NSAIDs, Opioids, Cannabinoids and the Control of Pain by the Central Nervous System 英文参考文献.docVIP

Pharmaceuticals 2010, 3, 1335-1347; doi:10.3390/ph3051335 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review NSAIDs, Opioids, Cannabinoids and the Control of Pain by the Central Nervous System Horacio Vanegas *, Enrique Vazquez and Victor Tortorici Instituto Venezolano de Investigaciones Cientificas (IVIC), Apartado 20632, Caracas 1020A, Venezuela; E-Mails: enriquevr@ (E.V.); victort@ivic.gob.ve (V.T.) * Author to whom correspondence should be addressed; E-Mail: horaciovan@; Tel.: +58-212-504-1456; Fax: +58-212-504-1093 Received: 23 March 2010; in revised form: 14 April 2010 / Accepted: 21 April 2010/ Published: 29 April 2010 Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) act upon peripheral tissues and upon the central nervous system to produce analgesia. A major central target of NSAIDs is the descending pain control system. The rostral structures of the descending pain control system send impulses towards the spinal cord and regulate the transmission of pain messages. Key structures of the descending pain control system are the periaqueductal gray matter (PAG) and the rostral ventromedial region of the medulla (RVM), both of which are critical targets for endogenous opioids and opiate pharmaceuticals. NSAIDs also act upon PAG and RVM to produce analgesia and, if repeatedly administered, induce tolerance to themselves and cross-tolerance to opioids. Experimental evidence shows that this is due to an interaction of NSAIDs with endogenous opioids along the descending pain control system. Analgesia by NSAIDs along the descending pain control system also requires an activation of the CB1 endocannabinoid receptor. Several experimental approaches suggest that opioids, NSAIDs and cannabinoids in PAG and RVM cooperate to decrease GABAergic inhibition and thus enhance the descending flow of impulses that inhibit pain. Keywords: NSAID; opioid; cannabinoid; descending pain