Selective and long-lasting neural blockade with resiniferatoxin prevents inflammatory pain hypersensitivity.

Abstract

Capsaicin can produce a selective and long-lasting neural blockade. Resiniferatoxin (RTX) is an ultrapotent vanilloid agonist with a unique spectrum of activities different from that of capsaicin. We sought to determine whether a single application of RTX to a peripheral nerve could completely prevent the long-lasting mechanical hyperalgesia caused by carrageenan injection. In rat experiments, RTX (0.001%) was administered percutaneously to the sciatic and saphenous nerves before the intraplantar injection of carrageenan. Responses to noxious mechanical (pressure on the paw) and thermal (hot plate) stimulations and changes in paw circumference were measured at various time intervals for 8 days after treatment. The administration of RTX resulted in mechanical and thermal hypoalgesia (for 2 and 8 days, respectively). Inflammatory hyperalgesia was completely prevented by the precarrageenan injection of RTX. Inflammatory enhancement of paw circumference was reduced by RTX (12.0 +/- 2.4 mm versus 6.9 +/- 3.4 mm, P < 0.005). We suggest that the selective nature of the effect of vanilloid agonists on nociception could provide an opportunity for prolonged neural blockade when early mobilization and/or preservation of protective sensation are required. We report that an ultrapotent vanilloid agonist resiniferatoxin can provide a selective and long-lasting neural blockade. Applied to the sciatic and saphenous nerves, it completely prevented pain hypersensitivity caused by prolonged inflammatory process (injection of carrageenan into the paw).