Spontaneous pain following spinal nerve injury in mice.
Autotomy behavior is frequently observed in rats and mice in which the nerves of the hindlimb are severed, denervating the paw. This is the neuroma model of neuropathic pain. A large body of evidence suggests that this behavior reflects the presence of spontaneous dysesthesia and pain. In contrast, autotomy typically does not develop in partial nerve injury pain models, leading to the belief that these animals develop hypersensibility to applied stimuli (allodynia and hyperalgesia), but not spontaneous pain. We have modified the widely used Chung (spinal nerve ligation [SNL]) model of neuropathic pain in a way that retains the fundamental neural lesion, but eliminates nociceptive sensory cover of the paw. These animals performed autotomy. Moreover, the heritable across strains predisposition to spontaneous pain behavior in this new proximal denervation model (SNN) was highly correlated with pain phenotype in the neuroma model suggesting that the pain mechanism in the two models is the same. Relative reproducibility of strain predispositions across laboratories was verified. These data indicate that the neural substrate for spontaneous pain is present in the Chung-SNL model, and perhaps in the other partial nerve injury models as well, but that spontaneous pain is not expressed as autotomy in these models because there is protective nociceptive sensory cover.
Minert
Anne
A
Department of Cell and Animal Biology, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Gabay
Eran
E
Dominguez
Cecilia
C
Wiesenfeld-Hallin
Zsuzsanna
Z
Devor
Marshall
M
D000818:Animals; D003714:Denervation / Q000009:adverse effects; D004195:Disease Models, Animal; D020428:Femoral Neuropathy / Q000503:physiopathology; D006614:Hindlimb / Q000294:innervation / Q000503:physiopathology; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D008026:Ligation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009437:Neuralgia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D009619:Nociceptors / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D020426:Sciatic Neuropathy / Q000503:physiopathology; D012652:Self Mutilation / Q000209:etiology / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000503:physiopathology; D012867:Skin / Q000294:innervation / Q000503:physiopathology; D013127:Spinal Nerves / Q000293:injuries* / Q000503:physiopathology*