The Involvement of the Nitric Oxide in the Effects and Expression of Opioid Receptors During Peripheral Inflammation

$63.10 plus tax (Refund Policy)

Buy Article:

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

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707781368469

Affiliations: Laboratori de Neurofarmacologia Molecular, Institut de Neurociencies, Universitat Autonoma de Barcelona, Facultat de Ciencies. Edifici C-2-Sud, Unitat de Fisiologia Animal. 08193 Bellaterra,Barcelona, Spain.

Publication date: August 1, 2007

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
Related content

Tools

Favourites

Share Content

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more