Acute and Chronic Pain Processing in the Thalamocortical System of Humans and Animal Models

Human brain mechanisms of pain perception and regulation in health and disease

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Pain Affect Encoded in Human Anterior Cingulate But Not Somatosensory Cortex

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Chronic back pain is associated with decreased prefrontal and thalamic gray matter density

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Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat

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A new view of pain as a homeostatic emotion

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Chronic pain and medullary descending facilitation

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Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types

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Neuroanatomy of the pain system and of the pathways that modulate pain

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The tripartite synapse: roles for gliotransmission in health and disease

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An astrocytic basis of epilepsy

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Neuropathic pain and spinal microglia: a big problem from molecules in ‘small’ glia

Tsuda, M., Inoue, K., & Salter, M. W. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.12.002 · Cited by 795 · see citing works

P AIN M ECHANISMS : Labeled Lines Versus Convergence in Central Processing

Craig, A. D. (2003) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.26.041002.131022 · Cited by 749 · see citing works

Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states

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Structural plasticity and reorganisation in chronic pain

Kuner, R., & Flor, H. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.162 · Cited by 700 · see citing works

The thalamic reticular nucleus: structure, function and concept

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Central post-stroke pain: clinical characteristics, pathophysiology, and management

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Central representation of chronic ongoing neuropathic pain studied by positron emission tomography

Hsieh, J., Belfrage, M., Stone‐Elander, S., Hansson, P. T., & Ingvar, M. (1995) · Pain · doi:10.1016/0304-3959(95)00048-w · Cited by 636 · see citing works

A thalamic nucleus specific for pain and temperature sensation

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Pain pathways and parabrachial circuits in the rat.

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Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy

Yarnitsky, D., Granot, M., Nahman‐Averbuch, H., Khamaisi, M., & Granovsky, Y. (2012) · Pain · doi:10.1016/j.pain.2012.02.021 · Cited by 561 · see citing works

Neuropathic Pain: Principles of Diagnosis and Treatment

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Dissociation of sensory and affective dimensions of pain using hypnotic modulation.

Rainville, P., Carrier, B., Hofbauer, R. K., Bushnell, C. M., & Duncan, G. H. (1999) · Pain · doi:10.1016/s0304-3959(99)00048-2 · Cited by 530 · see citing works

A Peptide c-Jun N-Terminal Kinase (JNK) Inhibitor Blocks Mechanical Allodynia after Spinal Nerve Ligation: Respective Roles of JNK Activation in Primary Sensory Neurons and Spinal Astrocytes for Neuropathic Pain Development and Maintenance

Zhuang, Z., Wen, Y., Zhang, D.-R., Borsello, T., Bonny, C., Strichartz, G. R., Décosterd, I., & Ji, R. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5290-05.2006 · Cited by 523 · see citing works

Infraslow oscillations modulate excitability and interictal epileptic activity in the human cortex during sleep

Vanhatalo, S., Palva, J. M., Holmes, M., Miller, J. W., Voipio, J., & Kaila, K. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0305375101 · Cited by 517 · see citing works

Evidence for brain glial activation in chronic pain patients

Loggia, M. L., Chonde, D. B., Akeju, O., Arabasz, G., Catana, C., Edwards, R. R., Hill, E., Hsu, S., Izquierdo-Garcia, D., Ji, R.-R., et al. (2015) · Brain · doi:10.1093/brain/awu377 · Cited by 503 · see citing works

Increased EEG power and slowed dominant frequency in patients with neurogenic pain

Sarnthein, J., Stern, J., Aufenberg, C., Rousson, V., & Jeanmonod, D. (2005) · Brain · doi:10.1093/brain/awh631 · Cited by 485 · see citing works

Importance of glial activation in neuropathic pain

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Asymbolia for pain: a sensory‐limbic disconnection syndrome

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Blocking Caspase Activity Prevents Transsynaptic Neuronal Apoptosis and the Loss of Inhibition in Lamina II of the Dorsal Horn after Peripheral Nerve Injury

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Paying attention to the thalamic reticular nucleus

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Diencephalic mechanisms of pain sensation

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Deep brain stimulation for pain relief: A meta-analysis

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Fibromyalgia in women

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Low–threshold calcium spike bursts in the human thalamus

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Dissociable neural responses related to pain intensity, stimulus intensity, and stimulus awareness within the anterior cingulate cortex: a parametric single-trial laser functional magnetic resonance imaging study.

Büchel, C., Bornhövd, K., Quante, M., Glauche, V., Bromm, B., & Weiller, C. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-03-00970.2002 · Cited by 380 · see citing works

Pain following spinal cord injury

Siddall, P., & Loeser, J. D. (2001) · Spinal Cord · doi:10.1038/sj.sc.3101116 · Cited by 370 · see citing works

Transsynaptic degeneration in the superficial dorsal horn after sciatic nerve injury: effects of a chronic constriction injury, transection, and strychnine

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Brain imaging of neuropathic pain

Moisset, X., & Bouhassira, D. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.03.054 · Cited by 338 · see citing works

Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain

Iadarola, M. J., Max, M. B., Berman, K. F., Byas‐Smith, M. G., Coghill, R. C., Gracely, R. H., & Bennett, G. J. (1995) · Pain · doi:10.1016/0304-3959(95)00015-k · Cited by 337 · see citing works

Persistent EEG overactivation in the cortical pain matrix of neurogenic pain patients

Stern, J., Jeanmonod, D., & Sarnthein, J. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.12.042 · Cited by 334 · see citing works

The mediodorsal thalamus as a higher order thalamic relay nucleus important for learning and decision-making

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Phantom body pain in paraplegics: Evidence for a central “pattern generating mechanism” for pain

Melzack, R., & Loeser, J. D. (1977) · Pain · doi:10.1016/0304-3959(77)90133-6 · Cited by 317 · see citing works

The cells of origin of the primate spinothalamic tract

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Characteristics of the bursting pattern of action potentials that occurs in the thalamus of patients with central pain

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Connexin-43 induces chemokine release from spinal cord astrocytes to maintain late-phase neuropathic pain in mice

Chen, G., Park, C., Xie, R., Berta, T., Nedergaard, M., & Ji, R. (2014) · Brain · doi:10.1093/brain/awu140 · Cited by 302 · see citing works

CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms

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Spinothalamic tract neurons that project to medial and/or lateral thalamic nuclei: evidence for a physiologically novel population of spinal cord neurons

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Astrocytes and Ischemic Injury

Takano, T., Oberheim, N., Cotrina, M. L., & Nedergaard, M. (2008) · Stroke · doi:10.1161/strokeaha.108.533166 · Cited by 285 · see citing works

Glial Cells and Chronic Pain

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Spatial and temporal activation of spinal glial cells: Role of gliopathy in central neuropathic pain following spinal cord injury in rats

Gwak, Y. S., Kang, J., Unabia, G. C., & Hulsebosch, C. E. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.10.010 · Cited by 270 · see citing works

Responses of neurons in primate ventral posterior lateral nucleus to noxious stimuli

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Neuronal and microglial mechanisms of neuropathic pain

Zhuo, M., Wu, G., & Wu, L. (2011) · Molecular Brain · doi:10.1186/1756-6606-4-31 · Cited by 256 · see citing works

Pain affect without pain sensation in a patient with a postcentral lesion

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Different Pain, Different Brain: Thalamic Anatomy in Neuropathic and Non-Neuropathic Chronic Pain Syndromes

Gustin, S. M., Peck, C. C., Wilcox, S. L., Nash, P. G., Murray, G. M., & Henderson, L. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5980-10.2011 · Cited by 245 · see citing works

Thalamic Inhibition: Diverse Sources, Diverse Scales

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Somatotopic Activation in the Human Trigeminal Pain Pathway

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Thalamic Control of Visceral Nociception Mediated by T-Type Ca 2+ Channels

Kim, D., Park, D., Choi, S., Lee, S., Sun, M., Kim, C., & Shin, H. (2003) · Science · doi:10.1126/science.1088886 · Cited by 228 · see citing works

Convergence of Cortical and Sensory Driver Inputs on Single Thalamocortical Cells

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Arthritic pain is processed in brain areas concerned with emotions and fear

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Gray matter alterations in chronic pain: A network-oriented meta-analytic approach

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Squirrel monkey lateral thalamus. I. Somatic nociresponsive neurons and their relation to spinothalamic terminals

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Possible role of spinal astrocytes in maintaining chronic pain sensitization: review of current evidence with focus on bFGF/JNK pathway

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Proton magnetic resonance spectroscopy of the thalamus in patients with chronic neuropathic pain after spinal cord injury.

Pattany, P. M., Yezierski, R. P., Widerström-Noga, E. G., Bowen, B. C., Martinez‐Arizala, A., Garcia, B. R., & Quencer, R. M. (2002) · PubMed Central · Cited by 181 · see citing works

Chronic pain: lost inhibition?

Henderson, L. A., Peck, C. C., Petersen, E. T., Rae, C. D., Youssef, A. M., Reeves, J. M., Wilcox, S. L., Akhter, R., Murray, G. M., & Gustin, S. M. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.0174-13.2013 · Cited by 180 · see citing works

Chronic-Pain-Associated Astrocytic Reaction in the Spinal Cord Dorsal Horn of Human Immunodeficiency Virus-Infected Patients

Shi, Y., Gelman, B. B., Lisinicchia, J. G., & Tang, S. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5628-11.2012 · Cited by 177 · see citing works

Abnormal thalamocortical activity in patients with Complex Regional Pain Syndrome (CRPS) Type I

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An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain

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High thalamocortical theta coherence in patients with neurogenic pain

Sarnthein, J., & Jeanmonod, D. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.10.019 · Cited by 174 · see citing works

Suppression of Noxious Stimulus-Evoked Activity in the Ventral Posterolateral Nucleus of the Thalamus by a Cannabinoid Agonist: Correlation between Electrophysiological and Antinociceptive Effects

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Labeled lines meet and talk: population coding of somatic sensations

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Central poststroke pain and Wallenberg's lateral medullary infarction: Frequency, character, and determinants in 63 patients

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Neuronal and microglial mechanisms for neuropathic pain in the spinal dorsal horn and anterior cingulate cortex

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Brain Anatomy Changes Associated with Persistent Neuropathic Pain Following Spinal Cord Injury

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Neuronal responsiveness in the ventrobasal thalamic complex of rats with an experimental peripheral mononeuropathy

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Spinal Cord Injury Immediately Changes the State of the Brain

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Thalamic neuronal activity in rats with mechanical allodynia following contusive spinal cord injury

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Chronic Neuropathic Pain: It's about the Rhythm

Alshelh, Z., Pietro, F. D., Youssef, A. M., Reeves, J. M., Macey, P. M., Vickers, E. R., Peck, C. C., Murray, G. M., & Henderson, L. A. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2768-15.2016 · Cited by 148 · see citing works

Zona Incerta: A Role in Central Pain

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Coordinate-based meta-analysis of experimentally induced and chronic persistent neuropathic pain

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Driver or Coincidence Detector: Modal Switch of a Corticothalamic Giant Synapse Controlled by Spontaneous Activity and Short-Term Depression

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A spino-reticulo-thalamic pathway in the rat: An anatomical study with reference to pain transmission

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Cell death in the superficial dorsal horn in a model of neuropathic pain

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Cortical control of adaptation and sensory relay mode in the thalamus

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A comparison of the burst activity of lateral thalamic neurons in chronic pain and non-pain patients

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Neuronal activity in the region of the thalamic principal sensory nucleus (ventralis caudalis) in patients with pain following amputations

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Thalamic pain: anatomical and physiological indices of prediction

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Chronic deafferentation in monkeys differentially affects nociceptive and nonnociceptive pathways distinguished by specific calcium-binding proteins and down-regulates gamma-aminobutyric acid type A receptors at thalamic levels.

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Is large myelinated fiber loss associated with hyperalgesia in a model of experimental peripheral neuropathy in the rat?

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Thalamic activity and biochemical changes in individuals with neuropathic pain after spinal cord injury

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Brain activity associated with painfully hot stimuli applied to the upper limb: A meta‐analysis

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Long-term trans-synaptic glial responses in the human thalamus after peripheral nerve injury

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Lesions Limited to the Human Thalamic Principal Somatosensory Nucleus (Ventral Caudal) Are Associated with Loss of Cold Sensations and Central Pain

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Mast cell–glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide

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Functional plasticity in primate somatosensory thalamus following chronic lesion of the ventral lateral spinal cord

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Development, refinement, and validation of an equine musculoskeletal pain scale

Auer, U., Kelemen, Z., Vogl, C., von Ritgen, S., Haddad, R., Borda, L. T., Gabmaier, C., Breteler, J., & Jenner, F. (2024) · Frontiers in Pain Research · doi:10.3389/fpain.2023.1292299 · Cited by 16 · see citing works

Effect of experimental orthodontic pain on gray and white matter functional connectivity

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Fibromyalgia pathogenesis explained by a neuroendocrine multistable model

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Thalamocortical bistable switch as a theoretical model of fibromyalgia pathogenesis inferred from a literature survey

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Selected pathobiological features and principles of pharmacological pain management

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Secondary somatosensory cortex glutamatergic innervation of the thalamus facilitates pain

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Aberrant dynamic functional connectivity of thalamocortical circuitry in major depressive disorder

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Distinct Roles of Astrocytes and GABAergic Neurons in the Paraventricular Thalamic Nucleus in Modulating Diabetic Neuropathic Pain

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Evaluation of Neuropathic Pain in a Rat Model of Total Brachial Plexus Avulsion from Behavior to Brain Metabolism

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Functional characterization of nociceptive mechanisms involved in fibromyalgia and electroacupuncture

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Conditioned pain modulation affects the N2/P2 complex but not the N1 wave: A pilot study with laser‐evoked potentials

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Thermosensory thalamus: parallel processing across model organisms

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A systematic review and coordinate-based meta-analysis of fMRI studies on acupuncture at LR 3

Rao, Y., Ge, L., & Wu, J. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1341567 · Cited by 11 · see citing works

Neuroscientific results of experimental studies on the control of acute pain with hypnosis and suggested analgesia

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Radiomodulation in Mixed, Complex Cancer Pain by Triple Target Irradiation in the Brain: A Preliminary Experience

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White matter microstructure predicts measures of clinical symptoms in chronic back pain patients

Robertson, J. W., Aristi, G., & Hashmi, J. (2022) · NeuroImage: Clinical · doi:10.1016/j.nicl.2022.103309 · Cited by 12 · see citing works

Sensory, Affective, and Cognitive Effects of Trigeminal Injury in Mice

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Decreased Functional Connectivity of the Core Pain Matrix in Herpes Zoster and Postherpetic Neuralgia Patients

Yang, J., Jiang, X., Gu, L., Li, J., Wu, Y., Li, L., Xiong, J., Lv, H., Kuang, H., & Jiang, J. P. (2023) · Brain Sciences · doi:10.3390/brainsci13101357 · Cited by 9 · see citing works

Disrupted Resting-State Functional Connectivity and Effective Connectivity of the Nucleus Accumbens in Chronic Low Back Pain: A Cross-Sectional Study

Zhang, B., Guo, M., Dong, T., Yang, H., Zhang, Q., Yang, Q., Zhou, X., Mao, C., & Zhang, M. (2024) · Journal of Pain Research · doi:10.2147/jpr.s455239 · Cited by 8 · see citing works

Increased Thalamocortical Functional Connectivity on Discontinuation of Treatment in Painful Diabetic Peripheral Neuropathy

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Neurometabolite alterations in traumatic brain injury and associations with chronic pain

Robayo, L. E., Govind, V., Salan, T., Cherup, N. P., Sheriff, S., Maudsley, A. A., & Widerström-Noga, E. G. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1125128 · Cited by 9 · see citing works

The role of the anterior pretectal nucleus in pain modulation: A comprehensive review

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Retigabine, a potassium channel opener, restores thalamocortical neuron functionality in a murine model of autoimmune encephalomyelitis

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Thalamocortical dysconnectivity is associated with pain in patients with knee osteoarthritis

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EEG neurofeedback for the treatment of neuropathic pain in the elderly—a mechanistic review

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Preservation of thalamic neuronal function may be a prerequisite for pain perception in diabetic neuropathy: A magnetic resonance spectroscopy study

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The insula represents a key neurobiological pain hub in psoriatic arthritis

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Dual-Target Radiosurgery for Concomitant Continuous Pain Presentation of Trigeminal Neuralgia: Radiomodulation Effect and Dose

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Methanol Extract of Thottea siliquosa (Lam.) Ding Hou Leaves Inhibits Carrageenan- and Formalin-Induced Paw Edema in Mice

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Neural Circuits of Chronic Pain

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Cerebral perfusion alterations in patients with trigeminal neuralgia as measured by pseudo-continuous arterial spin labeling

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Changes in brain functional connectivity associated with ongoing neuropathic pain in patients with painful polyneuropathies

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Brain networking pain and anxiety: From basic mechanism to future treatment

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Causal relationship between gastroesophageal reflux disease, Barrett's esophagus, and epilepsy: A bidirectional Mendelian randomization study

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Aberrant static and dynamic functional connectivity of insular cortex in patients with trigeminal neuralgia

Chen, Y., Li, S., Li, M., Huang, L., Jiang, M., Li, G., Chen, J., & Yan, J. (2025) · Scientific Reports · doi:10.1038/s41598-025-07468-7 · Cited by 4 · see citing works

Diffusion tensor imaging reveals sex differences in pain sensitivity of rats

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Cortical representation of experimental periodontal pain: a functional magnetic resonance imaging study

Maurer, A., Verma, D., Reddehase, A., Scheef, L., Radbruch, A., Attenberger, U. I., Jäger, A., & Boecker, H. (2021) · Scientific Reports · doi:10.1038/s41598-021-94775-4 · Cited by 4 · see citing works

Cortical integration and control of spontaneous neuropathic pain-like behaviour in mice

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Reevaluating thalamic contributions to pain: A translational framework for precision neuromodulation

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Environmental Enrichment Attenuates Repetitive Behavior and Alters the Functional Connectivity of Pain and Sensory Pathways in C58 Mice

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Insights on nervous system biology and anatomy

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Adolescents’ pain-related ontogeny shares a neural basis with adults’ chronic pain in basothalamo-cortical organization

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Thalamocortical and corticostriatal pathways in the progression from acute to chronic musculoskeletal pain: An fMRI study

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A Novel Investigation of an In‐Scanner Alternative to the Cold Pressor Test in Healthy Individuals

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Systematic review on effects of experimental orthodontic tooth displacement on brain activation assessed by fMRI

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Experimental pain modulation via hypnosis: Neurophysiological perspectives

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Functional MRI following sensory stimulation in rat monosodium iodoacetate model of osteoarthritis pain as a tool for drug therapy discovery

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Glymphatic dysfunction in trigeminal neuralgia: A multimodal MRI study

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P2X7 Receptor of Microglia Mediates Neuropathic pain by Regulating Autophagy After Chronic-Constriction InjuryPreprint

Zhong, Q., Huang, Y., Zhang, B., Li, T., Peng, F., Chang, J., chen, C., & Zhang, Z. (2021) · Research Square · doi:10.21203/rs.3.rs-663805/v1 · Cited by 1 · see citing works

Brainstem Structures Involved in the Generation of Reflex Cough

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Brain Mechanisms of Pain and Anxiety of Dental Patients

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Faculty Opinions recommendation of Gamma oscillations in somatosensory cortex recruit prefrontal and descending serotonergic pathways in aversion and nociception.

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Thalamocortical dysconnectivity in knee osteoarthritisPreprint

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Abnormal sensorimotor network in brain functional connectivity in herpes zoster and postherpetic neuralgia patientsPreprint

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Additional file 1 of Altered functional connectivity between hypothalamus and limbic system in fibromyalgia

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White matter reorganization of motor and affective-motivational networks in pain-indifferent carriers of the R221W mutationPreprint

Tamasauskas, A., Perini, I., Minde, J., Keller, S., Fallon, N., Frank, B., Morrison, I., & Marshall, A. (2025) · bioRxiv · doi:10.1101/2025.07.09.663977

From Adversity to Pain: Disrupted Insulo-Cingulo-Thalamic Dynamics in Emotional Abuse and NeglectPreprint

Georgia, A., Smith, B. H., Steele, J. D., & Colvin, L. (2025) · medRxiv · doi:10.1101/2025.09.23.25336443

Protocol for the TMaC Study: A Patient-Blinded, Randomised, Sham-Controlled, Parallel-Group Study Evaluating Effects of Repetitive Transcranial Magnetic Stimulation on Chronic Chemotherapy-Induced Pain in Bowel Cancer Patients

Moore, E. K., Gordon, C., Gauvin, B., Price, T. J., Slee, M., Wardill, H. R., Sidhu, S. K., & Bowen, J. M. (2025) · Biomedicine Hub · doi:10.1159/000549605

Investigation of endocannabinoids in plasma and their correlation with physical fitness and resting state functional connectivity of the periaqueductal grey in women with fibromyalgia: An exploratory secondary study

Ghafouri, B., Stensson, N., Simon, R. A., Mayo, L. M., Lund, E., Forsgren, M. F., Leinhard, O. D., Lundberg, P., & van Ettinger-Veenstra, H. (2025) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2025-0023

Anatomical and molecular organization of the nociceptive medial thalamusPreprint

Ejoh, L. L., Ortega, R. A. S., Wu, J. W. K., Elhiraika, A., Mahmood, M., Kim, K. S., Li, E., Joseph, O., Wooldridge, L. M., Wojick, J. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.05.692629

Modulatory effects of genetic vs. pharmacological HCN4 channel inhibition on stimuli transmission during acute pain

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White matter differences in motor and affective-motivational networks of pain-indifferent carriers of the R221W mutation

Tamasauskas, A., Perini, I., Minde, J., Keller, S. S., Fallon, N., Frank, B., Morrison, I., & Marshall, A. (2026) · Neurobiology of Pain · doi:10.1016/j.ynpai.2026.100211

Relations fonctionnelles entre cortex moteur et douleur

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Peripheral nerve injury increases the probability of thalamocortical burst firing remotely via microglia-dependent enhancement of tonic inhibition

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Deep brain stimulation as a treatment for chronic pain: a narrative and historical review.

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Effects of transcutaneous auricular nerve stimulation on thalamic relay: A randomized brain imaging study in chronic low back pain patients

Wu, Y., Kong, Q., Saccà, V., Reddy, S., Hodges, S., Li, Y., & Kong, J. (2026) · Brain Research · doi:10.1016/j.brainres.2026.150447

Cortical and brainstem mechanisms of pain: linking defensive responses, descending modulation, and affective–sensory integration

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Hierarchically and Temporally Distinct Ca 2+ Signaling Across Thalamic Nuclei During Nociceptive Stimulation

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A hierarchical framework for nociplastic pain mechanisms

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Nociceptive sensitivity in rats under chronic unpredictable mild stress following administration of innate immune response receptor blocker

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Pain processing in the thalamocortical system

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Chapter 6 The role of the thalamus in pain

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Dynamics of circadian thalamocortical flow of information during a peripheral neuropathic pain condition

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Altered connectivity between the thalamus and somatosensory cortex during chronic pain

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