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

Abstract

Nitric oxide (NO) is believed to be an important messenger molecule in signal transduction pathways that enhance nociceptive transmission in the central nervous system (CNS). The role of nitric oxide synthase (NOS) I and II, which synthesize NO, in central sensitization induced by an intradermal capsaicin injection was investigated. To elucidate whether changes in NOS I and NOS II activities caused by capsaicin injection contribute to behavioral changes, responses to von Frey filaments with two different innocuous bending forces applied on the rat foot were tested. The allodynic responses induced by capsaicin injection in the foot were partially reversed by the administration of either the selective NOS I inhibitor, 7-nitroindazole (7-NINA), or the selective NOS II inhibitor, 2-amino-5,6-dihydro-6-methyl-4 H-1,3-thiazine (AMT). To confirm changes at the level of single nociceptive neurons, extracellular recordings were made from rat dorsal horn neurons. The electrophysiological results showed that increased responses to noxious and innocuous stimuli caused by capsaicin injection were blocked by either 7-NINA or AMT delivered through a microdialysis fiber inserted through the dorsal horn. 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 that both cause NO release that contributes to the secondary hyperalgesia and allodynia following this noxious chemical stimulus.