Genetic Dissection Of Brain To Spinal Cord Neural Circuits For Craniofacial Pain-induced Hindpaw Mechanical Allodynia In Mice

Compared with body pain,craniofacial pain often brings more intense pain feeling and pain aversion to patients.Clinical studies have shown that patients with craniofacial pain are often accompanied by somatic allodynia complications.The craniofacial sensory information is transmitted to the brainstem through the trigeminal ganglion,and then transmitted to the upstream brain area;somatosensory information is transmitted to the spinal cord through the dorsal root ganglion,and then transmitted to the brainstem and upstream brain areas after being relayed by the spinal cord dorsal horn.More importantly,mechanical allodynia pathway is gated in the spinal cord.Therefore,in case of craniofacial pain induced somatic allodynia,the gate of the spinal cord dorsal horn must be opened.The role of rostral ventromedial medulla(RVM)in the descending regulation of pain information transmission is the most widely studied.RVM is the final relay of the brain’s descending regulation of the spinal cord.RVM receives descending regulation information from the upstream brain area and projects it to the spinal cord dorsal horn.However,under pathological conditions,how RVM plays a descending regulatory role has not been fully studied.In this project,we use a Craniofacial pain induced hind paw mechanical hypersensitivity(CFH)mouse disease model,using experimental techniques including behavior test,whole-cell patch clamp in spinal cord slice with attached dorsal root and acute brain slice,in situ hybridization,immunofluorescence staining,chemical genetics,neural circuit tracing using virus or fluorescent dye to study the role of RVM on the descending regulation circuits and the local neural circuits in the spinal cord dorsal horn in this process,and what changes have occurred.The main results are as follows:Established a technique that whole-cell patch clamp in spinal cord transverse slice with attached dorsal root;Whisker pad injection of capsaicin can stably induce the behavioral phenotype of hind paw mechanical allodynia and open the Aβ pathway in the spinal cord dorsal horn in mice;RVM GABAergic/Glycinergic neurons project to the spinal dorsal horn dynorphin positive neurons to play a role of descending facilitation and mediate CFH;Somatostatin positive neurons in spinal dorsal horn mediate CFH;Whisker pad injection of capsaicin open the Aβ pathway that projecting from the spinal dorsal horn to the lateral parabrachial nucleus.This project studied the role of the descending modulation circuits of RVM to the spinal cord and the local circuits of the spinal dorsal horn under disease conditions,and initially clarified the cellular mechanism of the brainstem descending modulation of the spinal cord allodynia neural circuits,which provides possible targets and theoretical basis for clinical treatment and drug development of related diseases.