Characterization of chronic constriction of the saphenous nerve, a model of neuropathic pain in mice showing rapid molecular and electrophysiological changes.
Neuropathic pain is one of the most inextricable problems encountered in clinics, because few facts are known about its etiology. Nerve injury often leads to allodynia and hyperalgesia, which are symptoms of neuropathic pain. The aim of this study was to understand some molecular and electrophysiological mechanisms of neuropathic pain after chronic constriction of the saphenous nerve (CCS) in mice. After surgery, CCS mice displayed significant allodynia and hyperalgesia, which were sensitive to acute systemic injection of morphine (4 mg/kg), gabapentin (50 mg/kg), amitriptyline (10 mg/kg), and the cannabinoid agonist WIN 55,212-2 (5 mg/kg). These behavioral changes were accompanied after surgery by an increase of c-Fos expression and by an overexpression of mu-opioid and cannabinoid CB1 and CB2 receptors in the spinal cord and the dorsal hind paw skin. In combination with the skin-nerve preparation, this model showed a decrease in functional receptive fields downstream to the injury and the apparition of A-fiber ectopic discharges. In conclusion, CCS injury induced behavioral, molecular, and electrophysiological rearrangements that might help us in better understanding the peripheral mechanisms of neuropathic pain. This model takes advantage of the possible use in the future of genetically modified mice and of an exclusively sensory nerve for a comprehensive study of peripheral mechanisms of neuropathic pain.
Walczak
Jean-Sébastien
JS
Department of Pharmacology, Université de Montréal, Montréal, Québec, Canada.
Pichette
Vincent
V
Leblond
François
F
Desbiens
Karine
K
Beaulieu
Pierre
P
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005267:Femoral Nerve / Q000293:injuries* / Q000378:metabolism* / Q000503:physiopathology; D020428:Femoral Neuropathy / Q000378:metabolism* / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000503:physiopathology; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism
D000700:Analgesics; D016760:Proto-Oncogene Proteins c-fos; D043882:Receptors, Cannabinoid; D017450:Receptors, Opioid, mu