Carbonic anhydrase inhibition and the management of neuropathic pain

Introduction: Neuropathic pain affects up to 8% of the population with few therapeutic options for its management. No specific drugs are approved for its treatment.

Areas covered: Recent advances in understanding the pathological mechanisms of this syndrome and the biochemical/pharmacological characterization of novel drug targets, evidenced carbonic anhydrase (CA, EC 4.2.1.1) inhibition as a new approach for designing antineuropathic pain agents. Expert commentary: Peripheral nerve injury negatively influences spinal γ-aminobutyric (GABA)-ergic networks via a reduction in the neuron-specific potassium-chloride (K(+)-Cl(-)) cotransporter (KCC2), which leads to neuropathic allodynia. CA inhibitors (CAIs) reduce the bicarbonate-dependent depolarization of GABAA receptors, showing analgesic effects. Novel classes of selective sulfonamide CA II/VII inhibitors showed highly improved efficacy in animal models of neuropathic pain, compared to acetazolamide, offering the basis for the development of specific therapies of this syndrome based on selective CA isoforms inhibition.