RESEARCH ARTICLE


Focal Inflammation Causes Carbenoxolone-Sensitive Tactile Hypersensitivity in Mice



Regina Hanstein1, Julie B. Zhao1, Rajshekhar Basak2, David N. Smith1, Yonatan Y. Zuckerman3, Menachem Hanani3, David C. Spray1, Maria Gulinello*, 2
1 Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2 Behavioral Core Facility, Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA
3 Laboratory of Experimental Surgery, Hebrew University-Hadassah Medical School, Mount Scopus, Jerusalem 91240, Israel


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Creative Commons License
© 2010 Hanstein et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Behavioral Core Facility, Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Tel: 718-430-4042; Fax: 718-430-8821; E-mail: maria.gulinello@einstein.yu.edu


Abstract

A focal and transitory inflammation induced by injection of complete Freund's adjuvant (CFA) in the submandibular skin of mice elicits pain behavior that persists for several weeks after the initial inflammation has resolved.Chronic pain, assessed as tactile hypersensitivity to stimulation with von Frey filaments, was evident from 1-7 weeks following CFA injection, although inflammation at the injection site was resolved by 3-4 weeks. In contrast, there were no changes in tactile sensitivity in the paw (un-injected site for comparison), no alterations in open field behavior and no differences in a functional observation battery evident in CFA-treated mice compared to controls (saline-injected) or to baseline (before CFA injection). Neither strain (Balb/c vs. C57BL/6) nor sex differences in baseline tactile threshold were significant in the submandibular skin. CFA-induced tactile hypersensitivity was also not a function of strain or sex. A single intraperitoneal injection of the gap junction blocker carbenoxolone (CBX) restored normal tactile thresholds in CFA-treated mice when administered at the peak of inflammation (1 week), after significant resolution of inflammation (3 weeks) or after total resolution of inflammation (4 and 5 weeks) without altering the tactile threshold of control subjects,tactile threshold in the paw or open field behavior. Thus, in this novel model of post-inflammatory pain, transitory inflammation induced persistent sex- and strain-independent behavioral hypersensitivity that was reversed by the gap junction blocker CBX, suggesting neuronal and/or glial plasticity as a major component of the chronic pain

Keywords: Trigeminal Ganglion, Orofacial Pain, Tactile Sensitivity, Gap Junction, Mouse Strain, Sex Difference, Chronic Pain, Von Frey.