Injury-specific functional alteration of N-type voltage-gated calcium channels in synaptic transmission of primary afferent C-fibers in the rat spinal superficial dorsal horn

• Published in: European journal of pharmacology Vol. 772; pp. 11 - 21
• Main Authors: Takasu, Keiko, Ogawa, Koichi, Minami, Kazuhisa, Shinohara, Shunji, Kato, Akira
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.02.2016
• Subjects: Animals; Calcium Channel Blockers - pharmacology; Calcium Channels, N-Type - metabolism; EPSCs; Excitatory Postsynaptic Potentials - drug effects; Ganglia, Spinal - cytology; Ganglia, Spinal - drug effects; Ganglia, Spinal - injuries; Ganglia, Spinal - metabolism; Male; N-type voltage-gated calcium channel; Nerve Fibers, Myelinated - drug effects; Nerve Fibers, Myelinated - metabolism; Nerve Fibers, Myelinated - physiology; Nerve Fibers, Unmyelinated - drug effects; Nerve Fibers, Unmyelinated - metabolism; Nerve Fibers, Unmyelinated - physiology; Neuralgia - metabolism; Neuralgia - pathology; Neuralgia - physiopathology; Neuropathic pain; Rats; Rats, Sprague-Dawley; Spinal cord; Spinal nerve ligation; Substantia gelatinosa; Substantia Gelatinosa - cytology; Substantia Gelatinosa - drug effects; Substantia Gelatinosa - metabolism; Synaptic Transmission - drug effects; Spinal nerve ligation; Spinal cord; AMPA; EPSCs; CNQX; ω-CgTX; Neuropathic pain; SNL; TRP; ω-AgaIVA; SG; Substantia gelatinosa; DRG; eEPSCs; GABA; NMDA; N-type voltage-gated calcium channel; ATP; VGCCs
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2015.12.031

We investigated functional alterations of voltage-gated calcium channels (VGCCs) in excitatory synaptic transmission from primary afferent A- and C-fibers after peripheral nerve injury. Patch-clamp recordings were performed on substantia gelatinosa (SG) neurons of spinal cord slices with an attached dorsal root, prepared from L5 spinal nerve-ligated (SNL) rats. The effects of neuronal VGCC blockers, ω-conotoxin GVIA (ω-CgTX) for N-type channels and ω-agatoxin IVA (ω-AgaIVA) for P/Q-type channels, on evoked excitatory postsynaptic currents (eEPSCs) by stimulation of A- or C-fibers were studied. Besides, electrophysiological assay using dorsal root ganglion (DRG) and immunohistochemistry were done. In naïve rats, ω-CgTX (0.1–1μM) reduced more effectively A-fiber eEPSCs than C-fiber ones. After nerve injury, ω-CgTX produced great inhibition of C-fiber eEPSCs in slices with the injured L5 dorsal root of SNL model rats, as compared to sham-operated rats. By contrast, in slices with the non-injured L4 one, inhibitory effects of ω-CgTX were not changed. This occurred concurrently with increased expression of N-type VGCCs in L5 spinal dorsal horn and with enhanced Ca2+ currents through N-type VGCCs in small-sized (C-type) L5 DRG. In terms of A-fiber eEPSCs, ω-CgTX elicited similar inhibition in nerve-injured and sham-operated rats. ω-AgaIVA (0.1μM) had less effect on A- or C-fiber eEPSCs. These results indicate that N-type, but not P/Q-type, VGCCs mainly contribute to excitatory synaptic transmission from A- and C-fibers in the spinal dorsal horn. More importantly, following nerve injury, the functional contribution of N-type VGCCs to nociceptive transmission is increased in the pre-synaptic terminals of injured C-fibers.