- It is well known that the descending spinal pathway, which projects from the periaqueductal gray (PAG) to the rostral ventral medulla (RVM) and terminates at the dorsal horn of the spinal cord, is a powerful modulator of ascending nociceptive signals, and is a primary target of the analgesic actions of opioids and cannabinoids. Less well known is that within the ventral lateral PAG resides a population of dopamine neurons. Little is known about the function of these neurons in pain and analgesia. We are currently elucidating the circuit interactions of these neurons using electrophysiologic, optogenetic, chemogenetic, pharmacologic and behavioral techniques in transgenic mice.
- Just like in humans, there is tremendous diversity in the sensitivity to painful stimuli experienced by different strains of rats. However, no one has previously tried to characterize these differences or determine the genetic causes in a systematic way. In this project, we are using transcriptome profiling (RNA-seq) along with congenic, consomic, transgenic and epigenetic strategies to identify novel pathways responsible for the susceptibility to, or protection from, the progression from acute to chronic pain. Current pathways of interest include COMT and cathecholamine levels, and inflammation.
- Developing a novel model of temporomandibular disorder (TMD) in rats to characterize the effect of genetics, gender and sleep deprivation on the susceptibility to developing temporomandibular pain. No one has previously combined into one model a clinically relevant insult in genetically predisposed female rats using an operant behavioral endpoint to study the physiologic causes and consequences of TMD. Developing such a model would be a huge advance in the field. We expect the findings of this study will help clarify the human gender dimorphism in orofacial pain produced by TMDs, and will provide insight about gender-specific therapeutic strategies for this condition.