Condition Overview
WHAT IS CENTRAL SENSITISATION SYNDROME
Central Sensitisation Syndrome (CSS) is a condition where the central nervous system becomes chronically hypersensitised, amplifying and distorting sensory signals far beyond what is appropriate. It produces widespread pain, fatigue, cognitive impairment ("brain fog"), and heightened sensitivity to light, sound, smell, and touch.
It is not psychosomatic. It involves measurable neurobiological changes: altered synaptic plasticity, reduced descending pain inhibition, microglial activation, and neuroinflammation. It underlies fibromyalgia, ME/CFS, IBS, chronic migraines, TMJD, interstitial cystitis, POTS, and more.
The core challenge: CSS cannot be seen on standard imaging, which is why 83% of patients are initially misdiagnosed and average diagnosis takes 7.4 years globally.
MECHANISM
Amplified neuronal firing in dorsal horn + reduced descending inhibition. NMDA receptor upregulation is central.
ONSET TRIGGERS
Physical injury, surgery, infection, prolonged stress, inflammatory disease, any sustained nociceptive input can sensitise the CNS.
CORE SYMPTOMS
Allodynia · Hyperalgesia · Temporal summation · Widespread pain · Fatigue · Brain fog · Sleep dysfunction · Sensory hypersensitivity
DIAGNOSIS
CSI score ≥40. No blood test or imaging available. Clinical diagnosis of exclusion by a pain specialist.
WHO IS AFFECTED
All ages, all demographics. Women diagnosed 2–3× more often, though this likely reflects diagnostic bias, not true prevalence.
PROGNOSIS
Highly variable. The CNS retains neuroplasticity, with correct treatment, significant improvement is achievable. Recovery is non-linear.
Recalibrate for Chronic Pain
FROM FREE PORTAL TO PRACTICAL SUPPORT
This portal is part of the broader Recalibrate ecosystem: condition education, symptom patterns, practical support, and tools designed for people navigating chronic pain and nervous-system sensitisation in real life.
WHAT THIS PORTAL DOES
Explains CSS clearly, surfaces live research, highlights treatment evidence, and helps patients identify specialist pathways.
WHAT RECALIBRATE ADDS
A wider ecosystem for people living with persistent pain: understanding patterns, building consistency, and moving beyond fragmented information.
Related Condition Pathways
CSS OFTEN OVERLAPS WITH OTHER PORTALS
Fibromyalgia
Many fibromyalgia cases sit within the broader central sensitisation spectrum. Open Fibromyalgia portal →
Long COVID / ME-CFS
Post-viral illness often overlaps with sensory amplification, fatigue, and dysautonomia. Open Long COVID portal →
ADHD / Neurodivergence
Executive dysfunction, stress load, and chronic pain often interact in real patients. Open ADHD portal →
Recalibrate
Explore the wider chronic pain ecosystem at recalibratepain.com →
Latest Research
LIVE FROM PUBMED · AUTO-UPDATED ON EVERY VISIT
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How Central Sensitisation Develops
THE NEUROSCIENCE, MECHANISM & DIAGRAM
In a healthy nervous system, pain signals travel from the periphery to the brain and are modulated by descending inhibitory pathways. In CSS, this regulation breaks down. The amplifier gets stuck on high and the brakes stop working, often long after the original trigger has resolved.
CENTRAL SENSITISATION MECHANISM
ALLODYNIA
Pain from non-painful stimuli, light touch, clothing, mild temperature change.
HYPERALGESIA
Exaggerated pain from stimuli that should only cause mild discomfort.
WIND-UP
Repeated mild stimuli produce progressively increasing pain, temporal summation.
CSI Self-Assessment
CENTRAL SENSITISATION INVENTORY · 25 QUESTIONS · VALIDATED CLINICAL TOOL
The Central Sensitisation Inventory (CSI) is the most widely used validated clinical screening tool for CSS. A score ≥40 is clinically significant. This does not replace clinical diagnosis, take your score to a pain specialist.
1
I feel tired and unrefreshed when I wake from sleeping
NeverRarelySometimesOftenAlways
2
My muscles feel stiff or achy
NeverRarelySometimesOftenAlways
3
I have anxiety attacks
NeverRarelySometimesOftenAlways
4
I grind or clench my teeth
NeverRarelySometimesOftenAlways
5
I have problems with diarrhoea and/or constipation
NeverRarelySometimesOftenAlways
6
I need help performing daily activities
NeverRarelySometimesOftenAlways
7
I am sensitive to bright lights
NeverRarelySometimesOftenAlways
8
I get tired very easily when I am physically active
NeverRarelySometimesOftenAlways
9
I feel pain all over my body
NeverRarelySometimesOftenAlways
10
I have headaches
NeverRarelySometimesOftenAlways
11
I feel discomfort in my bladder and/or burning when I urinate
NeverRarelySometimesOftenAlways
12
I do not sleep well
NeverRarelySometimesOftenAlways
13
I have difficulty concentrating
NeverRarelySometimesOftenAlways
14
I have skin problems such as dryness, itchiness, or rashes
NeverRarelySometimesOftenAlways
15
Stress makes my physical symptoms worse
NeverRarelySometimesOftenAlways
16
I feel sad or depressed
NeverRarelySometimesOftenAlways
17
I have low energy
NeverRarelySometimesOftenAlways
18
I have muscle tension in my neck and shoulders
NeverRarelySometimesOftenAlways
19
I have pain in my jaw
NeverRarelySometimesOftenAlways
20
Certain smells, such as perfumes, make me feel ill
NeverRarelySometimesOftenAlways
21
I have to urinate frequently
NeverRarelySometimesOftenAlways
22
My legs feel uncomfortable and restless when I am trying to sleep
NeverRarelySometimesOftenAlways
23
I have difficulty remembering things
NeverRarelySometimesOftenAlways
24
I had trauma as a child
NeverRarelySometimesOftenAlways
25
I have pain in my pelvic area
NeverRarelySometimesOftenAlways
,
,
,
Take your score to a pain specialist. The CSI is a screening tool only.
Find a Pain Specialist →Treatment Evidence Tracker
GRADED A–D · WHAT THE RESEARCH ACTUALLY SAYS
A · STRONG RCTB · MODERATEC · EMERGINGD · LIMITED✕ AVOID
TREATMENTEVIDENCECATEGORY
Pain Neuroscience Education (PNE)
Teaching the neurobiology of pain, why pain doesn't equal damage. Reduces catastrophising, fear-avoidance, and perceived disability. Foundational to any CSS programme.
A · STRONG
🧠 Psychological
Graded Activity / Paced Exercise
Structured paced increases in activity calibrated to current capacity. Boom/bust cycling is destructive. Strong evidence over 12–24 weeks for raising pain thresholds.
A · STRONG
🏃 Physical
Chronic Pain–Focused CBT
Addresses catastrophising, avoidance behaviours, maladaptive pain beliefs. Must be pain-specific. Strongest when combined with physical therapy.
A · STRONG
🧠 Psychological
Sleep Restoration (CBT-I)
Disrupted sleep directly maintains CSS. Even one poor night measurably lowers pain thresholds. CBT-I is first-line over sleep medications.
A · STRONG
😴 Lifestyle
Multidisciplinary Pain Programme (MDP)
Structured intensive programme combining physiotherapy, psychology, occupational therapy, and medical management. Best outcomes in refractory CSS.
A · STRONG
🏥 Programme
Duloxetine (SNRI)
Enhances serotonin and noradrenaline, boosting descending inhibitory pathways. FDA-approved for fibromyalgia. Best-evidenced pharmacological option for CSS.
B · MODERATE
💊 Pharmacological
Pregabalin / Gabapentin
Reduces aberrant neuronal firing via α2δ calcium channel binding. Pregabalin licensed for fibromyalgia. Variable response. Common side effects: sedation, weight gain.
B · MODERATE
💊 Pharmacological
Mindfulness-Based Stress Reduction (MBSR)
8-week structured programme. fMRI studies show measurable changes in pain-related brain activation. Reduces catastrophising and improves psychological flexibility.
B · MODERATE
🧘 Mind-Body
Low-Dose Naltrexone (LDN)
1.5–4.5mg nightly modulates microglial activation and reduces neuroinflammation. Off-label. Growing Phase II/III evidence. Low side-effect profile.
C · EMERGING
💊 Pharmacological
rTMS (Repetitive Transcranial Magnetic Stimulation)
Non-invasive cortical stimulation. Multiple RCTs show benefit in fibromyalgia and chronic pain. Available in specialist pain and neurology centres.
C · EMERGING
⚡ Neuromodulation
Anti-inflammatory Nutrition / Gut-Brain Axis
Gut microbiome dysbiosis linked to neuroinflammation. Mediterranean diet correlates with reduced pain scores. Low-FODMAP for IBS-CSS overlap.
C · EMERGING
🥗 Nutrition
IV Ketamine Infusions
NMDA receptor antagonism produces significant short-term pain relief in refractory CSS. Limited long-term durability. Specialist anaesthesia/pain centres only.
D · LIMITED
💊 Interventional
Long-term Opioids
Contraindicated. Opioids cause opioid-induced hyperalgesia (OIH), paradoxically worsening central sensitisation over time. Avoid for CSS.
✕ AVOID
⛔ Harmful
Medication Reference Guide
DOSING, ONSET & SIDE EFFECTS · NOT A PRESCRIPTION
Duloxetine (Cymbalta)
SNRITYPICAL DOSE
30mg → 60–120mg/day
ONSET
4–6 weeks full effect
SIDE EFFECTS
Nausea, dry mouth, insomnia, sweating
Pregabalin (Lyrica)
α2δ LIGANDTYPICAL DOSE
75–300mg twice daily
ONSET
1–2 weeks
SIDE EFFECTS
Sedation, weight gain, dizziness
Gabapentin (Neurontin)
α2δ LIGANDTYPICAL DOSE
300–1200mg three times daily
ONSET
2–4 weeks
SIDE EFFECTS
Sedation, dizziness, weight gain
Low-Dose Naltrexone (LDN)
OFF-LABELTYPICAL DOSE
1.5–4.5mg at night
ONSET
4–12 weeks
SIDE EFFECTS
Vivid dreams, generally well tolerated
Amitriptyline (low dose)
TCATYPICAL DOSE
10–50mg at night
USED FOR
Sleep + pain at low dose
SIDE EFFECTS
Sedation, dry mouth, constipation
Milnacipran (Savella)
SNRITYPICAL DOSE
50–100mg twice daily
APPROVED FOR
Fibromyalgia (USA, Japan)
SIDE EFFECTS
Nausea, palpitations, raised BP
Active Clinical Trials
LIVE FROM CLINICALTRIALS.GOV · GLOBAL · CURRENTLY RECRUITING
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Verify eligibility at ClinicalTrials.gov · ISRCTN.com
Key Risks & Catalysts
WHAT WORSENS AND WHAT HELPS
⚠ WORSENING FACTORS
Sleep deprivation, even one night measurably lowers pain thresholds
Psychological stress, activates same neural threat pathways as physical pain
Boom/bust activity, overdoing on good days triggers severe flares
Long-term opioids, opioid-induced hyperalgesia worsens sensitivity
Inflammatory diet and gut dysbiosis, feeds neuroinflammatory cascade
Social isolation, removes positive input, maintains threat state
Catastrophising, fear of pain amplifies pain via cortical pathways
✓ IMPROVING CATALYSTS
Understanding pain neuroscience, reduces fear response and catastrophising
Paced, consistent movement, gradually recalibrates pain thresholds
Sleep restoration, foundational to CNS recovery
Nervous system regulation, breathwork, HRV training, vagal tone
Meaningful activity and positive social connection
Anti-inflammatory nutrition, Mediterranean diet pattern
Specialist multidisciplinary pain programme
The Typical CSS Patient Journey
WHAT MOST PATIENTS EXPERIENCE
1
Trigger Event
A physical injury, surgery, infection, or sustained stress. Initial pain is real and appropriate. In most people this resolves. In CSS, the nervous system stays in high-alert mode long after the trigger heals.
2
Persistent Pain, Confusion Begins
Pain continues despite healing. New symptoms emerge, fatigue, brain fog, widespread pain. Investigations return normal. Doctors are puzzled. Patients are told "nothing is wrong."
3
Diagnostic Odyssey (avg. 7.4 years globally)
Multiple specialists, multiple misdiagnoses, multiple failed treatments. Common wrong diagnoses: anxiety, depression, hypochondria. Many patients are dismissed or disbelieved.
4
CSS Diagnosis
A pain specialist identifies the pattern. CSI score confirms clinical picture. The diagnosis is simultaneously validating and daunting, but it opens the door to correct treatment for the first time.
5
Pain Neuroscience Education
Understanding that pain does not equal damage is transformative. Fear of movement begins to reduce. The catastrophising cycle starts to break. Often the single most important step in recovery.
6
Active Rehabilitation
Graded activity, sleep restoration, psychological support, appropriate medications. Progress is non-linear, setbacks are normal. The goal is long-term trend, not day-to-day perfection.
7
Recalibration, Long-term Management
CSS is manageable. Many patients achieve significant symptom reduction. Neuroplasticity means the sensitised nervous system can genuinely recalibrate over time. Recovery that once felt impossible becomes real.
Living With CSS
PRACTICAL DAILY MANAGEMENT STRATEGIES
😴 Sleep
Keep a consistent wake time, even on bad nights
Avoid screens 60 min before bed, blue light disrupts melatonin
Cool, dark room, core temp drop triggers sleep onset
Avoid napping past 2pm, disrupts sleep pressure
CBT-I over sleep medications long-term
🏃 Movement
Start smaller than you think you can, 5 min walks
Stop before you hurt, not when you hurt
Consistency beats intensity, every single time
Aquatic exercise often better tolerated initially
Track activity to find your baseline, not push limits
🧠 Pain Management
Re-read your pain neuroscience education regularly
Pain flares are not injury, your tissues are safe
Distraction genuinely reduces pain (not just coping)
Box breathing activates parasympathetic system
Experiment with cold/heat, both can help differently
🥗 Nutrition
Mediterranean diet, most evidence-supported pattern
Minimise ultra-processed foods, pro-inflammatory
Omega-3 (oily fish/supplement), anti-neuroinflammatory
Magnesium glycinate, NMDA modulation + sleep
Stable blood sugar reduces pain variability
🧘 Nervous System
4-7-8 breathing activates vagal tone, reduces arousal
Brief cold exposure, builds stress tolerance over time
Safe environments reduce threat perception
HRV training gives objective nervous system feedback
Reduce total life stress load, not just pain-specific
🤝 Social & Work
Explain CSS to key people, share this portal
Request workplace adjustments, CSS may qualify
Pace work tasks like physical activity, use breaks
Community reduces isolation, find people who get it
Avoid comparing your journey, CSS is highly individual
Global Specialist Directory
LEADING CSS RESEARCHERS, CLINICIANS & CENTRES
🇧🇪
Prof. Jo Nijs, Vrije Universiteit Brussel
World's foremost CSS researcher. Pain in Motion group. Originator of PNE protocols. 300+ peer-reviewed papers.
🇦🇺
Prof. Lorimer Moseley, University of South Australia
Explain Pain / Body in Mind group. Global authority on pain neuroscience education.
🇺🇸
Dr. Jarred Younger, UAB Neuroinflammation Lab
Leading LDN and neuroinflammation researcher. Multiple CSS and fibromyalgia clinical trials.
🇺🇸
Stanford Pain Management Centre
World-class multidisciplinary CSS programme. Ketamine, rTMS, and intensive outpatient protocols.
🇳🇱
Maastricht University Pain Research
Leading European CSS research centre. Multiple active clinical trials.
🇩🇪
DRK Schmerz-Zentrum Mainz
Germany's leading multidisciplinary chronic pain centre. Specialist CSS outpatient and day programmes.
🇬🇧
Bath Centre for Pain Services (RUH)
One of the UK's leading specialist pain rehabilitation centres. Inpatient and outpatient CSS programmes.
🌍
IASP Global Pain Specialist Directory
Find a pain specialist anywhere in the world. Searchable by country and specialty.
Global Patient Organisations
ADVOCACY, SUPPORT & RESOURCES WORLDWIDE
CSS Research Foundation
Dedicated CSS awareness, research funding, patient resources, and the official validated CSI tool.
GLOBALVisit →
Fibromyalgia Action UK
Support, advocacy and research for fibromyalgia and overlapping CSS conditions.
UKVisit →
National Fibromyalgia Association (NFA)
Patient advocacy, physician education, and research funding. Largest fibromyalgia/CSS org in the US.
USAVisit →
Pain Australia
National peak body for pain management. Patient resources, advocacy and research support.
AUSVisit →
European Pain Federation (EFIC)
Pan-European advocacy. Patient resources and access to European pain specialist networks.
EUVisit →
South African Pain Society
Pain specialist network and patient resources across South Africa.
ZAVisit →
Essential Books & Resources
THE BEST READING FOR CSS PATIENTS AND FAMILIES
📘
Explain Pain, Butler & Moseley
David Butler & Lorimer Moseley · noigroup.com
The foundational book on pain neuroscience education. Transforms how patients understand their pain. Essential first read. noigroup.com →
📗
Unlearn Your Pain, Dr Howard Schubiner
Howard Schubiner MD
Mind-body approach to chronic pain. Evidence-based programme combining neuroscience education with emotional processing techniques.
📙
The Way Out, Alan Gordon & Alon Ziv
New York Times Bestseller · Pain Reprocessing Therapy
Backed by RCT published in JAMA Psychiatry. Practical guide to retraining pain pathways.
📕
The Pain Relief Secret, Sarah Warren
Sarah Warren
Clinical Somatic Education guide, retraining the nervous system through targeted movement and body awareness.
🎙️
Pain Reframed Podcast, Todd Hargrove
Evidence-based chronic pain, neuroscience & movement science
Excellent ongoing education. Available on all major podcast platforms.
Landmark Research Papers
THE PAPERS THAT DEFINED MODERN CSS UNDERSTANDING
📄
Woolf CJ (2011), Central sensitisation: Implications for diagnosis and treatment
Pain, 152(3 Suppl):S2-15 · PMID: 20961685
The foundational paper formally defining CSS and its clinical implications. Read on PubMed →
📄
Younger J et al. (2013), LDN for the treatment of fibromyalgia
Arthritis & Rheumatology · PMID: 23359310
Pilot RCT: LDN reduced fibromyalgia symptoms 30% vs placebo. Launched a wave of LDN research. Read on PubMed →
📄
Mayer TG et al. (2012), Development and validation of the Central Sensitisation Inventory
Pain Practice, 12(4):276-285
Established the ≥40 threshold for clinically significant CSS. Search PubMed →
📄
Nijs J et al. (2020), PNE for chronic musculoskeletal pain
Physical Therapy, 100(10):1872-1884
Systematic review establishing PNE as evidence-based first-line for CSS. Search PubMed →
Frequently Asked Questions
COMMON QUESTIONS ABOUT CSS
Is CSS a real medical condition or "all in my head"?›
CSS is absolutely real. Multiple studies show measurable changes in brain activity, neuronal firing, neuroinflammatory markers, and spinal cord signalling. Standard imaging appearing normal doesn't mean the condition doesn't exist, it means current imaging lacks resolution to detect these changes.
Can CSS be cured?›
Not yet cured in the traditional sense, but significantly treatable. The CNS retains neuroplasticity throughout life, it can be recalibrated. Many patients achieve substantial symptom reduction and return to meaningful activities. Recovery is achievable with correct treatment.
What's the difference between CSS and fibromyalgia?›
Fibromyalgia is a clinical diagnosis describing a specific CSS presentation. CSS is the underlying neurological mechanism. Most researchers now consider fibromyalgia to be one of several CSS-spectrum conditions, alongside ME/CFS, IBS, chronic migraines, and others.
Why does exercise sometimes make CSS worse?›
The issue is not exercise, it's the intensity and pacing. When a sensitised nervous system is overloaded, it flares. The key is graded exercise: starting well below symptom threshold and increasing very gradually. Boom/bust cycling consistently produces worse outcomes.
Does stress really cause physical pain in CSS?›
Yes, the mechanism is well established. In a sensitised nervous system, psychological stressors activate the same neural threat pathways as physical pain. Stress hormones directly modulate pain processing circuits. Managing stress is therefore a legitimate, evidence-based pain management strategy.
How do I explain CSS to family and friends?›
"My nervous system is stuck in an alarm state. Like a smoke detector that goes off with no fire, the alarm is real, the response is real, but the calibration is wrong. It's not a choice, not weakness, not in my imagination. It's a neurological condition affecting how my brain processes signals." Share this portal with them.
Can children and teenagers have CSS?›
Yes, CSS can develop at any age, including childhood and adolescence. Juvenile fibromyalgia and chronic widespread pain in young people are often CSS presentations. Paediatric pain programmes using PNE and graded activity have strong evidence for effectiveness.
Is CSS related to Long COVID?›
Growing evidence suggests a significant proportion of Long COVID cases involve central sensitisation as a core mechanism, explaining widespread pain, fatigue, brain fog, and sensory hypersensitivity. Approximately 48% of Long COVID patients show signs of CSS on validated assessment tools.
Glossary
KEY CSS TERMINOLOGY EXPLAINED
Allodynia
Pain from stimuli not normally painful, light touch, clothing, mild temperature.
Hyperalgesia
Exaggerated pain response to stimuli that would normally cause only mild discomfort.
Temporal Summation
Progressive increase in pain from repeated identical stimuli, "wind-up" phenomenon.
Neuroplasticity
The brain's ability to reorganise, the neurological basis for recovery in CSS.
Descending Modulation
Brainstem inhibition of pain signals, reduced or absent in CSS.
Neuroinflammation
Inflammatory processes within the CNS, driven by microglial activation, a core CSS driver.
Microglia
Immune cells of the CNS. Overactivated in CSS, contributing to neuroinflammation.
CSI Score
Central Sensitisation Inventory. Validated 25-item screening tool. Score ≥40 = likely CSS.
OIH
Opioid-Induced Hyperalgesia. Paradoxical pain increase from long-term opioid use.
PNE
Pain Neuroscience Education. Evidence-based educational intervention. Reduces fear-avoidance.
NMDA Receptor
Glutamate receptor upregulated in CSS. Drives synaptic plasticity and central sensitisation.
Wind-Up
Spinal cord amplification of repeated stimuli. Key maintenance mechanism in CSS.
🤝
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