Received for publication December 30, 2004.
Revised February 22, 2005.
Accepted for publication February 23, 2005.

Acetazolamide, a carbonic anhydrase inhibitor, reverses inflammation-induced thermal hyperalgesia in rats

Abstract

Inflammatory pain is linked to reduction in tissue pH. Tissue proton generation is mainly mediated by carbonic anhydrases (CAs). We therefore hypothesized that inhibition of CAs with acetazolamide (ACTZ) increases the tissue pH and reverses inflammation-induced pain. CAs are also present in the central nervous system and control anion concentrations. Further, ACTZ has direct effects on ion channels involved in nociception. In the current study, responses to heat and mechanical stimuli (von Frey filaments) of the paw were assessed before and after carrageenan-induced muscle inflammation, and after treatment with ACTZ in rats. ACTZ was administered systemically, locally, or intrathecally 24 h after induction of inflammation. In separate studies, pH was measured in the inflamed and non-inflamed muscles, and after administration of ACTZ. Carrageenan injection to the gastrocnemius muscle produced heat hyperalgesia and mechanical allodynia of the paw. Systemic ACTZ reversed the heat hyperalgesia, but not mechanical allodynia. Similarly, injections of ACTZ into the inflamed muscle or intrathecally, reversed the heat hyperalgesia, but not mechanical allodynia. Surprisingly, the pH in the inflamed muscle was not reduced compared to noninflamed muscle. Thus, the current data do not support our hypothesis that ACTZ reduces inflammatory hyperalgesia by raising the reduced pH in muscle. Although the possibility of pH changes and role of CAs in the microenvironment cannot be ruled out, the mechanism of ACTZ -induced antihyperalgesia is not clear from this study. It is possible that inhibition of ion channels and/ or inhibition of spinally located CAs contribute to the observed antihyperalgesia.

Key words: acetazolamide, carbonic anhydrase, carrageenan, hyperalgesia, inflammation, pH