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Gene Linked to Greater Tolerance of Pain

May be predictor of pain after surgery, and a potential therapeutic target

WEDNESDAY, Nov. 1 (HealthDay News) -- The GTP cyclohydrolase gene, GCH1, is an essential component in neurotransmitter production and may also be a key modulator of pain sensitivity, according to a report in the Oct. 22 advance online edition of Nature Medicine. Individuals carrying particular variants of GCH1 seem to be more tolerant of acute pain.

Clifford J. Woolf, M.D., of Harvard Medical School in Boston, and colleagues identified the gene as one of many upregulated in the dorsal root ganglion following sciatic nerve injury. GTP cyclohydrolase activity produces tetrahydrobiopterin, or BH4, which is then used to produce neurotransmitters including dopamine.

Inhibiting new BH4 production in rats dramatically increased their tolerance to pain, the investigators found. Humans carrying a variation of GCH1, which renders the enzyme less active, were also more tolerant to pressure-induced pain tests and reported less chronic pain following back surgery.

"A treatment strategy that could reduce excess [BH4], but not constitutive concentrations of BH4…might prevent the establishment or maintenance of chronic pain," the authors write. "In addition, the identification of a predictor of the intensity and chronicity of pain will be a useful tool to assess an individual's risk for developing chronic pain."

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