Pregabalin as a Pain Therapeutic: Beyond Calcium Channels DOI Creative Commons
Sascha R.A. Alles, Stuart M. Cain, Terrance P. Snutch

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: April 15, 2020

Initially developed with the aim of generating new treatments for epilepsy, gabapentin and pregabalin ("gabapentinoids") were engineered to mimic action GABA modulate metabolism. Rather than their intended pharmacological on neurotransmission, instead they exhibit a high affinity α2δ-1and -2 subunits voltage-activated calcium channels, wherein binding gabapentinoids inhibits cellular influx attenuates neurotransmission. Despite lack activity levels, are effective at suppressing seizures subsequently approved as class antiepileptic therapy partial-onset epilepsy. Through same hypothesized molecular mechanism by controlling neuronal hyperexcitability, demonstrate clear efficacy in pain management, which has arguably been most extensively prescribed application date. In this review, we focus second-generation gabapentinoid widely employed treatment variety conditions. We also discuss wider functional roles  contributions that might play affecting physiological pathophysiological processes.

Language: Английский

Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury DOI Creative Commons
Cédric Peirs, Sean-Paul G. Williams, Xinyi Zhao

et al.

Neuron, Journal Year: 2020, Volume and Issue: 109(1), P. 73 - 90.e7

Published: Nov. 11, 2020

Language: Английский

Citations

152
Brain circuits for pain and its treatment DOI
Nicole Mercer Lindsay, Chong Chen, Gadi Gilam

et al.

Science Translational Medicine, Journal Year: 2021, Volume and Issue: 13(619)

Published: Nov. 10, 2021

Understanding the organization of brain’s pain circuits is critical for developing effective treatments patients suffering from chronic pain.

Language: Английский

Citations

148
Microglia-mediated degradation of perineuronal nets promotes pain DOI Open Access
Shannon Tansley, Ning Gu, Alba Ureña Guzmán

et al.

Science, Journal Year: 2022, Volume and Issue: 377(6601), P. 80 - 86

Published: May 26, 2022

Activation of microglia in the spinal cord dorsal horn after peripheral nerve injury contributes to development pain hypersensitivity. How activated selectively enhance activity nociceptive circuits is not well understood. We discovered that injury, degrade extracellular matrix structures, perineuronal nets (PNNs), lamina I horn. Lamina PNNs enwrap spinoparabrachial projection neurons, which integrate information and convey it supraspinal brain regions induce sensation. Degradation by enhances neurons induces pain-related behaviors. Thus, injury-induced degradation a mechanism augment output cause

Language: Английский

Citations

128
Neocortical circuits in pain and pain relief DOI
Linette Liqi Tan, Rohini Kuner

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(8), P. 458 - 471

Published: June 14, 2021

Language: Английский

Citations

112
A review of dorsal root ganglia and primary sensory neuron plasticity mediating inflammatory and chronic neuropathic pain DOI Creative Commons

Kyeongran Jang,

Sandra M. Garraway

Neurobiology of Pain, Journal Year: 2024, Volume and Issue: 15, P. 100151 - 100151

Published: Jan. 1, 2024

Pain is a sensory state resulting from complex integration of peripheral nociceptive inputs and central processing. consists adaptive pain that acute beneficial for healing maladaptive often persistent pathological. indeed heterogeneous, can be expressed as nociceptive, inflammatory, or neuropathic in nature. Neuropathic an example occurs after spinal cord injury (SCI), which triggers wide range neural plasticity. The processing underlies hypersensitivity well-studied the cord. However, recent investigations show plasticity leads to pain, including SCI, also exists at sites, such dorsal root ganglia (DRG), contains cell bodies neurons. This review discusses important role DRGs play inflammatory pain. Specifically, it highlights nociceptor hyperexcitability critical increased states. Furthermore, reviews prior literature on glutamate receptors, voltage-gated sodium channels (VGSC), brain-derived neurotrophic factor (BDNF) signaling DRG contributors We previously reviewed BDNF's bidirectional neuromodulator Here, we shift focus periphery discuss BDNF-TrkB expression nociceptors, non-nociceptor neurons, non-neuronal cells potential contributor induction persistence SCI. Overall, this presents comprehensive evaluation large work individually DRG, BDNF, understand their interaction

Language: Английский

Citations

23
Two-year outcomes using fast-acting sub-perception therapy for spinal cord stimulation: results of a real-world multicenter study in the United States DOI Creative Commons

Clark Metzger,

Blake Hammond,

Richard Ferro

et al.

Expert Review of Medical Devices, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 10

Published: Jan. 16, 2025

Background Fast-acting Sub-perception Therapy (FAST) is a novel spinal cord stimulation (SCS) modality delivering paresthesia-free pain relief. Our study evaluated the longer-term, real-world impact of FAST on chronic pain.

Language: Английский

Citations

2
Neuronal and microglial mechanisms for neuropathic pain in the spinal dorsal horn and anterior cingulate cortex DOI Creative Commons
Makoto Tsuda,

Kohei Koga,

Tao Chen

et al.

Journal of Neurochemistry, Journal Year: 2017, Volume and Issue: 141(4), P. 486 - 498

Published: March 2, 2017

Neuropathic pain is a debilitating chronic condition occurring after damage in the nervous system and refractory to currently available treatments. Major challenges include elucidating its mechanisms developing new medications treat it. Nerve injury-induced hypersensitivity involves aberrant excitability spinal dorsal horn (SDH) neurons as consequence of dysfunction inhibitory interneurons hyperactivity glial cells, especially microglia, immune cells central system. Evidence this found using animal models investigate molecular cellular neuropathic pain. The pathologically altered somatosensory signals SDH then convey brain regions, including anterior cingulate cortex (ACC). In these nerve injury produces pre- postsynaptic long-term plasticity, which contributes negative emotions anxiety associated with conditions. Furthermore, recent evidence also indicates that descending projection pathways from ACC directly indirectly (the top-down corticospinal network) regulate nociceptive sensory transmission SDH. Thus, understanding possible connection between ACC, neuron-microglia interaction, may provide us insights into used amplify related clues aid development therapeutic agents for management This article part special series "Pain".

Language: Английский

Citations

148
Defining a Spinal Microcircuit that Gates Myelinated Afferent Input: Implications for Tactile Allodynia DOI Creative Commons
Kieran A. Boyle, Mark A. Gradwell, Toshiharu Yasaka

et al.

Cell Reports, Journal Year: 2019, Volume and Issue: 28(2), P. 526 - 540.e6

Published: July 1, 2019

Chronic pain presents a major unmet clinical problem. The development of more effective treatments is hindered by our limited understanding the neuronal circuits underlying sensory perception. Here, we show that parvalbumin (PV)-expressing dorsal horn interneurons modulate passage information conveyed low-threshold mechanoreceptors (LTMRs) directly via presynaptic inhibition and also gate polysynaptic relay LTMR input to inhibiting lamina II excitatory whose axons project into I. We changes in functional properties these PV following peripheral nerve injury silencing cells unmasks circuit allows innocuous touch inputs activate increasing network activity laminae I–IV. Such are likely result tactile allodynia could be targeted for treatment mechanical pain.

Language: Английский

Citations

117
NMDA Receptor Activation Underlies the Loss of Spinal Dorsal Horn Neurons and the Transition to Persistent Pain after Peripheral Nerve Injury DOI Creative Commons
Perrine Inquimbert,

Martin Moll,

Alban Latrémolière

et al.

Cell Reports, Journal Year: 2018, Volume and Issue: 23(9), P. 2678 - 2689

Published: May 1, 2018

Peripheral nerve lesions provoke apoptosis in the dorsal horn of spinal cord. The cause cell death, involvement neurons, and relevance for processing somatosensory information are controversial. Here, we demonstrate a mouse model sciatic injury that glutamate-induced neurodegeneration loss γ-aminobutyric acid (GABA)ergic interneurons superficial promote transition from acute to chronic neuropathic pain. Conditional deletion Grin1, essential subunit N-methyl-d-aspartate-type glutamate receptors (NMDARs), protects neurons excitotoxicity preserves GABAergic inhibition. Mice deficient functional NMDARs exhibit normal nociceptive responses pain after injury, but this initial increase sensitivity is reversible. Eliminating fully prevents persistent pain-like behavior. Reduced mice lacking proapoptotic Bax confirmed significance neurodegeneration. We conclude NMDAR-mediated neuron death contributes development

Language: Английский

Citations

113
Recent advances in our understanding of the organization of dorsal horn neuron populations and their contribution to cutaneous mechanical allodynia DOI Creative Commons
Cédric Peirs, Radhouane Dallel, Andrew J. Todd

et al.

Journal of Neural Transmission, Journal Year: 2020, Volume and Issue: 127(4), P. 505 - 525

Published: April 1, 2020

Abstract The dorsal horns of the spinal cord and trigeminal nuclei in brainstem contain neuron populations that are critical to process sensory information. Neurons these areas highly heterogeneous their morphology, molecular phenotype intrinsic properties, making it difficult identify functionally distinct cell populations, determine how engaged pathophysiological conditions. There is a growing consensus concerning classification based on transcriptomic transductomic analyses horn. These approaches have led discovery several molecularly defined types been implicated cutaneous mechanical allodynia, prevalent difficult-to-treat symptom chronic pain, which touch becomes painful. main objective this review provide contemporary view horn neuronal describe recent advances our understanding they participate allodynia.

Language: Английский

Citations

99