Please use this identifier to cite or link to this item: http://nopr.niscair.res.in/handle/123456789/23407
Title: Cholinergic-NO-cGMP mediation of sildenafil-induced antinociception
Authors: Patil, Chandrashekhar S
Jain, Naveen K
Singh, Vijay Pal
Kulkarni, Shrinivas K
Keywords: PDE 5 inhibitors;Cholinergic;Cholinomimetic agents;NOS;Nociception
Issue Date: Apr-2004
Publisher: NISCAIR-CSIR, India
IPC Code: Int. Cl.7 A61K 45/00
Abstract: Acetylcholine and cholinomimetic agents with predominant muscarinic action are known to increase the concentration of cGMP by activation of nitric oxide signaling pathway in the nociceptive conditions. The present study was aimed to investigate the NO-cGMP-PDE5 pathway in nociceptive conditions in the experimental animals. Nociceptive threshold was assessed by acetic acid-induced writhing assay (chemonociception) or carrageenan-induced hyperalgesia. Sildenafil [1-5mg/kg, ip, 50-200 μg/paw, intraplantar (ipl)] produced dose dependent antinociception in both the tested models. Coadministration of acetylcholine (50 mcg/paw, ipl ) or cholinomimetic agent, neostigmine (0.1 mcg/kg, ip and 25 ng/paw, ipl) augmented the peripheral antinociceptive effect of sildenafil. This effect was sensitive to blockade by L-NAME (20 mg/kg, ip, 100 μg/paw, ipl), a non-selective NOS inhibitor and methylene blue (1 mg/kg, ip), a guanylate cyclase inhibitor,which per se had little or no effect in both the models of nociception. Further, the per se analgesic effect of acetylcholine and neostigmine was blocked by both L-NAME and methylene blue in the models of nociception, suggesting the activation of NOcGMP pathway. Also, both L-NAME and methylene blue blocked the per se analgesic effect of sildenafil. These results indicate the peripheral accumulation of cGMP may be responsible for antinociceptive effect, and a possible interaction between cholinergic agents and PDE5 system in models of nociception.
Page(s): 361-367
URI: http://hdl.handle.net/123456789/23407
ISSN: 0975-1009 (Online); 0019-5189 (Print)
Appears in Collections:IJEB Vol.42(04) [April 2004]

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