Peroxynitrite: a strategic linchpin of opioid analgesic tolerance
by
Salvemini D, Neumann WL.
Department of Internal Medicine,
Saint Louis University, St Louis, MO 63110, USA.
Trends Pharmacol Sci. 2009 Mar 2.

ABSTRACT

Severe pain syndromes reduce quality of life in patients with inflammatory and neoplastic diseases, partly because the reduced analgesic effectiveness accompanying chronic opiate therapy (i.e. tolerance) leads to escalating doses and distressing side effects. Accordingly, there is major interest in new approaches to maintain opiate efficacy during repetitive dosing without engendering tolerance or causing unacceptable side effects. Recent mounting evidence implicates nitroxidative stress caused by the presence of superoxide (O(2)(-)), nitric oxide (NO) and subsequently peroxynitrite (ONOO(-)) in opiate analgesic tolerance. Here, we provide a pharmacological basis for developing inhibitors of ONOO(-) biosynthesis and/or ONOO(-) scavengers as potent adjuncts to opiates in the management of chronic pain, addressing an issue of major clinical and socio-economic importance while laying the basis for interventions with strong therapeutic potential.

DAMGO
Arrestin
G protein
Morphine
Tramadol
Oxycodone
Mechanisms
Peroxynitrite
Endomorphins
Novelty and pain
Receptor regulation
Glycine anatagonists
Fentanyl and ketamine
Signalling mechanisms
The extended amygdala
Opioids, mood and cognition
Tolerance, sensitization and dependence
Anxiety, opioids, cholecystokinin and tolerance

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