• Lisa C Loram, Jacqueline A Harrison, Lindsey Chao, Frederick R Taylor, Anireddy Reddy, Carissa L Travis, Rona Giffard, Yousef Al-Abed, Kevin Tracey, Steven F Maier, and Linda R Watkins.
• Department of Psychology & Neuroscience, University of Colorado, Boulder, CO 80309, USA. Lisa.Loram@colorado.edu
• Brain Behav. Immun. 2010 Aug 1;24(6):959-67.

AbstractNicotinic acetylcholine receptors (nAchRs) are not only key receptors in the autonomic nervous system, but also are present on immune cells. The alpha seven subunit of nAchR (alpha7nAchR) suppresses pro-inflammation in peripheral monocytes by decreasing pro-inflammatory cytokine production. In spinal cord, alpha7nAchRs are found on microglia, which are known to induce and maintain pain. We predicted that alpha7nAchR agonists might attenuate intrathecal HIV-1 gp120-induced, pro-inflammatory cytokine- and microglia-dependent mechanical allodynia. Choline, a precursor for acetylcholine and selective agonist for alpha7nAchR, was administered intrathecally either with, or 30 min after, intrathecal gp120. Choline significantly blocked and reversed gp120-induced mechanical allodynia for at least 4 h after drug administration. In addition, intrathecal choline, delivered either with or 30 min after gp120, reduced gp120-induced IL-1beta protein and pro-inflammatory cytokine mRNAs within the lumbar spinal cord. A second alpha7nAchR agonist, GTS-21, also significantly reversed gp120-induced mechanical allodynia and lumbar spinal cord levels of pro-inflammatory cytokine mRNAs and IL-1beta protein. A role of microglia is suggested by the observation that intrathecal choline suppressed the gp120-induced expression of, cd11b, a macrophage/microglial activation marker. Taken together, the data support that alpha7nAchR may be a novel target for treating pain where microglia maintain the pro-inflammatory state within the spinal cord.Published by Elsevier Inc.

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