There is a need for a better understanding of mechanisms that drive chronic pain and the development of therapeutics that target these mechanisms. This research shows that peripheral nerve injury negatively influences spinal gamma-aminobutyric acid (GABA)ergic networks via a reduction in the neuron-specific K+-Cl- cotransporter KCC2. This process has been linked to the emergence of neuropathic allodynia.
Using behavioral pharmacology techniques, the authors demonstrate that spinal GABAA-mediated analgesia can be augmented, especially following nerve injury, via inhibition of carbonic anhydrases. Carbonic anhydrase inhibition alone also produces analgesia, suggesting these enzymes might be targeted for the treatment of pain.