Studies on the involvement of enkephalin in stimulation produced analgesia

Bourne, Gerald W. (1979) Studies on the involvement of enkephalin in stimulation produced analgesia. Masters thesis, Memorial University of Newfoundland.

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Abstract

Similarities between stimulation and opiate analgesia, together with the recent identification of central nervous system opiate receptors and endogenous opiate peptides has led to the proposal that periaqueductal gray (PAG) endorphins modulate pain perception. The specific hypothesis that PAG stimulation induces analgesia by the release of enkephalin was evaluated in rats using a specific competitive enkephalinase inhibitor (Gly-Gly-Phe-Met). -- In three studies the enkephalinase inhibitor was administered intracerebrally two millemeters caudal to an analgesia producing stimulation electrode in the PAG. Analgesia was assessed at two minute intervals using the tail flick test. Study I demonstrated that the enkephalinase inhibitor potentiated in intensity and duration the analgesic action of sub maximal PAG stimulation in a naloxone reversible manner. In Study II the potentiation effect on stimulation produced analgesia was shown to be directly dependent on enkephalinase inhibitor dose and was completely reversed by naloxone. In Study III using specific norepinephrine (6-OHDA) and serotonin (5.7-DHT) neurotoxins a serotonergic mechanism was shown to mediate enkephalinase inhibitor action. Additionally in these studies administration of enkephalinase inhibitor in the absence of stimulation was found to produce an attenuated naloxone reversible dose dependent analgesia. This antinociceptive action was also abolished by a spinal serotonin lesion. -- It was concluded that enkephalin within the PAG was released by stimulation and activated opiate receptors thereby producing analgesia. Thus endogenous enkephalin modulates the perception of pain.

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