Identification Of The Role Of Lateral Parabrachial Nucleus In Neuropathic Pain And Anxiety

The parabrachial nucleus(PBN)is known as a key node in the processing of pain which is involved in noxious information transmission and affective response,respectively.Previous studies have shown that multiple brain regions and circuits are involved in the production and transmission of nociceptive information.However,the neural mechanism of pain in brain is still elusive,especially in chronic pain.Thus,the basis of neural circuits for the clinical effective treatment needs to be strengthened.Here,in our studies,we characterized the neural circuits and function of LPBN neurons in chronic pain and negative emotion via a nerve ligation-induced neuropathic pain model in mice.To explore the neural circuits of LPBN in neuropathic pain,we provided the optogenetics,pharmacologic genetics,immunohistochemistry,patch clamp,in vivo calcium imaging and behavioral paradigm in this project.Using nerve ligation as a neuropathic pain model,we demonstrated LPBN neurons are critical in the processing of chronic pain and negative emotion.The activity of parabrachial glutamatergic neurons is increased in neuropathic pain-like hypersensitivity.Optogenetic activation of these neurons decreases the paw withdraw threshold and induces aversive behavior.Prolonged pharmacologic activation of LPBN glutamatergic neurons can mimic a chronic pain-like behavior.Interestingly,the GABAergic neurons which only consititute～10.1% of LPBN neurons selectively gate neuropathic pain-like behavior but not basal nociception and persistent activation of GABAergic LPBN neurons prevents neuropathic pain-like hypersensitivity.In addition,whole brain virus tracing experiments demonstrate that parabrachial circuits composed of its upstream and downstream nuclei play an important role in nociceptive transmission and negative emotions.In summary,we decipher the neural basis of parabrachial nucleus in chronic pain and negative emotion and these studies may provide a fundamentally new framework for understanding not only hypersensitivity but also developing anxiolytic treatments for pain-induced anxiety.