α9‐containing nicotinic acetylcholine receptors and the modulation of pain
Abstract
Neuropathic pain is a complex and debilitating syndrome for which there are few effective pharmacological treatments. Opioid‐based medications are initially effective for acute pain, but tolerance to their analgesic effects quickly develops, and long‐term use often leads to physical dependence and addiction. Furthermore, neuropathic pain is generally resistant to non‐steroidal anti‐inflammatory drugs. Other classes of medications including antidepressants, antiepileptics and voltage‐gated calcium channel inhibitors are only partially effective in most patients, may be associated with significant side effects and have few disease‐modifying effects on the underlying pathology. Medications that act through new mechanisms of action, and particularly ones that have disease‐modifying properties, would be highly desirable. In the last decade, a potential new target for the treatment of neuropathic pain has emerged: the α9‐containing nicotinic acetylcholine receptor (nAChR). Recent studies indicate that antagonists of α9‐containing nAChRs are analgesic in animal models of neuropathic pain. These nerve injury models include chronic constriction injury, partial sciatic nerve ligation, streptozotocin‐induced diabetic neuropathy and chemotherapeutic‐induced neuropathy. This review details the history and state of the field regarding the role that α9‐containing nAChRs may play in neuropathic pain. An alternative hypothesis that α‐conotoxins exert their therapeutic effect through blocking N‐type calcium channels via activation of GABAB receptors is also reviewed. Understanding how antagonists of α9‐containing nAChRs exert their therapeutic effects may ultimately result in the development of medications that not only treat but also prevent the development of neuropathic pain states.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 30, 2017
- Source ID
- 10.1111/bph.13931
Entities
People
- Arik J Hone
- Denis Servent
- J. Michael Mcintosh
Organizations
- FP7 Ideas: European Research Council
- National Institutes of Health
- United States Department of Defense
- University of Utah