Nitric oxide synthase in spinal cord central sensitization following intradermal injection of capsaicin

Nitric oxide (NO) is believed to be an important messenger molecule in sign al transduction pathways that enhance nociceptive transmission in the centr al nervous system (CNS). The role of nitric oxide synthase (NOS) I and II, which synthesize NO, in central sensitization induced by an intradermal cap saicin injection was investigated. To elucidate whether changes in NOS I an d NOS II activities caused by capsaicin injection contribute to behavioral changes, responses to von Frey filaments with two different innocuous bendi ng forces applied on the rat foot were tested. The allodynic responses indu ced by capsaicin injection in the foot were partially reversed by the admin istration of either the selective NOS I inhibitor, 7-nitroindazole (7-NINA) , or the selective NOS II inhibitor, 2-amino-5,6-dihydro-6-methyl-4H-1,3-th iazine (AMT). To confirm changes at the level of single nociceptive neurons , extracellular recordings were made from rat dorsal hom neurons. The elect rophysiological results showed that increased responses to noxious and inno cuous stimuli caused by capsaicin injection were blocked by either 7-NINA o r AMT delivered through a microdialysis fiber inserted through the dorsal h om. Finally, the expression of both NOS I and NOS II in the spinal cord as demonstrated by Western blots was increased by 20 min following intradermal capsaicin injection in the rat foot. These results suggest that both NOS I and NOS II are upregulated following intradermal capsaicin injection and t hat both cause NO release that contributes to the secondary hyperalgesia an d allodynia following this noxious chemical stimulus. (C) 2001 Internationa l Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.