Green, Mark; (1999) Intrinsic inhibitory systems and descending monoaminergic modulation of inflammatory nociception in the rat spinal cord. Doctoral thesis (Ph.D.), University College London.

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Abstract

Inflammation induced neuronal activity is generated in the periphery, and transmitted through the spinal cord. Descending monoaminergic systems that terminate in the dorsal horn of the spinal cord, and the intrinsic spinal GABAergic inhibitory system have been implicated in the modulation of pain, including the control of nociceptive transmission during inflammation. Using an in vivo electrophysiological approach, I investigated the role of GABAA and GABAB receptors, α2-adrenoceptors, and 5-HT1A, 5-HT3, and 5-HT4 receptors in the dorsal horn during formalin induced peripheral inflammation. The effects of intrathecally applied selective agonists and antagonists for these receptors on the electrically evoked Aβ-, Aδ-, and C-fibre responses of dorsal horn neurones in normal animals were compared to the effects of pretreatment with the drugs on the formalin response, in anaesthetized rats. My results show GABAA and GABAB receptor mediated inhibitions are involved in controlling the duration of the second persistent phase of the formalin response, and GABAA receptor mediated inhibition also contributes to the manifestation of the silent interphase period and the magnitude of the second phase. The α2-adrenoceptor mediated noradrenergic inhibitory system, and the 5-HT3 receptor mediated serotonergic excitatory system in the spinal cord appear to be dormant under normal conditions. However, during formalin induced inflammation these systems are activated, modulating the magnitude of the neuronal responses to formalin, and in the case of α2-mediated inhibition, controlling the duration of the response as well. Finally, 5-HT1A and 5-HT4 receptor mediated serotonergic systems in the spinal cord appear to have no endogenous role in the modulation of formalm induced inflammatory nociception. However, when activated, 5-HT1A and 5-HT4 receptors inhibit and facilitate respectively the neuronal responses to formalin, and may do so by selectively modulating Aδ-fibre mediated afferent activity. This thesis advances knowledge of endogenous spinal mechanisms affecting inflammatory nociceptive transmission in the rat.

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