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

A role for the cyclic AMP (CAMP)-protein kinase A (PKA) transduction cascad e in nociceptive processing has been identified. This study examined the ef fects 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 hypoalg esia to noxious stimulation, while a 10-fold higher dose (4.2 mu mol) induc ed 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 s pinal cord in a biphasic manner, and suggest that significant tonic activit y exists in this pathway. (C) 2001 Published by Elsevier Science Ireland Lt d.