METHODS FOR TREATING PAIN

摘要

The present invention features methods and compositions for preventing, reducing, or treating a traumatic, metabolic or toxic peripheral nerve lesio n or pain including, for example, neuropathic pain, inflammatory and nocicepti ve pain by administering to a mammal in need thereof a compound that reduces th e expression or activity of BH4. According to this invention, this reduction m ay be achieved by reducing the enzyme activity of any of the BH4 synthetic enzymes, such as GTP cyclohydrolase (GTPCH), sepiapterin reductase (SPR), or dihydropteridine reductase (DHPR); by antagonizing the cofactor function of BH4 on BH4-dependent enzymes; or by blocking BH4 binding to membrane bound receptors. The compounds of the invention may be administered alone or in combination with a second therapeutic agent. The invention also provides methods for diagnosing pain or a peripheral nerve lesion in a mammal by measuring the levels of BH4 or its metabolites in biological sample. Alternatively, pain or a peripheral nerve lesion may be diagnosed by measuri ng the levels or activity of any one of the BH4 synthetic enzymes in tissue samples of a mammal. Also disclosed are screening methods that make use of B H4 or BH4 synthetic enzymes, BH4-dependent enzymes, and BH4-binding receptors f or the identification of novel therapeutics for the treatment, prevention, or reduction of pain.