ReviewMethodsX2023
Temporal model for central sensitization: A hypothesis for mechanism and treatment using systemic manual therapy, a focused review.
Review in MethodsX, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed.
- Emerging Clinical Concepts in Pain Management of Ehlers-Danlos Syndrome.Current pain and headache reports · 2026Review
- Central sensitization-related symptoms in patients undergoing lumbar spine surgery: development and internal validation of a clinical prediction rule for first-stage screening.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Article
- A systematic scoping review and conceptual analysis of new-onset fibromyalgia manifestations after non-hospitalized COVID-19: empirics, definitions, methodologies, pathophysiology, mapping of literature, and knowledge gaps.Journal of translational medicine · 2026Article
- LC-IL but Not LC-PL Circuit Regulates Comorbid Mechanical Hyperalgesia and Anxiety in Male Rats with Chronic Post-Surgical Pain.Journal of pain research · 2026Article
- Insomnia Increases Susceptibility to Sciatica: Evidence from Mendelian Randomization and Integrative Genetic Analyses.Journal of pain research · 2026Article
- The Genetic Association Between Prescription Pain Medication Use and the Risk for Fibromyalgia: A Bidirectional and Multivariable Mendelian Randomization Analysis.Journal of pain research · 2025Article
Corrections and comments
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Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The purpose of this focused review is to develop a consolidated hypothesis as to the causes and mechanisms of central sensitization and a related model for a treatment approach using Systemic Manual Therapy (SMT). The key to understanding central sensitization is a firm grasp on structure and function of the Locus-coeruleus noradrenaline system (LC-NA). This system uses an elaborate switching mechanism to control the level and rate of activation of multiple systems. This review evaluates the mechanisms and temporal relationships behind four components: salient stimuli, threat coding, aberrant afferent input, and oxidative stress. The five-stage temporal model for central sensitization includes phasic activation of the LC-NA system, salient stimuli, threat coding of salient stimuli, central sensitization, and neural degeneration. The three components of treatment include temporarily reducing afferent visceral input, shifting humoral inflammatory activity away from the brain and outside the body, and reducing oxidative stress by making oxygenated blood more available around the LC and other stressed areas in the brain. The SMT protocols that could help in reduction of visceral afferent input are GUOU, Barral and LAUG. Protocols that should shift humoral inflammatory activity away from the brain or completely out of the body include UD and DCS. One protocol that can potentially reduce oxidative stress by making oxygenated blood more available around the LC is CCCV. Future research and hypothesis-testing strategies as well as limitations are further discussed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.