Carbonic anhydrase inhibition and the management of neuropathic pain

ABSTRACT

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 GABA_A 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.

KEYWORDS:

• Neuropathic pain
• carbonic anhydrase
• inhibitor
• acetazolamide
• topiramate
• brain CA isoforms

Declaration of interest

Research from the author’s laboratory was financed in part by several grants of the 6th and 7th Framework Programme of the European Union (DeZnIT, Metoxia, Gums and Joints, and Dynano projects). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.