A Drug Treatment for Chronic Pain and Erasing Its Memory

The reason why chronic pain is chronic appears to be linked to its persistent memory in the prefrontal cortex. A new study by Dr. Vania Apkarian, professor of physiology and anesthesiology at Northwestern University’s Feinberg School of Medicine, shows that treatment with a drug called D-cycloserine, apart from being effective in relieving the “emotional suffering” from old injuries, also reduces the sensitivity of old injury sites.

Dr. Apkarian’s previous work (2006) with functional MRI suggests that chronic pain, e.g., back pain, appears to activate the prefrontal cortex of the brain, in contrast to burns which acutely activate “lower” centers like the thalamus. Chronic pain appears to be due to memory traces that seem to linger on in the brain’s emotion and learning center, the prefrontal cortex. D-cycloserine, which has been used to treat phobias in the past decade, appears to be effective in particular to reduce the “emotional” component by its action on the prefrontal cortex. In one study on rats, Dr. Apkarian’s team found that the drug erased emotional suffering completely, compared to about 30 percent reduction in physical pain. In addition D-cycloserine also caused a significant reduction in the nerve pain as a result of cancer chemotherapy.

The other significant finding from the study is that the longer the memory of pain, the higher the level of activity in the prefrontal cortex, raising the possibility of “accumulation of pain memory.” Previously, Dr. Apkarian’s team had found that chronic back pain can cause up to 10 percent of loss of brain cells and tissue over time, as a direct effect of painful stimuli. The findings of this study imply that chronic pain is a neurologically debilitating process, which worsens without treatment in many cases. Drugs like cycloserine, in addition to reducing the “intensity of pain and reducing its suffering” may also help in lowering conventional analgesic requirements.

The study, funded by the National Institutes of Health (NIH), has been published in the online version of the journal Pain, and is due to appear in the print version later this fall.

As we understand chronic pain more and more, it is almost certain that many mechanisms are involved than we once thought, and complementary therapies like acupuncture and biofeedback may be effective through pathways other than simply pain fibers and their central connections. The good news about cycloserine is that once a course is administered, it is effective for 30 days or more after treatment. With a significant proportion of the population suffering from chronic pain (20 percent or greater), it appears to be promising indeed.

Reference:

Millecamps M, Apkarian V et al. D-Cycloserine reduces neuropathic pain behavior through limbic NMDA-mediated circuitry. Pain (Online edition – published April 20, 2007).