Genetic analysis of neuropathic pain-like behavior following peripheral nerve injury suggests a role of the major histocompatibility complex in development of allodynia.
Neuropathic pain is a common consequence of damage to the nervous system. We here report a genetic analysis of development of neuropathic pain-like behaviors after unilateral photochemically-induced ischemic sciatic nerve injury in a panel of inbred rat strains known to display different susceptibility to autoimmune neuroinflammation. Pain behavior was initially characterized in Dark-Agouti (DA; RT1(av1)), Piebald Virol Glaxo (PVG; RT1(c)), and in the major histocompatibility complex (MHC)-congenic strain PVG-RT1(av1). All strains developed mechanical hypersensitivity (allodynia) following nerve injury. However, the extent and duration of allodynia varied significantly among the strains, with PVG displaying more severe allodynia compared to DA rats. Interestingly, the response of PVG-RT1(avRT1) was similar to that of DA, suggesting regulation by the MHC locus. This notion was subsequently confirmed in an F2 cohort derived from crossing of the PVG and PVG-RT1(av1)strains, where allodynia was reduced in homozygous or heterozygous carriers of the RT1(av1) allele in comparison to rats homozygous for the RT1(c) allele. These results indicate that certain allelic variants of the MHC could influence susceptibility to develop and maintain neuropathic pain-like behavior following peripheral nerve injury in rats.
Dominguez
Cecilia A
CA
Section of Clinical Neurophysiology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, SE-17176 Stockholm, Sweden Medical Inflammation Research, Lund University, Lund, Sweden.
Lidman
Olle
O
Hao
Jing-Xia
JX
Diez
Margarita
M
Tuncel
Jonatan
J
Olsson
Tomas
T
Wiesenfeld-Hallin
Zsuzsanna
Z
Piehl
Fredrik
F
Xu
Xiao-Jun
XJ
D000818:Animals; D001522:Behavior, Animal; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006941:Hyperesthesia / Q000235:genetics*; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D009437:Neuralgia / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000235:genetics*; D051381:Rats; D013045:Species Specificity; D014110:Touch / Q000235:genetics*