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 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.

Figure 1

AZA had no analgesia in thermal-stimulated acute pain, but attenuated chemical-stimulated acute pain. (A) mouse tail-flick test (n=9–10), (B) mouse hot-plate test (n=9–10). The basal responses of mice to thermal stimuli were tested before drug administration. (C) mouse capsaicin test (n=10), (D) mouse formalin test (n=8–10), (E) mouse acetic acid-induced writhing test (n=10). (A) and (B), no statistical significant difference was obtained. (C), (D), and (E), ^cP<0.01 vs control.

Figure 2

Effects of AZA, MZA, and diazepam on locomotor activities. n=10/group. ^bP<0.05, ^cP<0.01 vs control.

Figure 3

AZA had no analgesia in chemical-stimulated acute pain by intrathecal injection. (A) mouse capsaicin test. (B) mouse formalin test. (C) mouse acetic acid-induced writhing test. n=10/group. No statistical significant difference was obtained.

Figure 4

MZA did not produce analgesia in both thermal- and chemical-stimulated acute pain. (A) mouse tail-flick test, (B) mouse hot-plate test. The basal responses of mice to thermal stimuli were tested before drug administration. (C) mouse capsaicin test, (D) mouse formalin test, (E) mouse acetic acid-induced writhing test. n=10/group. No statistical significant difference was obtained.

Figure 5

Diazepam did not produce analgesia in thermal- and chemical-stimulated acute pain. (A) mouse tail-flick test, (B) mouse hot-plate test. The basal responses of mice to thermal stimuli were tested before drug administration. (C) mouse capsaicin test, (D) mouse formalin test, (E) mouse acetic acid-induced writhing test. n=10/group. No statistical significant difference was obtained.