Presynaptic Enhancement of Transmission from Nociceptors Expressing Nav1.8 onto Lamina-I Spinothalamic Tract Neurons by Spared Nerve Injury in Mice DOI Creative Commons

Wei-Chen Hung 洪瑋辰,

Chih-Cheng Chen 陳志成,

Cheng-Tung Yen 嚴震東

et al.

eNeuro, Journal Year: 2024, Volume and Issue: 11(9), P. ENEURO.0087 - 24.2024

Published: Sept. 1, 2024

Alteration of synaptic function in the dorsal horn (DH) has been implicated as a cellular substrate for development neuropathic pain, but certain details remain unclear. In particular, lack information on types synapses that undergo functional changes hinders understanding disease pathogenesis from plasticity perspective. Here, we addressed this issue by using optogenetic and retrograde tracing ex vivo to selectively stimulate first-order nociceptors expressing Nav1.8 (NRs ) record responses spinothalamic tract neurons spinal lamina I (L1-STTNs). We found spared nerve injury (SNI) increased excitatory postsynaptic currents (EPSCs) L1-STTNs evoked photostimulation NRs (referred Nav1.8-STTN EPSCs). This effect was accompanied significant change failure rate paired-pulse ratio transmission L1-STTN frequency (not amplitude) spontaneous EPSCs recorded L1-STTNs. However, no observed AMPA NMDA receptor–mediated components or amplitude unitary constituting with extracellular Ca 2+ replaced Sr . addition, there small increase (approximately 10%) number showing immunoreactivity phosphorylated signal-regulated kinases mice after SNI compared sham. Similarly, only percentage showed lower action potential threshold SNI. conclusion, our results show induces presynaptic modulation at NR (consisting both peptidergic nonpeptidergic nociceptors) forming lateral tract.

Language: Английский

Differential modification of ascending spinal outputs in acute and chronic pain states DOI Creative Commons
David A. Yarmolinsky,

Xiangsunze Zeng,

Natalie MacKinnon-Booth

et al.

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Pain hypersensitivity arises from the induction of plasticity in peripheral and spinal somatosensory neurons, which modifies nociceptive input to brain, altering pain perception. We applied longitudinal calcium imaging dorsal projection neurons determine whether how representation stimuli anterolateral tract, principal pathway transmitting signals changes between distinct states. In healthy mice, we identified stable outputs selective for cooling or warming a neuronal ensemble activated by noxious thermal mechanical stimuli. Induction acute sensitization topical capsaicin transiently re-tuned output encode low-intensity contrast, nerve injury resulted persistent suppression innocuous coupled with activation normally silent population high-threshold neurons. These results demonstrate differential modulation brain during neuropathic

Language: Английский

Citations

1
The dorsal column nuclei scale mechanical sensitivity in naive and neuropathic pain states DOI Creative Commons
Aman Upadhyay, Mark A. Gradwell, Thomas J. Vajtay

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115556 - 115556

Published: April 1, 2025

Language: Английский

Citations

1
Transformation of neural coding for vibrotactile stimuli along the ascending somatosensory pathway DOI Creative Commons
Kuo-Sheng Lee, Alastair J. Loutit,

Dominica de Thomas Wagner

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(19), P. 3343 - 3353.e7

Published: Aug. 6, 2024

Language: Английский

Citations

6
Chronic, Battery‐Free, Fully Implantable Multimodal Spinal Cord Stimulator for Pain Modulation in Small Animal Models DOI Creative Commons
Allie J. Widman,

Taron Bashar,

Alex Burton

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Abstract Spinal cord stimulation (SCS) for chronic pain management is an invasive therapy involving surgical implantation of electrodes into spinal epidural space. While the clinical value and mechanistic action debated considerably in recent years, preclinical studies employing rodent models can provide invaluable insights regarding balance between efficacy complications as well understanding SCS therapy. However, current compatible devices require tethered power delivery or bulky batteries, severely limiting ability to probe long‐term This work introduces a tether‐free, small‐footprint, fully implantable, battery‐free device with models, capable delivering electrical at wide range frequency, amplitude, period via wireless communication adjustable on‐demand without direct interaction animal. The presented features capabilities devices, materials processes amendable scalable fabrication cost suitable one‐time use enabling high N studies. In this proof concept, implantable serves assess therapeutic various clinically relevant paradigms alleviating neuropathic pain. technology offers stability potential serve foundation future research development systems.

Language: Английский

Citations

0
Selective modification of ascending spinal outputs in acute and neuropathic pain states DOI Open Access
David A. Yarmolinsky,

Xiangsunze Zeng,

Natalie MacKinnon-Booth

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 9, 2024

Summary Pain hypersensitivity arises from the plasticity of peripheral and spinal somatosensory neurons, which modifies nociceptive input to brain alters pain perception. We utilized chronic calcium imaging dorsal horn neurons determine how representation stimuli in anterolateral tract, principal pathway transmitting signals brain, changes between distinct states. In healthy conditions, we identify stable, narrowly tuned outputs selective for cooling or warming, a neuronal ensemble activated by intense/noxious thermal mechanical stimuli. Induction an acute sensitization with capsaicin selectively transiently retunes output encode low-intensity contrast, nerve injury-induced neuropathic results persistent suppression innocuous coupled activation normally silent population high-threshold neurons. These demonstrate differential modulation specific during

Language: Английский

Citations

3
Parvalbumin gates chronic pain through the modulation of firing patterns in inhibitory neurons DOI Creative Commons

Haoyi Qiu,

Loïs S. Miraucourt, Hugues Petitjean

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(27)

Published: June 25, 2024

Spinal cord dorsal horn inhibition is critical to the processing of sensory inputs, and its impairment leads mechanical allodynia. How this decreased occurs whether restoration alleviates allodynic pain are poorly understood. Here, we show that a step in loss inhibitory tone change firing pattern parvalbumin (PV)-expressing neurons (PVNs). Our results PV, calcium-binding protein, controls activity PVNs by enabling them sustain high-frequency tonic patterns. Upon nerve injury, transition adaptive decrease their PV expression. Interestingly, necessary sufficient for development allodynia firing. This due recruitment calcium-activated potassium (SK) channels, blocking during chronic restores normal pain. findings indicate essential controlling preventing Developing approaches manipulate these mechanisms may lead different strategies relief.

Language: Английский

Citations

2
The Dorsal Column Nuclei Scale Mechanical Sensitivity in Naive and Neuropathic Pain States DOI Creative Commons
Aman Upadhyay, Mark A. Gradwell, Thomas J. Vajtay

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 23, 2024

Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading touch pain, known mechanical allodynia. Two main drivers peripheral information, mechanoreceptors (LTMRs) postsynaptic dorsal column neurons (PSDCs), terminate in brainstem nuclei (DCN). Activity within DRG, spinal cord, DCN have all been implicated mediating allodynia, yet remains understudied at cellular, circuit, functional levels compared other two. Here, we show that gracile nucleus (Gr) mediates sensitivity for contributes allodynia during neuropathic pain mice. We found Gr contains local inhibitory interneurons addition thalamus-projecting neurons, which are differentially innervated by primary afferents inputs. Functional manipulations these distinct neuronal populations resulted bidirectional changes sensitivity, but did not affect noxious or thermal sensitivity. silencing projection activating was able reduce hypersensitivity, enhancing inhibition ameliorate paw withdrawal signatures like shaking. Collectively, results suggest plays a specific role hypersensitivity low-threshold, innocuous activity affective, pain-associated phenotypes Therefore, circuits work tandem with traditional underlying resulting enhanced signaling brain pain.

Language: Английский

Citations

1
Peripheral direct current reduces naturally evoked nociceptive activity at the spinal cord in rodent models of pain DOI Creative Commons
Tom F. Su,

Jack D. Hamilton,

Yiru Guo

et al.

Journal of Neural Engineering, Journal Year: 2024, Volume and Issue: 21(2), P. 026044 - 026044

Published: April 1, 2024

Electrical neuromodulation is an established non-pharmacological treatment for chronic pain. However, existing devices using pulsatile stimulation typically inhibit pain pathways indirectly and are not suitable all types of Direct current (DC) a recently developed technology which affects small-diameter fibres more strongly than stimulation. Since nociceptors predominantly A

Language: Английский

Citations

1
The Dorsal Column Nuclei Scale Mechanical Sensitivity in Naive and Neuropathic Pain States DOI
Aman Upadhyay, Mark A. Gradwell, Thomas J. Vajtay

et al.

Published: Jan. 1, 2024

Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading touch pain, known mechanical allodynia. Two main drivers peripheral information, mechanoreceptors (LTMRs) postsynaptic dorsal column neurons (PSDCs), terminate in brainstem nuclei (DCN). Activity within DRG, spinal cord, DCN have all been implicated mediating allodynia, yet remains understudied at cellular, circuit, functional levels compared other two. Here, we show that gracile nucleus (Gr) mediates sensitivity for contributes allodynia during neuropathic pain mice. We found Gr contains local inhibitory interneurons addition thalamus-projecting neurons, which are differentially innervated by primary afferents inputs. Functional manipulations these distinct neuronal populations resulted bidirectional changes sensitivity, but did not affect noxious or thermal sensitivity. silencing projection activating was able reduce hypersensitivity, enhancing inhibition ameliorate paw withdrawal signatures like shaking. Collectively, results suggest plays a specific role hypersensitivity low-threshold, innocuous activity affective, pain-associated phenotypes Therefore, circuits work tandem with traditional underlying resulting enhanced signaling brain pain.

Language: Английский

Citations

1
Presynaptic Enhancement of Transmission from Nociceptors Expressing Nav1.8 onto Lamina-I Spinothalamic Tract Neurons by Spared Nerve Injury in Mice DOI Creative Commons

Wei-Chen Hung 洪瑋辰,

Chih-Cheng Chen 陳志成,

Cheng-Tung Yen 嚴震東

et al.

eNeuro, Journal Year: 2024, Volume and Issue: 11(9), P. ENEURO.0087 - 24.2024

Published: Sept. 1, 2024

Alteration of synaptic function in the dorsal horn (DH) has been implicated as a cellular substrate for development neuropathic pain, but certain details remain unclear. In particular, lack information on types synapses that undergo functional changes hinders understanding disease pathogenesis from plasticity perspective. Here, we addressed this issue by using optogenetic and retrograde tracing ex vivo to selectively stimulate first-order nociceptors expressing Nav1.8 (NRs ) record responses spinothalamic tract neurons spinal lamina I (L1-STTNs). We found spared nerve injury (SNI) increased excitatory postsynaptic currents (EPSCs) L1-STTNs evoked photostimulation NRs (referred Nav1.8-STTN EPSCs). This effect was accompanied significant change failure rate paired-pulse ratio transmission L1-STTN frequency (not amplitude) spontaneous EPSCs recorded L1-STTNs. However, no observed AMPA NMDA receptor–mediated components or amplitude unitary constituting with extracellular Ca 2+ replaced Sr . addition, there small increase (approximately 10%) number showing immunoreactivity phosphorylated signal-regulated kinases mice after SNI compared sham. Similarly, only percentage showed lower action potential threshold SNI. conclusion, our results show induces presynaptic modulation at NR (consisting both peptidergic nonpeptidergic nociceptors) forming lateral tract.

Language: Английский

Citations

0