Spinal Effects of Bicuculline: Modulation of an Allodynia-Like State by an A1-Receptor Agonist, Morphine, and an NMDA-Receptor Antagonist

Alison J. Reeve , Anthony H. Dickenson , and Nicola C. Kerr Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom Reeve, Alison J., Anthony H. Dickenson, and Nicola C. Kerr. Spinal effects of bicuculline: modulation of an allodynia-like state by an A 1 -receptor agonist, morphine, and an NMDA-receptor antagonist. J. Neurophysiol. 79: 1494-1507, 1998. Single-unit recordings were made in the intact anesthetized rat of the responses of dorsal horn neurons to C-, A -, and A -fiber stimulation. The postdischarge and windup responses of the same cells along with responses to innocuous stimuli, prod and brush, also were measured. The effects of ( )-bicuculline-methobromide (0.5, 5, 50, and 250 µg) were observed on these neuronal responses. The C- and A -fiber-evoked responses were facilitated significantly in a dose-dependent manner. The input was facilitated, but as the final overall response was not increased by the same factor, windup appeared to be reduced. However, postdischarge, resulting from the increase in the excitability produced by windup, tended to be facilitated. After doses of 5 µg bicuculline, stimulation at suprathreshold A -fiber-evoked activity caused enhanced firing, mainly at later latencies corresponding to A -fiber-evoked activity in normal animals. Few cells responded consistently to brush and so no significant change was observed. Responses evoked by innocuous pressure (prod) always were observed in cells that concurrently responded to electrical stimulation with a C-fiber response. This tactile response was facilitated significantly by bicuculline. The effects of N 6 -cyclopentyladenosine (N 6 -CPA), an adenosine A 1 -receptor agonist, was observed after pretreatment with 50 µg bicuculline, as were the effects of morphine and 7-chlorokynurenate (7-CK). N 6 -CPA inhibited prod, C- and A -fiber-evoked responses as well as the initial and overall final response to the train of C-fiber strength stimuli. Inhibitions were reversed with 8(p-sulphophenyl) theophylline. Morphine, the mu-receptor agonist, also inhibited the postbicuculline responses to prod, C-, and A -fiber responses and initial and final responses to a train of stimuli. Inhibitory effects of morphine were reversed partly by naloxone. 7-CK, an antagonist at the glycine site on the N -methyl- D -aspartate-receptor complex, inhibited the responses to C- and A -fiber-evoked activity as well as prod. The postdischarges were inhibited by this drug. Aga