L5-6 Spinal Nerve Ligation-induced Neuropathy Changes the Location and Function of Ca2+ Channels and Cdk5 and Affects the Compound Action Potential in Adjacent Intact L4 Afferent Fibers

Gómez, Kimberly; Vargas-Parada, Alberto; Duran, Paz; Sandoval, Alejandro; Delgado‐Lezama, Rodolfo; Khanna, Rajesh; Felix, Ricardo

doi:10.1016/j.neuroscience.2021.07.013

Cited by 7 publications

(8 citation statements)

References 57 publications

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“…A recent report showed an upregulation of Ca V 3.1 and Ca V 3.3 messenger RNA in TG in a similar model of trigeminal pain, 53 with only minor effects on Ca V 3.2. Our observation that an elevation of Ca V 3.2 expression occurred only in the SpC5 nucleus contrasts with findings showing a robust increase in Ca V 3.2 expression in dorsal root ganglion after sciatic nerve injury, 26,28,29,[35][36][37] but they are consistent with an upregulation of Ca V 3.2 in spinal cord tissue in different models of chronic pain. 8 On the other hand, in a model of spinal nerve ligation, 14 days post surgery, no difference in Ca V 3.2 channel expression was seen in spinal nerves.…”

Section: Discussioncontrasting

confidence: 99%

“…8 On the other hand, in a model of spinal nerve ligation, 14 days post surgery, no difference in Ca V 3.2 channel expression was seen in spinal nerves. 28,29 That said, the observation that Ca V 3.2 levels are increased in SpC5 but not ION or TG suggests that Ca V 3.2 may contribute to central rather than peripheral sensitization of the trigeminal pathway, which may be relevant to the potential therapeutic use of CNS permeant blockers such as Z944.…”

Section: Discussionmentioning

confidence: 99%

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CaV3.2 calcium channels contribute to trigeminal neuralgia

Gambeta

Gandini²,

Souza³

et al. 2022

Pain

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CaV3.2 calcium channels contribute to trigeminal neuralgia

Gambeta

Gandini²,

Souza³

et al. 2022

Pain

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“…Cdk5 inhibitors can inhibit neuralgia through the Cdk5-NR2A pathway (Yang et al, 2014 ) or attenuate the response of TRPA1 (Sulak et al, 2018 ). Cdk5 also plays a critical role in regulating myelin basic protein (MBP) fragment (Chernov et al, 2018 ), inflammatory pain (Zhu et al, 2021 ), and calcium channel (Gomez et al, 2020a , 2021 ) in NP. Cdk5 mediated cyclic AMP response element binding protein (CREB; Li et al, 2014 ) and regulated NP through Cdk5/PPAR γ pathway (Zhong et al, 2019 ).…”

Section: Neuropathic Pain (Np)mentioning

confidence: 99%

The role of Cdk5 in neurological disorders

Chen

et al. 2022

Front. Cell. Neurosci.

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Neurological disorders are a group of disorders with motor, sensory or cognitive damage, caused by dysfunction of the central or peripheral nervous system. Cyclin-dependent kinases 5 (Cdk5) is of vital significance for the development of the nervous system, including the migration and differentiation of neurons, the formation of synapses, and axon regeneration. However, when the nervous system is subject to pathological stimulation, aberrant activation of Cdk5 will induce abnormal phosphorylation of a variety of substrates, resulting in a cascade signaling pathway, and thus lead to pathological changes. Cdk5 is intimately related to the pathological mechanism of a variety of neurological disorders, such as A-β protein formation in Alzheimer’s disease, mitochondrial fragmentation in cerebral ischemia, and apoptosis of dopaminergic neurons in Parkinson’s disease. It is worth noting that Cdk5 inhibitors have been reported to have neuroprotective effects by inhibiting related pathological processes. Therefore, in this review, we will briefly introduce the physiological and pathological mechanisms of Cdk5 in the nervous system, focusing on the recent advances of Cdk5 in neurological disorders and the prospect of targeted Cdk5 for the treatment of neurological disorders.

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“…The upregulation of p35 occurs in the dorsal root ganglia following peripheral inflammation of the rodent hind paw via carrageenan 3 or complete Freund's adjuvant 5 or with neuropathic injury by spinal nerve ligation. 6 Further studies have shown that inflammatory cytokines including tumor necrosis factor α, transforming growth factor β, and nerve growth factor can trigger ERK1/2 activation to subsequently boost p35 expression and ultimately lead to increased Cdk5 activity. 4,7,8 Cdk5 hyperactivity in primary afferent neurons has consequently been implicated with pain hypersensitivity.…”

Section: Introductionmentioning

confidence: 99%

Activation of cyclin-dependent kinase 5 broadens action potentials in human sensory neurons

Tiwari,

Hall,

Ton

et al. 2023

Mol Pain

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Chronic pain is one of the most devastating and unpleasant conditions, associated with many pathological states. Tissue or nerve injuries induce extensive neurobiological plasticity in nociceptive neurons, which leads to chronic pain. Recent studies suggest that cyclin-dependent kinase 5 (CDK5) in primary afferents is a key neuronal kinase that modulates nociception through phosphorylation under pathological conditions. However, the impact of the CDK5 on nociceptor activity especially in human sensory neurons is not known. To determine the CDK5-mediated regulation of human dorsal root ganglia (hDRG) neuronal properties, we have performed the whole-cell patch clamp recordings in neurons dissociated from hDRG. CDK5 activation induced by overexpression of p35 depolarized the resting membrane potential (RMP) and reduced the rheobase currents as compared to the control neurons. CDK5 activation changed the shape of the action potential (AP) by increasing AP -rise time, -fall time, and -half width. The application of a prostaglandin E2 (PG) and bradykinin (BK) cocktail in control hDRG neurons induced the depolarization of RMP and the reduction of rheobase currents along with increased AP rise time. However, PG and BK applications failed to induce any significant changes in the p35-overexpressing group. We conclude that, in dissociated hDRGs neurons, CDK5 activation through the overexpression of p35 broadens the AP and that CDK5 may play important roles in the modulation of AP properties in human primary afferents under the condition in which CDK5 is upregulated, contributing to chronic pain.

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L5-6 Spinal Nerve Ligation-induced Neuropathy Changes the Location and Function of Ca2+ Channels and Cdk5 and Affects the Compound Action Potential in Adjacent Intact L4 Afferent Fibers

Cited by 7 publications

References 57 publications

CaV3.2 calcium channels contribute to trigeminal neuralgia

CaV3.2 calcium channels contribute to trigeminal neuralgia

The role of Cdk5 in neurological disorders

Activation of cyclin-dependent kinase 5 broadens action potentials in human sensory neurons

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