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Antinociceptive effects of gabapentin & its mechanism of action in experimental animal studies.

Kilic FS, Sirmagul B, Yildirim E, Oner S, Erol K - Indian J. Med. Res. (2012)

Bottom Line: While the L-NAME and cyproheptadine changed the central and peripheral effects of gabapentin, naloxone did not change these effects.PGE 2 and nNOS were found to have an important role in the antinociceptive effects of gabapentin at all doses and its combinations with L-NAME, cyproheptadine, indomethacine, and naloxone.These effects were also mediated by nNOS and PGE2.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Eşkisehir Osmangazi University, Medical School, Eşkisehir, Turkey.

ABSTRACT

Background & objectives: Several studies have shown the possible analgesic effects of gabapentin, widely used as an antiepileptic. Thus, clinical studies have been carried out especially for neuropathic syndroms. This study was undertaken to investigate experimentally whether gabapentin has analgesic effects in mice and rats.

Methods: The mice were divided into 10 groups (n=7) with various treatments to assess central and peripheral antinociceptive activity of gabapentin. Hot plate, tail clip and tail flick tests were applied for the investigation of central antinociceptive activity and the writhing test was applied for the investigation of peripheral antinociceptive activity. In addition, we also evaluated the levels of PGE 2 and nNOS on perfused hippocampus slices of rats.

Results: Gabapentin showed a peripheral antinociceptive effect at all doses and a central antinociceptive effect at 30mg/kg dose. While the L-NAME and cyproheptadine changed the central and peripheral effects of gabapentin, naloxone did not change these effects. In vitro studies showed that gabapentin significantly increased nNOS level. PGE 2 and nNOS were found to have an important role in the antinociceptive effects of gabapentin at all doses and its combinations with L-NAME, cyproheptadine, indomethacine, and naloxone. As expected, PGE 2 levels decreased in all groups, while nNOS levels increased, which is believed to be an adaptation mechanism.

Interpretation & conclusions: Our findings indicate that arachidonate, nitrergic and serotonergic systems play an important role in the antinociceptive activity of gabapentin except for the opioidergic system. Additionally, this effect occured centrally and peripherally. These effects were also mediated by nNOS and PGE2.

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The peripheral antinociceptive activity of gabapentin based on all groups. GBP, gabapentin; Cypro, cyproheptadine; L-Arg, L-arginine; Nalox, naloxone; L-NAME, L-nitro arginine methyl ester. *P<0.05 compared to control group. Values are mean ± SEM (n=7).
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Figure 2: The peripheral antinociceptive activity of gabapentin based on all groups. GBP, gabapentin; Cypro, cyproheptadine; L-Arg, L-arginine; Nalox, naloxone; L-NAME, L-nitro arginine methyl ester. *P<0.05 compared to control group. Values are mean ± SEM (n=7).

Mentions: In vivo antinociceptive activity in mice: Gabapentin exhibited antinociceptive effect through peripheral paths at all doses (Fig. 1). Further, 30 mg/kg gabapentin revealed a central antinociceptive effect at spinal and supraspinal level (Fig. 2). At 2 μg/kg dose cyproheptadine showed peripheral antinociceptive effect (Fig. 3), but revealed no central antinociceptive effect (Fig. 4).


Antinociceptive effects of gabapentin & its mechanism of action in experimental animal studies.

Kilic FS, Sirmagul B, Yildirim E, Oner S, Erol K - Indian J. Med. Res. (2012)

The peripheral antinociceptive activity of gabapentin based on all groups. GBP, gabapentin; Cypro, cyproheptadine; L-Arg, L-arginine; Nalox, naloxone; L-NAME, L-nitro arginine methyl ester. *P<0.05 compared to control group. Values are mean ± SEM (n=7).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3401692&req=5

Figure 2: The peripheral antinociceptive activity of gabapentin based on all groups. GBP, gabapentin; Cypro, cyproheptadine; L-Arg, L-arginine; Nalox, naloxone; L-NAME, L-nitro arginine methyl ester. *P<0.05 compared to control group. Values are mean ± SEM (n=7).
Mentions: In vivo antinociceptive activity in mice: Gabapentin exhibited antinociceptive effect through peripheral paths at all doses (Fig. 1). Further, 30 mg/kg gabapentin revealed a central antinociceptive effect at spinal and supraspinal level (Fig. 2). At 2 μg/kg dose cyproheptadine showed peripheral antinociceptive effect (Fig. 3), but revealed no central antinociceptive effect (Fig. 4).

Bottom Line: While the L-NAME and cyproheptadine changed the central and peripheral effects of gabapentin, naloxone did not change these effects.PGE 2 and nNOS were found to have an important role in the antinociceptive effects of gabapentin at all doses and its combinations with L-NAME, cyproheptadine, indomethacine, and naloxone.These effects were also mediated by nNOS and PGE2.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Eşkisehir Osmangazi University, Medical School, Eşkisehir, Turkey.

ABSTRACT

Background & objectives: Several studies have shown the possible analgesic effects of gabapentin, widely used as an antiepileptic. Thus, clinical studies have been carried out especially for neuropathic syndroms. This study was undertaken to investigate experimentally whether gabapentin has analgesic effects in mice and rats.

Methods: The mice were divided into 10 groups (n=7) with various treatments to assess central and peripheral antinociceptive activity of gabapentin. Hot plate, tail clip and tail flick tests were applied for the investigation of central antinociceptive activity and the writhing test was applied for the investigation of peripheral antinociceptive activity. In addition, we also evaluated the levels of PGE 2 and nNOS on perfused hippocampus slices of rats.

Results: Gabapentin showed a peripheral antinociceptive effect at all doses and a central antinociceptive effect at 30mg/kg dose. While the L-NAME and cyproheptadine changed the central and peripheral effects of gabapentin, naloxone did not change these effects. In vitro studies showed that gabapentin significantly increased nNOS level. PGE 2 and nNOS were found to have an important role in the antinociceptive effects of gabapentin at all doses and its combinations with L-NAME, cyproheptadine, indomethacine, and naloxone. As expected, PGE 2 levels decreased in all groups, while nNOS levels increased, which is believed to be an adaptation mechanism.

Interpretation & conclusions: Our findings indicate that arachidonate, nitrergic and serotonergic systems play an important role in the antinociceptive activity of gabapentin except for the opioidergic system. Additionally, this effect occured centrally and peripherally. These effects were also mediated by nNOS and PGE2.

Show MeSH
Related in: MedlinePlus