Microneurography in diabetic mice
Spontaneous burning pain is a common symptom of diabetic peripheral neuropathy in humans. Yet there are few objective measures and no clear surrogate marker for spontaneous pain in laboratory animals. The conventional electrophysiological test currently employed by the consortium (nerve conduction velocity measurement) is incapable of providing information regarding burning pain because this test measures only the amplitude and latency of the compound action potential produced by the large diameter (Aß) primary afferent fibers which supply low-threshold mechanoreceptors. Unlike the small-diameter (C) nociceptive fibers, Aß fibers do not contribute to the burning pain of diabetic neuropathy. Small fiber neuropathy can exist in the absence of large fiber neuropathy. Behavioral assays (measurement of withdrawal latencies in response to noxious thermal stimulation) provide only an indirect measure of diabetic neuropathy. Histologic assays (measurement of nerve fiber density in the skin) cannot substitute for direct measurements of nerve fiber discharge. For these reasons we propose to add microneurography to the arsenal employed for phenotyping diabetic mice. Microneurography has been used for decades in studies of the neural substrate of human somatosensory perception. There is a wealth of background information. Among other achievements, microneurographic studies in humans demonstrated that spontaneous burning pain in patients with diabetic neuropathy is associated with spontaneous action potential discharge in nociceptive C-fiber primary afferents. Recently the microneurography technique was adapted for recording C-fiber activity in rats. We propose to adapt this technique for use in mice. Comparison of the patterns of C-fiber discharge measured in diabetic humans who do or do not experience spontaneous burning pain to the patterns of the C-fiber activity measured in different strains of diabetic mice will ultimately permit the selection of the most representative mouse model of painful diabetic peripheral neuropathy.

Curation Flag Information