Journal article
Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice
Fundamental & clinical pharmacology, Vol.28(1), pp.104-113
02/2014
DOI: 10.1111/j.1472-8206.2012.01068.x
PMID: 22924641
Abstract
Dexmedetomidine (DEX) is a alpha(2)-adrenoceptor (alpha(2)-AR) agonist used as an anesthetic adjuvant and as sedative in critical care settings. Typically, alpha(2)-AR agonists release nitric oxide (NO) and subsequently activate NO-GMPc pathway and have been implicated with antinociception. In this study, we investigate the pharmacological mechanisms involved in the antinociceptive effects of DEX, using an acetic acid-induced writhing assay in mice. Saline or DEX (1, 2, 5, or 10 mu g/kg) was intravenously injected 5min before ip administration of acetic acid and the resulting abdominal constrictions were then counted for 10min. To investigate the possible mechanisms related to antinociceptive effect of DEX (10 mu g/kg), the animals were also pretreated with one of the following drugs: 7-nitroindazole (7-NI; 30mg/kg ip); 1H-[1,2,4] oxadiazole [4,3-a] quinoxaline-1-one (ODQ; 2.5mg/kg, ip); yohimbine (YOH; 1mg/kg, ip); atropine (ATRO; 2mg/kg, ip); glibenclamide (GLIB; 1 mg/kg, i.p.) and naloxone (NAL; 0.2mg/kg, ip). A rotarod and open-field performance test were performed with DEX at 10 mu g/kg dose. DEX demonstrated its potent antinociceptive effect in a dose-dependent manner. The pretreatment with 7-NI, ODQ, GLIB, ATRO, and YOH significantly reduced the antinociceptive affects of DEX. However, NAL showed no effecting DEX-induced antinociception. The rotarod and open-field tests confirmed there is no detectable sedation or even significant motor impairment with DEX at 10 mu g/kg dose. Our results suggest that the alpha(2)-AR and NO-GMPc pathways play important roles in the systemic antinociceptive effect of DEX in a murine model of inflammatory pain. Furthermore, the antinociceptive effect exerted by DEX appears to be dependent on K-ATP channels, independent of opioid receptor activity.
Details
- Title: Subtitle
- Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice
- Creators
- Rafael A. S. Rangel - Universidade do Estado do Rio de JaneiroBruno G. Marinho - Universidade Federal do Rio de JaneiroPatricia D. Fernandes - Universidade Federal do Rio de JaneiroRoberto S. de Moura - Universidade do Estado do Rio de JaneiroMarcos A. Lessa - Fundação Oswaldo Cruz
- Resource Type
- Journal article
- Publication Details
- Fundamental & clinical pharmacology, Vol.28(1), pp.104-113
- DOI
- 10.1111/j.1472-8206.2012.01068.x
- PMID
- 22924641
- NLM abbreviation
- Fundam Clin Pharmacol
- ISSN
- 0767-3981
- eISSN
- 1472-8206
- Publisher
- Wiley
- Number of pages
- 10
- Grant note
- FAPERJ; Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio De Janeiro (FAPERJ) Fiocruz CNPq; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ)
- Language
- English
- Date published
- 02/2014
- Academic Unit
- Anesthesia
- Record Identifier
- 9984656597602771
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