Ya-jie Sun1, Ying Chen2, Chong Pang2, Ning Wu2, Jin Li2. 1. 1] Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China [2] Now at Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. 2. Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Abstract
AIM: Acetazolamide (AZA), a carbonic anhydrase (CA) inhibitor, has been found to alleviate inflammatory and neuropathic pain in rats. In the present study, we investigated the effects of AZA on thermal- and chemical-stimulated acute pain in mice and the possible mechanisms underlying the effects. METHODS: Five acute pain models based on thermal and chemical stimuli were established to investigate the effects of AZA on different types of nociception in mice. The antinociceptive effects of methazolamide (another CA inhibitor) and diazepam (a positive allosteric modulator of GABAA receptor) were also examined. The drugs were administered either intraperitoneally (ip) or intrathecally. RESULTS: AZA (50-200 mg/kg, ip) did not produce analgesia in two thermal-stimulated acute pain models, ie, mouse tail-flick and hot-plate tests. In contrast, AZA (50-200 mg/kg, ip) dose-dependently reduced paw licking time in both capsaicin and formalin tests in mice. A similar result was observed in a mouse acetic acid-induced writhing test. However, AZA (10 nmol/mouse, intrathecally) did not produce significant analgesia in the 3 chemical-stimulated acute pain models. In addition, methazolamide (50-200 mg/kg, ip) and diazepam (0.25-1.0 mg/kg, ip) did not produce significant analgesia in either thermal- or chemical-stimulated acute pain. CONCLUSION: AZA produces analgesia in chemical-stimulated, but not thermal-stimulated acute pain in mice. The attenuation of chemical-stimulated acute pain by AZA may not be due to enhancement of GABAA receptor-mediated inhibition via inhibiting CA activity but rather a peripheral ion channel-related mechanism.
AIM: Acetazolamide (AZA), a carbonic anhydrase (CA) inhibitor, has been found to alleviate inflammatory and neuropathic pain in rats. In the present study, we investigated the effects of AZA on thermal- and chemical-stimulated acute pain in mice and the possible mechanisms underlying the effects. METHODS: Five acute pain models based on thermal and chemical stimuli were established to investigate the effects of AZA on different types of nociception in mice. The antinociceptive effects of methazolamide (another CA inhibitor) and diazepam (a positive allosteric modulator of GABAA receptor) were also examined. The drugs were administered either intraperitoneally (ip) or intrathecally. RESULTS:AZA (50-200 mg/kg, ip) did not produce analgesia in two thermal-stimulated acute pain models, ie, mouse tail-flick and hot-plate tests. In contrast, AZA (50-200 mg/kg, ip) dose-dependently reduced paw licking time in both capsaicin and formalin tests in mice. A similar result was observed in a mouseacetic acid-induced writhing test. However, AZA (10 nmol/mouse, intrathecally) did not produce significant analgesia in the 3 chemical-stimulated acute pain models. In addition, methazolamide (50-200 mg/kg, ip) and diazepam (0.25-1.0 mg/kg, ip) did not produce significant analgesia in either thermal- or chemical-stimulated acute pain. CONCLUSION:AZA produces analgesia in chemical-stimulated, but not thermal-stimulated acute pain in mice. The attenuation of chemical-stimulated acute pain by AZA may not be due to enhancement of GABAA receptor-mediated inhibition via inhibiting CA activity but rather a peripheral ion channel-related mechanism.
Authors: Irene Pourladian; Alex W Lois; Matthew J Frelich; Harvey J Woehlck; Michelle Weber; Andrew S Kastenmeier; Jon C Gould; Matthew I Goldblatt Journal: Surg Endosc Date: 2015-10-20 Impact factor: 4.584
Authors: John Ketz; Vijay Saxena; Samuel Arregui; Ashley Jackson; George J Schwartz; Takafumi Yagisawa; Robert L Fairchild; David S Hains; Andrew L Schwaderer Journal: Am J Physiol Renal Physiol Date: 2020-05-11