Enhancement of cutaneous nerve regeneration by 4-methylcatechol in resiniferatox

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J Neuropathol Exp Neurol. 2008 Feb;67(2):93-104.

Enhancement of cutaneous nerve regeneration by 4-methylcatechol in

resiniferatoxin-induced neuropathy.

Hsieh YL, Chiang H, Tseng TJ, Hsieh ST.

Department of Anatomy and Cell Biology, National Taiwan University

College of Medicine, National Taiwan University Hospital, Taipei,

Taiwan.

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.