Tuesday, September 20th
Hypothalamic Stress Circuits Regulate Prolactin to Promote Female-Selective Nociceptor Sensitization and Migraine-Like Pain
Migraine is a female predominant multiphasic neurological disorder. Imaging studies have demonstrated activation of the hypothalamus in the premonitory phase that often precedes the headache phase in most patients. Migraines are commonly associated with triggering events that can include external or internal stressors but how these disruptions lead to the headache phase is not known. Prolactin is secreted from the anterior pituitary and acts via a prolactin receptor that is expressed in two main isoforms. Data from preclinical studies will be presented to show that female mice have higher levels of prolactin and increased prolactin responses to stress that can be prevented by blocking stress circuits in the hypothalamus. Additionally, female mice have increased expression of prolactin receptor isoforms in the trigeminal and dorsal root ganglia. Genetic deletion or stress, disrupts the balance of prolactin receptor isoform expression, promoting nociceptor sensitization and migraine-like pain selectively in female mice. Pharmacological inhibition of circulating prolactin prevents nociceptor sensitization and migraine pain selectively in females. These data demonstrate a female-selective mechanism of nociceptor sensitization and provides a link between external or internal stress responses in the brain and nociceptors, the fundamental building blocks of pain, offering new therapeutic opportunities.