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 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 micromol) 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.
Dolan
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S
Division of Veterinary Physiology and Pharmacology, Department of Veterinary Preclinical Studies, University of Glasgow, Bearsden Road, Glasgow G61 1QH, UK. s.dolan@vet.gla.ac.uk
Nolan
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AM
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007278:Injections, Spinal; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009619:Nociceptors / Q000201:enzymology* / Q000502:physiology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D012756:Sheep; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D013449:Sulfonamides
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D013449:Sulfonamides; D015124:8-Bromo Cyclic Adenosine Monophosphate; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide