INCREASED DELAYED-TYPE HYPERSENSITIVITY IN RATS SUBJECTED TO UNILATERAL MONONEUROPATHY IS MEDIATED BY NEUROKININ-1 RECEPTORS

An animal model of peripheral mononeuropathy was utilized in the prese nt study to investigate the potential role of substance P (SP) in modi fying immune responses associated with chronic pain conditions. Animal s subjected to unilateral sciatic ligation and sham-operated animals w ere sensitized with keyhole limpet hemocyanin (KLH) and subsequently c hallenged in the ipsilateral or contralateral hind paw to produce a de layed-type hypersensitivity (DTH) response. Subcutaneous microdialysis and radioimmunoassay were used to measure interstitial fluid SP level s in the challenged tissue prior to and following immune challenge in control and neuropathic animals. Following immune challenge, there was a significant increase in the concentration of SP in tissue dialysate samples from the challenged paw of both sham-operated and neuropathic animals. However, tissue SP levels in neuropathic animals were more t han two-fold higher than those obtained from sham-operated controls fo llowing challenge. SP concentration remained elevated for 2.5 h follow ing immune challenge in neuropathic animals compared to 90 min in sham -operated animals. Compared with controls, neuropathic animals also ex hibited an increased DTH response that was reversed, in a dose-related fashion, by the non-peptide NK-1 receptor blocker L-703,606. The same antagonist had no effect in sham-operated animals. These data suggest that the increased DTH response in animals subjected to unilateral mo noneuropathy involves SP and NK-1 receptors present in the challenged tissue.