Fig. 3.

Tetrahydrobiopterin (BH4) is associated with pain hypersensitivity. A BH4 de novo production pathway. In patients carrying the pain-protective haplotype, stimulated lymphocytes produce less BH4 in patients who are less likely to develop chronic pain hypersensitivity. B Use of transgenic mouse models to specifically target the BH4 pathway reveals two major anatomical sites and cell types responsible for pain hypersensitivity: injured sensory neurons and macrophages within the sciatic nerve. Table describes existing rodent studies into BH4 and pain mechanisms. GCH1, GTP cyclohydrolase I; PTPS, pyruvoyl-tetrahydropterin synthase; SPR, sepiapterin reductase. vF, von Frey test; CF, calibrated forceps; HG, Hargreaves; HP, hot plate; TG, thermal gradient. Doses are indicated in brackets.