The aim of this investigation was to evaluate the role played by
cyclic nucleotides in the transduction of inflammatory
pain and
hyperalgesia. Unmyelinated afferents (n = 79) were exposed to stable analogues of
cyclic AMP and
cyclic GMP, to inflammatory mediators and to
Methylene Blue, an inhibitor of
guanylyl cyclase. Analogues of
cyclic AMP at a concentration of 1 mM (n = 9) but not 10 microM (n = 16) sensitized nociceptor responses to noxious heat and enhanced interstimulus activity. In addition. mechanical thresholds were moderately, but significantly lowered after superfusion of the
cyclic AMP analogue (1 mM). Addition of 10 microM
cyclic AMP analogue to a mixture of excitatory inflammatory mediators (
serotonin,
histamine,
bradykinin and
prostaglandin E2, 10 microM each) did not further increase nociceptor activity (n = 15), in contrast to a previous report that cAMP sensitized
bradykinin responses.
Cyclic GMP analogues (10 microM, 1 mM) did not alter heat sensitivity or mechanical thresholds of polymodal C-fibres, nor did they enhance the ongoing activity that resulted from repeated heat stimulation. After inhibition of
guanylyl cyclase with
Methylene Blue,
cyclic GMP analogues (1-10 microM) did not alter nociceptor responses evoked by application of the mixture of inflammatory mediators. The findings indicate that polymodal nociceptor sensitization and excitation is independent of
cyclic GMP.
Cyclic AMP can obviously contribute to the increased heat sensitivity of inflamed tissue, whereas
cyclic GMP might be of importance in the recruitment of "silent" nociceptors.