Optogenetic stimulation in motor cortex and PKCγ knockdown at dorsal root ganglions alter hyperalgesia behaviors in chronic compressed DRG pain rat model

摘要

Optogenetic stimulation in motor cortex and PKCy knockdown at dorsal root ganglions alter hyperalgesia behaviors in chronic compressed DRG pain rat model Neuropathic pain can be generated by chronic compression of dorsal root ganglion (DRG). DRGs harbor the cell bodies of pri- mary sensory neurons, which send afferent axons and convey sensory information from periphery to spinal cord. Protein kinase C gamma (PKCy), an essential enzyme for development of neuro- pathic pain, get increased in chronic nerve injury. Constricted DRG also produces enhanced repetitive firing in thalamus which causes neuropathic pain as well. Aims of this study were to find whether the optic stimulation of hindlimb motor cortex area can mediate the signal to the thalamus for controlling pain behaviors and blocking of protein kinase C gamma at DRG level can alleviate neuropathic pain in CCD rat model by disrupting the sensory signal from periph- eral nerve to spinal cord. Neuropathic pain was generated in rat model by chronic compression of left L4 and L5 DRG. Then knock- down PKCy delivered by adeno-associated viral vector was injected directly to the L4 and L5 DRGs. The animals were also subjected to optogenetic viral vector injection and stimulated under laser. The mechanical and thermal hyperalgesia tests were performed one day before surgery, at every 3 days after surgery, and 3 times under light stimulation (pre-, during, and post-stimulation). We recorded extracellular neural activities from the ventral posterolat- eral nucleus of thalamus. The viral vector location was confirmed by immunofluorescence. The mechanical threshold/latency and ther- mal latency tests showed hyperalgesia in the rat’s ipsilateral hind paw. After treatment, the DRG-shPKCy group showed improve- ment in paw withdrawal threshold and latency (PWT, PWL) in ipsilateral hind paw. The DRG-opto group also showed increase in PWT and PWL under optic stimulation compared to before and after stimulation. Concededly, this study indicates that optic stimulation of hind limb motor cortex and blocking of PKCy at DRG level abate neuropathic pain in CCD rat model.