Biphasic modulation of nociceptive processing by the cyclic AMP-protein kinase A signalling pathway in sheep spinal cord

Add time:08/27/2019    Source:sciencedirect.com

A role for the cyclic AMP (cAMP)-protein kinase A (PKA) transduction cascade in nociceptive processing has been identified. This study examined the effects of intrathecal treatment with the cAMP analogue 8-Bromo-cAMP and the PKA inhibitor H-89 dihydrochloride on nociceptive thresholds to mechanical stimulation in six adult sheep to define further the role of cAMP in spinal nociception. Treatment with 420 nmol 8-Br-cAMP induced significant hypoalgesia to noxious stimulation, while a 10-fold higher dose (4.2 μmol) induced mechanical hyperalgesia. Both of these behaviours were blocked by H-89 (38–380 nmol). Treatment with high dose H-89 (380 nmol) alone significantly increased nociceptive thresholds. These results demonstrate that activation of the cAMP-PKA signalling pathway modulates acute nociceptive events in spinal cord in a biphasic manner, and suggest that significant tonic activity exists in this pathway.

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