Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral
nerve
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system.
A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
s, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or organ function depending on which nerves are affected; in other words, neuropathy affecting
motor
An engine or motor is a machine designed to convert one or more forms of energy into mechanical energy.
Available energy sources include potential energy (e.g. energy of the Earth's gravitational field as exploited in hydroelectric power g ...
,
sensory, or
autonomic nerves
Autonomic can refer to:
* Autonomic nervous system, a division of the peripheral nervous system that supplies smooth muscle and glands, and thus influences the function of internal organs
*Autonomic computing
Autonomic computing (AC) is distribu ...
result in different symptoms. More than one type of nerve may be affected simultaneously. Peripheral neuropathy may be acute (with sudden onset, rapid progress) or chronic (symptoms begin subtly and progress slowly), and may be reversible or permanent.
Common causes include systemic diseases (such as
diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
or
leprosy
Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damag ...
), hyperglycemia-induced
glycation
Glycation (sometimes called non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic proces ...
,
vitamin deficiency
Vitamin deficiency is the condition of a long-term lack of a vitamin. When caused by not enough vitamin intake it is classified as a ''primary deficiency'', whereas when due to an underlying disorder such as malabsorption it is called a ''seconda ...
,
medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
(e.g.,
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
, or commonly prescribed
antibiotics
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
including
metronidazole
Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It i ...
and the
fluoroquinolone
A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as wel ...
class of antibiotics (such as
ciprofloxacin
Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin inf ...
,
levofloxacin
Levofloxacin, sold under the brand name Levaquin among others, is an antibiotic medication. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, H. pylori (in combination with other medications), ...
,
moxifloxacin
Moxifloxacin is an antibiotic, used to treat bacterial infections, including pneumonia, conjunctivitis, endocarditis, tuberculosis, and sinusitis. It can be given by mouth, by injection into a vein, and as an eye drop.
Common side effects incl ...
)), traumatic
injury
An injury is any physiological damage to living tissue caused by immediate physical stress. An injury can occur intentionally or unintentionally and may be caused by blunt trauma, penetrating trauma, burning, toxic exposure, asphyxiation, o ...
,
ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
,
radiation therapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
, excessive alcohol consumption,
immune system disease,
celiac disease
Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barl ...
,
non-celiac gluten sensitivity
Non-celiac gluten sensitivity (NCGS) or gluten sensitivity is "a clinical entity induced by the ingestion of gluten leading to intestinal and/or extraintestinal symptoms that improve once the gluten-containing foodstuff is removed from the diet, a ...
, or viral infection. It can also be
genetic (present from birth) or
idiopathic
An idiopathic disease is any disease with an unknown cause or mechanism of apparent wikt:spontaneous, spontaneous origin. From Ancient Greek, Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approxi ...
(no known cause).
In conventional medical
usage
The usage of a language is the ways in which its written and spoken variations are routinely employed by its speakers; that is, it refers to "the collective habits of a language's native speakers", as opposed to idealized models of how a language ...
, the word ''neuropathy'' (
neuro-, "nervous system" and
-pathy, "disease of") without modifier usually means ''peripheral neuropathy''.
Neuropathy affecting just one nerve is called "mononeuropathy" and neuropathy involving nerves in roughly the same areas on both sides of the body is called "symmetrical polyneuropathy" or simply "
polyneuropathy
Polyneuropathy ( poly- + neuro- + -pathy) is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hand ...
". When two or more (typically just a few, but sometimes many) separate nerves in disparate areas of the body are affected it is called "
mononeuritis multiplex
Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
", "multifocal mononeuropathy", or "multiple mononeuropathy".
[
Neuropathy may cause painful ]cramp
A cramp is a sudden, involuntary, painful skeletal muscle contraction or overshortening associated with electrical activity; while generally temporary and non-damaging, they can cause significant pain and a paralysis-like immobility of the aff ...
s, fasciculations (fine muscle twitching), muscle loss, bone degeneration, and changes in the skin, hair, and nails. Additionally, motor neuropathy may cause impaired balance and coordination or, most commonly, muscle weakness; sensory neuropathy may cause numbness to touch and vibration, reduced position sense causing poorer coordination and balance, reduced sensitivity to temperature change and pain, spontaneous tingling or burning pain, or 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 ...
(pain from normally nonpainful stimuli, such as light touch); and autonomic neuropathy
Autonomic neuropathy (AN or AAN) is a form of polyneuropathy that affects the non-voluntary, non-sensory nervous system (i.e., the autonomic nervous system), affecting mostly the internal organs such as the bladder muscles, the cardiovascular s ...
may produce diverse symptoms, depending on the affected glands and organs, but common symptoms are poor bladder control, abnormal blood pressure or heart rate, and reduced ability to sweat normally.[
]
Classification
Peripheral neuropathy may be classified according to the number and distribution of nerves affected (mononeuropathy, mononeuritis multiplex, or polyneuropathy), the type of nerve fiber predominantly affected (motor, sensory, autonomic), or the process affecting the nerves; e.g., inflammation (neuritis
Neuritis () is inflammation of a nerve or the general inflammation of the peripheral nervous system. Inflammation, and frequently concomitant demyelination, cause impaired transmission of neural signals and leads to aberrant nerve function. Neurit ...
), compression (compression neuropathy
Nerve compression syndrome, or compression neuropathy, or nerve entrapment syndrome, is a medical condition caused by direct pressure on a nerve. It is known colloquially as a ''trapped nerve'', though this may also refer to nerve root compres ...
), chemotherapy (chemotherapy-induced peripheral neuropathy
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 ...
). The affected nerves are found in an EMG (electromyography) / NCS (nerve conduction study) test and the classification is applied upon completion of the exam.
Mononeuropathy
Mononeuropathy is a type of neuropathy that only affects a single nerve
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system.
A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
. Diagnostically, it is important to distinguish it from polyneuropathy because when a single nerve is affected, it is more likely to be due to localized trauma or infection.
The most common cause of mononeuropathy is physical compression of the nerve, known as compression neuropathy
Nerve compression syndrome, or compression neuropathy, or nerve entrapment syndrome, is a medical condition caused by direct pressure on a nerve. It is known colloquially as a ''trapped nerve'', though this may also refer to nerve root compres ...
. Carpal tunnel syndrome
Carpal tunnel syndrome (CTS) is the collection of symptoms and signs associated with median neuropathy at the carpal tunnel. Most CTS is related to idiopathic compression of the median nerve as it travels through the wrist at the carpal tunn ...
and axillary nerve palsy are examples. Direct injury to a nerve, interruption of its blood supply resulting in (ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
), or 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 ...
also may cause mononeuropathy.
Polyneuropathy
"''Polyneuropathy''" is a pattern of nerve damage that is quite different from mononeuropathy, often more serious and affecting more areas of the body. The term "peripheral neuropathy" sometimes is used loosely to refer to polyneuropathy. In cases of polyneuropathy, many nerve cells in various parts of the body are affected, without regard to the nerve
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system.
A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
through which they pass; not all nerve cells are affected in any particular case. In distal axonopathy, one common pattern is that the cell bodies of neurons remain intact, but the axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
s are affected in proportion to their length; the longest axons are the most affected. Diabetic neuropathy
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 c ...
is the most common cause of this pattern. In demyelinating polyneuropathies, the myelin
Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...
sheath around axons is damaged, which affects the ability of the axons to conduct electrical impulses. The third and least common pattern affects the cell bodies
The soma (pl. ''somata'' or ''somas''), perikaryon (pl. ''perikarya''), neurocyton, or cell body is the bulbous, non-process portion of a neuron or other brain cell type, containing the cell nucleus. The word 'soma' comes from the Greek '' σῶ ...
of neurons directly. This usually picks out either the motor neuron
A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectl ...
s (known as motor neuron disease
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
) or the sensory neuron
Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded potentials. This process is called sensory transduction. The cell ...
s (known as ''sensory neuronopathy'' or ''dorsal root ganglionopathy'').
The effect of this is to cause symptoms in more than one part of the body, often symmetrically on left and right sides. As for any neuropathy, the chief symptoms include motor symptoms such as weakness or clumsiness of movement; and sensory symptoms such as unusual or unpleasant sensations such as tingling or burning; reduced ability to feel sensations such as texture or temperature, and impaired balance when standing or walking. In many polyneuropathies, these symptoms occur first and most severely in the feet. Autonomic symptoms also may occur, such as dizziness on standing up, erectile dysfunction
Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...
, and difficulty controlling urination.
Polyneuropathies usually are caused by processes that affect the body as a whole. Diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
and impaired glucose tolerance
Prediabetes is a component of the metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesit ...
are the most common causes. Hyperglycemia-induced formation of advanced glycation
Glycation (sometimes called non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic proces ...
end products (AGEs) is related to diabetic neuropathy. Other causes relate to the particular type of polyneuropathy, and there are many different causes of each type, including inflammatory diseases such as Lyme disease
Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the ''Borrelia'' bacterium, which is spread by ticks in the genus ''Ixodes''. The most common sign of infection is an expanding red rash, known as erythema migran ...
, vitamin deficiencies, blood disorders, and toxins (including alcohol and certain prescribed drugs).
Most types of polyneuropathy progress fairly slowly, over months or years, but rapidly progressive polyneuropathy also occurs. It is important to recognize that at one time it was thought that many of the cases of small fiber peripheral 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, periph ...
with typical symptoms of tingling, pain, and loss of sensation in the feet and hands were due to glucose intolerance
Prediabetes is a component of the metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesi ...
before a diagnosis of diabetes or pre-diabetes. However, in August 2015, the Mayo Clinic published a scientific study in the Journal of the Neurological Sciences showing "no significant increase in...symptoms...in the prediabetes group", and stated that "A search for alternate neuropathy causes is needed in patients with prediabetes."
The treatment of polyneuropathies is aimed firstly at eliminating or controlling the cause, secondly at maintaining muscle strength and physical function, and thirdly at controlling symptoms such as 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 continuous ...
.
Mononeuritis multiplex
Mononeuritis multiplex, occasionally termed polyneuritis multiplex, is simultaneous or sequential involvement of individual noncontiguous nerve trunk
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system.
A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
s, either partially or completely, evolving over days to years and typically presenting with acute or subacute loss of sensory and motor function of individual nerves
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system.
A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
. The pattern of involvement is asymmetric, however, as the disease progresses, deficit(s) becomes more confluent and symmetrical, making it difficult to differentiate from polyneuropathy. Therefore, attention to the pattern of early symptoms is important.
Mononeuritis multiplex is sometimes associated with a deep, aching pain that is worse at night and frequently in the lower back, hip, or leg. In people with diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
, mononeuritis multiplex typically is encountered as acute, unilateral, and severe thigh pain followed by anterior muscle weakness and loss of knee reflex.
Electrodiagnostic medicine
Electrodiagnosis (EDX) is a method of medical diagnosis that obtains information about diseases by passively recording the electrical activity of body parts (that is, their natural electrophysiology) or by measuring their response to external elect ...
studies will show multifocal sensory motor axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
al neuropathy.
It is caused by, or associated with, several medical conditions:
Autonomic neuropathy
Autonomic neuropathy is a form of polyneuropathy that affects the non-voluntary, non-sensory nervous system
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
(i.e., the autonomic nervous system
The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the peripheral nervous system that supplies viscera, internal organs, smooth muscle and glands. The autonomic nervous system is a control ...
), affecting mostly the internal organs such as the bladder
The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...
muscles, the cardiovascular system
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
, the digestive tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans a ...
, and the genital
A sex organ (or reproductive organ) is any part of an animal or plant that is involved in sexual reproduction. The reproductive organs together constitute the reproductive system. In animals, the testis in the male, and the ovary in the female, a ...
organs. These nerves are not under a person's conscious control and function automatically. Autonomic nerve fibers form large collections in the thorax, abdomen, and pelvis outside the spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
. They have connections with the spinal cord and ultimately the brain, however. Most commonly autonomic neuropathy is seen in persons with long-standing diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
type 1 and 2. In most—but not all—cases, autonomic neuropathy occurs alongside other forms of neuropathy, such as sensory neuropathy.
Autonomic neuropathy is one cause of malfunction of the autonomic nervous system, but not the only one; some conditions affecting the brain or spinal cord also may cause autonomic dysfunction
Dysautonomia or autonomic dysfunction is a condition in which the autonomic nervous system (ANS) does not work properly. This may affect the functioning of the heart, bladder, intestines, sweat glands, pupils, and blood vessels. Dysautonomia has ...
, such as multiple system atrophy
Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by autonomic dysfunction, tremors, slow movement, muscle rigidity, and postural instability (collectively known as parkinsonism) and ataxia. This is caused by progr ...
, and therefore, may cause similar symptoms to autonomic neuropathy.
The signs and symptoms of autonomic neuropathy include the following:
* Urinary bladder
The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...
conditions: bladder incontinence
Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life. It has been identified as an important issue in geria ...
or urine retention
Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include urinary incont ...
* Gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
: dysphagia
Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a disease#Terminology, condition in its own right.
It may be a sensation that suggests difficulty in the passag ...
, abdominal pain
Abdominal pain, also known as a stomach ache, is a symptom
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than ...
, nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
, vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose.
Vomiting can be the result of ailments like Food-poisoning, foo ...
, malabsorption
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety ...
, fecal incontinence
Fecal incontinence (FI), or in some forms encopresis, is a lack of control over defecation, leading to involuntary loss of bowel contents, both liquid stool elements and mucus, or solid feces. When this loss includes flatus (gas), it is referred ...
, gastroparesis
Gastroparesis (gastro- from Ancient Greek γαστήρ – gaster, "stomach"; and -paresis, πάρεσις – "partial paralysis"), also called delayed gastric emptying, is a medical disorder consisting of weak muscular contractions (peristalsis) ...
, diarrhoea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
, constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
* Cardiovascular system
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
: disturbances of heart rate (tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
, bradycardia
Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...
), orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...
, inadequate increase of heart rate on exertion
* Respiratory system
The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies grea ...
: impairments in the signals associated with regulation of breathing and gas exchange
Gas exchange is the physical process by which gases move passively by Diffusion#Diffusion vs. bulk flow, diffusion across a surface. For example, this surface might be the air/water interface of a water body, the surface of a gas bubble in a liqui ...
(central sleep apnea
Central sleep apnea (CSA) or central sleep apnea syndrome (CSAS) is a sleep-related disorder in which the effort to breathe is diminished or absent, typically for 10 to 30 seconds either intermittently or in cycles, and is usually associated w ...
, hypopnea
Hypopnea is overly shallow breathing or an abnormally low respiratory rate. Hypopnea is defined by some to be less severe than apnea (the complete cessation of breathing), while other researchers have discovered hypopnea to have a "similar if not ...
, bradypnea).
* Skin : thermal regulation, dryness through sweat disturbances
* Other areas: hypoglycemia
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...
unawareness, genital
A sex organ (or reproductive organ) is any part of an animal or plant that is involved in sexual reproduction. The reproductive organs together constitute the reproductive system. In animals, the testis in the male, and the ovary in the female, a ...
impotence
Neuritis
Neuritis is a general term for inflammation of a nerve
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system.
A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
or the general 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 ...
of the peripheral nervous system
The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...
. Symptoms depend on the nerves involved, but may include 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, ...
, paresthesia
Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...
(pins-and-needles), paresis
In medicine, paresis () is a condition typified by a weakness of voluntary movement, or by partial loss of voluntary movement or by impaired movement. When used without qualifiers, it usually refers to the limbs, but it can also be used to desc ...
(weakness), hypoesthesia
Hypoesthesia or numbness is a common side effect of various medical conditions that manifests as a reduced sense of touch or sensation, or a partial loss of sensitivity to sensory stimuli. In everyday speech this is generally referred to as nu ...
(numbness), anesthesia
Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...
, paralysis
Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...
, wasting, and disappearance of the reflexes
In biology, a reflex, or reflex action, is an involuntary, unplanned sequence or action and nearly instantaneous response to a Stimulus (physiology), stimulus.
Reflexes are found with varying levels of complexity in organisms with a nervous s ...
.
Causes of neuritis include:
Signs and symptoms
Those with diseases or dysfunctions of their nerves may present with problems in any of the normal nerve functions. Symptoms vary depending on the types of nerve fiber involved. In terms of sensory function, symptoms commonly include loss of function ("negative") symptoms, including numbness
Hypoesthesia or numbness is a common side effect of various medical conditions that manifests as a reduced sense of touch or sensation, or a partial loss of sensitivity to sensory stimuli. In everyday speech this is generally referred to as num ...
, tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...
, impairment of balance, and gait abnormality
Gait abnormality is a deviation from normal walking (gait). Watching a patient walk is the most important part of the neurological examination. Normal gait requires that many systems, including strength, sensation and coordination, function in an ...
. Gain of function (positive) symptoms include tingling
Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...
, 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, ...
, itch
Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...
ing, crawling, and pins-and-needles. Motor symptoms include loss of function ("negative") symptoms of weakness, tiredness, muscle atrophy, and gait abnormalities; and gain of function ("positive") symptoms of cramps
A cramp is a sudden, involuntary, painful skeletal muscle contraction or overshortening associated with electrical activity; while generally temporary and non-damaging, they can cause significant pain and a paralysis-like immobility of the aff ...
, and muscle twitch ( fasciculations).
In the most common form, length-dependent peripheral neuropathy, pain and parasthesia
Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...
appears symmetrically and generally at the terminals of the longest nerves, which are in the lower legs and feet. Sensory symptoms generally develop before motor symptoms such as weakness. Length-dependent peripheral neuropathy symptoms make a slow ascent of the lower limbs, while symptoms may never appear in the upper limbs; if they do, it will be around the time that leg symptoms reach the knee. When the nerves of the autonomic nervous system
The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the peripheral nervous system that supplies viscera, internal organs, smooth muscle and glands. The autonomic nervous system is a control ...
are affected, symptoms may include constipation, dry mouth, difficulty urinating, and dizziness when standing.
CAP-PRI Scale for diagnosis
A user-friendly, disease-specific, quality-of-life scale can be used to monitor how someone is doing living with the burden of chronic, sensorimotor polyneuropathy. This scale, called the Chronic, Acquired Polyneuropathy - Patient-reported Index (CAP-PRI), contains only 15 items and is completed by the person affected by polyneuropathy. The total score and individual item scores can be followed over time, with item scoring used by the patient and care-provider to estimate clinical status of some of the more common life domains and symptoms impacted by polyneuropathy.
Causes
The causes are grouped broadly as follows:
Diagnosis
Peripheral neuropathy may first be considered when an individual reports symptoms of numbness, tingling, and pain in feet. After ruling out a lesion in the central nervous system as a cause, diagnosis may be made on the basis of symptoms, laboratory and additional testing, clinical history, and a detailed examination.
During physical examination
In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally consists of a series of questions about the patien ...
, specifically a neurological examination
A neurological examination is the assessment of sensory neuron and motor responses, especially reflexes, to determine whether the nervous system is impaired. This typically includes a physical examination and a review of the patient's medical hist ...
, those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, although those with a pathology
Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in ...
(problem) of the nerves may be perfectly normal; may show proximal weakness, as in some inflammatory neuropathies, such as Guillain–Barré syndrome
Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain often ...
; or may show focal sensory disturbance or weakness, such as in mononeuropathies. Classically, ankle jerk reflex is absent in peripheral neuropathy.
A physical examination will involve testing the deep ankle reflex as well as examining the feet for any ulceration
An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
. For large fiber neuropathy, an exam will usually show an abnormally decreased sensation to vibration, which is tested with a 128-Hz tuning fork
A tuning fork is an acoustic resonator in the form of a two-pronged fork with the prongs (tines) formed from a U-shaped bar of elastic metal (usually steel). It resonates at a specific constant pitch when set vibrating by striking it against ...
, and decreased sensation of light touch when touched by a nylon monofilament.
Diagnostic tests include electromyography
Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph to produce a record called an electromyogram. An electromyog ...
(EMG) and nerve conduction studies
A nerve conduction study (NCS) is a medical diagnostic test commonly used to evaluate the function, especially the ability of electrical conduction, of the motor and sensory nerves of the human body. These tests may be performed by medical spec ...
(NCSs), which assess large myelinated nerve fibers. Testing for small-fiber peripheral neuropathies often relates to the autonomic nervous system
The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the peripheral nervous system that supplies viscera, internal organs, smooth muscle and glands. The autonomic nervous system is a control ...
function of small thinly- and unmyelinated fibers. These tests include a sweat test and a tilt table test. Diagnosis of small fiber involvement in peripheral neuropathy may also involve a skin biopsy in which a 3 mm-thick section of skin is removed from the calf by a punch biopsy, and is used to measure the skin intraepidermal nerve fiber density (IENFD), the density of nerves in the outer layer of the skin. Reduced density of the small nerves in the epidermis supports a diagnosis of small-fiber peripheral neuropathy.
In EMG testing, demyelinating neuropathy characteristically shows a reduction in conduction velocity and prolongation of distal and F-wave latencies, whereas axonal neuropathy shows a reduction in amplitude.
Laboratory tests include blood tests for vitamin B-12
Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. It ...
levels, a complete blood count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cell ...
, measurement of thyroid stimulating hormone
Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of ...
levels, a comprehensive metabolic panel
The comprehensive metabolic panel, or chemical screen (CMP; CPT code 80053), is a panel of 14 blood tests that serves as an initial broad medical screening tool. The CMP provides a rough check of kidney function, liver function, diabetic and p ...
screening for diabetes and pre-diabetes, and a serum immunofixation test, which tests for antibodies in the blood.
Treatment
The treatment of peripheral neuropathy varies based on the cause of the condition, and treating the underlying condition can aid in the management of neuropathy. When peripheral neuropathy results from diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
or prediabetes
Prediabetes is a component of the metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesit ...
, blood sugar management is key to treatment. In prediabetes in particular, strict blood sugar control can significantly alter the course of neuropathy. In peripheral neuropathy that stems from immune-mediated diseases, the underlying condition is treated with intravenous immunoglobulin
Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory dem ...
or steroids. When peripheral neuropathy results from vitamin deficiencies
Vitamin deficiency is the condition of a long-term lack of a vitamin. When caused by not enough vitamin intake it is classified as a ''primary deficiency'', whereas when due to an underlying disorder such as malabsorption it is called a ''secon ...
or other disorders, those are treated as well.
Medications
A range of medications that act on the central nervous system have been used to symptomatically treat neuropathic pain. Commonly used medications include tricyclic antidepressant
Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
s (such as nortriptyline
Nortriptyline, sold under the brand name Pamelor, among others, is a medication used to treat depression. This medicine is used for: neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. As with many a ...
, amitriptyline
Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder and a variety of pain syndromes from neuropathic pain to fibromyalgi ...
. imapramine, and desipramine
Desipramine, sold under the brand name Norpramin among others, is a tricyclic antidepressant (TCA) used in the treatment of depression. It acts as a relatively selective norepinephrine reuptake inhibitor, though it does also have other activiti ...
,) serotonin-norepinephrine reuptake inhibitor (SNRI) medications (duloxetine
Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, neuropathic pain and central sensitization. It is taken by mouth. It is a serotoni ...
, venlafaxine
Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin-norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, panic di ...
, and milnacipran
Milnacipran (trade names Ixel, Savella, Dalcipran, Toledomin) is a serotonin–norepinephrine reuptake inhibitor (SNRI) used in the clinical treatment of fibromyalgia. It is not approved for the clinical treatment of major depressive disorder in ...
) and antiepileptic medications (gabapentin
Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabet ...
, pregabalin
Pregabalin, sold under the brand name Lyrica among others, is an anticonvulsant, analgesic and anxiolytic medication used to treat epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, opioid withdrawal and generalized anxiety disord ...
, oxcarbazepine
Oxcarbazepine, sold under the brand name Trileptal among others, is a medication used to treat epilepsy. For epilepsy it is used for both focal seizures and generalized seizures. It has been used both alone and as add-on therapy in people with ...
zonisamide
Zonisamide, sold under the brand name Zonegran among others, is a medication used to treat the symptoms of epilepsy and Parkinson's disease. Chemically it is a sulfonamide. It serves as an anticonvulsant used primarily as an adjunctive therapy i ...
levetiracetam
Levetiracetam, sold under the brand name Keppra among others, is a medication used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures and is taken either by mouth as an immediate or extended release formul ...
, lamotrigine
Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut synd ...
, topiramate
Topiramate, sold under the brand name Topamax among others, is a carbonic anhydrase inhibitor medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence. For epilepsy this includes treatment for gener ...
, clonazepam
Clonazepam, sold under the brand names Klonopin and Rivotril, is a medication used to prevent and treat seizures, panic disorder, anxiety disorders, and the movement disorder known as akathisia. It is a tranquilizer of the benzodiazepine class ...
, phenytoin
Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...
, lacosamide
Lacosamide, sold under the brand name Vimpat among others, is a medication used for the treatment of partial-onset seizures and primary generalized tonic-clonic seizures. It is used by mouth or intravenously.
It is available as a generic medic ...
, sodium valproate
Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...
and carbamazepine
Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other m ...
). Opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
and opiate
An opiate, in classical pharmacology, is a substance derived from opium. In more modern usage, the term ''opioid'' is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain (including antagonis ...
medications (such as buprenorphine
Buprenorphine is an opioid used to treat opioid use disorder, acute pain, and chronic pain. It can be used under the tongue (sublingual), in the cheek (buccal), by injection (intravenous and subcutaneous), as a skin patch (transdermal ...
, morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
, methadone
Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroin ...
, fentanyl
Fentanyl, also spelled fentanil, is a very potent synthetic opioid used as a pain medication. Together with other drugs, fentanyl is used for anesthesia. It is also used illicitly as a recreational drug, sometimes mixed with heroin, cocaine ...
, hydromorphone
Hydromorphone, also known as dihydromorphinone, and sold under the brand name Dilaudid among others, is an opioid used to treat moderate to severe pain. Typically, long-term use is only recommended for pain due to cancer. It may be used by mou ...
, tramadol
Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an ...
and oxycodone
Oxycodone, sold under various brand names such as Roxicodone and OxyContin (which is the extended release form), is a strong, semi-synthetic opioid used medically for treatment of moderate to severe pain. It is highly addictive and a commonly ...
) are also often used to treat neuropathic pain.
As is revealed in many of the Cochrane systematic reviews listed below, studies of these medications for the treatment of neuropathic pain are often methodologically flawed and the evidence is potentially subject to major bias. In general, the evidence does not support the usage of antiepileptic and antidepressant medications for the treatment of neuropathic pain. Better designed clinical trials and further review from non-biased third parties are necessary to gauge just how useful for patients these medications truly are. Reviews of these systematic reviews are also necessary to assess for their failings.
It is also often the case that the aforementioned medications are prescribed for neuropathic pain conditions for which they had not been explicitly tested on or for which controlled research is severely lacking; or even for which evidence suggests that these medications are not effective. The NHS for example explicitly state that amitriptyline and gabapentin can be used for treating the pain of sciatica. This is despite both the lack of high quality evidence that demonstrates efficacy of these medications for that symptom, and also the prominence of generally moderate to high quality evidence that reveals that antiepileptics in specific, including gabapentin, demonstrate no efficacy in treating it.
Antidepressants
In general, according to Cochrane's systematic reviews, antidepressants have shown to either be ineffective for the treatment of neuropathic pain or the evidence available is inconclusive. Evidence also tends to be tainted by bias or issues with the methodology.
Cochrane systematically reviewed the evidence for the antidepressants nortriptyline, desipramine, venlafaxine and milnacipran and in all these cases found scant evidence to support their use for the treatment of neuropathic pain. All reviews were done between 2014 and 2015.
A 2015 Cochrane systematic review of amitriptyline found that there was no evidence supporting the use of amitriptyline
Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder and a variety of pain syndromes from neuropathic pain to fibromyalgi ...
that did not possess inherent bias. The authors believe amitriptyline may have an effect in some patients but that the effect is overestimated. A 2014 Cochrane systematic review of imipramine notes that the evidence suggesting benefit were "methodologically flawed and potentially subject to major bias."
A 2017 Cochrane systematic review assessed the benefit of antidepressant medications for several types of chronic non-cancer pains (including neuropathic pain) in children and adolescents and the authors found the evidence inconclusive.
Antiepileptics
A 2017 Cochrane systematic review found that daily dosages between (1800 - 3600) mg of gabapentin could provide good pain relief for pain associated with diabetic neuropathy only. This relief occurred for roughly (30 - 40)% of treated patients, while placebo had a (10 - 20)% response. Three of the seven authors of the review had conflicts of interest declared. In a 2019 Cochrane review of pregabalin the authors conclude that there is some evidence of efficacy in the treatment of pain deriving from post-herpetic neuralgia, diabetic neuropathy and post-traumatic neuropathic pain only. They also warned that many patients treated will have no benefit. Two of the five authors declared receiving payments from pharmaceutical companies.
A 2017 Cochrane systematic review found that oxcarbazepine had little evidence to support its use for treating diabetic neuropathy, radicular pain and other neuropathies. The authors also call for better studies. In a 2015 Cochrane systematic review the authors found a lack of evidence showing any effectiveness of zonisamide for the treatment of pain deriving from any peripheral neuropathy. A 2014 Cochrane review found that studies of levetiracetam showed no indication for its effectiveness at treating pain from any neuropathy. The authors also found that the evidence was possibly biased and that some patients experienced adverse events.
A 2013 Cochrane systematic review concluded that there was high quality evidence to suggest that lamotrigine is not effective for treating neuropathic pain, even at high dosages (200 - 400) mg. A 2013 Cochrane systematic review of topimirate found that the included data had a strong likelihood of major bias; despite this, it found no effectiveness for the drug in treating the pain associated with diabetic neuropathy. It had not been tested for any other type of neuropathy. Cochrane reviews from 2012 of clonazepam and phenytoin uncovered no evidence of sufficient quality to support their use in chronic neuropathic pain."
A 2012 Cochrane systematic review of lacosamide found it very likely that the drug is ineffective for treating neuropathic pain. The authors caution against positive interpretations of the evidence. For sodium valproate the authors of a 2011 Cochrane review found that "three studies no more than hint that sodium valproate may reduce pain in diabetic neuropathy". They discuss how there is a probable overestimate of effect due to the inherent problems with the data and conclude that the evidence does not support its usage. In a 2014 systematic review of carbamazepine the authors believe the drug to be of benefit for some people. No trials were considered greater than level III evidence; none were longer than 4 weeks in length or were deemed as having good reporting quality.
A 2017 Cochrane systematic review aiming to assess the benefit of antiepileptic medications for several types of chronic non-cancer pains (including neuropathic pain) in children and adolescents found the evidence inconclusive. Two of the ten authors of this study declared receiving payments from pharmaceutical companies.
Opioids
A Cochrane review of buprenorphine, fentanyl, hydromorphone and morphine, all dated between 2015 and 2017, and all for the treatment of neuropathic pain, found that there was insufficient evidence to comment on their efficacy. Conflicts of interest were declared by the authors in this review. A 2017 Cochrane review of methadone found very low quality evidence, three studies of limited quality, of its efficacy and safety. They could not formulate any conclusions about its relative efficacy and safety compared to a placebo.
For tramadol, Cochrane found that there was only modest information about the benefits of its usage for neuropathic pain. Studies were small, had potential risks of bias and apparent benefits increased with risk of bias. Overall the evidence was of low or very low quality and the authors state that it "does not provide a reliable indication of the likely effect". For oxycodone the authors found very low quality evidence showing its usefulness in treating diabetic neuropathy and postherpetic neuralgia only. One of the four authors declared receiving payments from pharmaceutical companies.
More generally, a 2013 review examining the overall efficacy of opioid therapy for the treatment of neuropathic pain found studies were often subject to bias and that their efficacy and safety was not deducible with the evidence available. A 2017 Cochrane review examining opioid therapy as a treatment for many non-cancer pain syndromes (including neuropathic pain) concluded, "There was no evidence from randomised controlled trials to support or refute the use of opioids to treat chronic non-cancer pain in children and adolescents."
Others
A 2016 Cochrane review of paracetamol
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol.
At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
for the treatment of neuropathic pain concluded that its benefit alone or in combination with codeine or dihydrocodeine is unknown.
Few studies have examined whether nonsteroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s are effective in treating peripheral neuropathy.
There is some evidence that symptomatic relief from the pain of peripheral neuropathy may be obtained by application of topical capsaicin
Capsaicin (8-methyl-''N''-vanillyl-6-nonenamide) ( or ) is an active component of chili peppers, which are plants belonging to the genus ''Capsicum''. It is a chemical irritant for mammals, including humans, and produces a sensation of burning ...
. Capsaicin is the factor that causes heat in chili peppers. However, the evidence suggesting that capsaicin applied to the skin reduces pain for peripheral neuropathy is of moderate to low quality and should be interpreted carefully before using this treatment option.
Evidence supports the use of cannabinoids
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...
for some forms of neuropathic pain. A 2018 Cochrane review of cannabis-based medicines for the treatment of chronic neuropathic pain included 16 studies. All of these studies included THC
Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC' ...
as a pharmacological component of the test group. The authors rated the quality of evidence as very low to moderate. The primary outcome was quoted as, "Cannabis
''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: ''Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternatively ...
-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo" but "the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality". The authors also conclude, "The potential benefits of cannabis-based medicine... might be outweighed by their potential harms."
A 2014 Cochrane review of topical lidocaine
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidoca ...
for the treatment of various peripheral neuropathies found its usage supported by a few low quality studies. The authors state that there are no high quality randomised control trials demonstrating its efficacy or safety profile.
A 2015 (updated in 2022) Cochrane review of topical clonidine
Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and c ...
for the treatment of diabetic neuropathy included two studies of 8 and 12 weeks in length; both of which compared topical clonidine to placebo and both of which were funded by the same drug manufacturer. The review found that topical clonidine may provide some benefit versus placebo. However, the authors state that the included trials are potentially subject to significant bias and that the evidence is of low to moderate quality.
A 2007 Cochrane review of aldose reductase inhibitor Aldose reductase inhibitors are a class of drugs being studied as a way to prevent eye and nerve damage in people with diabetes.
Mechanism
Their target, aldose reductase, is an enzyme that is normally present in many other parts of the body, and ...
s for the treatment of the pain deriving from diabetic polyneuropathy found it no better than placebo.
Medical devices
Transcutaneous electrical nerve stimulation
Transcutaneous electrical nerve stimulation (TENS or TNS) is the use of electric current produced by a device to stimulate the nerves for therapeutic purposes. TENS, by definition, covers the complete range of transcutaneously applied currents ...
(TENS) therapy is often used to treat various types of neuropathy. A 2010 review of three trials, for the treatment of diabetic neuropathy explicitly, involving a total of 78 patients found some improvement in pain scores after 4 and 6, but not 12 weeks of treatment and an overall improvement in neuropathic symptoms at 12 weeks. Another 2010 review of four trials, for the treatment of diabetic neuropathy, found significant improvement in pain and overall symptoms, with 38% of patients in one trial becoming asymptomatic. The treatment remains effective even after prolonged use, but symptoms return to baseline within a month of cessation of treatment.
These older reviews can be balanced with a more recent 2017 review of TENS for neuropathic pain by Cochrane which concluded that, "This review is unable to state the effect of TENS versus sham TENS for pain relief due to the very low quality of the included evidence... The very low quality of evidence means we have very limited confidence in the effect estimate reported." A very low quality of evidence means, 'multiple sources of potential bias' with a 'small number and size of studies'.
Surgery
In people with diabetic peripheral neuropathy, two reviews make a case for nerve decompression surgery as an effective means of pain relief and support claims for protection from foot ulceration. There is less evidence for efficacy of surgery for non-diabetic peripheral neuropathy of the legs and feet. One uncontrolled study did before/after comparisons with a minimum of one-year follow-up and reported improvements for pain relief, impaired balance and numbness. "There was no difference in outcomes between patients with diabetic versus idiopathic neuropathy in response to nerve decompression." There are no placebo-controlled trials for idiopathic peripheral neuropathy in the published scientific literature.
Diet
According to a review, strict gluten-free diet is an effective treatment when neuropathy is caused by gluten sensitivity, with or without the presence of digestive symptoms or intestinal injury.
Counselling
A 2015 review on the treatment of neuropathic pain with psychological therapy
Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of psychological methods, particularly when based on regular personal interaction, to help a person change behavior, increase happiness, and overcome pro ...
concluded that, "There is insufficient evidence of the efficacy and safety of psychological interventions for chronic neuropathic pain. The two available studies show no benefit of treatment over either waiting list or placebo control groups."
Alternative medicine
A 2019 Cochrane review of the treatment of herbal medicinal products for people with neuropathic pain for at least three months concluded that, "There was insufficient evidence to determine whether nutmeg
Nutmeg is the seed or ground spice of several species of the genus ''Myristica''. ''Myristica fragrans'' (fragrant nutmeg or true nutmeg) is a dark-leaved evergreen tree cultivated for two spices derived from its fruit: nutmeg, from its seed, an ...
or St John's wort
''Hypericum perforatum'', known as St. John's wort, is a flowering plant in the family Hypericaceae and the type species of the genus ''Hypericum''.
Possibly a hybrid between '' H. maculatum'' and '' H. attenuatum'', the species can be found a ...
has any meaningful efficacy in neuropathic pain conditions.The quality of the current evidence raises serious uncertainties about the estimates of effect observed, therefore, we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect."
A 2017 Cochrane review on the usage of acupuncture
Acupuncture is a form of alternative medicine and a component of traditional Chinese medicine (TCM) in which thin needles are inserted into the body. Acupuncture is a pseudoscience; the theories and practices of TCM are not based on scientifi ...
as a treatment for neuropathic pain concludes, "Due to the limited data available, there is insufficient evidence to support or refute the use of acupuncture for neuropathic pain in general, or for any specific neuropathic pain condition when compared with sham acupuncture or other active therapies." Also, "Most studies included a small sample size (fewer than 50 participants per treatment arm) and all studies were at high risk of bias for blinding of participants and personnel." Also, the authors state, "we did not identify any study comparing acupuncture with treatment as usual."
Alpha lipoic acid
Lipoic acid (LA), also known as α-lipoic acid, alpha-lipoic acid (ALA) and thioctic acid, is an organosulfur compound derived from caprylic acid (octanoic acid). ALA is made in animals normally, and is essential for aerobic metabolism. It is a ...
(ALA) with benfotiamine is a proposed pathogenic treatment for painful diabetic neuropathy only. The results of two systematic reviews state that oral ALA produced no clinically significant benefit, intravenous ALA administered over the course of three weeks may improve symptoms and that long-term treatment has not been investigated.
Research
A 2008 literature review concluded that, "based on principles of evidence-based medicine and evaluations of methodology, there is only a 'possible' association of celiac disease
Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barl ...
and peripheral neuropathy due to lower levels of evidence and conflicting evidence. There is not yet convincing evidence of causality."
A 2019 review concluded that "gluten neuropathy is a slowly progressive condition. About 25% of the patients will have evidence of enteropathy on biopsy (CD eliac disease but the presence or absence of an enteropathy does not influence the positive effect of a strict gluten-free diet."
Stem-cell therapy
Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition. , the only established therapy using stem cells is hematopoietic stem cell transplantation. This usually takes the form of a bone-marrow transplantation, but ...
is also being looked at as a possible means to repair peripheral nerve damage, however efficacy has not yet been demonstrated.
See also
* Scrambler therapy
* Giant axonal neuropathy
Giant axonal neuropathy is a rare, autosomal recessive neurological disorder that causes disorganization of neurofilaments. Neurofilaments form a structural framework that helps to define the shape and size of neurons and are essential for normal ...
References
Further reading
*
*
External links
Peripheral Neuropathy
from the US NIH
Peripheral Neuropathy
at the Mayo Clinic
{{DEFAULTSORT:Peripheral Neuropathy
Peripheral nervous system disorders
Myelin disorders