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The antihyperalgesic effect of levetiracetam in an inflammatory model of pain in rats: mechanism of action

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2010
1336.pdf (1.128Mb)
Authors
Micov, Ana
Tomić, Maja
Popović, B.
Stepanović-Petrović, Radica
Article (Published version)
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Abstract
BACKGROUND AND PURPOSE Levetiracetam, a novel antiepileptic drug, has recently been shown to have antinociceptive effects in various animal models of pain. The purpose of this study was to investigate the antihyperalgesic effect of levetiracetam and its mechanism of action, by examining the involvement of GABAergic, opioidergic, 5-hydroxytryptaminergic (5-HTergic) and adrenergic systems in its effect, in a rat model of inflammatory pain. EXPERIMENTAL APPROACH Rats were intraplantarly injected with the pro-inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of levetiracetam on carrageenan-induced hyperalgesia; and (ii) the effects of bicuculline (selective GABA(A) receptor antagonist), naloxone (non-selective opioid receptor antagonist), methysergide (non-selective 5-HT receptor antagonist) and yohimbine (selective alpha(2)-adrenoceptor antagonist) on the antihyperalgesic action of levetiracetam. RESULTS Levetiracetam (10-200 mg center dot kg-1; ...p.o.) significantly reduced, in a dose-dependent manner, the inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of levetiracetam was significantly decreased after administration of bicuculline (0.5-2 mg center dot kg-1; i.p.), naloxone (1-3 mg center dot kg-1; i.p.), methysergide (0.25-1 mg center dot kg-1; i.p.) and yohimbine (1-3 mg center dot kg-1; i.p.). CONCLUSIONS AND IMPLICATIONS These results show that levetiracetam produced antihyperalgesia which is at least in part mediated by GABA(A), opioid, 5-HT and alpha(2)-adrenergic receptors, in an inflammatory model of pain. The efficacy of levetiracetam in this animal model of inflammatory pain suggests that it could be a potentially important agent for treating inflammatory pain conditions in humans.

Keywords:
levetiracetam / inflammatory hyperalgesia / GABA(A) receptors / opioid receptors / 5-HT receptors / alpha(2)-adrenoceptors
Source:
British Journal of Pharmacology, 2010, 161, 2, 384-392
Publisher:
  • Wiley-Blackwell, Malden
Projects:
  • Ispitivanje mehanizma dejstva, interakcija i toksičnih efekata analgetika kao i vazoaktivnih supstanci (RS-145030)

DOI: 10.1111/j.1476-5381.2010.00877.x

ISSN: 0007-1188

PubMed: 20735422

WoS: 000281210400009

Scopus: 2-s2.0-77956027437
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URI
http://farfar.pharmacy.bg.ac.rs/handle/123456789/1338
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  • Radovi istraživača / Researchers’ publications
Institution
Pharmacy

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