Central Sensitization in Chronic Pain Conditions

Central sensitization refers to the heightened responsiveness of neurons within the central nervous system to normal or subthreshold afferent input, resulting in persistent pain and sensory hypersensitivity. This phenomenon involves synaptic plasticity in the dorsal horn, altered descending modulation and glial activation, which together amplify nociceptive signalling. Clinically, central sensitization underlies the widespread pain and tenderness observed in conditions such as fibromyalgia, chronic low back pain, osteoarthritis and rheumatoid arthritis. It also contributes to fatigue, sleep disturbance and mood disorders, reflecting the complex interplay between nociceptive, emotional and cognitive systems. Advances in neuroimaging and electrophysiology have revealed maladaptive changes in pain-processing networks, while psychometric tools have enabled phenotyping of patients according to central sensitivity profiles. Recognition of central sensitization as a distinct mechanism has driven the development of tailored interventions, including pharmacological agents that target central excitability, non-pharmacological approaches such as exercise and cognitive strategies, and multimodal programmes that integrate pain education with physical rehabilitation. Global efforts continue to refine diagnostic criteria and to identify biomarkers that predict treatment response, with the ultimate aim of personalising pain management and reducing the burden of chronic pain worldwide.

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Central Sensitization in Chronic Pain Conditions publication trend

The graph below shows the total number of articles in central sensitization in chronic pain conditions across all publications each year (not limited to Nature Index journals).

Technical terms

Central sensitization: Increased excitability and synaptic efficacy of central neurons that amplify pain signals and produce widespread hypersensitivity.

Nociplastic pain: Pain arising from altered nociception without clear evidence of tissue damage or neuropathy, often associated with central sensitization mechanisms.

Descending modulation: Neural pathways from brainstem centres that regulate spinal nociceptive transmission by inhibitory or facilitatory influences.

Central Sensitization Inventory (CSI): A self-report questionnaire designed to screen for symptoms related to central sensitivity syndromes.

Quantitative sensory testing (QST): A battery of psychophysical methods used to assess sensory thresholds and pain processing in clinical and research settings.

References

1. Establishing central sensitization inventory cut-off values in Dutch-speaking patients with chronic low back pain by unsupervised machine learning. Computers in Biology and Medicine (2024).
2. Nociplastic Pain Criteria or Recognition of Central Sensitization? Pain Phenotyping in the Past, Present and Future. Journal of Clinical Medicine (2021).
3. Central sensitization has major impact on quality of life in patients with axial spondyloarthritis. Seminars in Arthritis and Rheumatism (2021).
4. The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia. Arthritis Research & Therapy (2011).