Cited by 3,781Pain Mechanisms and TreatmentsPain Management and TreatmentNeuroscience and Neuropharmacology Research

The DOI matches its Crossref record; 75 of the 76 references it cites were found in a registry or an index.

Neuronal Plasticity: Increasing the Gain in Pain

Woolf, Clifford J., Salter, Michael W.·2000·Science

Open this paper in CoChat — free account

Abstract

We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is not homogeneous, however, and comprises three categories: physiological, inflammatory, and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an expression of neural plasticity-the capacity of neurons to change their function, chemical profile, or structure. Here, we develop a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain, identifying distinct forms of plasticity, which we term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity.

Integrity signals

Registry

Crossref · 10.1126/science.288.5472.1765

Cites

75 of 75 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The capsaicin receptor: a heat-activated ion channel in the pain pathway
Caterina, M. J., Schumacher, M. A., Tominaga, M., Rosen, T. A., Levine, J. D., & Julius, D. J. (1997) · Nature · doi:10.1038/39807 · Cited by 9,132
Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones
Mayer, M. L., Westbrook, G. L., & Guthrie, P. B. (1984) · Nature · doi:10.1038/309261a0 · Cited by 2,941
Long-Term Potentiation--A Decade of Progress?
Malenka, R. C., & Nicoll, A. R. A. (1999) · Science · doi:10.1126/science.285.5435.1870 · Cited by 2,729
Neuropathic pain: aetiology, symptoms, mechanisms, and management
Woolf, C. J., & Mannion, R. (1999) · The Lancet · doi:10.1016/s0140-6736(99)01307-0 · Cited by 2,231
Evidence for a central component of post-injury pain hypersensitivity
Woolf, C. J. (1983) · Nature · doi:10.1038/306686a0 · Cited by 2,157
A capsaicin-receptor homologue with a high threshold for noxious heat
Caterina, M. J., Rosen, T. A., Tominaga, M., Brake, A. J., & Julius, D. J. (1999) · Nature · doi:10.1038/18906 · Cited by 1,599
Peripheral nerve injury triggers central sprouting of myelinated afferents
Woolf, C. J., Shortland, P. J., & Coggeshall, R. E. (1992) · Nature · doi:10.1038/355075a0 · Cited by 1,083
The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways
Akopian, A. N., Souslova, V., England, S. G., Okuse, K., Ogata, N., Ure, J. M., Smith, A., Kerr, B. J., McMahon, S. B., Boyce, S., et al. (1999) · Nature Neuroscience · doi:10.1038/9195 · Cited by 828
Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity
Ji, R., Baba, H., Brenner, G. J., & Woolf, C. J. (1999) · Nature Neuroscience · doi:10.1038/16040 · Cited by 787
Messenger plasticity in primary sensory neurons following axotomy and its functional implications
Hökfelt, T. G. M., Zhang, X., & Wiesenfeld‐Hallin, Z. (1994) · Trends in Neurosciences · doi:10.1016/0166-2236(94)90031-0 · Cited by 742

Flagged first, then by citations

Show all 76 references

1 of the 76 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

Aley K. O., Levine J. D., J. Neurosci. 19, 22181 (1999).
Koltzenburg M., Wahren L. K., Torebjork H. E., Pfluegers Arch. 420, R52 (1992).

Sorted by citations

Items 501–600 of 1,014

Reward‐aversion circuitry in analgesia and pain: Implications for psychiatric disorders
Borsook, D., Becerra, L. R., Carlezon, W. A., Shaw, M. E., Renshaw, P. F., Elman, I., & Levine, J. D. (2006) · European Journal of Pain · doi:10.1016/j.ejpain.2005.12.005 · Cited by 124
Effect of Axillary Lymph Node Dissection on Prevalence and Intensity of Chronic and Phantom Pain After Breast Cancer Surgery
Steegers, M. A. H., Wolters, B., Evers, A. W. M., Strobbe, L. J. A., & Wilder‐Smith, O. H. G. (2008) · Journal of Pain · doi:10.1016/j.jpain.2008.04.001 · Cited by 121
New is the well-forgotten old: The use of dry cupping in musculoskeletal medicine
Rozenfeld, E., & Kalichman, L. (2015) · Journal of Bodywork and Movement Therapies · doi:10.1016/j.jbmt.2015.11.009 · Cited by 122
“It is likely that this manipulation of the skin and deeper tissue layers will stimulate the inhibitory receptive fields of cortically projecting multi receptive dorsal horn neurons or provoke diffuse noxious inhibitory controls (Le Bars, 2002; Ji and Woolf, 2001; Woolf and Salter, 2000).”
Acute and chronic whiplash disorders - a review
Sterner, Y., & Gerdle, B. U. C. (2004) · Journal of Rehabilitation Medicine · doi:10.1080/16501970410030742 · Cited by 122
“The net effect of these changes is a progressive increase of action potential discharge (64, 106).”
BackgroundInfluential
Role of adult hippocampal neurogenesis in persistent pain
Apkarian, A. V., Mutso, A., Centeno, M. V., Kan, L., Wu, M. V., Levinstein, M. R., Banisadr, G., Gobeske, K. T., Miller, R. J., Radulović, J., et al. (2015) · Pain · doi:10.1097/j.pain.0000000000000332 · Cited by 120
“Inflammatory tissue injuries give rise to peripheral and spinal cord reorganization specific to such injuries.(27,50) Such injuries are commonly associated with increased sensitivity to tactile, heat, and cold stimuli, and importantly the related behaviors and neural”
Background
A review of SSRIs and SNRIs in neuropathic pain
Lee, Y.-C., & Chen, P.-P. (2010) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2010.507192 · Cited by 128
“In the events following peripheral nerve injury, excessive nociceptive stimulation and the persistent barrages of impulses from primary afferents to the spinal cord may result in the degeneration and loss of inhibitory neurons in descending pathways leading to enhanced sensitivity and heightened excitability [15-17].”
Background
Role of curcumin in the management of pathological pain
Sun, J., Chen, F., Braun, C., Zhou, Y., Rittner, H. L., Tian, Y., Cai, X.-Y., & Ye, D. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.04.045 · Cited by 125
Dynamics of Pain: Fractal Dimension of Temporal Variability of Spontaneous Pain Differentiates Between Pain States
Foss, J. M., Apkarian, A. V., & Chialvo, D. R. (2005) · Journal of Neurophysiology · doi:10.1152/jn.00768.2005 · Cited by 117
Brain-derived neurotrophic factor contributes to spinal long-term potentiation and mechanical hypersensitivity by activation of spinal microglia in rat
Zhou, L., Yang, T., Xiao, W., Liu, Y., Xin, W., Chen, Y., Pang, R., Zang, Y., Li, Y.-Y., & Liu, X. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.09.025 · Cited by 122
“A large body of evidence has shown that central sensitization, referring to the augmented response of central signaling neurons, plays a key role in the initiation and maintenance of neuropathic pain (Campbell and Meyer, 2006; Woolf and Salter, 2000).”
Background
Thermal Thresholds Predict Painfulness of Diabetic Neuropathies
Krämer, H. H., Rolke, R., Bickel, A., & Birklein, F. (2004) · Diabetes Care · doi:10.2337/diacare.27.10.2386 · Cited by 121
“The most important mechanisms are the accumulation of sodium channels on injured axons (5), sympatho-afferent coupling (6), disinhibition of nociception (7), and peripheral or central sensitization (8).”
Background
Spinal injection of TNF‐α‐activated astrocytes produces persistent pain symptom mechanical allodynia by releasing monocyte chemoattractant protein‐1
Gao, Y., Zhang, L., & Ji, R. (2010) · Glia · doi:10.1002/glia.21056 · Cited by 126
Antinociceptive Action of Nitrous Oxide Is Mediated by Stimulation of Noradrenergic Neurons in the Brainstem and Activation of α2BAdrenoceptors
Sawamura, S., Kingery, W. S., Davies, M. F., Agashe, G. S., Clark, J. D., Kobilka, B. K., Hashimoto, T., & Maze, M. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-24-09242.2000 · Cited by 136
Circuitry and plasticity of the dorsal horn – Toward a better understanding of neuropathic pain
West, S. J., Bannister, K., Dickenson, A. H., & Bennett, D. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.020 · Cited by 129
“It is well acknowledged that central plasticity plays a role in the hypersensitivity seen following peripheral nerve injury (Dubner and Ruda, 1992; Woolf and Salter, 2000; dorsal horn –”
Background
Non-opioid IV adjuvants in the perioperative period: Pharmacological and clinical aspects of ketamine and gabapentinoids
Weinbroum, A. A. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.01.002 · Cited by 120
“Peripheral and central senitizations contribute to the postoperative hypersensitivity state hat is responsible for a decrease in pain threshold and for the estabishment of aberrant excitatory synaptic connections, both at the ite of injury (primary hyperalgesia) and in the surrounding uninured tissue (secondary hypera…”
Background
Immune mediators of chronic pelvic pain syndrome
Murphy, S. F., Schaeffer, A. J., & Thumbikat, P. (2014) · Nature Reviews Urology · doi:10.1038/nrurol.2014.63 · Cited by 117
Crystal structures of human glycine receptor α3 bound to a novel class of analgesic potentiators
Huang, X. Y., Shaffer, P. L., Ayube, S., Bregman, H. S., Chen, H., Lehto, S. G., Luther, J. A., Matson, D. J., McDonough, S. I., Michelsen, K., et al. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3329 · Cited by 120
Multimodal Analgesia for Total Joint Arthroplasty
Halawi, M. J., Grant, S. A., & Bolognesi, M. P. (2015) · Orthopedics · doi:10.3928/01477447-20150701-61 · Cited by 124
Muscle Pain: Understanding the Mechanisms
Mense, S., & Gerwin, R. D. (2010) · Springer eBooks · doi:10.1007/978-3-540-85021-2 · Cited by 120
Central Neuronal Plasticity, Low Back Pain and Spinal Manipulative Therapy
Boal, R., & Gillette, R. G. (2004) · Journal of Manipulative and Physiological Therapeutics · doi:10.1016/j.jmpt.2004.04.005 · Cited by 121
Serotonergic neural precursor cell grafts attenuate bilateral hyperexcitability of dorsal horn neurons after spinal hemisection in rat
Hains, B. C., Johnson, K. M., Eaton, M. J., Willis, W. D., & Hulsebosch, C. E. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00729-7 · Cited by 120
“... 1958; Murray and Goldberger, 1974, 1986; Polistina et al., 1990) which alters innervation density and laminar distribution; (8) transmitter/transporter/receptor plasticity that alter activation states of ion channels, and ion or G-coupled receptors (Hains et al., 2002b; Mills et al., 2001; Vera-Portocarrero et al.…”
Background
Up–Down Reader: An Open Source Program for Efficiently Processing 50% von Frey Thresholds
González‐Cano, R., Boivin, B., Bullock, D., Cornelissen, L., Andrews, N., & Costigan, M. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00433 · Cited by 118
“Tactile hyper-or hypo-sensitivity can be the result of rare congenic conditions (Bennett and Woods, 2014) or more commonly through disease, both inﬂammatory (Woolf and Salter, 2000) and neuropathic (Costigan et al., 2009).”
Background
Microsurgical Denervation of the Spermatic Cord for Chronic Orchialgia: Long-Term Results From a Single Center
Strom, K. H., & Levine, L. A. (2008) · The Journal of Urology · doi:10.1016/j.juro.2008.05.018 · Cited by 119
A Placebo-Controlled Randomized Crossover Trial of the N-Methyl-d-Aspartic Acid Receptor Antagonist, Memantine, in Patients with Chronic Phantom Limb Pain
Wiech, K., Kiefer, R. T., pfner, S. T., Preissl, H. T., Braun, C., Unertl, K. E., Flor, H., & Birbaumer, N. (2004) · Anesthesia & Analgesia · doi:10.1213/01.ane.0000096002.53818.bd · Cited by 119
“Among a variety of different receptors involved in the central processing of pain, NMDA receptors have been discussed as crucial for central sensitization after nerve trauma (1,33).”
Background
Depression and chronic pain
Holmes, A., Christelis, N., & Arnold, C. A. (2013) · The Medical Journal of Australia · doi:10.5694/mja12.10589 · Cited by 119
Human surrogate models of neuropathic pain
Binder, A. (2015) · Pain · doi:10.1097/j.pain.0000000000000460 · Cited by 119
“plasticity within the nociceptive system that is induced by the model method and comprises reversible modulation of the nociceptive system.(8,33) Pain models never display phase 3”
Method
Oscillatory mechanism in primary sensory neurones
Amir, R., Liu, C., Kocsis, J. D., & Devor, M. G. (2002) · Brain · doi:10.1093/brain/awf037 · Cited by 119
Neuromuscular deficits after peripheral joint injury: A neurophysiological hypothesis
Ward, S., Pearce, A. J., Pietrosimone, B., Bennell, K. L., Clark, R. A., & Bryant, A. L. (2014) · Muscle & Nerve · doi:10.1002/mus.24463 · Cited by 118
Hippocampal neurokinin-1 receptor and brain-derived neurotrophic factor gene expression is decreased in rat models of pain and stress
Duric, V., & McCarson, K. E. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.04.002 · Cited by 118
Neurobiology of Chronic Tension-Type Headache
Ashina, M. (2004) · Cephalalgia · doi:10.1111/j.1468-2982.2003.00644.x · Cited by 118
Roles of CaMKII, PKA, and PKC in the Induction and Maintenance of LTP of C-Fiber-Evoked Field Potentials in Rat Spinal Dorsal Horn
Yang, H.-W., Hu, X.-D., Zhang, H., Xin, W., Li, M.-T., Zhang, T., Zhou, L., & Liu, X. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00735.2003 · Cited by 116
Patients initially diagnosed as ‘warm’ or ‘cold’ CRPS 1 show differences in central sensory processing some eight years after diagnosis: a quantitative sensory testing study
Vaneker, M., Wilder-smith, O., Schrombges, P., de Man-Hermsen, I., & Oerlemans, M. (2005) · Pain · doi:10.1016/j.pain.2005.02.031 · Cited by 79
Update on the role of non-opioids for postoperative pain treatment
Schug, S. A., & Manopas, A. R. (2007) · Best practice & research. Clinical anaesthesiology · doi:10.1016/j.bpa.2006.12.002 · Cited by 117
Functional and structural imaging of pain-induced neuroplasticity
Seifert, F. C., & Maihöfner, C. (2011) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0b013e32834a1079 · Cited by 123
Chapter 27 Neural Plasticity After Nerve Injury and Regeneration
Navarro, X. (2009) · International review of neurobiology · doi:10.1016/s0074-7742(09)87027-x · Cited by 117
Hypothalamo-pituitary-adrenal axis dysfunction as a contributory factor to chronic pain and depression
Blackburn-Munro, G. (2004) · Current Pain and Headache Reports · doi:10.1007/s11916-004-0025-9 · Cited by 119
Comparison of the pain suppressive effects of clinical and experimental painful conditioning stimuli
Bouhassira, D., Danziger, N., Atta, N., & Guirimand, F. (2003) · Brain · doi:10.1093/brain/awg106 · Cited by 117
“…pain remain uncertain, as the relationship between the stimulus intensity and the resulting sensation is signi®cantly modi®ed under pathological conditions by the reorganization and alterations of the nociceptive systems (Dubner and Gold, 1999; Julius and Basbaum, 2001; Woolf and Salter, 2000).”
Background
Neuropathic Central Pain
Schwartzman, R. J., Grothusen, J. R., Kiefer, T. R., & Rohr, P. (2001) · Archives of Neurology · doi:10.1001/archneur.58.10.1547 · Cited by 117
“Anatomic changes occur in the periphery, dorsal root ganglia, and DH of the spinal cord during prolonged pain states.(1) Peripheral nerve injury seems to preferentially affect C-fiber nociceptive neurons to a greater degree than A-fiber neurons.”
BackgroundInfluential
Coupling gene chip analyses and rat genetic variances in identifying potential target genes that may contribute to neuropathic allodynia development
Valder, C. R., Liu, J.-J., Song, Y.-H., & Luo, Z. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02016.x · Cited by 120
Pharmacological Treatment of Neuropathic Cancer Pain: A Comprehensive Review of the Current Literature
Vadalouca, A., Raptis, E., Μoka, Ε., Zis, P., Sykioti, P., & Siafaka, I. (2011) · Pain Practice · doi:10.1111/j.1533-2500.2011.00485.x · Cited by 116
“that treatment efficacy depends more on the underlying pathogenesis than on etiology.(1,3,6,28) Testing the validity of a narrow vs.”
Background
Neuroanatomy of lower gastrointestinal pain disorders.
Vermeulen, W., Man, J. G. D., Pelckmans, P., & de Winter, B. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i4.1005 · Cited by 105
Chronic postsurgical pain after nitrous oxide anesthesia
Chan, M. T. V., Wan, A. C. M., Gin, T., Leslie, K., & Myles, P. S. (2011) · Pain · doi:10.1016/j.pain.2011.07.015 · Cited by 116
“Emerging evidence suggests that neuronal plasticity after surgical trauma is crucial to the development of chronic pain after surgery [15,20,42,43].”
Background
Neuraxial Anesthesia Decreases Postoperative Systemic Infection Risk Compared with General Anesthesia in Knee Arthroplasty
Liu, J., Ma, C., Elkassabany, N. M., Fleisher, L. A., & Neuman, M. D. (2013) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e3182a1bf1c · Cited by 117
Long-term sensitization of primary afferents in adult rats exposed to neonatal colon pain
Lin, C., & Al–Chaer, E. D. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02358-8 · Cited by 113
UNRAVELLING THE PATHOPHYSIOLOGY OF COMPLEX REGIONAL PAIN SYNDROME: FOCUS ON SYMPATHETICALLY MAINTAINED PAIN
Gibbs, G. F., Drummond, P. D., Finch, P. M., & Phillips, J. K. (2008) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2007.04862.x · Cited by 116
The clinical role of NMDA receptor antagonists for the treatment of postoperative pain
Kock, M. F. D., & Lavand'homme, P. M. (2007) · Best practice & research. Clinical anaesthesiology · doi:10.1016/j.bpa.2006.12.006 · Cited by 116
Satellite glial cells express IL-6 and corresponding signal-transducing receptors in the dorsal root ganglia of rat neuropathic pain model
Dubový, P., Klusáková, I., Svíženská, I. H., & Brázda, V. (2010) · Neuron Glia Biology · doi:10.1017/s1740925x10000074 · Cited by 118
TMD and chronic pain: A current view
Furquim, B. D., Fiamengui, L. M. S. P., & Conti, P. C. R. (2015) · Dental Press Journal of Orthodontics · doi:10.1590/2176-9451.20.1.127-133.sar · Cited by 115
T Cells as an Emerging Target for Chronic Pain Therapy
Laumet, G. O., Ma, J., Robison, A. J., Kumari, S., Heijnen, C. J., & Kavelaars, A. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00216 · Cited by 117
The neuro-pathophysiology of temporomandibular disorders-related pain: a systematic review of structural and functional MRI studies
Yin, Y., He, S., Xu, J., You, W., Li, Q., Long, J., Luo, L., Kemp, G. J., Sweeney, J. A., Li, F. Y., et al. (2020) · The Journal of Headache and Pain · doi:10.1186/s10194-020-01131-4 · Cited by 125
Inflammation induced by Bothrops asper venom
Teixeira, C., Cury, Y., Moreira, V., Picolo, G., & Chaves, F. (2009) · Toxicon · doi:10.1016/j.toxicon.2009.05.026 · Cited by 115
Uncontrollable Stimulation Undermines Recovery after Spinal Cord Injury
Grau, J. W., Washburn, S. N., Hook, M. A., Ferguson, A. R., Crown, E. D., Garcia, G., Bolding, K. A., & Miranda, R. C. (2004) · Journal of Neurotrauma · doi:10.1089/neu.2004.21.1795 · Cited by 115
Knockdown of L Calcium Channel Subtypes: Differential Effects in Neuropathic Pain
Fossat, P., Dobremez, E., Bouali‐Benazzouz, R., Favereaux, A., Bertrand, S. S., Kilk, K., Léger, C., Cazalets, J., Langel, Ü., Landry, M., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3145-09.2010 · Cited by 122
“Chronic pain is associated with long-lasting changes in gene expression involving calcium channels (Woolf and Salter, 2000).”
BackgroundInfluential
Sensitization, glutamate, and the link between migraine and fibromyalgia
Sarchielli, P., Filippo, M. D., Nardi, K., & Calabresi, P. (2007) · Current Pain and Headache Reports · doi:10.1007/s11916-007-0216-2 · Cited by 115
“In light of these considerations, based on the apparent similarities in certain transmitters and implicated pathways, windup and windup maintenance have been proposed to likely reflect neural mechanisms related to the early phase of central sensitization, and thus are used as a model of central sensitization [ 13 ].”
Method
Segmental hypersensitivity and spinothalamic function in spinal cord injury pain
Finnerup, N. B., Sørensen, L. U., Biering‐Sørensen, F., Johannesen, I. L., & Jensen, T. S. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.06.001 · Cited by 114
Microglial Regulation of Neuropathic Pain
Tsuda, M., Masuda, T., Tozaki‐Saitoh, H., & Inoue, K. (2013) · Journal of Pharmacological Sciences · doi:10.1254/jphs.12r14cp · Cited by 114
Bilateral changes of TNF-α and IL-10 protein in the lumbar and cervical dorsal root ganglia following a unilateral chronic constriction injury of the sciatic nerve
Jančálek, R., Dubový, P., Svíženská, I. H., & Klusáková, I. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-11 · Cited by 114
Pathophysiology of bone cancer pain.
Sabino, M. A. C., & Mantyh, P. W. (2005) · PubMed · Cited by 114
Regulation of enteric functions by adenosine: Pathophysiological and pharmacological implications
Antonioli, L., Fornai, M., Colucci, R., Ghisu, N., Tuccori, M., Tacca, M. D., & Blandizzi, C. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2008.08.010 · Cited by 116
Local anaesthetics have different mechanisms and sites of action at the recombinant N‐methyl‐D‐aspartate (NMDA) receptors
Sugimoto, M., Uchida, I., & Mashimo, T. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705107 · Cited by 114
Acid Sensing Ion Channels in Dorsal Spinal Cord Neurons
Baron, A., Voilley, N., Lazdunski, M., & Lingueglia, É. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4975-07.2008 · Cited by 114
Chronic neuropathic pain: mechanisms, drug targets and measurement
Finnerup, N. B., Sindrup, S. H., & Jensen, T. S. (2007) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.2007.00474.x · Cited by 115
Calcitonin gene‐related peptide enhances release of native brain‐derived neurotrophic factor from trigeminal ganglion neurons
Buldyrev, I., Tanner, N. M., Hsieh, H., Dodd, E. G., Nguyen, L. T., & Bałkowiec, A. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04161.x · Cited by 114
Increased pain from muscle fascia following eccentric exercise: animal and human findings
Gibson, W., Arendt‐Nielsen, L., Taguchi, T., Mizumura, K., & Graven‐Nielsen, T. (2009) · Experimental Brain Research · doi:10.1007/s00221-008-1699-8 · Cited by 113
“central facilitatory eVects on pain perception (Woolf and Salter 2000).”
Spinal presynaptic inhibition in pain control.
Guo, D., & Hu, J. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.09.032 · Cited by 96
“Indeed, a decrease in inhibition, or ‘‘disinhibition’’, has been shown as an important substrate of many chronic pain models (Woolf, 2000; Baba et al., 2003; Cervero et al., 2003; Coull et al., 2003; Enna and McCarson, 2006; Gwak and Hulsebosch, 2011; Puri et al., 2012; Zeilhofer et al., 2012; Bardoni et al., 2013; Bo…”
The Prolonged Analgesic Effect of Epidural Ropivacaine in a Rat Model of Neuropathic Pain
Sato, C., Sakai, A., Ikeda, Y., Suzuki, H., & Sakamoto, A. (2008) · Anesthesia & Analgesia · doi:10.1213/01.ane.0000296460.91012.51 · Cited by 113
“Sustained activation of nociceptive pathways causes activity-dependent neural plasticity.(19) Such plastic Figure 3.”
Background
Chronic musculoskeletal pain: review of mechanisms and biochemical biomarkers as assessed by the microdialysis technique
Gerdle, B. U. C., Ghafouri, B., Ernberg, M. M., & Larsson, B. (2014) · Journal of Pain Research · doi:10.2147/jpr.s59144 · Cited by 112
Reticular Formation and Pain: The Past and the Future
Martins, I., & Tavares, I. (2017) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2017.00051 · Cited by 114
“Neuroplastic changes in key descending pain modulatory areas were shown to be crucial for the generation and maintenance of chronic pain (Woolf and Salter, 2000), the studies compiled here strongly suggest that the alterations occurring at the RVM-VLM-DRt triad during chronic pain are also fundamental to its maintenan…”
Background
Animal models of pain: Diversity and benefits
Abboud, C., Duveau, A., Bouali‐Benazzouz, R., Massé, K. L., Mattar, J., Brochoire, L., Fossat, P., Boué‐Grabot, É., Hleihel, W., & Landry, M. (2020) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2020.108997 · Cited by 114
Perioperative administration of the α2-adrenoceptor agonist clonidine at the site of nerve injury reduces the development of mechanical hypersensitivity and modulates local cytokine expression
Lavand'homme, M. P., & Eisenach, C. D. (2003) · Pain · doi:10.1016/s0304-3959(03)00221-5 · Cited by 113
Bradykinin Enhances AMPA and NMDA Receptor Activity in Spinal Cord Dorsal Horn Neurons by Activating Multiple Kinases to Produce Pain Hypersensitivity
Kohno, T., Wang, H., Amaya, F., Brenner, G. J., Cheng, J., Ji, R., & Woolf, C. J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5349-07.2008 · Cited by 114
“Central sensitization results from alterations in ionotropic NMDA and AMPA glutamate receptors that are attributable both to the trafficking of intracytoplasmic receptors to the membrane and to phosphorylation-mediated alterations in receptor/ion channel function (Woolf and Salter, 2000).”
Background
Pain Management in Trauma Patients
Cohen, S. P., Christo, P. J., & Moroz, L. (2004) · American Journal of Physical Medicine & Rehabilitation · doi:10.1097/01.phm.0000107499.24698.ca · Cited by 111
“changes in the nervous system.(2) The ability of neural tissue to change in response to repeated incoming stimuli, a property known as neuroplasticity, can lead to the development of chronic, disabling neuropathic pain when acute pain is poorly treated.”
Background
Kangaroo Care (Skin Contact) Reduces Crying Response to Pain in Preterm Neonates: Pilot Results
Kostandy, R. R., Ludington‐Hoe, S. M., Cong, X. S., Abouelfettoh, A. M., Bronson, C., Stankus, A., & Jarrell, J. R. (2008) · Pain Management Nursing · doi:10.1016/j.pmn.2007.11.004 · Cited by 113
“…the central neurons in the dorsal orn of the spinal cord and brainstem, causing them to espond to normal inputs in an exaggerated and exended manner (Woolf & Salter, 2000)]; either NPO or n ed by bolus feed (one complete amount of feeding iven over 20 minutes); and being cared-for in an ncubator.”
Background
Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis
Doucet, M. Y., Bertone, A. L., Hendrickson, D. A., Hughes, F. E., MacAllister, C. G., McClure, S. R., Reinemeyer, C. R., Rossier, Y., Sifferman, R. L., Vrins, A., et al. (2008) · Journal of the American Veterinary Medical Association · doi:10.2460/javma.232.1.91 · Cited by 112
Reduced potassium-chloride co-transporter expression in spinal cord dorsal horn neurons contributes to inflammatory pain hypersensitivity in rats
Zhang, W., Liu, L.-Y., & Xu, T. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2007.12.037 · Cited by 112
Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord
Bao, L., Wang, H. F., Cai, H., Tong, Y., Jin, S., Lu, Y., Grant, G., Hökfelt, T. G. M., & Zhang, X. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02080.x · Cited by 112
“Many studies on the mechanisms underlying neuropathic pain have demonstrated extensive structural and molecular plasticity of the neurons in the pain pathway following nerve injury (Dray et al., 1994; Ho ¨kfelt et al., 1994; Zigmond et al., 1996; Woolf & Mannion, 1999; Woolf & Salter, 2000 ) including a peripheral axo…”
Influential
Effect of oral gabapentin on postoperative epidural analgesia
Turan, A., Kaya, G., Karamanlıoğlu, B., Pamukçu, Z., & Apfel, C. C. (2005) · British Journal of Anaesthesia · doi:10.1093/bja/aei294 · Cited by 112
Randomized, controlled, cross-over clinical trial comparing intravenous midazolam sedation with nitrous oxide sedation in children undergoing dental extractions
Wilson, K., Girdler, N. M., & Welbury, R. R. (2003) · British Journal of Anaesthesia · doi:10.1093/bja/aeg278 · Cited by 110
TRP channels and pain
Cortright, D. N., Krause, J. E., & Broom, D. C. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2007.03.003 · Cited by 111
ATP and UTP excite sensory neurons and induce CREB phosphorylation through the metabotropic receptor, P2Y2
Molliver, D. C., Cook, S. P., Carlsten, J. A., Wright, D. E., & McCleskey, E. W. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02253.x · Cited by 110
Nociceptive Neuropeptide Increases and Periorbital Allodynia in a Model of Traumatic Brain Injury
Elliott, M. B., Oshinsky, M. L., Amenta, P. S., Awe, O. O., & Jallo, J. (2012) · Headache The Journal of Head and Face Pain · doi:10.1111/j.1526-4610.2012.02160.x · Cited by 110
“According to Woolf and Salter, longlasting alterations in the expression of transmitters, receptors, or ion channels may alter the normal response characteristics to innocuous stimuli, in turn eliciting allodynia.(13) Other post-traumatic disturbances such as sensitization of cortical sensory neurons, loss of inhibito…”
Analgesic Effects of a Single Preoperative Dose of Pregabalin after Laparoscopic Sleeve Gastrectomy
Schulmeyer, M. C. C., de la Maza, J., Ovalle, C., Farías, C., & Vives, I. (2009) · Obesity Surgery · doi:10.1007/s11695-009-9944-1 · Cited by 109
“In the last few years, there have been great advances in the understanding of the physiopathological mechanisms that trigger the postoperative pain response, which has been redefined as incisional pain [1–3].”
Background
The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation
Xiong, H.-Y., Hendrix, J., Schabrun, S. M., Wyns, A., Campenhout, J. V., Nijs, J., & Polli, A. (2024) · Biomolecules · doi:10.3390/biom14010071 · Cited by 119
“Consequently, pain stems from profound changes within the CNS, which not only amplifies responses to nociceptive inputs but also fails to suppress painful signals [56].”
Background
Identification of MEK1 as a novel target for the treatment of neuropathic pain
Ciruela, A., Dixon, A. K., Bramwell, S., González, M. I., Pinnock, R. D., & Lee, K. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705103 · Cited by 109
“Much of the cellular plasticity related to the hyperalgesic state may ultimately be regulated by temporal and spatial alterations in gene expression (Woolf & Salter, 2000).”
Background
ASIC2b-dependent Regulation of ASIC3, an Essential Acid-sensing Ion Channel Subunit in Sensory Neurons via the Partner Protein PICK-1
Deval, E., Salinas, M., Baron, A., Lingueglia, É., & Lazdunski, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313078200 · Cited by 109
Anticonvulsant and Antinociceptive Actions of Novel Adenosine Kinase Inhibitors
McGaraughty, S., Cowart, M., Jarvis, M. F., & Berman, R. (2005) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026053386845 · Cited by 109
Microglia and intractable chronic pain
Tsuda, M., Beggs, S., Salter, M. W., & Inoue, K. (2013) · Glia · doi:10.1002/glia.22379 · Cited by 113
An Analysis of Changes in Sensory Thresholds to Mild Tactile and Cold Stimuli after Experimental Spinal Cord Injury in the Rat
Lindsey, A. E., LoVerso, R. L., Tovar, C. A., Hill, C. E., Beattie, M. S., & Bresnahan, J. C. (2000) · Neurorehabilitation and neural repair · doi:10.1177/154596830001400405 · Cited by 108
Cellular, molecular, and epigenetic mechanisms in non-associative conditioning: Implications for pain and memory
Rahn, E. J., Karlsson, M. G., & Sweatt, J. D. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.06.008 · Cited by 113
“The first, more rapid temporal phase is dependent upon phosphorylation primarily associated with glutamatergic receptors and ion channel properties (for review see Woolf and Salter, 2000).”
Background
Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice
Liu, T., & Ji, R. (2012) · Neuroscience Bulletin · doi:10.1007/s12264-012-1207-9 · Cited by 110
“Second, both peripheral sensitization of primary sensory neurons and central sensitization of spinal cord and other CNS neurons are implicated in pain and itch hypersensitivity in pathological conditions([54-57]).”
Persistent Postmastectomy Pain and Pain-Related Physical and Emotional Functioning With and Without a Continuous Paravertebral Nerve Block: A Prospective 1-Year Follow-Up Assessment of a Randomized, Triple-Masked, Placebo-Controlled Study
Ilfeld, B. M., Madison, S. J., Suresh, P., Sandhu, N. S., Kormylo, N. J., Malhotra, N., Loland, V. J., Wallace, M. S., Mascha, E. J., Xu, Z., et al. (2014) · Annals of Surgical Oncology · doi:10.1245/s10434-014-4248-7 · Cited by 110
Group III metabotropic glutamate receptors inhibit hyperalgesia in animal models of inflammation and neuropathic pain
Goudet, C., Chapuy, E., Alloui, A., Acher, F., Pin, J., & Eschalier, A. (2007) · Pain · doi:10.1016/j.pain.2007.08.020 · Cited by 108
“The mGluRs regulate nociceptive processes at different levels of the nervous system and are critically involved in central sensitization which is associated with chronic pain [56].”
Is physiotherapy integrated virtual walking effective on pain, function, and kinesiophobia in patients with non-specific low-back pain? Randomised controlled trial
Yilmaz Yelvar, G. D., Çırak, Y., Dalkılınç, M., Parlak Demir, Y., Guner, Z., & Boydak, A. (2017) · European Spine Journal · doi:10.1007/s00586-016-4892-7 · Cited by 107
Pain amplification—A perspective on the how, why, when, and where of central sensitization
Woolf, C. J. (2018) · Journal of Applied Biobehavioral Research · doi:10.1111/jabr.12124 · Cited by 111
An overview of pathways encoding nociception.
Rodríguez‐Carballeira, M., Solans, R., Larrañaga, J. R., García-Hernández, F. J., Ríos-Fernández, R., Nieto, J., Solanich, X., Martínez‐Valle, F., Fonseca, E., Muñoz, F. J., et al. (2017) · PubMed · Cited by 107
Postoperative Morphine Use and Hyperalgesia Are Reduced by Preoperative but Not Intraoperative Epidural Analgesia
Katz, J. D., Cohen, L. G., Schmid, R., Chan, V. W. S., & Wowk, A. (2003) · Anesthesiology · doi:10.1097/00000542-200306000-00023 · Cited by 107
“The neurophysiology underlying these effects has been well described and involves an N-methyl-D-aspartate–mediated increase in dorsal horn neuron activity that follows the corelease of neuropeptides and excitatory amino acids from C fiber primary afferent terminals during tissue damage and inflammation.(13,42) The res…”
Background
Spinal Astrocytic Activation Contributes to Mechanical Allodynia in a Rat Chemotherapy-Induced Neuropathic Pain Model
Ji, X., Qian, N., Zhang, T., Li, J., Li, X., Wang, P., Zhao, D., Huang, G., Zhang, L., Zhou, F., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060733 · Cited by 107
“the induction and maintenance of persistent pain [9,57].”
Background
Pain and chronic pancreatitis: A complex interplay of multiple mechanisms
Poulsen, J. L. (2013) · World Journal of Gastroenterology · doi:10.3748/wjg.v19.i42.7282 · Cited by 106
Pain relief by gabapentin and pregabalin via supraspinal mechanisms after peripheral nerve injury
Tanabe, M., Takasu, K., Takeuchi, Y., & Ono, H. (2008) · Journal of Neuroscience Research · doi:10.1002/jnr.21786 · Cited by 107
Enteric glial cells: new players in gastrointestinal motility?
Bassotti, G., Villanacci, V., Antonelli, E., Morelli, A., & Salerni, B. (2007) · Laboratory Investigation · doi:10.1038/labinvest.3700564 · Cited by 107
Candidate Gene Studies of Human Pain Mechanisms
Belfer, I., Wu, T., Kingman, A., Krishnaraju, R. K., Goldman, D. A., Max, M. B., & Warltier, D. C. (2004) · Anesthesiology · doi:10.1097/00000542-200406000-00032 · Cited by 108

Authors: Woolf, C. J., & Salter, M. W.
Affiliations: Harvard University (US)
University of Toronto (CA)
Corresponding author: Woolf, Clifford J.
ORCID: Woolf, Clifford J.
Salter, Michael W.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2000-06-09
Volume: 288
Issue: 5472
Pages: 1765-1768
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.288.5472.1765
OpenAlex: W2133316133
Cited by: 3,781
References: 76
Citations by year: 2026: 62 · 2025: 101 · 2024: 96 · 2023: 104 · 2022: 99 · 2021: 99 · 2020: 129 · 2019: 112 · 2018: 124 · 2017: 140 · 2016: 150 · 2015: 170 · 2014: 142 · 2013: 188 · 2012: 166
FWCI: 13.94
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: neuroplasticity, pain, hyperalgesia, primary sensory neurons, dorsal horn neurons, neuropathic pain, inflammatory pain, plasticity mechanisms, pain modulation
MeSH terms: Animals, Humans, Inflammation, Models, Neurological, Synaptic Transmission, Neuronal Plasticity, Neurons, Afferent, Nociceptors, Pain, Signal Transduction, Posterior Horn Cells, Peripheral Nerve Injuries

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Neuronal Plasticity: Increasing the Gain in Pain

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks