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PAIN MEDICINE

Perineural Resiniferatoxin Prevents Hyperalgesia in a Rat Model of Postoperative Pain

Igor Kissin, MD, PhD^*, Natasha Davison, BS^*, and Edwin L. Bradley, Jr, PhD

*Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and Department of Biostatistics, University of Alabama at Birmingham

Address correspondence and reprint requests to Igor Kissin, MD, PhD, Department of Anesthesiology, MRB611, BWH, 75 Francis St., Boston, MA 02115-6195. Address e-mail to kissin{at}zeus.bwh.harvard.edu.

Resiniferatoxin (RTX) is a vanilloid agonist with a unique spectrum of activities. Vanilloids bind to the transient receptor potential ion channel subtype 1, a nonselective cation ionophore important in the integration of different noxious signals. Vanilloid agonists selectively decrease sensitivity to noxious stimuli. In this study, we sought to determine whether perineural RTX prevents hyperalgesia in a model of incisional pain. In a rat model, RTX was administered percutaneously to the sciatic and saphenous nerves before the plantar incision. The withdrawal response to von Frey filaments, the struggle response to pressure on the paw, and pain scoring based on weight bearing were measured before RTX and at various intervals for 8 days after RTX. A percutaneous injection of RTX (0.0003%) to the sciatic (0.1 mL) and saphenous (0.05 mL) nerves completely prevented incisional hyperalgesia. Two hours after incision, the withdrawal threshold was 51 mN without and 456 mN with RTX (P < 0.0001). RTX also prevented the incision-induced decrease in struggle threshold and abolished the pain behavior associated with weight bearing. We conclude that RTX provides a type of neural blockade when postoperative pain is abolished and that nonpainful sensations and motor functions are preserved.

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