Vanderah, et al. (2001): Mechanisms of opioid-induced pain and antinociceptive tolerance: descending facilitation and spinal dynorphin

[Wise Young]

Mechanisms of opioid-induced pain and antinociceptive tolerance: descending facilitation and spinal dynorphin [Topical review]
Todd W. Vanderah, Michael H. Ossipov, Josephine Lai, T. Philip Malan Jr. and Frank Porreca
Pain, 2001, 92:1-2:5-9


Manuscript received 1 March 2001 Revised 12 March 2001 Accepted 12 March 2001;
Abstract

There is no abstract for this article. The text below is the first paragraph of text within the article.
Although opioid analgesic tolerance is recognized experimentally and clinically ( Foley 1995), the mechanisms underlying this phenomenon remain largely unknown. At the physiological level, tolerance to opioid antinociception can be blocked or prevented by inhibition of many diverse endogenous transmitter and receptor systems. Among the many different substances that have been shown to prevent and/or reverse opioid antinociceptive tolerance, perhaps the most well studied are NMDA receptor antagonists (e.g. Trujillo and Akil, 1991; Mao et al., 1995; Manning et al. 1996; Kest et al., 1997; Celerier et al. 1999 ). Many of these studies have suggested possible mechanisms by which the modulation of opioid antinociceptive tolerance by NMDA antagonists might occur. Most proposed mechanisms have focused on the likely co-localization of NMDA and opioid receptors and common intracellular pathways, though a key concern was the failure to clearly identify the source of possible NMDA receptor activation during prolonged opioid exposure (e.g. Mao et al., 1995). An additional complicating factor in the interpretation of mechanisms by which modulation of opioid antinociceptive tolerance might occur is the great diversity of substances that have been reported to produce such effects. These include, among others, CGRP antagonists ( Menard et al., 1996; Powell et al., 2000 ), NO synthase inhibitors ( Powell et al., 1999), calcium channel blockers ( Aley and Levine, 1997), CCK antagonists ( Xu et al., 1992), cyclooxygenase inhibitors ( Powell et al., 1999) and protein kinase C inhibitors ( Mao et al., 1995). That so many systems can be identified to modulate opioid antinociceptive tolerance makes it difficult to implicate a common cellular mechanism for the actions of all these substances. For this reason, we have focused on possible commonalities in the endogenous mechanisms which promote, rather than block, opioid antinociceptive tolerance.