The role of corticolimbic perineuronal nets in mice with chronic neuropathic pain.

Chronic pain is associated with maladaptive plasticity of corticolimbic brain regions. Perineuronal nets (PNNs), specialized extracellular matrix structures that surround neurons, regulate brain plasticity. We investigated the role of PNNs in the spared-nerve injury (SNI) model of neuropathic pain. We observed increased PNNs in the prefrontal cortex and nucleus accumbens of SNI mice. However, targeted degradation of PNNs in the prefrontal cortex exacerbated mechanical sensitivity in both SNI and sham mice without altering cold allodynia perception. By contrast, degradation of PNNs in the nucleus accumbens reduced allodynia in SNI mice. These findings indicate distinct regional roles of corticolimbic PNNs in neuropathic pain.