Neubert JK, Mannes AJ, Karai LJ, Jenkins AC, Zawatski L, Abu-Asab
M, Iadarola MJ.Perineural resiniferatoxin selectively
inhibits inflammatory hyperalgesia.
Mol Pain. 2008 Jan 16;4:3.
College of Dentistry Department of Orthodontics, University
of Florida, Gainesville, FL, USA.
jneubert@dental.ufl.edu
Resiniferatoxin is an ultrapotent capsaicin analog that
binds to the transient receptor potential channel, vanilloid
subfamily member 1 . There is a large body of evidence
supporting a role for receptor potential channel, vanilloid
subfamily member 1 in noxious-mediated and inflammatory hyperalgesic responses. In this study, we evaluated low, graded,
doses of perineural as a method for regional pain control.
We hypothesized that this approach can provide long-term, but
reversible, blockade of a portion of nociceptive afferent fibers
within peripheral nerves when given at a site remote from the
neuronal perikarya in the dorsal root ganglia. Following
perineural application to the sciatic nerve, we demonstrated
a significant inhibition of inflammatory nociception that was
dose- and time-dependent. At the same time, treated animals
maintained normal proprioceptive sensations and motor control,
and other nociceptive responses were largely unaffected. Using a
range of mechanical and thermal algesic tests, we found that the
most sensitive measure following perineural administration
was inhibition of inflammatory hyperalgesia. Recovery studies
showed that physiologic sensory function could return as early
as two weeks post- treatment, however, immunohistochemical
examination of the DRG revealed a partial, but significant
reduction in the number of the
receptor potential channel, vanilloid subfamily member 1
-positive neurons. We
propose that this method could represent a beneficial treatment
for a range of chronic pain problems, including neuropathic and
inflammatory pain not responding to other therapies.
PMID: 18199335 |
