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Abstract Rageenan into the left hind paw. The latency of paw withdrawal from a thermal stimulus was used as a measure of hyperalgesia in awake rats. MK-801 (1.6 mg/kg, i.p., or 31.5 μg, intrathecal) significantly attenuated thermal hyperalgesia and reduced its duration in comparison to saline-injected rats (P < 0.05). The receptive field size of nociceptive-specific and wide-dynamic-range neurons in the superficial and deep spinal dorsal horn recorded 24 h after injection of CFA was significantly reduced to 73 ± 6% (P < 0.05, n = 8) and 74 ± 4% (P < 0.05, n = 8) of control values, respectively, by a cumulative dose of 3 mg/kg of MK-801 (i.v.). MK-801 (2 mg/kg) prevented the expansion of the receptive fields of dorsal horn neurons recorded 5 ± 0.4 h (n = 5) after intradermal injection of CFA as compared to saline-injected rats (P < 0.05). MK-801 had no significant effect on receptive field size of dorsal horn neurons in rats without CFA-induced inflammation but blocked a transient expansion of the receptive fields induced by 1 Hz, C-fiber intensity electrical stimulation of the sciatic nerve. The background activity and noxious heat-evoked response of dorsal horn neurons in rats with CFA-induced inflammation were primarily inhibited and noxious pinch-evoked activity was both facilitated and inhibited by the administration of MK-801. These results support the hypothesis that NMDA receptors are involved in the dorsal horn neuronal plasticity and behavioral hyperalgesia that follows peripheral tissue inflammation. ∗Correspondence to: Ke Ren, Ph.D., NAB, NIDR, NIH, Building 30, Room B-20, 9000 Rockville Pike, Bethesda, MD 20892, USA. Tel.: (301) 496-4565; FAX: (301) 402-0667 E-mail: REN@YODA.NIDR.NIH.GOV (Received 9 January 1992; revised 25 February 1992; accepted 26 February 1992.) © Lippincott-Raven Publishers....