The Known Biology of Neuropathic Pain and Its Relevance to Pain Management DOI Creative Commons
Peter A. Smith

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, Год журнала: 2023, Номер 51(1), С. 32 - 39

Опубликована: Фев. 17, 2023

ABSTRACT: Patients with neuropathic pain are heterogeneous in pathophysiology, etiology, and clinical presentation. Signs symptoms determined by the nature of injury factors such as genetics, sex, prior injury, age, culture, environment. Basic science has provided general information about etiology studying consequences peripheral rodent models. This is associated release inflammatory cytokines, chemokines, growth that sensitize sensory nerve endings, alter gene expression, promote post-translational modification proteins, ion channel function. leads to spontaneous activity primary afferent neurons crucial for onset persistence secondary mediators colony-stimulating factor 1 from terminals. These tertiary brain-derived neurotrophic interleukin-1β microglia astrocytes. Tertiary facilitate transmission nociceptive at spinal, thalamic, cortical levels. For most part, these findings have failed identify new therapeutic approaches. More recent basic better mirrored situation addressing pathophysiology specific types refinement methodology, attention various contributory sex. Improved quantification profiles each patient their distribution into defined clusters may improve translation between practice. If can be traced back cellular molecular aspects this lead personalized medicine approaches dictate a rational approach individual.

Язык: Английский

Parabrachial Calca neurons drive nociplasticity DOI Creative Commons
Logan Condon,

Ying Yu,

Sekun Park

и другие.

Cell Reports, Год журнала: 2024, Номер 43(4), С. 114057 - 114057

Опубликована: Апрель 1, 2024

Pain that persists beyond the time required for tissue healing and pain arises in absence of injury, collectively referred to as nociplastic pain, are poorly understood phenomena mediated by plasticity within central nervous system. The parabrachial nucleus (PBN) is a hub relays aversive sensory information appears play role nociplasticity. Here, preventing PBN Calca neurons from releasing neurotransmitters, we demonstrate activation necessary manifestation maintenance chronic pain. Additionally, directly stimulating neurons, neuron activity sufficient drive Aversive stimuli multiple modalities, such exposure nitroglycerin, cisplatin, or lithium chloride, can nociplasticity Calca-neuron-dependent manner. events form increased excitability; however, neuroplasticity also occur downstream circuitry.

Язык: Английский

Процитировано

14
Nerve injury disrupts temporal processing in the spinal cord dorsal horn through alterations in PV+ interneurons DOI Creative Commons

Genelle Rankin,

Anda M. Chirila,

Alan J. Emanuel

и другие.

Cell Reports, Год журнала: 2024, Номер 43(2), С. 113718 - 113718

Опубликована: Янв. 30, 2024

How mechanical allodynia following nerve injury is encoded in patterns of neural activity the spinal cord dorsal horn (DH) remains incompletely understood. We address this mice using spared model neuropathic pain and vivo electrophysiological recordings. Surprisingly, despite dramatic behavioral over-reactivity to stimuli injury, an overall increase sensitivity or reactivity DH neurons not observed. do, however, observe a marked decrease correlated firing patterns, including synchrony stimulus-evoked firing, across DH. Alterations temporal are recapitulated by silencing parvalbumin+ (PV+) interneurons, previously implicated allodynia, as allodynic pain-like behaviors. These findings reveal decorrelated network activity, driven alterations PV+ prominent feature suggest restoration proper potential therapeutic strategy treat chronic pain.

Язык: Английский

Процитировано

10
Differential modification of ascending spinal outputs in acute and chronic pain states DOI Creative Commons
David A. Yarmolinsky,

Xiangsunze Zeng,

Natalie MacKinnon-Booth

и другие.

Neuron, Год журнала: 2025, Номер unknown

Опубликована: Фев. 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

Язык: Английский

Процитировано

2
A Functional Topographic Map for Spinal Sensorimotor Reflexes DOI Creative Commons
Graziana Gatto, Steeve Bourane, Xiangyu Ren

и другие.

Neuron, Год журнала: 2020, Номер 109(1), С. 91 - 104.e5

Опубликована: Ноя. 11, 2020

Язык: Английский

Процитировано

68
Presynaptic Inhibition of Pain and Touch in the Spinal Cord: From Receptors to Circuits DOI Open Access
Antonella Comitato, Rita Bardoni

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(1), С. 414 - 414

Опубликована: Янв. 2, 2021

Sensory primary afferent fibers, conveying touch, pain, itch, and proprioception, synapse onto spinal cord dorsal horn neurons. Primary central terminals express a wide variety of receptors that modulate glutamate peptide release. Regulation the amount timing neurotransmitter release critically affects integration postsynaptic responses coding sensory information. The role GABA (γ-aminobutyric acid) expressed on is particularly important in processing, both physiological conditions sensitized states induced by chronic pain. During last decade, techniques opto- chemogenetic stimulation neuronal selective labeling have provided interesting insights this topic. This review focused recent advances about modulatory effects presynaptic GABAergic neural circuits involved these mechanisms.

Язык: Английский

Процитировано

45
Spinal cord retinoic acid receptor signaling gates mechanical hypersensitivity in neuropathic pain DOI Creative Commons
Bing Cao, Grégory Scherrer, Lu Chen

и другие.

Neuron, Год журнала: 2022, Номер 110(24), С. 4108 - 4124.e6

Опубликована: Окт. 11, 2022

Язык: Английский

Процитировано

37
Multiscale Computer Model of the Spinal Dorsal Horn Reveals Changes in Network Processing Associated with Chronic Pain DOI Creative Commons
Laura Medlock, Kazutaka Sekiguchi, Sungho Hong

и другие.

Journal of Neuroscience, Год журнала: 2022, Номер 42(15), С. 3133 - 3149

Опубликована: Март 1, 2022

Pain-related sensory input is processed in the spinal dorsal horn (SDH) before being relayed to brain. That processing profoundly influences whether stimuli are correctly or incorrectly perceived as painful. Significant advances have been made identifying types of excitatory and inhibitory neurons that comprise SDH, there some information about how neuron connected, but it remains unclear overall circuit processes disrupted under chronic pain conditions. To explore SDH function, we developed a computational model tightly constrained by experimental data. Our comprises conductance-based models reproduce characteristic firing patterns neurons. Excitatory populations, defined their expression genetic markers, spiking pattern, morphology, were synaptically connected according available qualitative Using algorithm, synaptic weights tuned projection rates (model output) based on primary afferent input) across range mechanical stimulus intensities. Disparate weight combinations could produce equivalent revealing degeneracy may underlie heterogeneous responses different circuits perturbations pathologic insults. validate our model, verified responded reduction inhibition (i.e., disinhibition) ablation specific manner consistent with experiments. Thus validated, offers valuable resource for interpreting results testing hypotheses

Язык: Английский

Процитировано

36
Spinal neuropeptide Y Y1 receptor-expressing neurons are a pharmacotherapeutic target for the alleviation of neuropathic pain DOI Creative Commons
Tyler S. Nelson, Ghanshyam P. Sinha, Diogo Francisco da Silva dos Santos

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(46)

Опубликована: Ноя. 7, 2022

Peripheral nerve injury sensitizes a complex network of spinal cord dorsal horn (DH) neurons to produce allodynia and neuropathic pain. The identification druggable target within this has remained elusive, but promising candidate is the neuropeptide Y (NPY) Y1 receptor-expressing interneuron (Y1-IN) population. We report that spared (SNI) enhanced excitability Y1-INs elicited (mechanical cold hypersensitivity) affective Similarly, chemogenetic or optogenetic activation in uninjured mice behavioral signs spontaneous, allodynic, SNI-induced was reduced by inhibition Y1-INs, intrathecal administration Y1-selective agonist. Conditional deletion

Язык: Английский

Процитировано

30
Endophilin A2 controls touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking DOI Creative Commons

Man-Xiu Xie,

Ren-Chun Lai,

Yi-Bin Xiao

и другие.

Military Medical Research, Год журнала: 2024, Номер 11(1)

Опубликована: Март 12, 2024

Abstract Background Tactile and mechanical pain are crucial to our interaction with the environment, yet underpinning molecular mechanism is still elusive. Endophilin A2 (EndoA2) an evolutionarily conserved protein that documented in endocytosis pathway. However, role of EndoA2 regulation sensitivity its underlying mechanisms currently unclear. Methods Male female C57BL/6 mice (8–12 weeks) male cynomolgus monkeys (7–10 years old) were used experiments. Nerve injury-, inflammatory-, chemotherapy-induced pathological models established for this study. Behavioral tests touch, pain, heat cold performed nonhuman primates. Western blotting, immunostaining, co-immunoprecipitation, proximity ligation patch-clamp recordings gain insight into mechanisms. Results The results showed was primarily distributed neurofilament-200-positive (NF200 + ) medium-to-large diameter dorsal root ganglion (DRG) neurons humans. Loss mouse NF200 DRG selectively impaired tactile allodynia. Furthermore, interacted mechanically sensitive ion channel Piezo2 promoted membrane trafficking neurons. Moreover, as adaptor protein, also bound kinesin family member 5B (KIF5B), which involved EndoA2-mediated process Piezo2. damaged Piezo2-mediated rapidly adapting activated currents, re-expression rescued MA currents. In addition, interference suppressed touch hypersensitivity Conclusions Our data reveal KIF5B/EndoA2/Piezo2 complex essential sustaining transmission signals. regulates allodynia via kinesin-mediated sensory findings identify a potential new target treatment pain.

Язык: Английский

Процитировано

7
The dorsal column nuclei scale mechanical sensitivity in naive and neuropathic pain states DOI Creative Commons
Aman Upadhyay, Mark A. Gradwell, Thomas J. Vajtay

и другие.

Cell Reports, Год журнала: 2025, Номер 44(4), С. 115556 - 115556

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

1