Hsieh Y.-L.Chiang H.Tseng T.-J.SUNG-TSANG HSIEH2020-03-022020-03-0220080022-3069https://www.scopus.com/inward/record.uri?eid=2-s2.0-42949122538&doi=10.1097%2fnen.0b013e3181630bb8&partnerID=40&md5=f5d938d22a27a0b122bb3159f7362069https://scholars.lib.ntu.edu.tw/handle/123456789/467774To generate an experimental neuropathy model in which smalldiameter sensory nerves are specifically affected and to test a potential treatment, adult mice were given a single injection (50 μg/kg, i.p.) of the capsaicin analog resiniferatoxin (RTX). On Day 7 after RTX treatment, there was a 53% reduction in unmyelinated nerve density in the medial plantar nerve (p = 0.0067) and a 66% reduction in epidermal nerve density of hind paw skin (p = 0.0004) compared with vehicle-treated controls. Substance PYimmunoreactive dorsal root ganglion neurons were also markedly depleted (p = 0.0001). These effects were associated with the functional deficit of prolonged withdrawal latencies to heat stimuli (p = 0.0007) on a hot plate test. The potential therapeutic effects of 4-methylcatechol (4MC) on this neuropathy were then tested by daily injections of 4MC (10 μg/kg,i.p.) from Days 7 to 35 after neuropathy induction. On Day 35, 4MCtreated mice had an increase in unmyelinated (p = 0.014) and epidermal nerve (p = 0.0013) densities and a reduction in thermal withdrawal latency (p = 0.0091) compared with RTX-only controls. These results indicate that 4MC promoted regeneration of unmyelinated nerves in experimental RTX-induced neuropathy and enhanced function. Copyright ? 2008 by the American Association of Neuropathologists, Inc.[SDGs]SDG34 methylcatechol; 4-methylcatechol; calcitonin gene related peptide; capsaicin; catechol derivative; diterpene; neuroprotective agent; PGP9.5 protein, mouse; resiniferatoxin; substance P; ubiquitin thiolesterase; animal; article; chemically induced disorder; disease model; drug effect; drug interaction; hyperalgesia; innervation; Institute for Cancer Research mouse; male; metabolism; mouse; nerve conduction; nerve regeneration; nonmyelinated nerve; pathology; pathophysiology; peripheral neuropathy; physiology; reaction time; skin; spinal ganglion; ultrastructure; Animals; Calcitonin Gene-Related Peptide; Capsaicin; Catechols; Disease Models, Animal; Diterpenes; Drug Interactions; Ganglia, Spinal; Hyperalgesia; Male; Mice; Mice, Inbred ICR; Nerve Fibers, Unmyelinated; Nerve Regeneration; Neural Conduction; Neuroprotective Agents; Peripheral Nervous System Diseases; Reaction Time; Skin; Substance P; Ubiquitin Thiolesterasejournal article10.1097/nen.0b013e3181630bb8182192592-s2.0-42949122538