Nociplastic pain or central sensitisation is a type of

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

which is mechanically different from the normal

nociceptive pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

caused by

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

and tissue damage or the

neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli ( allodynia). It may have continuo ...

which results from nerve damage. It may occur in combination with the other types of pain or in isolation. Its location may be generalised or multifocal and it can be more intense than would be expected from any associated physical cause. Its causes are not fully understood but it is thought to be a dysfunction of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

whose processing of

pain signal Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

s may have become distorted or sensitised. The concept and term was formally added to the

taxonomy Taxonomy is the practice and science of categorization or classification. A taxonomy (or taxonomical classification) is a scheme of classification, especially a hierarchical classification, in which things are organized into groups or types. ...

of the

International Association for the Study of Pain The International Association for the Study of Pain (IASP) is an international learned society promoting research, education, and policies for the understanding, prevention, and treatment of pain. IASP was founded in 1973 under the leadership of ...

following the recommendation of a task force in 2017. The root terms are Latin ''nocēre'', meaning to hurt, and Greek ''πλαστός'', meaning development or formation in a medical context. This type of pain typically arises in some

chronic pain Chronic pain is classified as pain that lasts longer than three to six months. In medicine, the distinction between acute and chronic pain is sometimes determined by the amount of time since onset. Two commonly used markers are pain that continues ...

conditions, with the archetypal condition being

fibromyalgia Fibromyalgia (FM) is a medical condition defined by the presence of chronic widespread pain, fatigue, waking unrefreshed, cognitive symptoms, lower abdominal pain or cramps, and depression. Other symptoms include insomnia and a general hype ...

. It may be a factor in

long COVID Long COVID or long-haul COVID (also known as post-COVID-19 syndrome, post-COVID-19 condition, post-acute sequelae of COVID-19 (PASC), or chronic COVID syndrome (CCS)) is a condition characterized by long-term health problems persisting or app ...

. Exercise is commonly prescribed for such conditions. Nociplastic pain has also been hypothesized to play a role in the persistence of medically unexplained symptoms.

Definition

Nociplastic pain is a longterm complex pain, one of three mechanisms of

, defined by the

as "pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain". The other two mechanisms are

and

. Widespread pain and increased pain have been suggested as important clinical features. Central sensitization is a broader term referring to a hyperexcitability of the

nervous system In Biology, biology, the nervous system is the Complex system, highly complex part of an animal that coordinates its Behavior, actions and Sense, sensory information by transmitting action potential, signals to and from different parts of its ...

, usually including

hyperalgesia Hyperalgesia ( or ; 'hyper' from Greek ὑπέρ (huper, “over”), '-algesia' from Greek algos, ἄλγος (pain)) is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and ca ...

(increased sensitivity to pain), and

allodynia Allodynia is a condition in which pain is caused by a stimulus that does not normally elicit pain. For example, bad sunburn can cause temporary allodynia, and touching sunburned skin, or running cold or warm water over it, can be very painful. It i ...

(painful perception of non-painful stimuli). An even broader term is that of central sensitivity syndromes, referring to syndromes characterized by the hyperexcitement of central

neuron A neuron, neurone, or nerve cell is an membrane potential#Cell excitability, electrically excitable cell (biology), cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous ...

s. These include

irritable bowel syndrome Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms ma ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a resul ...

chronic fatigue syndrome Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME) or ME/CFS, is a complex, debilitating, long-term medical condition. The Pathophysiology, causes and mechanisms of the disease are not fully understood. Distinguishing c ...

and temporomandibular disorder.

Mechanism

Its causes are not fully understood but it is thought to be a dysfunction of the

whose processing of

s may have become distorted or sensitised. Specific

locations that have been suggested are nociceptive

s, spinal and supraspinal structures, the dorsal horn and others.

Diagnosis

It is diagnosed by its clinical features and lack of response to regular painkillers. Pain is experienced in several body parts, and is often widespread and intense. There may be associated tiredness, and difficulties with

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered ...

mood Mood may refer to: *Mood (psychology), a relatively long lasting emotional state Music *The Mood, a British pop band from 1981 to 1984 * Mood (band), hip hop artists * ''Mood'' (Jacquees album), 2016 * ''Moods'' (Barbara Mandrell album), 1978 ...

and

sleep Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited Perception, sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefuln ...

. It can occur on its own in conditions such as

tension headache Tension headache, also known as stress headache, or tension-type headache (TTH), is the most common type of primary headache. The pain can radiate from the lower back of the head, the neck, eyes or other muscle groups in the body typically affecti ...

, or combined with other pain categories such as in chronic back pain. Tools to measure central sensitization include sensory tests to painful stimuli, magnetic resonance imaging and measures of

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...

s and

neurotrophin Neurotrophins are a family of proteins that induce the survival, development, and function of neurons. They belong to a class of growth factors, secreted proteins that can signal particular cells to survive, differentiate, or grow. Growth facto ...

es in the

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...

and

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

. Self-report questionnaires such as the Central Sensitization Inventory and the Sensory Hypersensitivity Scale are also used.

Treatment

Treatment generally requires both physical and psychological therapies, along with pain neuroscience education.

References

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