "We are saying there's a cognitive memory and emotional component in the brain that seems abnormal. Easing that may have a bigger effect on suffering." Chronic pain is not caused by a single mechanism, Apkarian noted. Sensory abnormalities in people with chronic pain probably drive this memory abnormality. One of Apkarian's studies with rats tried to separately measure their emotional suffering and their physical pain after being treated with the drug (The rats had chronic pain from a healed limb injury). The results indicated the animals' emotional suffering decreased much more than their physical pain. While the physical pain appeared to be reduced 30 per cent - their emotional suffering completely disappeared. Based on the animal results, the next step will be to test the drug in clinical trials, Apkarian said. When we do this in a clinical trial, we expect people to say I still have the pain, but it's not bothering me anymore," Apkarian said. "We think they will have a physical awareness of the pain, but its emotional consequences will have decreased." He said the drug potentially may lower the amount of standard analgesics people have to use. In Apkarian's previous study, published in late 2006, he revealed that chronic back pain appears in a different part of the brain than the discomfort of burning your finger, for example. With a functional MRI, he found that chronic back pain shows up in the prefrontal cortex. By contrast, the acute sensory pain of the burned finger appears in the sensory part of the thalamus. Apkarian also found that the longer a person has been suffering from chronic pain, the more activity in the prefrontal cortex. He was able to predict the years of their suffering from the MRI. It's cumulative memory," he explained. "I can predict with 90 per cent accuracy how many years they have been living in that pain without even asking them the question."

The study will be published online in Pain: The Journal of the International Association for the Study of Pain

This appears to be the abstract for the article in question:

Pain. 2007 Apr 19
d-Cycloserine reduces neuropathic pain behavior through limbic NMDA-mediated circuitry.Millecamps M, Centeno MV, Berra HH, Rudick CN, Lavarello S, Tkatch T, Apkarian AV.
Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave., Chicago, IL 60611, United States.

Human brain imaging studies suggest that chronic neuropathic pain has a strong emotional component that is mediated by medial prefrontal cortex (mPFC) activity; in rodents, the mPFC is involved in emotional and cognitive aspects of behavior, including the extinction of Pavlovian fear conditioning. Together, these findings suggest that the cortex may modulate the memory trace of pain. As d-cycloserine (DCS), a partial agonist of the NMDA receptor, can enhance learning and potentiate the extinction of acquired fear, in the present study we tested its efficacy in neuropathic pain behavior. In rats with spared nerve injury (SNI), repeated daily oral administration of DCS reduced mechanical sensitivity of the injured limb in a dose-dependent manner; this effect continued for weeks after the cessation of DCS treatment. In addition, re-exposure to DCS further enhanced antinociceptive behavior. Repeated oral DCS administration also reduced cancer chemotherapy drug-induced neuropathic pain behavior. Infusions of DCS directly into the mPFC (especially within prelimbic cortex) or the amygdala (but not into thalamus, insula, or occipital cortex) acutely induced antinociception in SNI rats. The antinociceptive effect of intra-mPFC DCS infusions was mimicked by NMDA and glycine, and blocked by HA 966. In the mPFC of SNI rats, NR2B expression was down-regulated; however, this effect was reversed with repeated oral DCS. Lastly, infusions of DCS into mPFC reversed place avoidance behavior induced by mechanical stimulation of the injured paw in SNI rats. These findings indicate that limbic NMDA-mediated circuitry is involved in long-term reduction in neuropathic pain behavior.

PMID: 17449176

I will try and post a copy if I can get my hands on it.

Mike

I found this information VERY interesting, especially as it coincides with so much of what I've learned about pain myself over the years, both by living with it and by studying the mechanisms of pain thoroughly. Like almost everything else that goes on in the body, the cause of pain is a chain reaction. It includes two seperate stimuli for each sensation of pain, one of which reaches the brain a second or two before the other, creating an echo effect. The two also lead to seperate areas of the brain, one of which deals with protection of the body and the other in an area linked to memory.

The human body never stops trying to heal itself, which is why so many physical changes occur in those with chronic pain. I've read studies where autopsies which were performed on long-term chronic patients revealed that the nerve cells in their bodies had developed more ganglia than those in a normal person. Chemical changes take place. The spine man thicken up to fifty percent. In essence, the body can become more sensitive to the pain as a strategy to try to identify its source.

Thanks again for posting this, Mike. I really did enjoy it.

I've found this to be very common while working with my clients.

Rick