Epidural resiniferatoxin induced prolonged regional analgesia to pain

Adequate treatment of cancer pain remains a significant clinical problem. T o reduce side effects of treatment, intrathecal and epidural routes of admi nistration have been used where appropriate to reduce the total dose of age nt administered while achieving regional control. Resiniferatoxin (RTX), an ultrapotent capsaicin analog, gives long-term desensitization of nocicepti on via C-fiber sensory neurons. We evaluate here the analgesic effect on ra ts of epidurally administered RTX, using latency of response to a thermal s timulus in unrestrained animals. Results were compared with those for syste mically administered RTX. Vehicle or graded doses of RTX were injected subc utaneously (s.c.) or through an indwelling lumbar (L4) epidural catheter as a single dose. Both routes of application of RTX produced profound thermal analgesia, reaching a plateau within 4-6 h and showing no restoration of p ain sensitivity over 7 days. Vehicle was without effect. For the epidural r oute, the effect was selective as expected for the targeted spinal cord reg ion, whereas the subcutaneous administration of RTX had a generalized analg esic effect. At doses yielding a tripling of back paw withdrawal latency, e pidural treatment was 25-fold more effective than the subcutaneous route of application. Consistent with the regional selectivity of the lumbar epidur al route, the front paws showed no more effect than by systemic RTX treatme nt. Binding experiments with [H-3]RTX provided further evidence of the segm ental desensitization induced by epidural RTX. We conclude that epidural ad ministration of RTX at the lumbar spinal level produces profound, long-last ing, segmental analgesia to C-Fiber mediated pain in the rat. (C) 1999 Else vier Science B.V. ALT rights reserved.