Sullivan, Ann F.; (1995) Electrophysiological studies on the roles of opioids in spinal antinociception. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The spinal cord is important in the relay of sensory information, in particular pain, and is a target for pharmacological modulation to produce analgesia. This thesis describes the use of electrophysiological techniques to investigate spinal opioid analgesia. Extracellular recordings were made of single convergent neurones responding to both noxious (C fibre) and innocuous (Aβ fibre) cutaneous input in the intact halothane anaesthetized rat. The electrically-evoked C fibre response was dose-dependently inhibited by intrathecal administration of μ, δ and κ opioid agonists with a much lesser effect on Aβ-evoked responses indicating a selective spinal antinociceptive action. The more prolonged nociceptive neuronal response to formalin was also depressed, with greater potency, by prior administration of selective opioid agonists. However opioid potency was considerably reduced if administered after initiation of the formalin response. The separate and sole involvement of μ and δ opioid receptors in the inhibitory action of μ and δ opioid agonists respectively was confirmed by the use of selective antagonists. Inhibitions by κ opioid agonists, although opioid in nature, were not reduced by selective κ opioid antagonists in the adult rat but were antagonized in the 21 day old rat pup, indicating developmental changes in this opioid receptor. Activation of spinal α2 adrenoceptors also produced potent dose- dependent selective inhibitions of C fibre-evoked responses and potentiated μ but not δ opioid spinal anti nociception. In contrast cholecystokinin and FLFQPQRFamide attenuated μ but not δ opioid antinociception and also reduced α2 adrenergic mediated inhibitions. CCKB antagonists potentiated opioid but not α2 adrenergic antinociception. The study demonstrates independent roles for μ and δ opioid receptors in spinal antinociception but only the former were subject to the positive and negative modulatory mechanisms investigated, a differentiation which may be important in future understanding of pain mechanisms and treatment.

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