Nerve injury-induced calcium channel alpha-2-delta-1 protein dysregulation leads to increased pre-synaptic excitatory input into deep dorsal horn neurons and neuropathic allodynia

• Published in: European journal of pain 2015-10, Vol.19 (9), p.1267-1276
• Main Authors: Zhou, C., Luo, Z.D.
• Format: Article
• Language: English
• Subjects: Animals; Calcium Channels - metabolism; Disease Models, Animal; Excitatory Postsynaptic Potentials - physiology; Hyperalgesia - etiology; Hyperalgesia - metabolism; Hyperalgesia - physiopathology; Male; Mice; Mice, Transgenic; Neuralgia - etiology; Neuralgia - metabolism; Neuralgia - physiopathology; Peripheral Nerve Injuries - complications; Peripheral Nerve Injuries - metabolism; Peripheral Nerve Injuries - physiopathology; Posterior Horn Cells - physiology; Spinal Nerves - injuries; Touch Perception - physiology; Up-Regulation
• ISSN: 1090-3801; 1532-2149
• DOI: 10.1002/ejp.656

Background Up‐regulation of voltage‐gated calcium channel α2δ1 subunit post spinal nerve ligation (SNL) injury or in α2δ1‐overexpressing transgenic (Tg) mice correlates with tactile allodynia, a pain state mediated mainly by Aβ sensory fibres forming synaptic connections with deep dorsal horn (DDH) neurons. It is not clear, however, whether dysregulated α2δ1 alters DDH synaptic neurotransmission that underlies tactile allodynia development post nerve injury. Methods Tactile allodynia was tested in the SNL and α2δ1 Tg models. Miniature excitatory/inhibitory post‐synaptic currents were recorded in DDH neurons from these animal models using whole‐cell patch clamp slice recording techniques. Results There was a significant increase in the frequency, but not amplitude, of miniature excitatory post‐synaptic currents (mEPSC) in DDH neurons that correlated with tactile allodynia in SNL and α2δ1 Tg mice. Gabapentin, an α2δ1 ligand that is known to block tactile allodynia in these models, also normalized mEPSC frequency dose‐dependently in DDH neurons from SNL and α2δ1 Tg mice. In contrast, neither frequency nor amplitude of miniature inhibitory post‐synaptic currents was altered in DDH neurons from SNL and α2δ1 Tg mice. Conclusion Our data suggest that α2δ1 dysregulation is highly likely contributing to tactile allodynia through a pre‐synaptic mechanism involving facilitation of excitatory synaptic neurotransmission in DDH of spinal cord.