期刊
EUROPEAN JOURNAL OF PAIN
卷 19, 期 5, 页码 639-648出版社
WILEY-BLACKWELL
DOI: 10.1002/ejp.585
关键词
-
资金
- NIH [NS064341, DE021847]
- Rehabilitation Medicine Scientist Training Program fellowship [K12 HD001097]
- Institute for Clinical and Translational Science faculty career development fellowship (KL-2) [UL1 TR000153]
BackgroundOverexpression of the voltage-gated calcium channel (VGCC) alpha-2-delta1 subunit protein (Ca-v21) has been shown to cause pain states. However, whether VGCC are involved in pain states driven by abnormal Ca-v21 expression is not known. MethodsIntrathecal injection of N-, P/Q- and L-type VGCC blockers were tested in two models: a transgenic neuronal Ca-v21 overexpression (TG) model with behavioural hypersensitivity and a spinal nerve ligation (SNL) model with Ca-v21 overexpression in sensory pathways and neuropathy pain states. ResultsThe nociceptive response to mechanical stimuli was significantly attenuated in both models with -conotoxin GVIA (an N-type VGCC blocker) and nifedipine (an L-type VGCC blocker), in which -conotoxin GVIA appeared more potent than nifedipine. Treatments with -agatoxin IVA (P-VGCC blocker), but not -conotoxin MVIIC (Q-VGCC blocker) had similar potency in the TG model as the N-type VGCC blocker, while both -agatoxin IVA and -conotoxin MVIIC had minimal effects in the SNL model compared with controls. ConclusionThese findings suggest that, at the spinal level, N- and L-type VGCC are likely involved in behavioural hypersensitivity states driven by Ca-v21 overexpression. Q-type VGCC has minimal effects in both models. The anti-nociceptive effects of P-type VGCC blocker in the Ca-v21 TG mice, but minimally at the SNL model with presynaptic Ca-v21 up-regulation, suggest that its potential action site(s) is at the post-synaptic and/or supraspinal level. These findings support that N-, L- and P/Q-type VGCC have differential contributions to behavioural hypersensitivity modulated by Ca-v21 dysregulation at the spinal cord level.
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