Abstract | UNLABELLED:
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.
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Authors | Mahendra Bishnoi, Christine A Bosgraaf, Louis S Premkumar |
Journal | The journal of pain
(J Pain)
Vol. 12
Issue 9
Pg. 991-1003
(Sep 2011)
ISSN: 1528-8447 [Electronic] United States |
PMID | 21680254
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Diterpenes
- TRPV Cation Channels
- Trpv1 protein, rat
- resiniferatoxin
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Topics |
- Acute Pain
(drug therapy, metabolism, physiopathology)
- Analgesia
(methods)
- Animals
- Diterpenes
(administration & dosage)
- Efferent Pathways
(drug effects, physiology, physiopathology)
- Hot Temperature
(adverse effects)
- Injections, Spinal
- Male
- Pain Measurement
(methods)
- Physical Stimulation
(adverse effects)
- Rats
- Rats, Sprague-Dawley
- TRPV Cation Channels
(agonists, biosynthesis, physiology)
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