Quantitative sensory testing | |
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Specialty | Neurology |
Quantitative sensory testing (QST) is a panel of diagnostic tests used to assess somatosensory function, in the context of research and as a supplemental tool in the diagnosis of somatosensory disorders, including pain insensitivity, painless and painful neuropathy. The panel of tests examine a broad range of different sensations, including hot, cold, touch, vibration. It has both positive and negative tests (can test for increased or reduced sensitivity). QST reflects a formalisation of existing neurological tests into a standardised battery designed to detect subtle changes in sensory function. [1] Large datasets representing normal responses to sensory tests have been established to quantitate deviation from the mean and allow comparison with normal patients. It is thought that a detailed evaluation of somatosensory function may be useful in identifying subtypes of pain and as a potential tool to identify asymptomatic neuropathy, [2] which may represent up to 50% of total people with neuropathy (or loss of the nerve fibres). In clinical use, it is often combined with other tests such as clinical electrophysiology. [3] In research settings it is increasingly applied in combination with advanced imaging such as fMRI, epidermis "nerve" biopsies and microneurography to classify subtypes of painful disorders. [4]
The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain (IASP) have recommended the clinical use of QST in the diagnosis and evaluation of patients with small and large fibre neuropathy as well as screening for deficits of the somatosensory system (which may include deficits in the brain for instance). The group also recommend that the technique not be used in patients in litigation, or with severe learning or cognitive deficits as it is likely to be inaccurate due to its psychophysical basis. The recommendations are based on large trials suggesting inter-test reliability of the method. [5]
Standard parameters are evaluated using calibrated testing apparatus. The tests can be performed in multiple areas of the body; the areas are limited by the existing available normal sensory data. All of the tests are repeated several times. [1] A widely used set of parameters was proposed by the German Research Network on Neuropathic Pain. Subject values are compared to normal data to determine whether the subject has a deficit in any modality.
Test | Abbreviation | Brief Description | Purpose |
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Mechanical Detection Threshold | MDT | Graded Von Frey filaments - that deliver increasing stimulus intensity are applied to the subject, the first stimulus to be perceived is recorded. | Identify dysfunction in Aβ fibres |
Vibration Detection Threshold | VDT | A tuning fork is placed on a bony prominence such as the elbow or knee, the subject reports when they can no longer detect vibration. | Identify dysfunction in Aβ fibres |
Cold Detection Threshold | CDT | A peltier device applies an increasingly cold stimulus, the subject reports when they can feel cold. | Identify dysfunction of Aδ fibres |
Paradoxical Heat Sensations | PHS | Alternating stimuli of hot and cold are applied, the subject is asked if they feel heat when a cold stimulus is applied during this procedure. | Either the dysfunction of Aδ fibres or the disruption of central cold processing. |
Warm Detection Threshold | WDT | A peltier device is used to warm and area of the body, the subject reports when they feel warmth. | Detect changes warm detection. C fibres are thought to contribute but the relative contributions are disputed. |
Wind-up Ratio | WUR | The subject is asked to compare the perceived stimulus intensity of a single pin prick to ten consecutive pin pricks. | Detect abnormal amplification of pain stimuli. |
Mechanical Pain Threshold | MPT | A custom pin stimulator is used, it delivers pins at increasing force, the subject is asked to report the first detection of sharpness. | Identify dysfunction of Aδ fibres, and C-fibers |
Mechanical Pain Sensitivity | MPS | The same stimulator is used, a force ~8X higher than the threshold is used and the subject is asked to rate their pain on a 100 point scale. | Identify dysfunction of Aδ fibres, and C-fibers |
Cold Pain Threshold | CPT | A peltier device applies an increasingly cold stimulus, the subject is asked to report when they feel pain. | Identify dysfunction of Aδ fibres |
Heat Pain Threshold | HPT | A peltier device applies an increasingly hot stimulus, the subject is asked to report when they feel pain. | Identify dysfunction of C fibres |
Pressure Pain Threshold | PPT | A pressure application device is used to apply graded pressure, the subject is asked to report the point at which they feel pain. | Identify dysfunction of Aδ fibres, and C-fibers |
Dynamic Mechanical Allodynia | ALL/DMA | Pain score is reported for a moving innocuous mechanical stimuli, such as a cotton tip. | Identify presence of allodynia |
In addition to diagnostic confidence with neuropathy, additional reasons may encourage the use of QST.
It is thought that patients with neuropathic pain can be grouped into clusters based on their sensory profiles and that this may have a role in determining treatment. [6] After-the fact (or Post Hoc) analysis of the responders to treatments in clinical trials have suggested different clinical responses may cluster based on phenotype and preliminary clinical trials suggest some analgesics show a greater efficacy in patient subtypes. [6] The european medicines agency allow the classification of patients by QST in clinical trials. It is proposed that in cases where efficacy is only shown in one identified QST group, the drug will only be approved for use with those patients. Additionally, in Europe, QST is now allowed as a secondary outcome in clinical trials. [7]
The early identification of neuropathy particularly in diabetic neuropathy may be useful to identify people with asymptomatic neuropathy. Asymptomatic neuropathy is a clinical concern because patients with untreated neuropathy may develop ulcers and damage due to a loss of protective sensation. [8]
QST relies on psychophysical report of responses to stimuli. As a result it may be subject to patient biases. Nerve conduction studies may provide a more reliable metric in certain clinical situations. [3] However, nerve conduction studies poorly identify hypersensitivity, QST can identify both loss and gain of function. [9] Psychophysical tests are generally affected by other difficult to control factors, such as stress, the experience of the tester, the room the test is in, the novelty of the environment and the person's temperament. The test is time consuming and may take an hour to perform, and for monitoring require multiple visits. [3]
Charcot–Marie–Tooth disease (CMT) is a hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. This disease is the most commonly inherited neurological disorder, affecting about one in 2,500 people. It is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940), and the Briton Howard Henry Tooth (1856–1925).
Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic changes such as urinary symptoms. These changes are thought to result from a microvascular injury involving small blood vessels that supply nerves. Relatively common conditions which may be associated with diabetic neuropathy include distal symmetric polyneuropathy; third, fourth, or sixth cranial nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; and autonomic neuropathy.
Peripheral neuropathy, often shortened to neuropathy, is a general term describing damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerves are affected. Neuropathy affecting motor, sensory, or autonomic nerves result in different symptoms. More than one type of nerve may be affected simultaneously. Peripheral neuropathy may be acute or chronic, and may be reversible or permanent.
Polyneuropathy is damage or disease affecting peripheral nerves in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hands and feet and may progress to the arms and legs and sometimes to other parts of the body where it may affect the autonomic nervous system. It may be acute or chronic. A number of different disorders may cause polyneuropathy, including diabetes and some types of Guillain–Barré syndrome.
Hyperalgesia is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and can cause hypersensitivity to stimulus. Prostaglandins E and F are largely responsible for sensitizing the nociceptors. Temporary increased sensitivity to pain also occurs as part of sickness behavior, the evolved response to infection.
Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous and/or episodic (paroxysmal) components. The latter resemble stabbings or electric shocks. Common qualities include burning or coldness, "pins and needles" sensations, numbness and itching.
Neuralgia is pain in the distribution of a nerve or nerves, as in intercostal neuralgia, trigeminal neuralgia, and glossopharyngeal neuralgia.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disease of the peripheral nervous system characterized by progressive weakness and impaired sensory function in the legs and arms. The disorder is sometimes called chronic relapsing polyneuropathy (CRP) or chronic inflammatory demyelinating polyradiculoneuropathy. CIDP is closely related to Guillain–Barré syndrome and it is considered the chronic counterpart of that acute disease. Its symptoms are also similar to progressive inflammatory neuropathy. It is one of several types of neuropathy.
Small fiber peripheral neuropathy is a type of peripheral neuropathy that occurs from damage to the small unmyelinated and myelinated peripheral nerve fibers. These fibers, categorized as C fibers and small Aδ fibers, are present in skin, peripheral nerves, and organs. The role of these nerves is to innervate some skin sensations and help control autonomic function. It is estimated that 15–20 million people in the United States have some form of peripheral neuropathy.
Group C nerve fibers are one of three classes of nerve fiber in the central nervous system (CNS) and peripheral nervous system (PNS). The C group fibers are unmyelinated and have a small diameter and low conduction velocity, whereas Groups A and B are myelinated. Group C fibers include postganglionic fibers in the autonomic nervous system (ANS), and nerve fibers at the dorsal roots. These fibers carry sensory information.
Ranirestat is an aldose reductase inhibitor being developed for the treatment of diabetic neuropathy by Dainippon Sumitomo Pharma and PharmaKyorin. It has been granted orphan drug status. The drug is to be used orally.
Nav1.8 is a sodium ion channel subtype that in humans is encoded by the SCN10A gene.
Anterior interosseous syndrome is a medical condition in which damage to the anterior interosseous nerve (AIN), a distal motor and sensory branch of the median nerve, classically with severe weakness of the pincer movement of the thumb and index finger, and can cause transient pain in the wrist.
Nerve compression syndrome, or compression neuropathy, or nerve entrapment syndrome, is a medical condition caused by chronic, direct pressure on a peripheral nerve. It is known colloquially as a trapped nerve, though this may also refer to nerve root compression. Its symptoms include pain, tingling, numbness and muscle weakness. The symptoms affect just one particular part of the body, depending on which nerve is affected. The diagnosis is largely clinical and can be confirmed with diagnostic nerve blocks. Occasionally imaging and electrophysiology studies aid in the diagnosis. Timely diagnosis is important as untreated chronic nerve compression may cause permanent damage. A surgical nerve decompression can relieve pressure on the nerve but cannot always reverse the physiological changes that occurred before treatment. Nerve injury by a single episode of physical trauma is in one sense an acute compression neuropathy but is not usually included under this heading, as chronic compression takes a unique pathophysiological course.
Palmitoylethanolamide (PEA) is an endogenous fatty acid amide, and lipid modulator PEA has been studied in in vitro and in vivo systems using exogenously added or dosed compound; there is evidence that it binds to a nuclear receptor, through which it exerts a variety of biological effects, some related to chronic inflammation and pain.
Chemotherapy-induced peripheral neuropathy (CIPN) is a nerve-damaging side effect of antineoplastic agents in the common cancer treatment, chemotherapy. CIPN afflicts between 30% and 40% of patients undergoing chemotherapy. Antineoplastic agents in chemotherapy are designed to eliminate rapidly dividing cancer cells, but they can also damage healthy structures, including the peripheral nervous system. CIPN involves various symptoms such as tingling, pain, and numbness in the hands and feet. These symptoms can impair activities of daily living, such as typing or dressing, reduce balance, and increase risk of falls and hospitalizations. They can also give cause to reduce or discontinue chemotherapy. Researchers have conducted clinical trials and studies to uncover the various symptoms, causes, pathogenesis, diagnoses, risk factors, and treatments of CIPN.
EMA401 is a drug under development for the treatment of peripheral neuropathic pain. Trials were discontinued in 2015, with new trials scheduled to begin March, 2018. It was initially established as a potential drug option for patients suffering pain caused by postherpetic neuralgia. It may also be useful for treating various types of chronic neuropathic pain EMA401 has shown efficacy in preclinical models of shingles, diabetes, osteoarthritis, HIV and chemotherapy. EMA401 is a competitive antagonist of angiotensin II type 2 receptor (AT2R) being developed by the Australian biotechnology company Spinifex Pharmaceuticals. EMA401 target angiotensin II type 2 receptors, which may have importance for painful sensitisation.
Ocular neuropathic pain is a spectrum of disorders of ocular pain which are caused by damage or disease affecting the nerves. Ocular neuropathic pain is frequently associated with damaged or dysfunctional corneal nerves, but the condition can also be caused by peripheral or centralized sensitization. The condition shares some characteristics with somatic neuropathic pain in that it is similarly associated with abnormal sensations (dysesthesia) or pain from normally non-painful stimuli (allodynia), but until recent years has been poorly understood by the medical community, and frequently dismissed by ophthalmologists who were not trained to identify neuropathic pain as a source of unexplained eye pain beyond objective findings noted on slit-lamp examination.
Peripheral mononeuropathy is a nerve related disease where a single nerve, that is used to transport messages from the brain to the peripheral body, is diseased or damaged. Peripheral neuropathy is a general term that indicates any disorder of the peripheral nervous system. The name of the disorder itself can be broken down in order to understand this better; peripheral: in regard to peripheral neuropathy, refers to outside of the brain and spinal cord; neuro: means nerve related; -pathy; means disease. Peripheral mononeuropathy is a disorder that links to Peripheral Neuropathy, as it only effects a single peripheral nerve rather than several damaged or diseased nerves throughout the body. Healthy peripheral nerves are able to “carry messages from the brain and spinal cord to muscles, organs, and other body tissues”.
Vasculitic neuropathy is a peripheral neuropathic disease. In a vasculitic neuropathy there is damage to the vessels that supply blood to the nerves. It can be as part of a systemic problem or can exist as a single-organ issue only affecting the peripheral nervous system (PNS). It is diagnosed with the use of electrophysiological testing, blood tests, nerve biopsy and clinical examination. It is a serious medical condition that can cause prolonged morbidity and disability and generally requires treatment. Treatment depends on the type but it is mostly with corticosteroids or immunomodulating therapies.