Dorsal root ganglion neurons show increased expression of the calcium channel α2δ-1 subunit following partial sciatic nerve injury

Abstract

Neuropathic pain is associated with changes in the electrophysiological and neurochemical properties of injured primary afferent neurons. A mRNA differential display study in rat L 4/5 dorsal root ganglia (DRGs) revealed upregulation of the calcium channel α2δ-1 subunit 2 weeks after partial sciatic nerve ligation (Seltzer model of neuropathic pain). The upregulated transcript appeared to represent previously unidentified sequence from the 3′-untranslated region of rat α2δ-1 mRNA. In situ hybridization using L 5 DRGs from sham operated rats showed that 73, 40 and 19% of small (<700 μm 2), medium (700–1100 μm 2) and large (>1100 μm 2) neuronal profiles, respectively, expressed α2δ-1 mRNA. Two weeks following nerve injury there was a significant ipsilateral increase, both in the percentage of DRG neurons expressing α2δ-1 mRNA and in the intensity of the hybridization signal. Comparison of this ipsilateral expression with that in sham animals, revealed that for small, medium and large neurons, respectively, the proportion of neurons labelled increased by 1.2-, 1.8- and 2.7-fold, while the hybridization signal in α2δ-1-labelled neurons increased by 2.8-, 2.5- and 3.7-fold. The most intensely labelled neuronal profiles in ipsilateral, sham and contralateral DRGs, were generally those with small cross-sectional areas. The α2δ-1 auxiliary subunit is known to modulate calcium channel function in heterologous expression systems via its association with the pore-forming α1 calcium channel subunit. Therefore the increased levels of this subunit in the populations of primary afferents described may, via modulation of calcium-dependent processes such as neurotransmitter release and neuronal excitability, influence the processing of sensory information.