E Chang1, X Chen, M Kim, N Gong, S Bhatia, Z D Luo. 1. Department of Anesthesiology and Perioperative Care, University of California Irvine, Irvine, USA; Department of Physical Medicine and Rehabilitation, University of California Irvine, Irvine, USA; Reeve-Irvine Research Center for Spinal Cord Injury, University of California Irvine, Irvine, USA.
Abstract
BACKGROUND: Overexpression of the voltage-gated calcium channel (VGCC) alpha-2-delta1 subunit protein (Cav α2 δ1 ) has been shown to cause pain states. However, whether VGCC are involved in pain states driven by abnormal Cav α2 δ1 expression is not known. METHODS: Intrathecal injection of N-, P/Q- and L-type VGCC blockers were tested in two models: a transgenic neuronal Cav α2 δ1 overexpression (TG) model with behavioural hypersensitivity and a spinal nerve ligation (SNL) model with Cav α2 δ1 overexpression in sensory pathways and neuropathy pain states. RESULTS: The nociceptive response to mechanical stimuli was significantly attenuated in both models with ω-conotoxin GVIA (an N-type VGCC blocker) and nifedipine (an L-type VGCC blocker), in which ω-conotoxin GVIA appeared more potent than nifedipine. Treatments with ω-agatoxin IVA (P-VGCC blocker), but not ω-conotoxin MVIIC (Q-VGCC blocker) had similar potency in the TG model as the N-type VGCC blocker, while both ω-agatoxin IVA and ω-conotoxin MVIIC had minimal effects in the SNL model compared with controls. CONCLUSION: These findings suggest that, at the spinal level, N- and L-type VGCC are likely involved in behavioural hypersensitivity states driven by Cav α2 δ1 overexpression. Q-type VGCC has minimal effects in both models. The anti-nociceptive effects of P-type VGCC blocker in the Cav α2 δ1 TG mice, but minimally at the SNL model with presynaptic Cav α2 δ1 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 Cav α2 δ1 dysregulation at the spinal cord level.
BACKGROUND: Overexpression of the voltage-gated calcium channel (VGCC) alpha-2-delta1 subunit protein (Cav α2 δ1 ) has been shown to cause pain states. However, whether VGCC are involved in pain states driven by abnormal Cav α2 δ1 expression is not known. METHODS: Intrathecal injection of N-, P/Q- and L-type VGCC blockers were tested in two models: a transgenic neuronal Cav α2 δ1 overexpression (TG) model with behavioural hypersensitivity and a spinal nerve ligation (SNL) model with Cav α2 δ1 overexpression in sensory pathways and neuropathy pain states. RESULTS: The nociceptive response to mechanical stimuli was significantly attenuated in both models with ω-conotoxin GVIA (an N-type VGCC blocker) and nifedipine (an L-type VGCC blocker), in which ω-conotoxin GVIA appeared more potent than nifedipine. Treatments with ω-agatoxin IVA (P-VGCC blocker), but not ω-conotoxin MVIIC (Q-VGCC blocker) had similar potency in the TG model as the N-type VGCC blocker, while both ω-agatoxin IVA and ω-conotoxin MVIIC had minimal effects in the SNL model compared with controls. CONCLUSION: These findings suggest that, at the spinal level, N- and L-type VGCC are likely involved in behavioural hypersensitivity states driven by Cav α2 δ1 overexpression. Q-type VGCC has minimal effects in both models. The anti-nociceptive effects of P-type VGCC blocker in the Cav α2 δ1 TG mice, but minimally at the SNL model with presynaptic Cav α2 δ1 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 Cav α2 δ1 dysregulation at the spinal cord level.
Authors: D R Hillyard; V D Monje; I M Mintz; B P Bean; L Nadasdi; J Ramachandran; G Miljanich; A Azimi-Zoonooz; J M McIntosh; L J Cruz Journal: Neuron Date: 1992-07 Impact factor: 17.173
Authors: Chun-Ying Li; Xiu-Lin Zhang; Elizabeth A Matthews; Kang-Wu Li; Ambereen Kurwa; Amin Boroujerdi; Jimmy Gross; Michael S Gold; Anthony H Dickenson; Guoping Feng; Z David Luo Journal: Pain Date: 2006-06-09 Impact factor: 6.961
Authors: Amin Boroujerdi; Hee Kee Kim; Yeoung Su Lyu; Doo-Sik Kim; Katherine W Figueroa; Jin Mo Chung; David Z Luo Journal: Pain Date: 2008-06-20 Impact factor: 6.961
Authors: Osvaldo J M Nascimento; Bruno L Pessoa; Marco Orsini; Pedro Ribeiro; Eduardo Davidovich; Camila Pupe; Pedro Moreira Filho; Ricardo Menezes Dornas; Lucas Masiero; Juliana Bittencourt; Victor Hugo Bastos Journal: Neurol Int Date: 2016-06-29
Authors: Sascha Ra Alles; Esperanza Garcia; Sridhar Balasubramanyan; Karen Jones; John R Tyson; Twinkle Joy; Terrance P Snutch; Peter A Smith Journal: Mol Pain Date: 2018 Jan-Dec Impact factor: 3.395