Prostaglandin-mediated inhibition of serotonin signaling controls the affective component of inflammatory pain.

Pain is fundamentally unpleasant and induces a negative affective state. The affective component of pain is mediated by circuits that are distinct from those mediating the sensory-discriminative component. Here, we have investigated the role of prostaglandins in the affective dimension of pain using a rodent pain assay based on conditioned place aversion to formalin injection, an inflammatory noxious stimulus. We found that place aversion induced by inflammatory pain depends on prostaglandin E2 that is synthesized by cyclooxygenase 2 in neural cells. Further, mice lacking the prostaglandin E2 receptor EP3 selectively on serotonergic cells or selectively in the area of the dorsal raphe nucleus failed to form an aversion to formalin-induced pain, as did mice lacking the serotonin transporter. Chemogenetic manipulations revealed that EP3 receptor activation elicited conditioned place aversion to pain via inhibition of serotonergic neurons. In contrast to their role in inflammatory pain aversion, EP3 receptors on serotonergic cells were dispensable for acute nociceptive behaviors and for aversion induced by thermal pain or a κ opioid receptor agonist. Collectively, our findings show that prostaglandin-mediated modulation of serotonergic transmission controls the affective component of inflammatory pain.

Comparison of complications in free flap reconstruction for osteoradionecrosis in patients with or without hyperbaric oxygen therapy.

BACKGROUND: Hyperbaric oxygen (HBO) therapy induces native tissue oxygenation. The hypothesis was patients with mandibular osteoradionecrosis (ORN) and a history of HBO therapy would have less free flap reconstruction complications than patients without HBO therapy. METHODS: We conducted a multisite retrospective review involving radical debridement and free flap reconstruction for ORN between January 1, 1995 and June 30, 2011. Patients were stratified based on receiving prior HBO therapy or not. RESULTS: Thirty-nine of 89 patients (43.8%) had HBO therapy whereas 50 of 89 (56.2%) did not. The HBO therapy group had significantly less patients with diabetes. There was no statistical difference in overall complication in patients between groups (p = .5478). However, there was marginal significance of increased infections in the patients with a history of HBO therapy (p = .0545). CONCLUSION: Although no significant differences in free flap reconstruction complication rates were observed between these 2 patient cohorts, there was marginal significance of increased infections in the patients with a history of HBO therapy. A prospective multi-institutional randomized study examining issues of infection would address issues inherent in this retrospective study.