To identify possible mechanisms underlying temperature’s effect on migraines.

Temperature changes trigger migraine, at minimum, in a subset of migraine patients. To our knowledge, no publications explore the possible underlying molecular mechanisms. Here, we identify pathways by which temperature may trigger migraine.

PubMed, Embase and Scopus databases were searched using the terms “thermoregulation” OR “temperature” AND “molecular mechanism” to produce a list of molecular markers involved in thermoregulation. Each marker from this list was searched on the above databases with the term “migraine” for germane preclinical or clinical investigations into migraine pathogenesis.

Well-studied molecular players include transient receptor potential cation channel members, TMPRM8 and TRPV, which are peripheral cold and warm sensors, respectively. Variants of each alter migraine risk, and both channels are potential therapeutic targets based on promising preclinical studies. Pathways through the median preoptic nucleus (MnPO) and dorsomedial hypothalamus (DMH), regions highly implicated in thermoregulation, involve prostaglandin E2 (PGE2), brain-derived neutropenic factor (BDNF), and pituitary adenylate cyclase-activating peptide (PACAP), which have garnered increasing clinical support for their role in migraine. We also summarize lesser studied metabolic pathways associated with temperature change and implicated in migraine pathogenesis, including those of short chain fatty acids, 5-HT, sphingolipids, aerobic and anaerobic glycolytic enzymes, lipolysis, glycogen synthesis, and glucose regulation. 

This review synthesizes recent studies that provide insight into the mechanisms that mediate temperature influence on migraine pathogenesis. These findings additionally highlight several potential therapeutic targets for further research in those with temperature sensitive migraine.