Major surgery is usually followed by postoperative pain, which can become chronic. Reporting in Science Immunology, Starkl et al. identify mast cells as important regulators of surgical injury-induced pain hypersensitivity and define a mast cell-specific metabolic network that could potentially be targeted therapeutically.

The authors found that surgical injury (paw incision) in mice results in high mast cell production of GCH1, a rate-limiting enzyme involved in de novo synthesis of the BH4 metabolite. BH4 is an essential cofactor for tryptophan hydroxylase (TPH1), which converts tryptophan to serotonin.