Enhancement of cutaneous nerve regeneration by 4-methylcatechol in resiniferatoxin-induced neuropathy.
To generate an experimental neuropathy model in which small-diameter sensory nerves are specifically affected and to test a potential treatment, adult mice were given a single injection (50 microg/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 P-immunoreactive 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 microg/kg, i.p.) from Days 7 to 35 after neuropathy induction. On Day 35, 4MC-treated 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.
Hsieh
Yu-Lin
YL
Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Chiang
Hao
H
Tseng
To-Jung
TJ
Hsieh
Sung-Tsang
ST
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin; D002396:Catechols / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004224:Diterpenes; D004347:Drug Interactions; D005727:Ganglia, Spinal / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D011930:Reaction Time / Q000187:drug effects; D012867:Skin / Q000294:innervation*; D013373:Substance P / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
D002396:Catechols; D004224:Diterpenes; D018696:Neuroprotective Agents; C018599:4-methylcatechol; D013373:Substance P; C024353:resiniferatoxin; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin