Peripheral Mechanisms of Opioid Analgesia
Traditionally, opioids are considered to exert analgesic effects through actions within the central nervous system (CNS) (see also chaps. 31, 32, 33 and 36 of this volume). Recently, however, evidence has begun to accumulate that opioid antinociception can be brought about by activation of opioid receptors located outside the CNS. One of the earliest reports was that of Wood (1855), who showed that morphine elicited analgesic effects when applied topically to “painful areas” in the periphery. Since then there have been numerous clinical and experimental reports of similar observations. However, most of the former are merely anecdotal and many of the latter have been discounted because of their lack of demonstration of principal criteria for opioid receptor-mediated effects, in particular naloxone reversibility. Moreover, the question as to whether these effects result from a truly peripheral rather than from a central site of action (e.g., via uptake of the agent into the circulation and transport to the CNS) has been raised repeatedly. This chapter will give an overview of controlled experimental and clinical studies examining peripheral antinociceptive actions of opioids and will discuss mechanisms and potential implications for novel therapeutic approaches.
KeywordsDorsal Root Ganglion Opioid Receptor Antinociceptive Effect Inflame Tissue Opioid Analgesia
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