Abstract
Resiniferatoxin (RTX) is a potent agonist of TRPV1, which possesses unique properties
that can be utilized to treat certain modalities of pain. In the present study, systemic
intraperitoneal (i.p.) administration of RTX resulted in a significant decrease in
acute thermal pain sensitivity, whereas localized intrathecal (i.t.) administration
had no effect on acute thermal pain sensitivity. Both i.p. and i.t. administration
of RTX prevented TRPV1-induced nocifensive behavior and inflammatory thermal hypersensitivity.
There were no alterations in mechanical sensitivity either by i.p. or i.t. administration
of RTX. In spinal dorsal horn (L4-L6), TRPV1 and substance P immunoreactivity were
abolished following i.p. and i.t. administration of RTX. In dorsal root ganglia (DRG),
TRPV1 immunoreactivity was diminished following i.p. administration, but was unaffected
following i.t. administration of RTX. Following i.p. administration, basal and evoked
calcitonin gene-related peptide release were reduced both in the spinal cord and peripheral
tissues. However, following i.t. administration, basal and evoked calcitonin gene-related
peptide release were reduced in spinal cord (L4-L6), but were unaffected in peripheral
tissues. Both i.p. and i.t. RTX administration lowered the body temperature acutely,
but this effect reversed with time. Targeting TRPV1-expressing nerve terminals at
the spinal cord can selectively abolish inflammatory thermal hypersensitivity without
affecting acute thermal sensitivity and can preserve the efferent functions of DRG
neurons at the peripheral nerve terminals. I.t. administration of RTX can be considered
as a strategy for treating certain chronic and debilitating pain conditions.
Perspective
Localized administration of RTX in spinal cord could be a useful strategy to treat
chronic debilitating pain arising from certain conditions such as cancer and at the
same time could maintain normal physiological peripheral efferent functions mediated
by TRPV1.
Key words
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Article info
Publication history
Published online: June 17, 2011
Accepted:
March 16,
2011
Received in revised form:
January 25,
2011
Received:
October 29,
2010
Footnotes
Supported by grants from National Institutes of Health (DA028017) and EAM award from SIUSOM.
There is no conflict of interest among authors.
Identification
Copyright
© 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.
