Methyl xanthines, adenosine 3',5'-cyclic monophosphate and the spinal transmission of nociceptive information

1 In spinal cats anaesthetized with either alpha-chloralose or sodium pentobarbitone, a study was made of the effects of adenosine 3',5'-cyclic monophosphate (cyclic AMP), mono- and di-butyryl cyclic AMP and the methyl xanthines, theophylline and isobutyl methyl xanthine (IBMX), on the responses of neurones of laminae I, IV and V to noxious and innocuous skin stimuli. The compounds were administered from micropipettes positioned in the substantia gelatinosa. IBMX was also given intravenously.2 When administered in the substantia gelatinosa, neither cyclic AMP, its butyryl derivatives, nor the methyl xanthines had any effect on the excitation of neurones of spinal laminae IV and V by noxious heating of the skin or deflection of hairs. When the nociceptive responses of cells had been reduced by electrophoretic morphine, methyl xanthines and cyclic AMP failed to modify the effects of morphine on these deeper neurones. Electrophoretically administered naloxone reversed the effect of morphine.3 Intravenously administered IBMX (1 to 2 mg/kg) produced large transient increases in the firing rate of both C fibres and the excitation of dorsal horn neurones by noxious heating of the skin. These increases coincided with decreases in the mean systemic blood pressure, and probably resulted from increased temperatures being attained in the dermis by each noxious stimulus. When dorsal horn neurones were activated by electrical stimulation of the tibial nerve by a stimulus adequate to excite C fibres, intravenous IBMX produced a small or no increase in the number of spikes per stimulus.4 These results in the spinal cord do not support the hypothesis that the inhibition of synthesis of cyclic AMP is relevant to the analgesic action of morphine in mammals.