Autotomy behavior correlates with the DRG and spinal expression of sodium channels in inbred mouse strains.

Abstract

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 alpha-subunits Na(v)1.3, Na(v)1.5, Na(v)1.6, and Na(v)1.7, 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, Na(v)1.6, Na(v)1.7 and Contactin were abundantly expressed in control animals. Following nerve injury, the residual mRNA levels of Na(v)1.6 (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 Na(v)1.6, and possibly Contactin to neuropathic pain in the neuroma model in mice.

• Authors: Anna-Karin Persson, Jonas Thun, Xiao-Jun Xu, Zsuzsanna Wiesenfeld-Hallin, Mikael Ström, Marshall Devor, Olle Lidman, Kaj Fried
• Journal: Brain research (Brain Res) Vol. 1285 Pg. 1-13 (Aug 18 2009) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 19524556 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules, Neuronal
• Contactins
• NAV1.6 Voltage-Gated Sodium Channel
• Nerve Tissue Proteins
• RNA, Messenger
• Scn8a protein, mouse
• Sodium Channels

Topics

• Animals
• Cell Adhesion Molecules, Neuronal (genetics, metabolism)
• Contactins
• Disease Models, Animal
• Ganglia, Spinal (metabolism, physiopathology)
• Gene Expression Regulation (genetics)
• Ion Channel Gating (genetics)
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Inbred CBA
• NAV1.6 Voltage-Gated Sodium Channel
• Nerve Tissue Proteins (genetics, metabolism)
• Neuralgia (genetics, metabolism, physiopathology)
• Nociceptors (metabolism)
• Peripheral Nervous System Diseases (genetics, metabolism, physiopathology)
• Phenotype
• Posterior Horn Cells (metabolism)
• RNA, Messenger (metabolism)
• Sciatic Neuropathy (genetics, metabolism, physiopathology)
• Self Mutilation (genetics, metabolism, physiopathology)
• Sensory Receptor Cells (metabolism)
• Sodium Channels (genetics, metabolism)
• Species Specificity
• Spinal Cord (metabolism, physiopathology)