Abstract
Peripheral inflammation enhances the antinociceptive effects of opioid receptor agonists through the activation of peripheral opioid receptors whose expression also increases during inflammatory pain. Similarly, intestinal inflammation also increases the antitransit and antiexudative effects of opioids as well as the expression of neuronal and extra-neuronal opioid receptors located in the gut. Nitric oxide has been described either as pro- or antiinflammatory and could produce both pro- and antinociceptive effects. In addition, numerous studies have shown that the L-arginine-nitric oxide-cGMP system participates in the antinociceptive and in the intestinal effects produced by opioids during peripheral inflammation by enhancing their effects. Thus, substances capable of inhibiting cyclic guanosine-3,5-monophosphate (cGMP) degradation or nitric oxide donors increase the analgesic effects of opioid receptor agonists during peripheral inflammation. At the same time, the administration of nitric oxide synthase (NOS) or guanylate cyclase inhibitors decreases those effects. In accordance with these results, different clinical trials have also demonstrated that the co-administration of nitric oxide donors with opioids is highly beneficial in the treatment of pain in patients. In the gut, nitric oxide has a further pro- and antiinflammatory action. It is also involved in the enhanced antitransit and antiexudative effects produced by opioids and in the up-regulation of the μ-opioid receptor gene transcription observed in the inflamed intestine. To sum up, a better knowledge of the involvement of the L-arginine-nitric oxide- cGMP pathway in the opioid mechanisms of action and a better understanding of the pathways that regulate the expression of opioid receptors during peripheral inflammation are essential to developing improved analgesic/antiinflammatory therapies.
Keywords: Antiinflammatory, antinociception, gastrointestinal transit, gene expression, inflammation, intestine, knockout mice, nitric oxide, nitric oxide synthase, opioids
Current Medicinal Chemistry
Title: The Involvement of the Nitric Oxide in the Effects and Expression of Opioid Receptors During Peripheral Inflammation
Volume: 14 Issue: 18
Author(s): Olga Pol
Affiliation:
Keywords: Antiinflammatory, antinociception, gastrointestinal transit, gene expression, inflammation, intestine, knockout mice, nitric oxide, nitric oxide synthase, opioids
Abstract: Peripheral inflammation enhances the antinociceptive effects of opioid receptor agonists through the activation of peripheral opioid receptors whose expression also increases during inflammatory pain. Similarly, intestinal inflammation also increases the antitransit and antiexudative effects of opioids as well as the expression of neuronal and extra-neuronal opioid receptors located in the gut. Nitric oxide has been described either as pro- or antiinflammatory and could produce both pro- and antinociceptive effects. In addition, numerous studies have shown that the L-arginine-nitric oxide-cGMP system participates in the antinociceptive and in the intestinal effects produced by opioids during peripheral inflammation by enhancing their effects. Thus, substances capable of inhibiting cyclic guanosine-3,5-monophosphate (cGMP) degradation or nitric oxide donors increase the analgesic effects of opioid receptor agonists during peripheral inflammation. At the same time, the administration of nitric oxide synthase (NOS) or guanylate cyclase inhibitors decreases those effects. In accordance with these results, different clinical trials have also demonstrated that the co-administration of nitric oxide donors with opioids is highly beneficial in the treatment of pain in patients. In the gut, nitric oxide has a further pro- and antiinflammatory action. It is also involved in the enhanced antitransit and antiexudative effects produced by opioids and in the up-regulation of the μ-opioid receptor gene transcription observed in the inflamed intestine. To sum up, a better knowledge of the involvement of the L-arginine-nitric oxide- cGMP pathway in the opioid mechanisms of action and a better understanding of the pathways that regulate the expression of opioid receptors during peripheral inflammation are essential to developing improved analgesic/antiinflammatory therapies.
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Cite this article as:
Olga Pol , The Involvement of the Nitric Oxide in the Effects and Expression of Opioid Receptors During Peripheral Inflammation, Current Medicinal Chemistry 2007; 14 (18) . https://dx.doi.org/10.2174/092986707781368469
DOI https://dx.doi.org/10.2174/092986707781368469 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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