Dorsal root ganglion neurons show increased expression of the calcium channel alpha 2 delta-1 subunit following partial sciatic nerve injury

Neuropathic pain is associated with changes in the electrophysiological and neurochemical properties of injured primary afferent neurons. A mRNA diffe rential display study in rat L-4/5 dorsal root ganglia (DRGs) revealed upre gulation of the calcium channel alpha2 delta -1 subunit 2 weeks after parti al sciatic nerve ligation (Seltzer model of neuropathic pain). The upregula ted transcript appeared to represent previously unidentified sequence from the 3 ' -untranslated region of rat alpha2 delta -1 mRNA. In situ hybridiza tion using LS DRGs from sham operated rats showed that 73, 40 and 19% of sm all (< 700 mum(2)), medium (700-1100 mum(2)) and large (> 1100 mum(2)) neur onal profiles, respectively, expressed alpha2 delta -1 mRNA. Two weeks foll owing nerve injury there was a significant ipsilateral increase, both in th e percentage of DRG neurons expressing alpha2 delta -1 mRNA and in the inte nsity of the hybridization signal. Comparison of this ipsilateral expressio n with that in sham animals, revealed that for small, medium and large neur ons, respectively, the proportion of neurons labelled increased by 1.2-, 1. 8- and 2.7-fold, while the hybridization signal in alpha2 delta -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 general ly those with small cross-sectional areas. The alpha2 delta -1 auxiliary su bunit is known to modulate calcium channel function in heterologous express ion systems via its association with the pore-forming al calcium channel su bunit. Therefore the increased levels of this subunit in the populations of primary afferents described may, via modulation of calcium-dependent proce sses such as neurotransmitter release and neuronal excitability, influence the processing of sensory information. (C) 2001 Elsevier Science B.V. All r ights reserved.