Calcium signalling through L‐type calcium channels: role in pathophysiology of spinal nociceptive transmission

Roca-Lapirot, Olivier; Radwani, Houda; Aby, Franck; Nagy, Frédéric; Landry, Marc; Fossat, Pascal

doi:10.1111/bph.13747

Cited by 54 publications

(61 citation statements)

References 135 publications

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“…It is also possible to co‐culture DRG and spinal cord neurons to investigate nociceptive function (Yu et al ., ). Postsynaptic expression of Ca V 1 family voltage‐gated Ca 2+ channels in the dorsal horn may also contribute to maintenance of pathological pain (Roca‐Lapirot et al ., ). Thus, the Ca V 1.2 channel is expressed somatically and at proximal dendritic shafts, and Ca V 1.3 channels at distal somato‐dendritic compartments.…”

Section: Measuring Ion Channel Function In Nociceptive Pathwaysmentioning

confidence: 97%

Recent advances in targeting ion channels to treat chronic pain

Stevens¹,

Stephens

2018

British J Pharmacology

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Section: Measuring Ion Channel Function In Nociceptive Pathwaysmentioning

confidence: 97%

Recent advances in targeting ion channels to treat chronic pain

Stevens¹,

Stephens

2018

British J Pharmacology

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“…We assessed the role of ILs in windup of the flexion reflex, using two different families of blockers [14]. First, we applied 100 µg of verapamil, a blocker of the phenylalkylamine family.…”

Section: Windup Of the Flexion Reflex Is Sensitive To Il Blockers Inmentioning

confidence: 99%

“…Repetitive nociceptive stimulations of the ipsilateral paw elicit a windup of nociceptive flexion. It has been shown that windup of the flexion reflex in juvenile rats depends on a synaptic balance between excitation and inhibition that allows expression of intrinsic properties [11,13,14]. However, the flexion reflex is the output of a neural circuit that comprises both DHNs and motor neurons, and the latter ones also exhibit a windup of their discharge that presents the same molecular sensitivity as windup of DHNs [8,9,15].…”

Section: Introductionmentioning

confidence: 99%

Windup of Nociceptive Flexion Reflex Depends on Synaptic and Intrinsic Properties of Dorsal Horn Neurons in Adult Rats

Aby

Bouali‐Benazzouz

Landry

et al. 2019

IJMS

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Windup, a progressive increase in spinal response to repetitive stimulations of nociceptive peripheral fibers, is a useful model to study central sensitization to pain. Windup is expressed by neurons in both the dorsal and ventral horn of the spinal cord. In juvenile rats, it has been demonstrated both in vivo and in vitro that windup depends on calcium-dependent intrinsic properties and their modulation by synaptic components. However, the involvement of these two components in the adults remains controversial. In the present study, by means of electromyographic and extracellular recordings, we show that windup in adults, in vivo, depends on a synaptic balance between excitatory N-methyl-D-aspartate (NMDA) receptors and inhibitory glycinergic receptors. We also demonstrate the involvement of L-type calcium channels in both the dorsal and ventral horn of the spinal cord. These results indicate that windup in adults is similar to juvenile rats and that windup properties are the same regardless of the spinal network, i.e., sensory or motor.

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“…Intrathecal delivery preclinically of channel blockers (nifedipine, verapamil and benzothiazepines) have shown efficiency in altering injury induced hyperpathia. 73 …”

Section: Survey Of Current Targets Of Pain Therapeuticsmentioning

confidence: 99%

Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics

Knezevic

Yekkirala

Yaksh

2017

Anesthesia &Amp; Analgesia

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Opioids Opioids represent an efficacious therapeutic modality for some, but not all pain states. Singular reliance on opioid therapy for pain management, has limitations and abuse potential has deleterious consequences for patient and society. Our understanding of pain biology has yielded insights and opportunities for alternatives to conventional opioid agonists. The aim is to have efficacious therapies, with acceptable side effect profiles and minimal abuse potential, which is to say an absence of re-enforcing activity in the absence of a pain state. The present work provides a non-exclusive overview of current drug targets and potential future directions of research and development. We discuss channels activators and blockers, including: sodium channel blockers, potassium channel activators and calcium channel blockers; glutamate receptor targeted agents, including: NMDA, AMPA and metabotropic receptors). Further, we discuss therapeutics targeted at GABA, alpha2 adrenergic and opioid receptors. We also considered antagonists of angiotensin 2 and Toll receptors, and agonists/antagonists of adenosine, purine receptors. And cannabinoids. Novel targets considered are those focusing on lipid mediators and anti-inflammatory cytokines. Of interest is development of novel targeting strategies which produce long-term alterations in pain signaling, including viral transfection and toxins. We consider issues in the development of drugable molecules, including preclinical screening. While there are examples of successful translation, mechanistically promising pre-clinical candidates may unexpectedly fail during clinical trials because the preclinical models may not recapitulate the particular human pain condition being addressed. Molecular target characterization can diminish the disconnect between preclinical and humans’ targets, which should assist in developing non-addictive analgesics.

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Calcium signalling through L‐type calcium channels: role in pathophysiology of spinal nociceptive transmission

Abstract: This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.

Cited by 54 publications

References 135 publications

Recent advances in targeting ion channels to treat chronic pain

Recent advances in targeting ion channels to treat chronic pain

Windup of Nociceptive Flexion Reflex Depends on Synaptic and Intrinsic Properties of Dorsal Horn Neurons in Adult Rats

Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics

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