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Electrophysiological characterization of spinal neuron sensitization by elevated calcium channel alpha‐2‐delta‐1 subunit protein
Author(s) -
Zhou C.,
Luo Z.D.
Publication year - 2014
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/j.1532-2149.2013.00416.x
Subject(s) - spinal cord , excitatory postsynaptic potential , inhibitory postsynaptic potential , calcium channel , gabapentin , electrophysiology , nociception , hyperalgesia , patch clamp , chemistry , neurotransmission , neuropathic pain , nociceptor , neuroscience , calcium imaging , voltage dependent calcium channel , calcium , anatomy , anesthesia , medicine , biology , receptor , pathology , biochemistry , alternative medicine , organic chemistry
Background Voltage‐gated calcium channel α 2 δ 1 subunit is the binding site for gabapentin, an effective drug in controlling neuropathic pain states including thermal hyperalgesia. Hyperalgesia to noxious thermal stimuli in both spinal nerve‐ligated ( SNL ) and voltage‐gated calcium channel α 2 δ 1 overexpressing transgenic ( T g) mice correlates with higher α 2 δ 1 levels in dorsal root ganglia and dorsal spinal cord. In this study, we investigated whether abnormal synaptic transmission is responsible for thermal hyperalgesia induced by elevated α 2 δ 1 expression in these models. Methods Behavioural sensitivities to thermal stimuli were test in L 4 SNL and sham mice, as well as in α 2 δ 1 T g and wild‐type mice. Miniature excitatory ( mEPSC ) and inhibitory ( mIPSC ) post‐synaptic currents were recorded in superficial dorsal spinal cord neurons from these models using whole‐cell patch clamp slice recording techniques. Results The frequency, but not amplitude, of mEPSC in superficial dorsal horn neurons was increased in SNL and α 2 δ 1 T g mice, which could be attenuated by gabapentin dose dependently. Intrathecal α 2 δ 1 antisense oligodeoxynucleotide treatment diminished increased mEPSC frequency and gabapentin's inhibitory effects in elevated mEPSC frequency in the SNL mice. In contrast, neither the frequency nor the amplitude of mIPSC was altered in superficial dorsal horn neurons from the SNL and α 2 δ 1 T g mice. Conclusions Our findings support a role of peripheral nerve injury‐induced α 2 δ 1 in enhancing pre‐synaptic excitatory input onto superficial dorsal spinal cord neurons that contributes to nociception development.