(162) Pre-surgical intraplantar resiniferatoxin decreases post-operative pain in rats with plantar incision

Abstract

Post-operative pain is a major cause of morbidity and suffering. Central sensitization during surgical intervention has been implicated in the development of chronic pain this may, in part, be due to inadequate peri-operative and post-operative analgesia. Neurons expressing TRPV1 (transient receptor potential cation channel subfamily V) have been implicated in nociception in a variety of pain models. The present study investigated therapeutic and molecular aspects of perioperative ablation of TRPV1-containing peripheral nerve terminals with intraplantar RTX (resiniferatoxin) in a surgical incision pain model. Furthermore, as RTX has algesic actions before institution of analgesia, the effect of lidocaine administered before RTX on post-operative hyperalgesia was investigated. Sprague-Dawley rats were administered RTX and/or lidocaine in the perioperative window prior to intraplantar incision in a 2x2 factorial design. Evoked pain to mechanical and thermal stimulation was assessed, as was spontaneous pain with measurement of guarding and home cage monitoring. RNA was extracted from spinal cord dorsal horn on post-operative day 2 for transcriptomic analysis. Plantar incision caused thermal hyperalgesia, but intraplantar RTX attenuated responses to noxious infrared diode laser thermal A-delta or C-fiber stimulation during the 4 days of the study (p<0.05). Mechanical allodynia, measured by Von Frey stimulation, was pronounced over the first 2 post-operative days, and was also attenuated by pre-emptive RTX. Guarding of the wound was most pronounced at 4 hours and 24 hours pre-emptive RTX attenuated this measure of spontaneous pain (assessed by guarding score, p<0.05). Mechanical pain sensation, measured by pinprick, was preserved after RTX treatment, as was motoric function (measured by time spent on rotarod). Lidocaine pre-treatment had no effect on any of the behavioral assays. Transcriptomic analysis for differential gene expression was also undertaken. Peri-operative administration of RTX, delivered in a clinically relevant manner, was efficacious in decreasing post-operative pain.