Abstract：
BACKGROUND AND PURPOSE:Catechol-O-methyltransferase (COMT) inhibitors are used in Parkinson's disease in which pain is an important symptom. COMT polymorphisms modulate pain and opioid analgesia in humans. In rats, COMT inhibitors have been shown to be pro-nociceptive in acute pain models, but also to attenuate allodynia and hyperalgesia in a model of diabetic neuropathy. Here, we have assessed the effects of acute and repeated administrations of COMT inhibitors on mechanical, thermal and carrageenan-induced nociception in male mice. EXPERIMENTAL APPROACH:We used single and repeated administration of a peripherally restricted, short-acting (nitecapone) and also a centrally acting (3,5-dinitrocatechol, OR-486) COMT inhibitor. We also tested CGP 28014, an indirect inhibitor of COMT enzyme. Effects of OR-486 on thermal nociception were also studied in COMT deficient mice. Effects on spinal pathways were assessed in rats given intrathecal nitecapone. KEY RESULTS:After single administration, both nitecapone and OR-486 reduced mechanical nociceptive thresholds and thermal nociceptive latencies (hot plate test) at 2 and 3 h, regardless of their brain penetration. These effects were still present after chronic treatment with COMT inhibitors for 5 days. Intraplantar injection of carrageenan reduced nociceptive latencies and both COMT inhibitors potentiated this reduction without modifying inflammation. CGP 28014 shortened paw flick latencies. OR-486 did not modify hot plate times in Comt gene deficient mice. Intrathecal nitecapone modified neither thermal nor mechanical nociception. CONCLUSIONS AND IMPLICATIONS:Pro-nociceptive effects of COMT inhibitors were confirmed. The pro-nociceptive effects were primarily mediated via mechanisms acting outside the brain and spinal cord. COMT protein was required for these actions.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kambur O,Talka R,Ansah OB,Kontinen VK,Pertovaara A,Kalso E,Männistö PTdoi
10.1111/j.1476-5381.2010.00999.xsubject
Has Abstractpub_date
2010-12-01 00:00:00pages
1553-65issue
7eissn
0007-1188issn
1476-5381pii
BPH999journal_volume
161pub_type
杂志文章abstract：BACKGROUND AND PURPOSE:Activation of cannabinoid receptors decreases emesis, inflammation, gastric acid secretion and intestinal motility. The ability to modulate intestinal permeability in inflammation may be important in therapy aimed at maintaining epithelial barrier integrity. The aim of the present study was to de...
journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1987.tb10295.x
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doi：10.1111/j.1476-5381.1996.tb15280.x
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更新日期：1997-03-01 00:00:00
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