Acetazolamide attenuates chemical-stimulated but not thermal-stimulated acute pain in mice

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 GABA A 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 hotplate 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 GABA A receptor-mediated inhibition via inhibiting CA activity but rather a peripheral ion channel-related mechanism.

Comparison of intraperitoneal bupivacaine, acetazolamide, and placebo on pain relief after laparoscopic cholecystectomy surgery: A clinical trial

“…Previous studies have shown that one of the mechanisms of pain creation is tissue acidosis. Acetazolamide, either oral or IV, is a potent inhibitor of the carbonic anhydrase enzyme, which one of its known effects is tissue metabolic acidosis (27-29). In Woehlck study, acetazolamide led to a significant reduction in referral pains, which was in favor of our findings (17).…”

5-HT_1A Receptors Mediate Analgesia Induced by Emulsified Sevoflurane in Thermal Nociception but Have Little Effect on Chemical Nociception

“…First, thermal-stimulated pain is transmitted by Aδ and C fibers, whereas chemical-stimulated pain is only transmitted by C fibers [37]. Second, the role of ion channels and receptors in thermal-stimulated acute pain is not completely the same as in chemical-stimulated acute pain [13,38,39,40]. 5-HT 1A Rs in the spinal cord may be important targets of the analgesic effect of sevoflurane on the thermal nociception, but they have little relationship to the anti-chemical chemical nociception effect of sevoflurane.…”

Acetazolamide reduces postoperative pain following laparoscopic inguinal herniorrhaphy

“…The buildup of carbonic acid is thought to contribute to postoperative pain by irritating the peripheral nerves. Additionally, acetazolamide has been shown to reduce neuropathic pain through the augmentation of GABA A signaling pathways [5][6][7].…”