Functions of NO-GC1 and NO-GC2 in pain processing
© Petersen et al. 2015
Published: 2 September 2015
Chronic pain in response to tissue inflammation (inflammatory pain) or nerve injury (neuropathic pain) is often unresponsive to currently available treatments. A large body of evidence indicates that production of nitric oxide (NO) and activation of NO-sensitive guanylyl cyclase (NO-GC) essentially contributes to the processing of chronic pain. NO-GC is a heterodimer consisting of one α subunit (α1 or α2) and one β1 subunit and exists in two isoforms (NO-GC1 and NO-GC2). However, the functional role of NO-GC1 and NO-GC2 in pain processing remains poorly understood. Here, we investigated the expression of NO-GC isoforms in pain-relevant tissues (dorsal root ganglia and the spinal cord) and characterized the nociceptive behavior of mice lacking α1 or α2 in models of acute nociceptive, inflammatory and neuropathic pain.
Our behavioral data point to different and partly contrary functions of NO-GC1 and NO-GC2 in the processing of inflammatory and neuropathic pain. The expression of NO-GC isoforms in dorsal root ganglia and the spinal cord is restricted to specific neuronal and non-neuronal cell populations. It remains to be determined which targets mediate the pain-relevant effects of NO-GC1 and NO-GC2.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.