We have employed a combination of physiological, pharmacological and behavioral approaches to the study of somatosensory systems related to pain and analgesia. The involvement of NMDA receptors in altered neuronal activity and behavioral hyperalgesia in rats with adjuvant-induced inflammation was studied. The activity of spinal dorsal horn neurons was recorded in rats before and after administration of an NMDA receptor antagonist, MK-801. The receptive field size of nociceptive-specific (NS) and wide-dynamic-range (WDR) neurons in the superficial and deep spinal dorsal horn recorded 24 after injection of complete Freund's adjuvant (CFA) into the left hindpaw was significantly reduced. MK-801 also prevented the expansion of the receptive fields of dorsal horn neurons recorded 5 hours after injection of CFA. MK-801 had no significant effect on receptive field size of dorsal horn neurons in rats without adjuvant--induced inflammation. However, MK-801 did block a transient expansion of the receptive fields induced by repeated C-fiber intensity electrical stimulation of the sciatic nerve. The background activity and noxious heat evoked response of dorsal horn neurons in rats with adjuvant-induced inflammation were primarily inhibited. We characterized the effects of NMDA receptor antagonists on behavioral hyperalgesia during hindpaw inflammation following intraperitoneal or intrathecal injection by determining paw withdrawal latencies from a thermal stimulus. The NMDA receptor antagonists significantly attenuated adjuvant-induced thermal hyperalgesia and reduced its duration. These results support the hypothesis that NMDA receptors are involved in the dorsal horn neuronal plasticity and behavioral hyperalgesia that follows peripheral tissue inflammation.
