Pinpointing the mechanisms that underlie emotional responses to pain

Signaling by molecules called prostaglandins plays a key role in the body's response to inflammation. Prostaglandins been linked to the sensory perception of pain, but their role in the emotional response to pain is unclear. This week in the JCI, a study conducted by David Engblom's lab at Linköping University in Sweden has demonstrated that the aversive effects of inflammatory pain are driven by prostaglandin signaling specifically on serotonin-producing neurons in the brainstem.

When the researchers selectively blocked prostaglandin synthesis in neurons, mice displayed reduced aversive responses to inflammation-induced pain. Furthermore, mice lacking prostaglandin receptors on serotonin-producing neurons and mice lacking the serotonin transporter also exhibited less pain-avoidance behavior. Prostaglandin signaling in serotonin neurons was not required for aversive responses to high temperatures, suggesting that this pain-aversive signaling pathway is specific to inflammatory pain. These findings suggest that the effects of prostaglandin on serotonin signaling are key drivers of the emotional response to pain, implicating a pathway that may be targeted in future therapeutics for managing pain in chronic inflammatory conditions.