Behavioral and molecular basis of cholinergic modulation of pain: Focus on nicotinic acetylcholine receptors

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Abstract

Nicotinic acetylcholine receptors (nAChRs) have emerged as a novel therapeutic strategy for pain and inflammatory disorders. In particular, α4β2∗, α7, and α9α10 nAChR subtypes have been investigated as potential targets to treat pain. The nAChRs are distributed on the pain transmission pathways, including central and peripheral nervous systems and immune cells as well. Several agonists for α4β2∗ nAChR subtypes have been investigated in multiple animal pain models with promising results. However, studies in human indicated a narrow therapeutic window for α4β2∗ agonists. Furthermore, animal studies suggest that using agonists for α7 nAChR subtype and antagonists for α9α10 nAChR subtypes are potential novel therapies for chronic pain management, including inflammatory and neuropathic pain. More recently, alternative nAChRs ligands such as positive allosteric modulators and silent agonists have shown potential to develop into new treatments for chronic pain.

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Toma, W., Ulker, E., Alqasem, M., AlSharari, S. D., McIntosh, J. M., & Damaj, M. I. (2020). Behavioral and molecular basis of cholinergic modulation of pain: Focus on nicotinic acetylcholine receptors. In Current Topics in Behavioral Neurosciences (Vol. 45, pp. 153–166). Springer Science and Business Media Deutschland GmbH. https://doi.org/10.1007/7854_2020_135

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