Vanilloid receptor 1-positive neurons mediate thermal hyperalgesia and tactile allodynia

Gabriel C. Tender, Yuan Yuan Li, Jian Guo Cui

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background context: The vanilloid receptor 1 (VR1) is expressed by the type II A-delta and C-fiber neurons, functioning as a molecular integrator for nociception. VR1 can be selectively ablated by resiniferatoxin (RTX), an ultra-potent excitotoxic agonist, when injected into sensory ganglia. Purpose: To evaluate the role of the VR1-positive neurons in neuropathic pain. Study design: Photochemical injury to rat sciatic nerve (Gazelius model). Methods: Two groups of rats underwent the photochemical injury and RTX treatment. RTX was injected in the dorsal root ganglia (DRGs) of the L3, L4, L5, and L6 nerve roots, either after or before the nerve injury. The animals were tested for thermal hyperalgesia (noxious heat stimuli) and mechanical allodynia (von Frey filaments). Immunohistochemical analysis of the DRGs was performed after euthanasia. Results: In the tactile allodynic rats, RTX injection in the DRGs improved the average withdrawal threshold from 1.62 g to 5.68 g. Immunohistochemical labeling showed that almost all VR1-positive neurons were eliminated. When RTX was administrated into the ipsilateral DRGs before the nerve injury, this treatment prevented the development of tactile allodynia in 12 out of 14 rats. Immunohistochemical staining revealed that the VR1-positive neurons were eliminated in the rats that did not develop tactile allodynia, whereas they were still present in the allodynic rats. Conclusions: VR1-positive neurons are essential for the development of mechanical allodynia. In rats already exhibiting neuropathic pain, the VR1-positive neurons mediate the most sensitive part of mechanical allodynia. RTX injection in sensory ganglia may represent a novel treatment for neuropathic pain.

Original languageEnglish
Pages (from-to)351-358
Number of pages8
JournalSpine Journal
Volume8
Issue number2
DOIs
StatePublished - Mar 1 2008

Fingerprint

Hyperalgesia
Neurons
Spinal Ganglia
Neuralgia
Sensory Ganglia
Wounds and Injuries
TRPV Cation Channels
Unmyelinated Nerve Fibers
Nociceptors
Injections
Nociception
Euthanasia
Touch
Sciatic Nerve
vanilloid receptor subtype 1
resiniferatoxin
Therapeutics
Hot Temperature
Staining and Labeling

Keywords

  • Allodynia
  • Hyperalgesia
  • Neuropathic pain
  • Rat
  • Resiniferatoxin
  • Sciatic nerve injury
  • Vanilloid receptor 1

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Vanilloid receptor 1-positive neurons mediate thermal hyperalgesia and tactile allodynia. / Tender, Gabriel C.; Li, Yuan Yuan; Cui, Jian Guo.

In: Spine Journal, Vol. 8, No. 2, 01.03.2008, p. 351-358.

Research output: Contribution to journalArticle

Tender, Gabriel C. ; Li, Yuan Yuan ; Cui, Jian Guo. / Vanilloid receptor 1-positive neurons mediate thermal hyperalgesia and tactile allodynia. In: Spine Journal. 2008 ; Vol. 8, No. 2. pp. 351-358.
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abstract = "Background context: The vanilloid receptor 1 (VR1) is expressed by the type II A-delta and C-fiber neurons, functioning as a molecular integrator for nociception. VR1 can be selectively ablated by resiniferatoxin (RTX), an ultra-potent excitotoxic agonist, when injected into sensory ganglia. Purpose: To evaluate the role of the VR1-positive neurons in neuropathic pain. Study design: Photochemical injury to rat sciatic nerve (Gazelius model). Methods: Two groups of rats underwent the photochemical injury and RTX treatment. RTX was injected in the dorsal root ganglia (DRGs) of the L3, L4, L5, and L6 nerve roots, either after or before the nerve injury. The animals were tested for thermal hyperalgesia (noxious heat stimuli) and mechanical allodynia (von Frey filaments). Immunohistochemical analysis of the DRGs was performed after euthanasia. Results: In the tactile allodynic rats, RTX injection in the DRGs improved the average withdrawal threshold from 1.62 g to 5.68 g. Immunohistochemical labeling showed that almost all VR1-positive neurons were eliminated. When RTX was administrated into the ipsilateral DRGs before the nerve injury, this treatment prevented the development of tactile allodynia in 12 out of 14 rats. Immunohistochemical staining revealed that the VR1-positive neurons were eliminated in the rats that did not develop tactile allodynia, whereas they were still present in the allodynic rats. Conclusions: VR1-positive neurons are essential for the development of mechanical allodynia. In rats already exhibiting neuropathic pain, the VR1-positive neurons mediate the most sensitive part of mechanical allodynia. RTX injection in sensory ganglia may represent a novel treatment for neuropathic pain.",
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