Nitric oxide mediates the central sensitization of primate spinothalamic tract neurons

Nitric oxide (NO) has been proposed to contribute to the development of hyp eralgesia by activating the NO/guanosine 3',5'-cyclic monophosphate (cGMP) signal transduction pathway in the spinal cord. We have examined the effect s of NO on the responses of primate spinothalamic tract (STT) neurons to pe ripheral cutaneous stimuli and on the sensitization of STT cells following intradermal injection of capsaicin. The NO level within the spinal dorsal h orn was increased by microdialysis of a NO donor, 3-morpholinosydnonimine ( SIN-1). SIN-1 enhanced the responses of STT cells to both weak and strong m echanical stimulation of the skin. This effect was preferentially on deep w ide dynamic range STT neurons. The responses of none of the neurons tested to noxious heat stimuli were significantly changed when SIN-1 was administe red. Intradermal injection of capsaicin increased dramatically the content of NO metabolites, NO2-/NO3- within the dorsal hem. This effect was attenua ted by pretreatment of the spinal cord with a nitric oxide synthase (NOS) i nhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Sensitization of STT c ells induced by intradermal injection of capsaicin was also prevented by pr etreatment of the dorsal horn with the NOS inhibitors, L-NAME or 7-nitroind azole. Blockade of NOS did not significantly affect the responses of STT ce lls to peripheral stimulation in the absence of capsaicin injection. The da ta suggest that NO contributes to the development and maintenance of centra l sensitization of STT cells and the resultant mechanical hyperalgesia and allodynia after peripheral tissue damage or inflammation. NO seems to play little role in signaling peripheral stimuli under physiological conditions.