Central Pain Syndrome Fast Facts

Central pain syndrome (CPS) is a neurological condition in which a person feels pain even when there is little or no stimulus that should cause pain.

CPS is caused by damage to the central nervous system. This damage may come from a variety of causes.

Up to 10% of people who experience a stroke, 40% of those with a spinal cord injury, and 30% of people with multiple sclerosis are affected by CPS.

CPS is not fatal, but is usually a life-long affliction and can cause significant disabilities.

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CPS is caused by damage to the central nervous system. This damage may come from a variety of causes.

What is Central Pain Syndrome?

Central pain syndrome (CPS) is a neurological condition in which a medical condition or injury causes damage to the pain-communicating pathways in the central nervous system (the brain or spinal cord). The damage interferes with the normal transmission of pain signals from the peripheral nervous system to the brain’s pain-processing center. As a result, the affected person experiences a sensation of pain when there is little or no stimulus present.

CPS may be caused by many conditions or injuries that damage nerve tissue in the central nervous system. As a result, symptoms of the disorder can vary widely from case to case, depending on the location and severity of the damage.

Symptoms of CPS

CPS symptoms vary significantly in intensity, duration, and location from person to person. Sometimes an individual’s symptoms may vary in intensity throughout the day, and pain may be triggered or worsened by external triggers or emotional states.

Common symptoms of CPS can include:

  • Constant pain, loss of sensation, tingling, or burning sensations with little or no pain-producing stimulus
  • Painful sensations, either in specific parts of the body (e.g., the hands or feet) or over a wide area
  • Painful sensations that come and go
  • Exaggerated sensation in reaction to painful stimulus
  • Pain sensation caused by a non-pain-producing stimulus such as a light touch
  • Pain sensation that gets worse because of external triggers such as stress, strong emotions, or exposure to cold temperatures

What Causes Central Pain Syndrome?

CPS can be caused by any of several medical conditions or neurological injuries that cause damage to the central nervous system anywhere between the spinal cord and the brain’s pain-processing center.

Common causes of CPS include:

Is Central Pain Syndrome Hereditary?

CPS itself may have a genetic component, with people having a family history of the disorder at higher risk of developing CPS themselves. In addition, the underlying cause of nerve damage in CPS is often a condition such as a stroke, which may also have a family-history connection.

People at risk for a stroke often have a family history of:

  • High blood pressure
  • High levels of cholesterol, especially “bad” cholesterol or LDL
  • High triglyceride values
  • Inherited bleeding disorders
  • Sickle cell disease
  • Blockage in the neck or brain arteries
  • An arteriovenous malformation (AVM), a tangle of abnormal blood vessels in the brain

How Is Central Pain Syndrome Detected?

CPS often develops immediately or soon after the event or injury that causes neurological damage. However, in some cases, it develops over a long time after the triggering event.

Possible early signs of CPS include:

  • Pain, tingling, or burning that appears to have no cause
  • Pain that is triggered by unusual stimuli such as light touch, cold temperatures, or mood
  • Hypersensitivity to painful stimuli
  • Vague or distorted sensations
  • Painful tingling in the feet

How Is Central Pain Syndrome Diagnosed?

To pinpoint the cause of CPS symptoms, doctors look for a pattern of symptoms, risk factors, and family history. The diagnostic process typically includes physical examinations, tests, and a review of medical and family history.

Diagnostic steps may include:

  • A physical exam. This exam aims to rule out specific physical conditions that could be causing the symptoms.
  • Neurological tests. These tests measure the function of the patient’s nervous system. They evaluate functions such as balance, reflexes, memory, visual perception, and language.
  • Screening questionnaires. These assessments aim to measure the extent and severity of pain symptoms.
  • Imaging scans. These tests, such as MRIs, CTs, and PET scans, look for signs of damage to the central nervous system.

How Is Central Pain Syndrome Treated?

CPS is not curable, and conventional pain-relieving medications, such as NSAIDs or opioids, are usually ineffective at controlling symptoms. However, combining other medications and non-pharmaceutical therapies can help reduce the effects of CPS in many people.

Commonly prescribed medications include:

  • Antidepressants such as duloxetine, venlafaxine, or amitriptyline
  • Anticonvulsants such as pregabalin, gabapentin, or lamotrigine

Possible non-drug treatments include:

  • Motor cortex stimulation (MCS)
  • Deep brain stimulation (DBS)
  • Transcranial magnetic stimulation (TMS)
  • Cognitive-behavioral therapy (CBT)
  • Stress reduction therapy
  • Hypnosis

How Does Central Pain Syndrome Progress?

CPS sometimes develops quickly after a triggering event such as a stroke, traumatic brain injury, or spinal cord injury. The onset of the pain may be immediate or within a day of the central nervous system injury. In many cases, CPS symptoms don’t emerge until months or years later.

Although most people do find some relief from pain with treatment, complete resolution of symptoms is rare. CPS is usually permanent once it begins, and dealing with the pain on a long-term basis can lead to significant complications, such as:

  • Opioid use and abuse
  • Cognitive or memory problems
  • Sleep disruptions
  • Mood disorders
  • Mobility impairment
  • Social isolation

How Is Central Pain Syndrome Prevented?

There is no known way to prevent CPS.

Central Pain Syndrome Caregiver Tips

If you’re responsible for taking care of someone with CPS, keep these tips in mind:

  • Learn as much as you can about CPS.
  • Be as involved as possible with the sufferer’s medical care so that you can ask questions of doctors and other healthcare professionals.
  • Don’t hesitate to ask for help from other family members or friends.
  • Don’t feel guilty if you feel frustrated or angry with the sufferer.
  • Take time for yourself whenever possible, and don’t neglect your own emotional and physical needs.
  • Find a support group for caregivers.

Central Pain Syndrome Brain Science

The pain associated with CPS occurs when the pain-transmitting nerves of the central nervous system (CNS) become hypersensitized to signals from the peripheral nerves. These nerves branch out to the organs and extremities from the spinal cord. As a result of the increased sensitivity of the CNS nerves, abnormal pain perception can occur in several different ways, including:

  • Hypersensitivity to painful stimuli, so that small painful inputs cause an exaggerated perception of pain
  • Sensitivity to non-painful stimuli, so that something innocuous like a light touch causes a sensation of pain
  • Widened range of pain perception, so that a painful stimulus causes pain perception in an area beyond the area of injury

At one time, scientists thought that CPS was primarily caused by damage to the brain’s pain-processing center, the thalamus. It was also thought that the damage was usually caused by a stroke. More recent research has shown that CPS can occur when there is damage anywhere along the pathways that transmit pain through the CNS, from the spinal cord to the brain stem to the brain’s outer layer, the cortex. This damage can arise from many different sources, not just strokes.

Central Pain Syndrome Research

Title: Nitrous Oxide as Treatment for Fibromyalgia

Stage: Recruiting

Principal investigator: Peter Nagele, MD, MSc 

University of Chicago

Chicago, IL

Investigators are conducting this trial to determine the efficacy of nitrous oxide on fibromyalgia, a chronic, debilitating disorder typified by widespread musculoskeletal pain, accompanied by symptoms of fatigue, affected sleep, memory issues, and mood disorders.

Studies suggest that the chronic widespread pain seen in fibromyalgia patients has a neurogenic origin. Higher levels of ascending pathway neurochemicals, including nerve growth factor, substance P, and brain-derived neurotrophic factor, are present in the cerebrospinal fluid (CSF) of fibromyalgia patients when compared to healthy controls. In addition, glutamate levels can be elevated in both the CSF and brain of fibromyalgia patients. Glutamate may play a central role, by acting on the NMDA receptors to increase the central amplification of pain perception, which is thought to manifest as allodynia and hyperalgesia in fibromyalgia patients. NMDA receptors are thus an attractive target for fibromyalgia therapeutic drug development.

In four other randomized controlled trial(s) to evaluate ketamine an NMDA-receptor antagonist; two demonstrated an acute reduction in VAS pain scores (20- to -25 points) 90- to 120-minutes following IV ketamine 0.3 mg/kg compared with placebo; while the other two using different drug concentrations and dose regimen (0.3 mg/kg over 30 minutes and 0.5 mg/kg for 3 hours) showed a 0.5- to a 0.9-point reduction in pain scores (10-cm VAS) at 90 to 180 minutes following IV ketamine compared with placebo. Although all four trials demonstrated significant acute pain improvement during and immediately following the infusions, there were no sustained improvements.

Given nitrous oxide is another drug with known NMDA-receptor antagonism, this trial will evaluate the efficacy of inhaled 50% nitrous oxide compared to a placebo (oxygen-air mixture). Study participants with a clinical diagnosis of fibromyalgia, meeting 2016-Fibromyalgia Diagnostic Criteria (2016-ACR) and neuropathic pain criterion, will be randomly assigned to receive two 60-minute inhalation sessions (50% nitrous oxide and placebo).

Treatment outcomes will be monitored using diagnostic tools measuring functionality, pain, and mood:

  • Numeric Pain Rating Scale (NPRS)
  • Revised Fibromyalgia Impact Questionnaire (FIQR)
  • Patient’s Global Impression of Change Scale (PGIC)
  • Hospital Anxiety and Depression Scale (HADS)
  • Computerized Adaptive Test-Mental Health (CAT-MH)


Title: Sleep and Pain Interventions in Women With Fibromyalgia (SPIN-II)

Stage: Recruiting

Principal investigator: Christina McCrae, PhD 

University of Missouri-Columbia

Columbia, MO

Insomnia affects 67-88% of chronic pain patients. SPIN II is a randomized controlled clinical trial that will compare the effects of two cognitive-behavioral sleep treatments in women with fibromyalgia and insomnia. This trial will yield important information about the roles of sleep, arousal, and brain structure and function in the development and maintenance of chronic pain in women with fibromyalgia.

This mechanistic trial will assess sleep, pain, arousal, and neural imagining outcomes at baseline, post-8-week behavioral treatment (CBT-I or SHE), as well as at 6 and 12-month follow-ups. This information will provide novel information about the neural structures and functional networks associated with chronic pain, and their manipulation through a cognitive behavioral intervention to improve insomnia. Demonstrating that a relatively brief intervention can reverse or resolve pain-related maladaptive neural plasticity, and improve or resolve clinical pain symptoms would have immediate and far-reaching implications for millions of chronic pain sufferers and the US healthcare system and economy.


Title: Assessing the Impact of Exercise Based Intensive Interdisciplinary Pain Treatment (IIPT) on Endogenous Pain Modulation in Youth With Chronic Pain Syndromes

Stage: Not Yet Recruiting

Principal investigator: Julie M. Shulman, PT, PhD 

Boston Children’s Hospital

Waltham, MA

This work will answer two critical questions: 1) Does intensive interdisciplinary pain treatment (IIPT) involving aerobic exercise help normalize pain processing in youth with chronic pain syndromes, and 2) Are aerobic fitness levels and the ability to modulate pain interrelated?

Currently, medications are ineffective in improving pain and disability in youth with chronic pain syndromes, and identifying non-pharmacologic treatments, such as IIPT, that help strengthen the nervous system’s ability to modulate or turn pain signals down will improve outcomes and quality of life for youth suffering from chronic pain. This study will help determine whether exercise-based IIPT leads to physiologic improvements in how pain is processed, specifically if youth with chronic pain can better turn the pain down during the offset analgesia test after an exercise-based IIPT treatment, and also help elucidate the link between a child’s aerobic fitness and their ability to modulate pain.

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