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The local peripheral antihyperalgesic effect of levetiracetam and its mechanism of action in an inflammatory pain model.
Anesth Analg. 2012 Dec; 115(6):1457-66.A&A

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/anti-edematous 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 μ-opioid receptor antagonist); yohimbine (a selective α(2)-adrenoceptor antagonist), BRL 44408 (a selective α(2A)-adrenoceptor antagonist), MK-912 (a selective α(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-HT(1B/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 hind-paw.

CONCLUSIONS

Our results show that levetiracetam produces local peripheral antihyperalgesic and anti-edematous effects in a rat model of localized inflammation. Antihyperalgesia is at least in part mediated by peripheral μ-opioid, α2A,C-adrenergic, A1 adenosine, and 5-HT1B/1D receptors, but not by GABAA 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.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, P.O. Box 146, 11221, Belgrade, Serbia. racabbr@eunet.rsNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23144430

Citation

Stepanović-Petrović, Radica M., et al. "The Local Peripheral Antihyperalgesic Effect of Levetiracetam and Its Mechanism of Action in an Inflammatory Pain Model." Anesthesia and Analgesia, vol. 115, no. 6, 2012, pp. 1457-66.
Stepanović-Petrović RM, Micov AM, Tomić MA, et al. The local peripheral antihyperalgesic effect of levetiracetam and its mechanism of action in an inflammatory pain model. Anesth Analg. 2012;115(6):1457-66.
Stepanović-Petrović, R. M., Micov, A. M., Tomić, M. A., & Ugrešić, N. D. (2012). The local peripheral antihyperalgesic effect of levetiracetam and its mechanism of action in an inflammatory pain model. Anesthesia and Analgesia, 115(6), 1457-66. https://doi.org/10.1213/ANE.0b013e31826c7fc2
Stepanović-Petrović RM, et al. The Local Peripheral Antihyperalgesic Effect of Levetiracetam and Its Mechanism of Action in an Inflammatory Pain Model. Anesth Analg. 2012;115(6):1457-66. PubMed PMID: 23144430.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The local peripheral antihyperalgesic effect of levetiracetam and its mechanism of action in an inflammatory pain model. AU - Stepanović-Petrović,Radica M, AU - Micov,Ana M, AU - Tomić,Maja A, AU - Ugrešić,Nenad D, Y1 - 2012/11/09/ PY - 2012/11/13/entrez PY - 2012/11/13/pubmed PY - 2013/1/30/medline SP - 1457 EP - 66 JF - Anesthesia and analgesia JO - Anesth Analg VL - 115 IS - 6 N2 - 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/anti-edematous 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 μ-opioid receptor antagonist); yohimbine (a selective α(2)-adrenoceptor antagonist), BRL 44408 (a selective α(2A)-adrenoceptor antagonist), MK-912 (a selective α(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-HT(1B/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 hind-paw. CONCLUSIONS: Our results show that levetiracetam produces local peripheral antihyperalgesic and anti-edematous effects in a rat model of localized inflammation. Antihyperalgesia is at least in part mediated by peripheral μ-opioid, α2A,C-adrenergic, A1 adenosine, and 5-HT1B/1D receptors, but not by GABAA 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. SN - 1526-7598 UR - https://www.unboundmedicine.com/medline/citation/23144430/The_local_peripheral_antihyperalgesic_effect_of_levetiracetam_and_its_mechanism_of_action_in_an_inflammatory_pain_model_ L2 - https://doi.org/10.1213/ANE.0b013e31826c7fc2 DB - PRIME DP - Unbound Medicine ER -