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
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.
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In the citing paper
“Sometimes, however, central neural processing can be 'modified' so that initially peripherally induced central sensitization becomes independent of peripheral sensitization”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Woolf and Salter, 2000
In the citing paper
“Central sensitization is initiated by peripheral sensitization (Fig. 1) and maintained by continued input to the CNS from sensitized sensory afferent fibers”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Woolf and Salter, 2000
In the citing paper
“Changes in activity of peripherally sensitized fibers, due to estradiol and sympathetic modulation in the rat model, can 'modulate' activity of centrally sensitized neurons to affect pain severity”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Woolf and Salter, 2000
In the citing paper
“Central pain sensitization (CPS) results from neuronal plasticity that involves structural and functional changes in the central nervous system (CNS).”
From Effectiveness of acceptance and commitment therapy in central pain sensitization syndromes: A systematic review (2021) · cites this paper as [1]
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Microglia-Mediated Regulation of Neuropathic Pain: Molecular and Cellular Mechanisms
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“A consequence of sensory neurone hyperexcitability is multiple transient changes in the way that pain is processed within the dorsal horn (Woolf and Salter, 2000).”
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“In addition, the roles of NMDA receptor activation in the development of persistent neuropathic pain have been demonstrated previously (Woolf, 1983; Woolf and Salter, 2000).”
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Gottrup, H., Kristensen, A. D., Bach, F. W., & Jensen, T. S. (2003) · Pain · doi:10.1016/s0304-3959(02)00415-3 · Cited by 78
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“Early studies indicated that central sensitization was a result of activation of NMDA receptors; however, recently, evidence points toward NMDA-independent central sensitization also contributing to plasticity (Woolf and Costigan, 1999; Woolf and Salter, 2000).”
BackgroundBradykinin and peripheral sensitization
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Inhibition of Cytosolic Phospholipase A2α: Hit to Lead Optimization
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Studies of the organization of the human nociceptive withdrawal reflex*†
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Do burn injuries during infancy affect pain and sensory sensitivity in later childhood?
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“, long-lasting, activity-induced neuroplastic changes of central pain pathways [51].”
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Pereira, E. A. C., Boccard, S., Linhares, P., Chamadoira, C., Rosas, M. J., Abreu, P., Rebelo, V., Vaz, R. M., & Aziz, T. Z. (2013) · Neurosurgical FOCUS · doi:10.3171/2013.7.focus1346 · Cited by 77
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Polyamine deficient diet to relieve pain hypersensitivity
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“As previously suggested [32,43], clinical pain is not only a reflection of nociceptive stimulus intensity, but is to a large extent the expression of neural plasticity including both peripheral and central sensitization.”
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Mechanisms that drive bone pain across the lifespan
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RetractedTranslating nociceptor sensitivity: the role of axonal protein synthesis in nociceptor physiology
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“consistent with the suggestion that similar mechanisms may be involved in the process of peripheral sensitization leading to persistent pain ( Woolf and Salter, 2000 ).”
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Peripheral nerve injuries, pain, and neuroplasticity
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Postoperative Pain Management in Pediatric Spinal Fusion Surgery for Idiopathic Scoliosis
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InfluentialPeripheral TGF-β1 Signaling Is a Critical Event in Bone Cancer-Induced Hyperalgesia in Rodents
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“Central sensitization has been implicated as a driving mechanism responsible for many chronic pain states [26,45,52].”
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“For example, inflammation initiates plasticity in the spinal dorsal horn, contributing to chronic pain (Woolf and Salter, 2000) via mechanisms involving interactions between spinal microglia and second-order sensory neurons (Coull et al.”
BackgroundPharmacotherapy for Neuropathic Pain
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Preemptive Analgesia at the Crossroad
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“Notably, in primary sensory ganglia and in the dorsal horn of the spinal cord multiple functional and anatomical alterations of neurons follow peripheral nerve injury (Costigan et al., 2009; Scholz and Woolf, 2002; Woolf and Salter, 2000).”
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“[11].”
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Ion Channel Targets and Treatment Efficacy in Neuropathic Pain
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The known knowns of microglia–neuronal signalling in neuropathic pain
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P2 receptors, microglial cytokines and chemokines, and neuropathic pain
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“One function of the descending inhibitory pathway is to “focus” the excitation of the dorsal horn neurons by suppressing surrounding neuronal activity [39], a role attributed to the “diffuse noxious inhibitory controls” phenomenon [40].”
BackgroundPrevention of central sensitization and pain by N-methyl-D-aspartate receptor antagonists
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“The role of hyperexcitability or wind-up, induction of central sensitization, changes in dorsal horn (neuronal 4,8 of NR1, NR2 (types B, C, and D), and NR3 (types A and B) subunits.”
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“35,50,51 In addition to directly inflamed meningeal and cortical tissues, periosteal inflammation also contributes to activation of the trigeminal ganglia neurons after closed-head injury.”
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“In addition to spontaneous and stimulus-evoked pain, there is stimulus-induced pain (Woolf and Decosterd, 1999; Woolf and Salter, 2000).”
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Metadata
- Authors
- Woolf, C. J., & Salter, M. W.
- Affiliations
- Harvard University (US)
- University of Toronto (CA)
- Corresponding author
- Woolf, Clifford J.
- Venue
- Science
- Published
- 2000-06-09
- Volume
- 288
- Issue
- 5472
- Pages
- 1765-1768
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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
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