Polymyalgia rheumatica (PMR) is characterized by aching proximal muscles and systemic inflammation. We explored the pain-eliciting mechanisms by measuring interstitial levels in muscle of potentially pain-inducing substances as well as local blood flow. Twenty glucocorticoid-naive patients with newly diagnosed PMR and 20 controls were examined before and after 14days of prednisolone (20mg/day). Concentrations of glutamate, prostaglandin E(2) (PGE(2)), bradykinin, serotonin, adenosine triphosphate, lactate, pyruvate, and potassium as well as extraction of (3)H(2)O were measured in symptomatic vastus lateralis and trapezius muscles using microdialysis. Plasma levels were measured simultaneously. To be considered potentially pain inducing, interstitial concentrations of candidates should be higher in patients vs. controls, be normalized by prednisolone, and be higher in muscle vs. plasma. Prednisolone abolished symptoms in all patients within 2days. Before treatment glutamate in both muscles (vastus: 60±7 vs. 38±7µmol/L; trapezius: 60±6 vs. 43±7µmol/L) and PGE(2) in vastus (911±200 vs. 496±122pg/mL) were higher in patients than in controls (P