TY - JOUR
T1 - Autotomy behavior correlates with the DRG and spinal expression of sodium channels in inbred mouse strains
AU - Persson, Anna Karin
AU - Thun, Jonas
AU - Xu, Xiao Jun
AU - Wiesenfeld-Hallin, Zsuzsanna
AU - Ström, Mikael
AU - Devor, Marshall
AU - Lidman, Olle
AU - Fried, Kaj
PY - 2009/8/18
Y1 - 2009/8/18
N2 - Patients who have suffered nerve injury show profound inter-individual variability in neuropathic pain even when the precipitating injury is nearly identical. Variability in pain behavior is also observed across inbred strains of mice where it has been attributed to genetic polymorphisms. Identification of cellular correlates of pain variability across strains can advance the understanding of underlying pain mechanisms. Voltage-gated sodium channels (VGSCs) play a major role in the generation and propagation of action potentials in the primary afferents and are therefore of obvious importance for pain phenotype. Here, we examined the mRNA expression levels of the VGSC α-subunits Nav1.3, Nav1.5, Nav1.6, and Nav1.7, as well as the auxiliary VGSC-related molecule, Contactin. Dorsal root ganglia (DRG) and spinal cords from 5 inbred mouse strains with contrasting pain phenotype (AKR/J, C3H/HeJ, C57BL/6J, C58/J and CBA/J) were analyzed 7 days following sciatic and saphenous nerve transection. In the DRG, Nav1.6, Nav1.7 and Contactin were abundantly expressed in control animals. Following nerve injury, the residual mRNA levels of Nav1.6 (downregulated in two of the strains) correlated tightly to the extent of autotomy behavior. A suggestive correlation was also seen for the post-injury mRNA levels of Contactin (downregulated in all strains) with autotomy. Thus, our results suggest a contribution by DRG Nav1.6, and possibly Contactin to neuropathic pain in the neuroma model in mice.
AB - Patients who have suffered nerve injury show profound inter-individual variability in neuropathic pain even when the precipitating injury is nearly identical. Variability in pain behavior is also observed across inbred strains of mice where it has been attributed to genetic polymorphisms. Identification of cellular correlates of pain variability across strains can advance the understanding of underlying pain mechanisms. Voltage-gated sodium channels (VGSCs) play a major role in the generation and propagation of action potentials in the primary afferents and are therefore of obvious importance for pain phenotype. Here, we examined the mRNA expression levels of the VGSC α-subunits Nav1.3, Nav1.5, Nav1.6, and Nav1.7, as well as the auxiliary VGSC-related molecule, Contactin. Dorsal root ganglia (DRG) and spinal cords from 5 inbred mouse strains with contrasting pain phenotype (AKR/J, C3H/HeJ, C57BL/6J, C58/J and CBA/J) were analyzed 7 days following sciatic and saphenous nerve transection. In the DRG, Nav1.6, Nav1.7 and Contactin were abundantly expressed in control animals. Following nerve injury, the residual mRNA levels of Nav1.6 (downregulated in two of the strains) correlated tightly to the extent of autotomy behavior. A suggestive correlation was also seen for the post-injury mRNA levels of Contactin (downregulated in all strains) with autotomy. Thus, our results suggest a contribution by DRG Nav1.6, and possibly Contactin to neuropathic pain in the neuroma model in mice.
KW - Dorsal root ganglion
KW - Gene regulation
KW - Neuropathic pain
KW - Pain genetics
KW - Sciatic nerve
KW - Voltage-gated sodium channels
UR - http://www.scopus.com/inward/record.url?scp=67749120555&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2009.06.012
DO - 10.1016/j.brainres.2009.06.012
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C2 - 19524556
AN - SCOPUS:67749120555
SN - 0006-8993
VL - 1285
SP - 1
EP - 13
JO - Brain Research
JF - Brain Research
ER -