C-Fiber mechanoheat (C-MH) nociceptors from the saphenous nerve were s
tudied, in control rats and in rats that underwent surgical sympathect
omy. Intradermal injection, alone, of either norepinephrine (NE) or th
e calcium ionophore, A23187, did not affect mechanical threshold. The
combination of A23187 and NE, however, significantly decreased mechani
cal threshold. In the presence of the alpha(2)-adrenergic antagonist,
yohimbine, or the cyclooxygenase inhibitor, indomethacin, C-MHs were n
ot sensitized by the combination of NE + A23187. One week after surgic
al sympathectomy, the number of C-MHs sensitized by NE + A23187 was si
gnificantly reduced. In summary, NE appears to sensitize nociceptors i
ndirectly. These data are compatible with the suggestion that a sympat
hetic postganglionic neuron-dependent release of prostaglandins mediat
es the sensitization. NE appears to act at an alpha(2)-adrenergic rece
ptor, only in the presence of an increased intracellular Ca2+.