Delayed sympathetic dependence in the spared nerve injury (SNI) model of neuropathic pain.
BACKGROUND
Clinical and experimental studies of neuropathic pain support the hypothesis that a functional coupling between postganglionic sympathetic efferent and sensory afferent fibers contributes to the pain. We investigated whether neuropathic pain-related behavior in the spared nerve injury (SNI) rat model is dependent on the sympathetic nervous system.


RESULTS
Permanent chemical sympathectomy was achieved by daily injection of guanethidine (50 mg/kg s.c.) from age P8 to P21. SNI was performed at adulthood followed by 11 weeks of mechanical and thermal hypersensitivity testing. A significant but limited effect of the sympathectomy on SNI-induced pain sensitivity was observed. The effect was delayed and restricted to cold allodynia-like behavior: SNI-related cold scores were lower in the sympathectomized group compared to the control group at 8 and 11 weeks after the nerve injury but not before. Mechanical hypersensitivity tests (pinprick and von Frey hair threshold tests) showed no difference between groups during the study period. Concomitantly, pericellular tyrosine-hydroxylase immunoreactive basket structures were observed around dorsal root ganglia (DRG) neurons 8 weeks after SNI, but were absent at earlier time points after SNI and in sham operated controls.


CONCLUSIONS
These results suggest that the early establishment of neuropathic pain-related behavior after distal nerve injury such as in the SNI model is mechanistically independent of the sympathetic system, whereas the system contributes to the maintenance, albeit after a delay of many weeks, of response to cold-related stimuli.
Anesthesiology Pain Research Unit, Department of Anesthesiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland. marie.pertin@unil.ch
Marie
M
Pertin
Andrew J
AJ
Allchorne
Ahmed T
AT
Beggah
Clifford J
CJ
Woolf
Isabelle
I
Decosterd
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006145:Guanethidine / Q000008:administration & dosage / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009437:Neuralgia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013127:Spinal Nerves / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D013562:Sympathectomy / Q000379:methods; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014446:Tyrosine 3-Monooxygenase; D006145:Guanethidine