S S Essawy1, A A Elbaz. 1. Department of Pharmacology, Suez Canal University, Ismailia, Egypt. sohaessawy@yahoo.com
Abstract
BACKGROUND: Inhibition of xanthine oxidase by allopurinol increases hypoxanthine and xanthine, which are converted to purines, including the inhibitory neuromodulator adenosine. AIM: We aimed to investigate the antinociceptive effects of allopurinol in thermal and chemical pain models in mice and to evaluate its possible antinociceptive mechanism by using selective adenosine receptors A1, A2A antagonists in mice. MATERIALS AND METHODS: Sixty four adult male mice were used. Mice received an intraperitoneal injection of vehicle or allopurinol (50-200 mg/kg). Assessment of antinociceptive effects and locomotor activity were performed in three models of acute pain; a thermal model and two chemical model. RESULTS: Allopurinol presented dose-dependent antinociceptive effects in all models with no obvious motor deficits. The opioid antagonist naloxone did not reverse these effects. The selective A1 antagonist, DPCPX, and the selective A2A antagonist, ZM241385, completely prevented allopurinol-induced antinociception. CONCLUSIONS: Allopurinol-induced antinociception may be related to adenosine accumulation. Allopurinol seems to be well tolerated with no locomotor side effects at high doses and it may be useful to treat pain syndromes.
BACKGROUND: Inhibition of xanthine oxidase by allopurinol increases hypoxanthine and xanthine, which are converted to purines, including the inhibitory neuromodulator adenosine. AIM: We aimed to investigate the antinociceptive effects of allopurinol in thermal and chemical pain models in mice and to evaluate its possible antinociceptive mechanism by using selective adenosine receptors A1, A2A antagonists in mice. MATERIALS AND METHODS: Sixty four adult male mice were used. Mice received an intraperitoneal injection of vehicle or allopurinol (50-200 mg/kg). Assessment of antinociceptive effects and locomotor activity were performed in three models of acute pain; a thermal model and two chemical model. RESULTS:Allopurinol presented dose-dependent antinociceptive effects in all models with no obvious motor deficits. The opioid antagonist naloxone did not reverse these effects. The selective A1 antagonist, DPCPX, and the selective A2A antagonist, ZM241385, completely prevented allopurinol-induced antinociception. CONCLUSIONS:Allopurinol-induced antinociception may be related to adenosine accumulation. Allopurinol seems to be well tolerated with no locomotor side effects at high doses and it may be useful to treat pain syndromes.
Authors: André P Schmidt; Enderson D de Oliveira; Aécio C Fagundes; Gisele Hansel; Renata O Pedrini; Aline Valdameri; Eduarda S Martinelli; Sérgio R G Schmidt; Cristiano F Andrade; Diogo R Lara; Diogo O Souza Journal: J Anesth Date: 2021-08-14 Impact factor: 2.078