A neuroimmune interaction in painful peripheral neuropathy

Background: In almost every neuropathic pain state caused by peripheral ner ve damage, whether due to trauma or disease, both structural damage and an inflammatory response exist. Objective: The goal of this study was to determine the contribution, separa te from the effects of the structural lesion, of the inflammatory response to neuropathic pain. Methods: Two sets of experiments were performed. In the first, an experimen tal inflammation of the nerve (a neuritis) and an experimental inflammation of the muscle (a myositis control group) were produced in two groups of ra ts. The pain responses to stimuli applied to the sciatic nerve territory on the plantar hind paw were evaluated through tests of (1) heat hyperalgesia ; (2) mechanical allodynia; (3) mechanical hyperalgesia; and (4) cold allod ynia. In the second set of experiments, thalidomide or cyclosporin-A was us ed to block the production of immune modulators in the neuritis model and i n a chronic constriction injury model (which involves structural damage and an inflammatory response in the sciatic nerve) to determine the contributi on of the immune response to the pain observed in the first set of experime nts. Results: In experiment I, rats with the neuritis but not those with the myo sitis developed neuropathic pain symptoms. In experiment 2, thalidomide pro duced a partial but significant reduction in pain in the chronic constricti on injury model across all four tests, but there was no effect in the neuri tis model in any of the tests. Cyclosporin-A resulted in a dose-related red uction in pain in both models across all four tests. Conclusions: These data suggest the possibility of an important interaction between the immune system and the nervous system in neuropathic pain and s uggest that drugs modulating the immune system may be useful therapies in a t least some neuropathic pain states.