SYM-2081 a kainate receptor antagonist reduces allodynia and hyperalgesia in a freeze injury model of neuropathic pain

Cold-freeze injury at -4 degrees C to the rat sciatic nerve produces mechan ical allodynia and thermal hyperalgesia [M.A. Kleive, P.S. Jungbluth, J.A. Uhlenkamp, K.C. Kajander, Cold injury to rat sciatic nerve induces thermal hyperalgesia or analgesia, gth World Congress on Pain, Vancouver, BC, Canad a, August 1996 (Abstract).]. The NMDA receptor, an excitatory amino acid (E AA) receptor, appears to be involved in the development of allodynia and hy peralgesia following nerve injury, The role, if any, of the kainate recepto r, another EAA receptor, remains unknown. In the current study, we evaluate d a whether (2S,4R)-4-methylglutamic acid (SYM-2081), a recently developed kainate receptor antagonist, attenuates increased responsiveness following cold injury to the sciatic nerve. During baseline testing, Sprague-Dawley r ats were evaluated for frequency of withdrawal from van Frey filaments and latency of withdrawal from a radiant thermal source. Animals were then anes thetized, the left sciatic nerve was exposed, and the nerve was cooled to - 4 degrees C for 15 min (n = 24). For control rats (n = 24), all procedures were identical except that the nerve was maintained at 37 degrees C. Testin g resumed on the third day following surgery. On the fifth post-operative d ay, SYM-2081 (150 or 100 mg/kg), fentanyl citrate (0.04 mg/kg) or vehicle w as injected intraperitoneally. Injury to the rat sciatic nerve induced a si gnificant increase in withdrawal frequency and a significant decrease in wi thdrawal latency (ANOVA, p < 0.05). SYM-2081 and fentanyl significantly red uced these responses (p < 0.05). These results suggest that kainate and opi oid receptors are involved in the mechanical allodynia and thermal hyperalg esia that develop following cold injury to the sciatic nerve. (C) 2000 Publ ished by Elsevier Science B.V. All rights reserved.