CURRENT RESEARCH PROJECTS
SEX DIFFERENCES IN SEROTONERGIC MODULATION OF TRIGEMINAL PAIN
Approximately a quarter of the population experiences craniofacial pain mediated by the trigeminal neurosensory system. Many are more common in women, such as migraine and temporomandibular pain disorder. Our theory for this prevalence is hormone modulation of trigeminal pain mechanisms in females. We are currently examining the effects of gonadal hormones on the peripheral serotonergic system and trigeminal sensory neurons in rats and human tissues. Our work is critical to understanding how hormones may regulate the pronociceptive activity of peripheral serotonin. Further, we are examining the sexually dimorphic effect of stress on trigeminal pain behaviors and neurocircuitry.
Funded by NIDCR R15 DE025970 to Averitt and F31 DE031959 to Cantu.
SEX DIFFERENCES IN NEUROIMMUNE MODULATION OF TRIGEMINAL SENSORY NEURONS
Numerous studies indicate a strong serotonergic pain mechanism in craniofacial pain disorders, yet the mechanism explaining the female predominance is not known. Fluctuating estradiol (E2) across the rodent estrous cycle, which is comparable to the human menstrual cycle, exacerbates 5HT-evoked thermal hyperalgesia. Since macrophages express the two classical estrogen receptor (ER) subtypes, ERα and ERβ, as well as the membrane-bound G protein-coupled estrogen receptor, GPER, it is possible that macrophages may be influenced by fluctuating E2. In this manner, E2 may modulate the macrophage contribution to initiating and/or maintaining the neuroinflammation observed in sexually dimorphic chronic orofacial pain disorders, specifically TMD. We are currently exploring whether E2 regulates neuroimmune communication in the trigeminal system which underlies sex differences in mechanical allodynia in a mouse model of TMD pain.
Funded by NIDCR R15 DE025970-02 to Averitt
BURN PAIN MECHANISMS AND NON-OPIOID ANALGESIA
Pain associated with burn injuries is poorly managed and the underlying mechanisms of burn pain chronification are understudied. While opioids have provided potent analgesia for several decades, the use of opioids in chronic pain patients remains suboptimal due to the numerous negative effects mediated by the central nervous system. Our research program seeks to identify and develop non-opioid pain medications to be administered at the site of injury for peripheral analgesia. Our current studies are focused on a plant that is native to our area in the Southeastern U.S., Euphorbia bicolor. We have reported that E. bicolor-evoked analgesia is multimodal, occurring via at least 3 mechanisms crucial to chronic pain and does not target opioid receptors. We are currently in discovery of the phytochemicals that may represent novel non-opioid analgesics.
In collaboration with plant biochemist Camelia Maier, Ph.D. (TWU), military medicine scientist John Clifford, Ph.D. (U.S. Army Institute of Surgical Research), and medicinal chemist Doug Frantz, Ph.D. (UTSA)
