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The Local Peripheral Antihyperalgesic Effect of Levetiracetam and Its Mechanism of Action in an Inflammatory Pain Model
dc.creator | Stepanović-Petrović, Radica | |
dc.creator | Micov, Ana | |
dc.creator | Tomić, Maja | |
dc.creator | Ugrešić, Nenad | |
dc.date.accessioned | 2019-09-02T11:28:26Z | |
dc.date.available | 2019-09-02T11:28:26Z | |
dc.date.issued | 2012 | |
dc.identifier.issn | 0003-2999 | |
dc.identifier.uri | https://farfar.pharmacy.bg.ac.rs/handle/123456789/1679 | |
dc.description.abstract | BACKGROUND: We have recently shown that levetiracetam, administered systemically, exerts an antihyperalgesic effect in a rat inflammatory pain model. In this study, we examined whether levetiracetam has local peripheral antihyperalgesic/antiedematous effects in the same model of localized inflammation and whether opioidergic, adrenergic, purinergic, 5-HTergic, and GABAergic receptors are involved in its antihyperalgesic action. METHODS: Rats were intraplantarly (IPL) injected with carrageenan. A paw pressure test was used to determine the effect/s of (a) levetiracetam when applied IPL, on carrageenan-induced hyperalgesia, and (b) naloxone (a nonselective opioid receptor antagonist), CTAP (a selective mu-opioid receptor antagonist); yohimbine (a selective alpha(2)-adrenoceptor antagonist), BRL 44408 (a selective alpha(2A)-adrenoceptor antagonist), MK-912 (a selective alpha(2C)-adrenoceptor antagonist); caffeine (a nonselective adenosine receptor antagonist), DPCPX (a selective adenosine A(1) receptor antagonist); methysergide (a nonselective 5-HT receptor antagonist), GR 127935 (a selective 5-HT1B/1D receptor antagonist); and bicuculline (a selective GABA(A) receptor antagonist), all applied IPL, on the levetiracetam-induced antihyperalgesia. Moreover, levetiracetam's influence on paw inflammatory edema was measured by plethysmometry. RESULTS: Levetiracetam (200-1000 nmol/paw) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia and edema induced by carrageenan. Naloxone (75-300 nmol/paw), CTAP (1-5 nmol/paw); yohimbine (130-520 nmol/paw), BRL 44408 (50-200 nmol/paw), MK-912 (5-20 nmol/paw); caffeine (500-1500 nmol/paw), DPCPX (3-30 nmol/paw); methysergide (10-100 nmol/paw) and GR 127935 (50-200 nmol/paw); but not bicuculline (400 nmol/paw), significantly depressed the antihyperalgesic effects of levetiracetam (1000 nmol/paw). The effects of levetiracetam and antagonists were attributed to local peripheral effects because they were not observed after administration into the contralateral hindpaw. CONCLUSIONS: Our results show that levetiracetam produces local peripheral antihyperalgesic and antiedematous effects in a rat model of localized inflammation. Antihyperalgesia is at least in part mediated by peripheral mu-opioid, alpha(2A,C)-adrenergic, A(1) adenosine, and 5-HT1B/1D receptors, but not by GABA(A) receptors. These findings could contribute toward a better understanding of the analgesic effects of levetiracetam, and improved treatments of inflammatory pain with a lower incidence of systemic side effects and drug interactions of levetiracetam. (Anesth Analg, 2012;115:1457-66) | en |
dc.publisher | Lippincott Williams & Wilkins, Philadelphia | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175045/RS// | |
dc.rights | restrictedAccess | |
dc.source | Anesthesia and Analgesia | |
dc.title | The Local Peripheral Antihyperalgesic Effect of Levetiracetam and Its Mechanism of Action in an Inflammatory Pain Model | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Томић, Маја; Мицов, Aна; Степановић-Петровић, Радица; Угрешић, Ненад; | |
dc.citation.volume | 115 | |
dc.citation.issue | 6 | |
dc.citation.spage | 1457 | |
dc.citation.epage | 1466 | |
dc.citation.other | 115(6): 1457-1466 | |
dc.citation.rank | M21 | |
dc.identifier.wos | 000311593800031 | |
dc.identifier.doi | 10.1213/ANE.0b013e31826c7fc2 | |
dc.identifier.pmid | 23144430 | |
dc.identifier.scopus | 2-s2.0-84870243260 | |
dc.type.version | publishedVersion |