Opioid Actions in Primary-Afferent Fibers—Involvement in Analgesia and Anesthesia 英文参考文献.docVIP

Pharmaceuticals 2011, 4, 343-365; doi:10.3390/ph4020343 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Opioid Actions in Primary-Afferent Fibers—Involvement in Analgesia and Anesthesia Eiichi Kumamoto *, Kotaro Mizuta and Tsugumi Fujita Department of Physiology, Saga Medical School,5-1-1 Nabeshima, Saga 849-8501, Japan; E-Mails:edu.cc.saga-u.ac.jp (K.M.); fujitat@cc.saga-u.ac.jp (T.F.) * Author to whom correspondence should be addressed; E-Mail: kumamote@cc.saga-u.ac.jp; Tel.: +81-952-34-2273; Fax: +81-952-34-2013. Received: 14 December 2010; in revised form: 17 January 2011 / Accepted: 25 January 2011 / Published: 28 January 2011 Abstract: Opioids inhibit glutamatergic excitatory transmission from the periphery by activating G-protein coupled opioid receptors in the central terminals of primary-afferent neurons in the spinal substantia gelatinosa, resulting in antinociception. Opioid receptor activation in the peripheral terminals of primary-afferent neurons inhibits the production of action potentials in response to nociceptive stimuli given to the periphery, leading to antinociception. Opioids also exhibit a local anesthetic effect without opioid receptor activation in peripheral nerve fibers. This review article will focus on analgesia and anesthesia produced by the actions of opioids on primary-afferent fibers. Keywords: opioids; spinal dorsal horn; excitatory synaptic transmission; primary-afferent fiber; action potential conduction 1. Introduction Nociceptive stimuli given to the skin produce an action potential (AP) in the peripheral terminals of primary-afferent neurons. Such an AP conducts through fine myelinated Aδ and unmyelinated C primary-afferent glutamatergic fibers contained in the dorsal root to the superficial laminae of the dorsal horn, especially the substantia gelatinosa (SG; lamina II of Rex