Morphine-induced Modulation of Nociceptive Spinal Dorsal Horn Neuronal Activities after Formalin-induced Inflammatory Pain

Morphine-induced Modulation of Nociceptive Spinal Dorsal Horn Neuronal Activities after Formalin-induced Inflammatory Pain

In this study, we examined the morphine-induced modulation of the nociceptive spinal dorsal horn neuronal activities before and after formalin-induced inflammatory pain. Intradermal injection of formalin induced time-dependent changes in the spontaneous activity of nociceptive dorsal horn neurons. In na&#239;ve cats before the injection of formalin, iontophoretically applied morphine attenuated the naturally and electrically evoked neuronal responses of dorsal horn neurons. However, neuronal responses after the formalin-induced inflammation were significantly increased by morphine. Bicuculline, GABA<SUB>A</SUB> antagonist, increased the naturally and electrically evoked neuronal responses of dorsal horn neurons. This increase in neuronal responses due to bicuculline after the formalin-induced inflammation was larger than that in the na&#239;ve state, suggesting that basal GABA<SUB>A</SUB> tone increased after the formalin injection. Muscimol, GABA<SUB>A</SUB> agonist, reduced the neuronal responses before the treatment with formalin, but not after formalin treatment, again indicating an increase in the GABAergic basal tone after the formalin injection which saturated the neuronal responses to GABA agonist. Morphine-induced increase in the spinal nociceptive responses after formalin treatment was inhibited by co-application of muscimol. These data suggest that formalin-induced inflammation increases GABA<SUB>A</SUB> basal tone and the inhibition of this augmented GABA<SUB>A</SUB> basal tone by morphine results in a paradoxical morphine- induced increase in the spinal nociceptive neuronal responses after the formalin-induced inflammation.