Participation of the Nitric Oxide–cGMP Pathway in the Peripheral Antinociceptive Effect of Nimesulide

Authors: JAIN N.K.¹; PATIL C.S.²; KULKARNI S.K.¹; SINGH A.²

Source: Analgesia, Volume 6, Numbers 1-3, 2002 , pp. 27-37(11)

Publisher: Cognizant Communication Corporation

Abstract:

Background: Nitric oxide (NO) is a free radical that plays an important role in many physiological and pathological processes. Evidence suggests that NO–cGMP signaling pathway participates in the nociceptive mechanism.

Purpose: The present study was aimed to explore the role of NO–cGMP pathway in nimesulide-induced antinociception in experimental animals.

Methods: Both peripheral (acetic acid-induced chemonociception or carrageenan-induced hyperalgesia) and central nociception (tail flick or hot plate methods) were used.

Results: Nimesulide exhibited dose-dependent (1, 2, 5, and 10 mg/kg, PO) antinociception against acetic acid-induced writhing and tail flick or hot plate assays in mice. Local administration of nimesulide (25–50 g/paw, intraplantar) also attenuated carrageenan-induced hyperalgesia. In peripheral nociceptive reaction (acetic acid-induced chemonociception), the antinociceptive effect of nimesulide (2 mg/kg, PO) was enhanced by coadministration of sodium nitroprusside (0.25 mg/kg, IP), a nitric oxide donor, and L-arginine (50 mg/kg, IP), a nitric oxide synthase precursor. Nimesulide-induced analgesia was significantly blocked by methylene blue (1 mg/kg, IP), a guanlylate cyclase inhibitor, and L-NAME (10 mg/kg, IP), a nitric oxide synthase inhibitor. Both these agents also reversed the facilitatory effect of L-arginine (50 mg/kg, IP) and sodium nitroprusside (0.25 mg/kg, IP) on nimesulide analgesia. Furthermore, methylene blue (100 g/paw, intraplantar) also blocked the nimesulide-induced local effect. L-NAME (10 mg/kg, IP) and methylene blue (1 mg/kg, IP), however, failed to reverse the nimesulide-induced antinociception in tail flick or hot plate assay.

Conclusion: These results suggest that, besides the inhibitory action on prostaglandin synthesis, the activation of the NO–cGMP pathway plays an important role in the peripheral antinociceptive action of nimesulide.

Keywords: Nimesulide Antinociception Nitric oxide cGMP L-NAM

Language: English

Document Type: Research article

Affiliations: 1: *Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160 014, India 2: †R&D Division, Panacea Biotec Ltd., P.O. Lalru, Chandigarh Road, Punjab-140 501, India

Publication date: 2002-01-01

• From 2003 onwards, published as Reviews in Analgesia

• In this: publication
• By this: publisher
• In this Subject: Animal Culture ,  Pharmacology ,  Veterinary Medicine
• By this author: JAIN N.K. ;  PATIL C.S. ;  KULKARNI S.K. ;  SINGH A.

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