The effects of a non-competitive NMDA receptor antagonist, MK-801, on behavioral hyperalgesia and dorsal horn neuronal activity in rats with unilateral inflammation

• Published in: Pain (Amsterdam) Vol. 50; no. 3; pp. 331 - 344
• Main Authors: Ren, Ke, Hylden, Janice L.K., Williams, Gene M., Ruda, M.A., Dubner, Ronald
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.09.1992; Elsevier
• Subjects: Animals; Behavior, Animal - drug effects; Biological and medical sciences; Complete Freud's adjuvant; Dizocilpine Maleate - pharmacology; Electric Stimulation; Freund's Adjuvant; Hyperalgesia; Hyperalgesia - physiopathology; Inflammation; Male; Medical sciences; MK-801; Myelitis - chemically induced; Myelitis - pathology; Myelitis - physiopathology; Nervous system involvement in other diseases. Miscellaneous; Neurology; Neurons - drug effects; Neurons - physiology; Pain; Physical Stimulation; Rats; Receptive field; Spinal Cord - drug effects; Spinal Cord - pathology; Spinal dorsal horn; Spinal dorsal horn; MK-801; Receptive field; Inflammation; Hyperalgesia; Complete Freud's adjuvant; Nervous system diseases; Pathophysiology; Rat; Rodentia; Central nervous system; Glutamate receptor; Vertebrata; Experimental disease; Mammalia; Animal; Antagonist; NMDA receptor
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/0304-3959(92)90039-E

The involvement of NMDA receptors in rats with peripheral inflammation and hyperalgesia was evaluated by administration of the non-competitive NMDA receptor antagonist, MK-801. Inflammation and hyperalgesia was induced by intradermal injection of complete Freund's adjuvant (CFA) or carrageenan 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.