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Papers of the Week

Papers: 24 Apr 2021 - 30 Apr 2021

Animal Studies

2021 Apr 27

Cell Rep



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


Huang J, Zhang Z, Gambeta E, Chen L, Zamponi GW
Cell Rep. 2021 Apr 27; 35(4):109033.
PMID: 33910011.


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