15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Nicotinic acetylcholine receptors in neuropathic and inflammatory pain

      1 , 1 , 2 , 3
      FEBS Letters
      Wiley

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          <p class="first" id="P1">Nicotinic acetylcholine receptors (nAChRs) are actively being investigated as therapeutic targets for the treatment of pain and inflammation, but despite more than 30 years of research, there are currently no FDA approved analgesics that target these receptors. Much of the initial research effort focused on the α4β2 subtype, but more recently, additional subtypes have been identified as promising new therapeutic targets and include α6β4, α7 and α9-containing subtypes. This Review will focus on the distribution of these nAChRs in the cell types involved in neuropathic pain and inflammation as well as current pharmacological compounds that target them. </p>

          Related collections

          Most cited references158

          • Record: found
          • Abstract: found
          • Article: not found

          Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation.

          Excessive inflammation and tumour-necrosis factor (TNF) synthesis cause morbidity and mortality in diverse human diseases including endotoxaemia, sepsis, rheumatoid arthritis and inflammatory bowel disease. Highly conserved, endogenous mechanisms normally regulate the magnitude of innate immune responses and prevent excessive inflammation. The nervous system, through the vagus nerve, can inhibit significantly and rapidly the release of macrophage TNF, and attenuate systemic inflammatory responses. This physiological mechanism, termed the 'cholinergic anti-inflammatory pathway' has major implications in immunology and in therapeutics; however, the identity of the essential macrophage acetylcholine-mediated (cholinergic) receptor that responds to vagus nerve signals was previously unknown. Here we report that the nicotinic acetylcholine receptor alpha7 subunit is required for acetylcholine inhibition of macrophage TNF release. Electrical stimulation of the vagus nerve inhibits TNF synthesis in wild-type mice, but fails to inhibit TNF synthesis in alpha7-deficient mice. Thus, the nicotinic acetylcholine receptor alpha7 subunit is essential for inhibiting cytokine synthesis by the cholinergic anti-inflammatory pathway.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mammalian nicotinic acetylcholine receptors: from structure to function.

            The classical studies of nicotine by Langley at the turn of the 20th century introduced the concept of a "receptive substance," from which the idea of a "receptor" came to light. Subsequent studies aided by the Torpedo electric organ, a rich source of muscle-type nicotinic receptors (nAChRs), and the discovery of alpha-bungarotoxin, a snake toxin that binds pseudo-irreversibly to the muscle nAChR, resulted in the muscle nAChR being the best characterized ligand-gated ion channel hitherto. With the advancement of functional and genetic studies in the late 1980s, the existence of nAChRs in the mammalian brain was confirmed and the realization that the numerous nAChR subtypes contribute to the psychoactive properties of nicotine and other drugs of abuse and to the neuropathology of various diseases, including Alzheimer's, Parkinson's, and schizophrenia, has since emerged. This review provides a comprehensive overview of these findings and the more recent revelations of the impact that the rich diversity in function and expression of this receptor family has on neuronal and nonneuronal cells throughout the body. Despite these numerous developments, our understanding of the contributions of specific neuronal nAChR subtypes to the many facets of physiology throughout the body remains in its infancy.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis.

              Physiological anti-inflammatory mechanisms can potentially be exploited for the treatment of inflammatory disorders. Here we report that the neurotransmitter acetylcholine inhibits HMGB1 release from human macrophages by signaling through a nicotinic acetylcholine receptor. Nicotine, a selective cholinergic agonist, is more efficient than acetylcholine and inhibits HMGB1 release induced by either endotoxin or tumor necrosis factor-alpha (TNF-alpha). Nicotinic stimulation prevents activation of the NF-kappaB pathway and inhibits HMGB1 secretion through a specific 'nicotinic anti-inflammatory pathway' that requires the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). In vivo, treatment with nicotine attenuates serum HMGB1 levels and improves survival in experimental models of sepsis, even when treatment is started after the onset of the disease. These results reveal acetylcholine as the first known physiological inhibitor of HMGB1 release from human macrophages and suggest that selective nicotinic agonists for the alpha7nAChR might have therapeutic potential for the treatment of sepsis.
                Bookmark

                Author and article information

                Journal
                FEBS Letters
                FEBS Lett
                Wiley
                00145793
                April 2018
                April 2018
                October 27 2017
                : 592
                : 7
                : 1045-1062
                Affiliations
                [1 ]Department of Biology; University of Utah; Salt Lake City UT USA
                [2 ]Department of Psychiatry; University of Utah; Salt Lake City UT USA
                [3 ]George E. Whalen Veterans Affairs Medical Center; Salt Lake City UT USA
                Article
                10.1002/1873-3468.12884
                5899685
                29030971
                ba597497-7654-4efa-b3da-3c74f9c3efce
                © 2017

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#am

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                History

                Comments

                Comment on this article

                scite_

                Similar content3,372

                Cited by40

                Most referenced authors1,774