Alpha-2 adrenergic agonists such as clonidine may be used to treat the pain associated with painful diabetic neuropathy (PDN) only in a subset of these patients. Targeted nociceptors (pain fibers) must be functionally expressed in the skin in order for clonidine to have a therapeutic effect. Neuropathies associated with pain differ with respect to the expression of nociceptors in the skin. Clonidine targets alpha-2 adrenergic receptors on the terminals of nociceptors. The presence of the targeted nociceptors may be determined by topical application of a TRPV1 agonist such as capsaicin. Patients who detect the capsaicin as a pain stimulus applied near the painful area have expression in the skin of the requisite targeted nociceptors and the targeted alpha-2 adrenergic receptors. The test is referred to as a capsaicin challenge test. This test significantly improves clinical outcomes in topical neuropathic pain treatment.
