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


OBJECTIVE
To evaluate the role of the VR1-positive neurons in neuropathic pain.


METHODS
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.
Tender
Gabriel C
GC
Department of Neurosurgery, Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Li
Yuan-Yuan
YY
Cui
Jian-Guo
JG
D000818:Animals; D004224:Diterpenes / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism*
D004224:Diterpenes; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C024353:resiniferatoxin