Journal
PAIN
Volume 120, Issue 1-2, Pages 170-181Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.pain.2005.10.028
Keywords
nitric oxide; hyperalgesia; chronic inflammation; neuropathic pain; iNOS
Categories
Ask authors/readers for more resources
Nitric oxide (NO), synthesised by different isoforms of nitric oxide synthase (NOS), has been linked with the development and maintenance of nociception. We studied the role of the inducible isoform, iNOS, in two different rat pain models with an inflammatory component. iNOS was immunohistochemically detected locally in the paw 6 h after Freund's Complete Adjuvant (FCA) injection, showing a plateau at 24-72 h and falling slowly in the following weeks. This correlated with the late phase of the hypersensitivity to pain revealed in the behavioural tests. A highly selective iNOS inhibitor GW274150 (1-30 mg/kg orally, 24 h after FCA) suppressed the accumulation of nitrite in the inflamed paw indicating substantial iNOS inhibition. At the same time it partially reversed FCA-induced hypersensitivity to pain and edema in a dose-dependent manner. After Chronic Constriction Injury (CCI) surgery to the sciatic nerve, iNOS presence was only detected locally in the region of the nerve (inflammatory cells). GW274150 (3-30 mg/kg orally, 21 days after surgery) also reversed significantly the CCI-associated hypersensitivity to pain. No iNOS was detectable in dorsal root ganglia, spinal cord or brain in either model. This study demonstrates a role for peripherally-expressed iNOS in pain conditions with an inflammatory component and the potential value of iNOS inhibitors in such conditions. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available