Spinal cord is the initial stage along the thermosensory pathway that integrates and processes temperature information from the peripheral thermosensory neurons. After tissue and nerve injury, there are significant changes at the level of the spinal cord and these maladaptive events often result in thermal allodynia (innocuous temperature perceived as painful) and hyperalgesia (normal noxious temperature elicit pain of greaterintensity).Theheterogeneityoftheneurochemicalorganizationofthedorsalspinalcordposeamajor challengeforstudyingspinalcordcircuitryanditschangesinpaincondition.Understandingtherolesofdistinct celltypesholdthekeytodecipheringtheneuralcircuitsinthedorsalhorn.Here,weproposetomakeuseofa newlydevelopedinvivospinalcordimagingplatform,apreciselycontrolledtemperaturestimulussystem,and transgenicmouselinestodissecttheroleofeachcelltypeinprocessingtemperatureinformationinthespinal cord. In this proposal, we focus on spinal inhibitory interneurons as they are important for gating the transmissionofpaininformationtothebrain,andlossofinhibitionhasbeenproposedasageneralmechanism forthermalhypersensitivityaftertissueandnerveinjury.
In aim1, wewillimagethermosensoryresponsesin different types of inhibitory interneurons, and examine the impact of silencing their activities on the sensory response in the rest of the circuitry.
In aim2, we will perform the similar experiments in animal models of inflammatory pain to determine the changes in thermosensory responses of each type of inhibitory interneurons and their effect on other spinal neurons during inflammatory pain. The results from proposed workwillnotonlyprovidebasicknowledgeonneurobiologyofthermosensation,butalsopotentiallygenerate insightsusefulfortreatingpain.
Thermosensation is a fundamental and essential sense, which often undergoes maladaptive changes after tissue or nerve injury. Here we propose to combine genetic and pharmacogenetic tools with a novel in vivo two-photonimagingplatformtostudytheencodingoftemperatureinformationinthespinalcordandhowthis coding scheme is altered by chronic pain. Results from this work could help identify new therapeutic targets fortreatingchronicpain.
