ReviewEuropean journal of pain (London, England)2025
Assessing signs of central sensitization: A critical review of physiological measures in experimentally induced secondary hyperalgesia.
Review in European journal of pain (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed.
- Beware of What You Expect? A Partial Replication Study on the Behavioral and Psychophysiological Effects of Negative Expectations on Mechanical Hypersensitivity.Psychophysiology · 2026Trial
- Relationship Between Central Sensitization and Genetic Polymorphisms-A Case-Control Study in Fibromyalgia.European journal of pain (London, England) · 2026Trial
- Prepulse inhibition of the blink reflex in functional neurological disorder and fibromyalgia.Brain : a journal of neurology · 2026Article
- High Prevalence and Clinical Impact of Fibromyalgia in Functional Motor Disorder.Movement disorders clinical practice · 2026Article
- Pressure point: blood flow restriction exercise and the pain paradox in musculoskeletal injury and persistent pain populations-a narrative review.Frontiers in pain research (Lausanne, Switzerland) · 2026Review
- The intrinsic reason why the term "central sensitization" should be refined, by introducing the terms "spinal sensitization", "pain-related brain network sensitization", and "psychosocial-related sensitization".Frontiers in pain research (Lausanne, Switzerland) · 2026Article
- The N13 somatosensory evoked potential in complex regional pain syndrome - A potential marker for central sensitization?Clinical neurophysiology practice · 2026Article
- The effect of psychological manipulations on the development of secondary hyperalgesia: a critical review.Pain reports · 2025Review
- Review
- Assessing signs of central sensitization: A critical review of physiological measures in experimentally induced secondary hyperalgesia.European journal of pain (London, England) · 2025Review
- The intrinsic reason why complementary tests (clinical neurophysiology, neuroimaging, skin biopsy) cannot establish the diagnosis of neuropathic pain.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- Understanding neuropathic pain: the role of neurophysiological tests in unveiling underlying mechanisms.Journal of anesthesia, analgesia and critical care · 2024Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesCentral sensitization (CS) is believed to play a role in many chronic pain conditions. Direct non-invasive recording from single nociceptive neurons is not feasible in humans, complicating CS establishment. This review discusses how secondary hyperalgesia (SHA), considered a manifestation of CS, affects physiological measures in healthy individuals and if these measures could indicate CS. It addresses controversies about heat sensitivity changes, the role of tactile afferents in mechanical hypersensitivity and detecting SHA through electrical stimuli. Additionally, it reviews the potential of neurophysiological measures to indicate CS presence. DATABASES AND DATA TREATMENT: Four databases, PubMed, ScienceDirect, Scopus and Cochrane Library, were searched using terms linked to 'hyperalgesia'. The search was limited to research articles in English conducted in humans until 2023.
resultsEvidence for heat hyperalgesia in the SHA area is sparse and seems to depend on the experimental method used. Minimal or no involvement of tactile afferents in SHA was found. At the spinal level, the threshold of the nociceptive withdrawal reflex (RIII) is consistently reduced during experimentally induced SHA. The RIII area and the spinal somatosensory potential (N13-SEP) amplitude are modulated only with long-lasting nociceptive input. At the brain level, pinprick-evoked potentials within the SHA area are increased.
conclusionsMechanical pinprick hyperalgesia is the most reliable behavioural readout for SHA, while the RIII threshold is the most sensitive neurophysiological readout. Due to scarce data on reliability, sensitivity and specificity, none of the revised neurophysiological methods is currently suitable for CS identification at the individual level. SIGNIFICANCE: Gathering evidence for CS in humans is a crucial research focus, especially with the increasing interest in concepts such as 'central sensitization-like pain' or 'nociplastic pain'. This review clarifies which readouts, among the different behavioural and neurophysiological proxies tested in experimental settings, can be used to infer the presence of CS in humans.
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