An orbitofrontal cortex to midbrain projection modulates hypersensitivity after peripheral nerve injury

• DOI: 10.1016/j.celrep.2021.109033
• Publication Date: 2021-04-27T16:20:46Z
• Authors: Junting Huang; Zizhen Zhang; Eder Gambeta; Lina Chen; Gerald W. Zamponi
• Keywords: Periaqueductal gray; Nerve Injury; SNi; Allodynia; Rostral ventromedial medulla; Bursting

Neuropathic pain is a debilitating condition that often refractory to treatment. The network of neural substrates for transmission and control within the brain complex remains poorly understood. Through combination neuronal tracing, optogenetics, chemogenetics, electrophysiological recordings, behavioral assessment, we demonstrate activation layer 5 pyramidal neurons in ventrolateral orbitofrontal cortex (vlOFC) attenuates mechanical thermal hypersensitivity cold allodynia mice with neuropathic induced by spared nerve injury (SNI). These vlOFC output project posterior periaqueductal gray (vlPAG) region receive inputs from ventromedial thalamus (VM). Specific optogenetic chemogenetic vlOFC-vlPAG VM-vlOFC circuits inhibits associated neuropathy. Thus, reveal modulatory role its projections vlPAG circuit processing hypersensitive nociception.