Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10455073 | Brain, Behavior, and Immunity | 2010 | 9 Pages |
Abstract
Nicotinic 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 (α7nAchR) suppresses pro-inflammation in peripheral monocytes by decreasing pro-inflammatory cytokine production. In spinal cord, α7nAchRs are found on microglia, which are known to induce and maintain pain. We predicted that α7nAchR 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 α7nAchR, 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-1β protein and pro-inflammatory cytokine mRNAs within the lumbar spinal cord. A second α7nAchR agonist, GTS-21, also significantly reversed gp120-induced mechanical allodynia and lumbar spinal cord levels of pro-inflammatory cytokine mRNAs and IL-1β 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 α7nAchR may be a novel target for treating pain where microglia maintain the pro-inflammatory state within the spinal cord.
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Authors
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, Linda R. Watkins,