Trigeminal nerve

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Trigeminal_nerve

Trigeminal nerve
Schematic illustration of the trigeminal nerve and the organs (or structures) it supplies

In neuroanatomy, the trigeminal nerve (lit. triplet nerve), also known as the fifth cranial nerve, cranial nerve V, or simply CN V, is a cranial nerve responsible for sensation in the face and motor functions such as biting and chewing; it is the most complex of the cranial nerves. Its name (trigeminal, from Latin tri- 'three', and -geminus 'twin') derives from each of the two nerves (one on each side of the pons) having three major branches: the ophthalmic nerve (V₁), the maxillary nerve (V₂), and the mandibular nerve (V₃). The ophthalmic and maxillary nerves are purely sensory, whereas the mandibular nerve supplies motor as well as sensory (or "cutaneous") functions. Adding to the complexity of this nerve is that autonomic nerve fibers as well as special sensory fibers (taste) are contained within it.

The motor division of the trigeminal nerve derives from the basal plate of the embryonic pons, and the sensory division originates in the cranial neural crest. Sensory information from the face and body is processed by parallel pathways in the central nervous system.

Structure

Origin

From the trigeminal ganglion, a single, large sensory root (radix sensoria s. portio major) enters the brainstem at the level of the pons. Immediately adjacent to the sensory root, a smaller motor root (radix motoria s. portio minor) emerges from the pons slightly rostrally and medially to the sensory root.

Motor fibers pass through the trigeminal ganglion without synapsing on their way to peripheral muscles, their cell bodies being located in the nucleus of the fifth nerve, deep within the pons.

Trigeminal ganglion

The three major branches of the trigeminal nerve—the ophthalmic nerve (V₁), the maxillary nerve (V₂) and the mandibular nerve (V₃)—converge on the trigeminal ganglion (also called the semilunar ganglion or gasserian ganglion), located within Meckel's cave and containing the cell bodies of incoming sensory-nerve fibers. The trigeminal ganglion is analogous to the dorsal root ganglia of the spinal cord, which contain the cell bodies of incoming sensory fibers from the rest of the body.

Dermatome distribution of the trigeminal nerve

Sensory branches

Dermatome distribution of the trigeminal nerve

The ophthalmic, maxillary and mandibular branches leave the skull through three separate foramina: the superior orbital fissure, the foramen rotundum and the foramen ovale, respectively. The ophthalmic nerve (V₁) carries sensory information from the scalp and forehead, the upper eyelid, the conjunctiva and cornea of the eye, the nose (including the tip of the nose, except alae nasi), the nasal mucosa, the frontal sinuses and parts of the meninges (the dura and blood vessels). The maxillary nerve (V₂) carries sensory information from the lower eyelid and cheek, the nares and upper lip, the upper teeth and gums, the nasal mucosa, the palate and roof of the pharynx, the maxillary, ethmoid and sphenoid sinuses and parts of the meninges. The mandibular nerve (V₃) carries sensory information from the lower lip, the lower teeth and gums, the chin and jaw (except the angle of the jaw, which is supplied by C2-C3), parts of the external ear and parts of the meninges. The mandibular nerve carries touch-position and pain-temperature sensations from the mouth. Although it does not carry taste sensation (the chorda tympani is responsible for taste), one of its branches—the lingual nerve—carries sensation from the tongue.

The peripheral processes of mesencephalic nucleus of V neurons run in the motor root of the trigeminal nerve and terminate in the muscle spindles in the muscles of mastication. They are proprioceptive fibers, conveying information regarding the location of the masticatory muscles. The central processes of mesencephalic V neurons synapse in the motor nucleus V.

Dermatomes

The areas of cutaneous distribution (dermatomes) of the three sensory branches of the trigeminal nerve have sharp borders with relatively little overlap (unlike dermatomes in the rest of the body, which have considerable overlap). The injection of a local anesthetic, such as lidocaine, results in the complete loss of sensation from well-defined areas of the face and mouth. For example, teeth on one side of the jaw can be numbed by injecting the mandibular nerve. Occasionally, injury or disease processes may affect two (or all three) branches of the trigeminal nerve; in these cases, the involved branches may be termed:

• V1/V2 distribution – Referring to the ophthalmic and maxillary branches
• V2/V3 distribution – Referring to the maxillary and mandibular branches
• V1-V3 distribution – Referring to all three branches

Nerves on the left side of the jaw slightly outnumber the nerves on the right side of the jaw.

Function

The sensory function of the trigeminal nerve is to provide tactile, proprioceptive, and nociceptive afference to the face and mouth. Its motor function activates the muscles of mastication, the tensor tympani, tensor veli palatini, mylohyoid and the anterior belly of the digastric.

The trigeminal nerve carries general somatic afferent fibers (GSA), which innervate the skin of the face via ophthalmic (V1), maxillary (V2) and mandibular (V3) divisions. The trigeminal nerve also carries special visceral efferent (SVE) axons, which innervate the muscles of mastication via the mandibular (V3) division.

Muscles

The motor component of the mandibular division (V3) of the trigeminal nerve controls the movement of eight muscles, including the four muscles of mastication: the masseter, the temporal muscle, and the medial and lateral pterygoids. The other four muscles are the tensor veli palatini, the mylohyoid, the anterior belly of the digastric and the tensor tympani.

With the exception of the tensor tympani, all these muscles are involved in biting, chewing and swallowing and all have bilateral cortical representation. A unilateral central lesion (for example, a stroke), no matter how large, is unlikely to produce an observable deficit. Injury to a peripheral nerve can cause paralysis of muscles on one side of the jaw, with the jaw deviating towards the paralyzed side when it opens. This direction of the mandible is due to the action of the functioning pterygoids on the opposite side.

Sensation

Main article: Somatosensory system

The two basic types of sensation are touch-position and pain-temperature. Touch-position input comes to attention immediately, but pain-temperature input reaches the level of consciousness after a delay; when a person steps on a pin, the awareness of stepping on something is immediate but the pain associated with it is delayed.

Touch-position information is generally carried by myelinated (fast-conducting) nerve fibers, and pain-temperature information by unmyelinated (slow-conducting) fibers. The primary sensory receptors for touch-position (Meissner's corpuscles, Merkel's receptors, Pacinian corpuscles, Ruffini's corpuscles, hair receptors, muscle spindle organs and Golgi tendon organs) are structurally more complex than those for pain-temperature, which are nerve endings.

Sensation in this context refers to the conscious perception of touch-position and pain-temperature information, rather than the special senses (smell, sight, taste, hearing and balance) processed by different cranial nerves and sent to the cerebral cortex through different pathways. The perception of magnetic fields, electrical fields, low-frequency vibrations and infrared radiation by some nonhuman vertebrates is processed by their equivalent of the fifth cranial nerve.

Touch in this context refers to the perception of detailed, localized tactile information, such as two-point discrimination (the difference between touching one point and two closely spaced points) or the difference between coarse, medium or fine sandpaper. People without touch-position perception can feel the surface of their bodies and perceive touch in a broad sense, but they lack perceptual detail.

Position, in this context, refers to conscious proprioception. Proprioceptors (muscle spindle and Golgi tendon organs) provide information about joint position and muscle movement. Although much of this information is processed at an unconscious level (primarily by the cerebellum and the vestibular nuclei), some is available at a conscious level.

Touch-position and pain-temperature sensations are processed by different pathways in the central nervous system. This hard-wired distinction is maintained up to the cerebral cortex. Within the cerebral cortex, sensations are linked with other cortical areas.

Sensory pathways

Sensory pathways from the periphery to the cortex are separate for touch-position and pain-temperature sensations. All sensory information is sent to specific nuclei in the thalamus. Thalamic nuclei, in turn, send information to specific areas in the cerebral cortex. Each pathway consists of three bundles of nerve fibers connected in series:

The secondary neurons in each pathway decussate (cross the spinal cord or brainstem), because the spinal cord develops in segments. Decussated fibers later reach and connect these segments with the higher centers. The optic chiasm is the primary cause of decussation; nasal fibers of the optic nerve cross (so each cerebral hemisphere receives contralateral—opposite—vision) to keep the interneuronal connections responsible for processing information short. All sensory and motor pathways converge and diverge to the contralateral hemisphere.

Although sensory pathways are often depicted as chains of individual neurons connected in series, this is an oversimplification. Sensory information is processed and modified at each level in the chain by interneurons and input from other areas of the nervous system. For example, cells in the main trigeminal nucleus (Main V in the diagram below) receive input from the reticular formation and cerebellar cortex. This information contributes to the final output of the cells in Main V to the thalamus.

C = Cervical segment, S = Sacral segment, VPL = Ventral posterolateral nucleus, SI = Primary somatosensory cortex, VM = Ventromedial prefrontal cortex, MD = Medial dorsal thalamic nucleus, IL = Intralaminar nucleus, VPM = Ventral posteromedial nucleus, Main V = Main trigeminal nucleus, Spinal V = Spinal trigeminal nucleus

Touch-position information from the body is carried to the thalamus by the medial lemniscus, and from the face by the trigeminal lemniscus (both the anterior and posterior trigeminothalamic tracts). Pain-temperature information from the body is carried to the thalamus by the spinothalamic tract, and from the face by the anterior division of the trigeminal lemniscus (also called the anterior trigeminothalamic tract).

Pathways for touch-position and pain-temperature sensations from the face and body merge in the brainstem, and touch-position and pain-temperature sensory maps of the entire body are projected onto the thalamus. From the thalamus, touch-position and pain-temperature information is projected onto the cerebral cortex.

Summary

The complex processing of pain-temperature information in the thalamus and cerebral cortex (as opposed to the relatively simple, straightforward processing of touch-position information) reflects a phylogenetically older, more primitive sensory system. The detailed information received from peripheral touch-position receptors is superimposed on a background of awareness, memory and emotions partially set by peripheral pain-temperature receptors.

Although thresholds for touch-position perception are relatively easy to measure, those for pain-temperature perception are difficult to define and measure. "Touch" is an objective sensation, but "pain" is an individualized sensation which varies among different people and is conditioned by memory and emotion. Anatomical differences between the pathways for touch-position perception and pain-temperature sensation help explain why pain, especially chronic pain, is difficult to manage.

Trigeminal nuclei

Brainstem nuclei: Red = Motor; Blue = Sensory; Dark blue = Trigeminal nucleus

All sensory information from the face, both touch-position and pain-temperature, is sent to the trigeminal nucleus. In classical anatomy most sensory information from the face is carried by the fifth nerve, but sensation from parts of the mouth, parts of the ear and parts of the meninges is carried by general somatic afferent fibers in cranial nerves VII (the facial nerve), IX (the glossopharyngeal nerve) and X (the vagus nerve).

All sensory fibers from these nerves terminate in the trigeminal nucleus. On entering the brainstem, sensory fibers from V, VII, IX and X are sorted and sent to the trigeminal nucleus (which contains a sensory map of the face and mouth). The spinal counterparts of the trigeminal nucleus (cells in the dorsal horn and dorsal column nuclei of the spinal cord) contain a sensory map of the rest of the body.

The trigeminal nucleus extends throughout the brainstem, from the midbrain to the medulla, continuing into the cervical cord (where it merges with the dorsal horn cells of the spinal cord). The nucleus is divided into three parts, visible in microscopic sections of the brainstem. From caudal to rostral (ascending from the medulla to the midbrain), they are the spinal trigeminal, the principal sensory and the mesencephalic nuclei. The parts of the trigeminal nucleus receive different types of sensory information; the spinal trigeminal nucleus receives pain-temperature fibers, the principal sensory nucleus receives touch-position fibers and the mesencephalic nucleus receives proprioceptor and mechanoreceptor fibers from the jaws and teeth.

Spinal trigeminal nucleus

The spinal trigeminal nucleus represents pain-temperature sensation from the face. Pain-temperature fibers from peripheral nociceptors are carried in cranial nerves V, VII, IX and X. On entering the brainstem, sensory fibers are grouped and sent to the spinal trigeminal nucleus. This bundle of incoming fibers can be identified in cross-sections of the pons and medulla as the spinal tract of the trigeminal nucleus, which parallels the spinal trigeminal nucleus. The spinal tract of V is analogous to, and continuous with, Lissauer's tract in the spinal cord.

The spinal trigeminal nucleus contains a pain-temperature sensory map of the face and mouth. From the spinal trigeminal nucleus, secondary fibers cross the midline and ascend in the trigeminothalamic (quintothalamic) tract to the contralateral thalamus. Pain-temperature fibers are sent to multiple thalamic nuclei. The central processing of pain-temperature information differs from the processing of touch-position information.

Somatotopic representation

Onion-skin distribution of the trigeminal nerve

Exactly how pain-temperature fibers from the face are distributed to the spinal trigeminal nucleus is disputed. The present general understanding is that pain-temperature information from all areas of the human body is represented in the spinal cord and brainstem in an ascending, caudal-to-rostral fashion. Information from the lower extremities is represented in the lumbar cord, and that from the upper extremities in the thoracic cord. Information from the neck and the back of the head is represented in the cervical cord, and that from the face and mouth in the spinal trigeminal nucleus.

Within the spinal trigeminal nucleus, information is represented in a layered, or "onion-skin" fashion. The lowest levels of the nucleus (in the upper cervical cord and lower medulla) represent peripheral areas of the face (the scalp, ears and chin). Higher levels (in the upper medulla) represent central areas (nose, cheeks and lips). The highest levels (in the pons) represent the mouth, teeth and pharyngeal cavity.

The onion skin distribution differs from the dermatome distribution of the peripheral branches of the fifth nerve. Lesions which destroy lower areas of the spinal trigeminal nucleus (but spare higher areas) preserve pain-temperature sensation in the nose (V₁), upper lip (V₂) and mouth (V₃) and remove pain-temperature sensation from the forehead (V₁), cheeks (V₂) and chin (V₃). Although analgesia in this distribution is "nonphysiologic" in the traditional sense (because it crosses several dermatomes), this analgesia is found in humans after surgical sectioning of the spinal tract of the trigeminal nucleus.

The spinal trigeminal nucleus sends pain-temperature information to the thalamus and sends information to the mesencephalon and the reticular formation of the brainstem. The latter pathways are analogous to the spinomesencephalic and spinoreticular tracts of the spinal cord, which send pain-temperature information from the rest of the body to the same areas. The mesencephalon modulates painful input before it reaches the level of consciousness. The reticular formation is responsible for the automatic (unconscious) orientation of the body to painful stimuli. Incidentally, Sulfur-containing compounds found in plants in the onion family stimulate receptors found in trigeminal ganglia, bypassing the olfactory system.

Principal nucleus

The principal nucleus represents touch-pressure sensation from the face. It is located in the pons, near the entrance for the fifth nerve. Fibers carrying touch-position information from the face and mouth via cranial nerves V, VII, IX, and X are sent to this nucleus when they enter the brainstem.

The principal nucleus contains a touch-position sensory map of the face and mouth, just as the spinal trigeminal nucleus contains a complete pain-temperature map. This nucleus is analogous to the dorsal column nuclei (the gracile and cuneate nuclei) of the spinal cord, which contain a touch-position map of the rest of the body.

From the principal nucleus, secondary fibers cross the midline and ascend in the ventral trigeminothalamic tract to the contralateral thalamus. The ventral trigeminothalamic tract runs parallel to the medial lemniscus, which carries touch-position information from the rest of the body to the thalamus.

Some sensory information from the teeth and jaws is sent from the principal nucleus to the ipsilateral thalamus via the small dorsal trigeminal tract. Touch-position information from the teeth and jaws of one side of the face is represented bilaterally in the thalamus and cortex.

Mesencephalic nucleus

The mesencephalic nucleus is not a true nucleus; it is a sensory ganglion (like the trigeminal ganglion) embedded in the brainstem and the sole exception to the rule that sensory information passes through peripheral sensory ganglia before entering the central nervous system. It has been found in all vertebrates except lampreys and hagfishes. They are the only vertebrates without jaws and have specific cells in their brainstems. These "internal ganglion" cells were discovered in the late 19th century by medical student Sigmund Freud.

Two types of sensory fibers have cell bodies in the mesencephalic nucleus: proprioceptor fibers from the jaw and mechanoreceptor fibers from the teeth. Some of these incoming fibers go to the motor nucleus of the trigeminal nerve (V), bypassing the pathways for conscious perception. The jaw jerk reflex is an example; tapping the jaw elicits a reflex closure of the jaw in the same way that tapping the knee elicits a reflex kick of the lower leg. Other incoming fibers from the teeth and jaws go to the main nucleus of V. This information is projected bilaterally to the thalamus and available for conscious perception.

Activities such as biting, chewing and swallowing require symmetrical, simultaneous coordination of both sides of the body. They are automatic activities, requiring little conscious attention and involving a sensory component (feedback about touch-position) processed at the unconscious level in the mesencephalic nucleus.

Pathways to the thalamus and cortex

Sensation has been defined as the conscious perception of touch-position and pain-temperature information. With the exception of smell, all sensory input (touch-position, pain-temperature, sight, taste, hearing and balance) is sent to the thalamus and then the cortex. The thalamus is anatomically subdivided into nuclei.

Touch-position sensation

Cortical homunculus

Touch-position information from the body is sent to the ventral posterolateral nucleus (VPL) of the thalamus. Touch-position information from the face is sent to the ventral posteromedial nucleus (VPM) of the thalamus. From the VPL and VPM, information is projected to the primary somatosensory cortex (SI) in the parietal lobe.

The representation of sensory information in the postcentral gyrus is organized somatotopically. Adjacent areas of the body are represented by adjacent areas in the cortex. When body parts are drawn in proportion to the density of their innervation, the result is a "little man": the cortical homunculus.

Many textbooks have reproduced the outdated Penfield-Rasmussen diagram [ref?], with the toes and genitals on the mesial surface of the cortex when they are actually represented on the convexity. The classic diagram implies a single primary sensory map of the body, when there are multiple primary maps. At least four separate, anatomically distinct sensory homunculi have been identified in the postcentral gyrus. They represent combinations of input from surface and deep receptors and rapidly and slowly adapting peripheral receptors; smooth objects will activate certain cells, and rough objects will activate other cells.

Information from all four maps in SI is sent to the secondary sensory cortex (SII) in the parietal lobe. SII contains two more sensory homunculi. Information from one side of the body is generally represented on the opposite side in SI, but on both sides in SII. Functional MRI imaging of a defined stimulus (for example, stroking the skin with a toothbrush) "lights up" a single focus in SI and two foci in SII.

Pain-temperature sensation

Pain-temperature information is sent to the VPL (body) and VPM (face) of the thalamus (the same nuclei which receive touch-position information). From the thalamus, pain-temperature and touch-position information is projected onto SI.

Unlike touch-position information, however, pain-temperature information is also sent to other thalamic nuclei and projected onto additional areas of the cerebral cortex. Some pain-temperature fibers are sent to the medial dorsal thalamic nucleus (MD), which projects to the anterior cingulate cortex. Other fibers are sent to the ventromedial (VM) nucleus of the thalamus, which projects to the insular cortex. Finally, some fibers are sent to the intralaminar nucleus (IL) of the thalamus via the reticular formation. The IL projects diffusely to all parts of the cerebral cortex.

The insular and cingulate cortices are parts of the brain which represent touch-position and pain-temperature in the context of other simultaneous perceptions (sight, smell, taste, hearing and balance) in the context of memory and emotional state. Peripheral pain-temperature information is channeled directly to the brain at a deep level, without prior processing. Touch-position information is handled differently. Diffuse thalamic projections from the IL and other thalamic nuclei are responsible for a given level of consciousness, with the thalamus and reticular formation "activating" the brain; peripheral pain-temperature information also feeds directly into this system.

Clinical significance

• Trigeminal neuralgia
• Cluster headache
• Migraine

Lateral medullary syndrome

Main article: Lateral medullary syndrome

Lateral medullary syndrome (Wallenberg syndrome) is a clinical demonstration of the anatomy of the trigeminal nerve, summarizing how it processes sensory information. A stroke usually affects only one side of the body; loss of sensation due to a stroke will be lateralized to the right or the left side of the body. The only exceptions to this rule are certain spinal-cord lesions and the medullary syndromes, of which Wallenberg syndrome is the best-known example. In this syndrome, a stroke causes a loss of pain-temperature sensation from one side of the face and the other side of the body.

This is explained by the anatomy of the brainstem. In the medulla, the ascending spinothalamic tract (which carries pain-temperature information from the opposite side of the body) is adjacent to the ascending spinal tract of the trigeminal nerve (which carries pain-temperature information from the same side of the face). A stroke which cuts off the blood supply to this area (for example, a clot in the posterior inferior cerebellar artery) destroys both tracts simultaneously. The result is a loss of pain-temperature (but not touch-position) sensation in a "checkerboard" pattern (ipsilateral face, contralateral body), facilitating diagnosis.

Sensory neuronopathy

Sensory neuronopathy (also known as sensory ganglionopathy) is a type of peripheral neuropathy in which sensory nerve cell bodies in the dorsal root ganglia, commonly including the trigeminal ganglion of the trigeminal nerve, are damaged due to a variety of mechanisms leading to sensory symptoms such as parasthesias, dysesthesias, or hyperalgesia in the affected nerve distribution including the distribution of the trigeminal nerve.

Reflex syncope

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Reflex_syncope

 

Reflex syncope
Other names	Neurally mediated syncope, neurocardiogenic syncope
Vagus nerve
Specialty	Neurology, cardiovascular
Symptoms	Loss of consciousness before which there may be sweating, decreased ability to see, ringing in the ears
Complications	Injury
Duration	Brief
Types	Vasovagal, situational, carotid sinus syncope
Diagnostic method	Based on symptoms after ruling out other possible causes
Differential diagnosis	Arrhythmia, orthostatic hypotension, seizure, hypoglycemia
Treatment	Avoiding triggers, drinking sufficient fluids, exercise, cardiac pacemaker
Medication	Midodrine, fludrocortisone
Frequency	> 1 per 1,000 people per year

Reflex syncope is a brief loss of consciousness due to a neurologically induced drop in blood pressure and/or a decrease in heart rate. Before an affected person passes out, there may be sweating, a decreased ability to see, or ringing in the ears. Occasionally, the person may twitch while unconscious. Complications of reflex syncope include injury due to a fall.

Reflex syncope is divided into three types: vasovagal, situational, and carotid sinus. Vasovagal syncope is typically triggered by seeing blood, pain, emotional stress, or prolonged standing. Situational syncope is often triggered by urination, swallowing, or coughing. Carotid sinus syncope is due to pressure on the carotid sinus in the neck. The underlying mechanism involves the nervous system slowing the heart rate and dilating blood vessels, resulting in low blood pressure and thus not enough blood flow to the brain. Diagnosis is based on the symptoms after ruling out other possible causes.

Recovery from a reflex syncope episode happens without specific treatment. Prevention of episodes involves avoiding a person's triggers. Drinking sufficient fluids, salt, and exercise may also be useful. If this is insufficient for treating vasovagal syncope, medications such as midodrine or fludrocortisone may be tried. Occasionally, a cardiac pacemaker may be used as treatment. Reflex syncope affects at least 1 in 1,000 people per year. It is the most common type of syncope, making up more than 50% of all cases.

Signs and symptoms

Episodes of vasovagal syncope are typically recurrent and usually occur when the predisposed person is exposed to a specific trigger. Before losing consciousness, the individual frequently experiences early signs or symptoms such as lightheadedness, nausea, the feeling of being extremely hot or cold (accompanied by sweating), ringing in the ears, an uncomfortable feeling in the heart, fuzzy thoughts, confusion, a slight inability to speak or form words (sometimes combined with mild stuttering), weakness and visual disturbances such as lights seeming too bright, fuzzy or tunnel vision, black cloud-like spots in vision, and a feeling of nervousness can occur as well. The symptoms may become more intense over several seconds to several minutes before the loss of consciousness (if it is lost). Onset usually occurs when a person is sitting up or standing.

When people lose consciousness, they fall down (unless prevented from doing so) and, when in this position, effective blood flow to the brain is immediately restored, allowing the person to regain consciousness. If the person does not fall into a fully flat, supine position, and the head remains elevated above the trunk, a state similar to a seizure may result from the blood's inability to return quickly to the brain, and the neurons in the body will fire off and generally cause muscles to twitch very slightly but mostly remain very tense.

The autonomic nervous system's physiological state (see below) leading to loss of consciousness may persist for several minutes, so

• If patients try to sit or stand when they wake up, they may pass out again
• The person may be nauseated, pale, and sweaty for several minutes or hours

Causes

Reflex syncope occurs in response to a trigger due to dysfunction of the heart rate and blood pressure regulating mechanism. When heart rate slows or blood pressure drops, the resulting lack of blood to the brain causes fainting.

Vasovagal

Typical triggers include:

• Prolonged standing
• Emotional stress
• Pain
• The sight of blood
• Fear of needles Time varying magnetic field (i.e. transcranial magnetic stimulation)

Situational

• After or during urination (micturition syncope)
• Straining, such as to have a bowel movement
• Coughing
• Swallowing
• Lifting a heavy weight

Carotid sinus

Pressing upon a certain spot in the neck. This may happen when wearing a tight collar, shaving, or turning the head.

Pathophysiology

Regardless of the trigger, the mechanism of syncope is similar in the various vasovagal syncope syndromes. The nucleus tractus solitarii of the brainstem is activated directly or indirectly by the triggering stimulus, resulting in simultaneous enhancement of parasympathetic nervous system (vagal) tone and withdrawal of sympathetic nervous system tone.

This results in a spectrum of hemodynamic responses:

1. On one end of the spectrum is the cardioinhibitory response, characterized by a drop in heart rate (negative chronotropic effect) and in contractility (negative inotropic effect) leading to a decrease in cardiac output that is significant enough to result in a loss of consciousness. It is thought that this response results primarily from enhancement in parasympathetic tone.
2. On the other end of the spectrum is the vasodepressor response, caused by a drop in blood pressure (to as low as 80/20) without much change in heart rate. This phenomenon occurs due to dilation of the blood vessels, probably as a result of withdrawal of sympathetic nervous system tone.
3. The majority of people with vasovagal syncope have a mixed response somewhere between these two ends of the spectrum.

One account for these physiological responses is the Bezold-Jarisch reflex.

Vasovagal syncope may be part of an evolved response, specifically, the fight-or-flight response.

Diagnosis

In addition to the mechanism described above, a number of other medical conditions may cause syncope. Making the correct diagnosis for loss of consciousness is difficult. The core of the diagnosis of vasovagal syncope rests upon a clear description of a typical pattern of triggers, symptoms, and time course.

It is pertinent to differentiate lightheadedness, seizures, vertigo, and low blood sugar as other causes.

In people with recurrent vasovagal syncope, diagnostic accuracy can often be improved with one of the following diagnostic tests:

• A tilt table test (results should be interpreted in the context of patients' clinical presentations and with an understanding of the sensitivity and specificity of the test)
• Implantation of an insertable loop recorder
• A Holter monitor or event monitor
• An echocardiogram
• An electrophysiology study

Treatment

Treatment for reflex syncope focuses on avoidance of triggers, restoring blood flow to the brain during an impending episode, and measures that interrupt or prevent the pathophysiologic mechanism described above.

Lifestyle changes

• The cornerstone of treatment is avoidance of triggers known to cause syncope in that person. However, research has shown that people show great reductions in vasovagal syncope through exposure-based exercises with therapists if the trigger is mental or emotional, e.g., sight of blood. However, if the trigger is a specific drug, then avoidance is the only treatment.
• A technique known as "applied tension" may be additionally useful in those who have syncope with exposure to blood. The technique is done by tightening the skeletal muscles for about 15 seconds when the exposure occurs and then slowing releasing them. This is then repeated every 30 seconds for a few minutes.
• Because vasovagal syncope causes a decrease in blood pressure, relaxing the entire body as a mode of avoidance is not favorable. A person can move or cross their legs and tighten leg muscles to keep blood pressure from dropping so significantly before an injection.
• Before known triggering events, the affected person may increase consumption of salt and fluids to increase blood volume. Sports drinks or drinks with electrolytes may be helpful.
• People should be educated on how to respond to further episodes of syncope, especially if they experience prodromal warning signs: they should lie down and raise their legs, or at least lower their head to increase blood flow to the brain. At the very least, upon the onset of initial symptoms the patient should try to relocate to a 'safe', perhaps cushioned, location in case of losing consciousness. Positioning themselves in a way where the impact from falling or collapsing would be minimized is ideal. The 'safe' area should be within close proximity, since, time is of the essence and these symptoms usually climax to loss of consciousness within a matter of minutes. If the individual has lost consciousness, he or she should be laid down in the recovery position. Tight clothing should be loosened. If the inciting factor is known, it should be removed if possible (for instance, the cause of pain).
• Wearing graded compression stockings may be helpful.

Medications

• Certain medications may also be helpful:
  • Beta blockers (β-adrenergic antagonists) were once the most common medication given; however, they have been shown to be ineffective in a variety of studies and are thus no longer prescribed. In addition, they may cause the syncope by lowering the blood pressure and heart rate.
  • Medications which may be effective include: CNS stimulants fludrocortisone, midodrine, SSRIs such as paroxetine or sertraline, disopyramide, and, in health-care settings where a syncope is anticipated, atropine or epinephrine (adrenaline).
• For people with the cardioinhibitory form of vasovagal syncope, implantation of a permanent pacemaker may be beneficial or even curative.

Types of long-term therapy for vasovagal syncope include

• Preload agents
• Vasoconstrictors
• Anticholinergic agents
• Negative cardiac inotropes
• Central agents
• Mechanical device
• Discontinuation of medications known to lower blood pressure may be helpful, but stopping antihypertensive drugs can also be dangerous in some people. Taking antihypertensive drugs may worsen the syncope, as the hypertension may have been the body's way to compensate for the low blood pressure.

Prognosis

Brief periods of unconsciousness usually cause no lasting harm to health. Reflex syncope can occur in otherwise healthy individuals, and has many possible causes, often trivial ones such as prolonged standing with the legs locked.

The main danger of vasovagal syncope (or dizzy spells from vertigo) is the risk of injury by falling while unconscious. Medication therapy could possibly prevent future vasovagal responses; however, for some individuals medication is ineffective and they will continue to have fainting episodes.

Peripheral neuropathy

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Peripheral_neuropathy

 

Peripheral neuropathy
Micrograph showing a vasculitic peripheral neuropathy; plastic embedded; Toluidine blue stain
Specialty	Neurology
Symptoms	Shooting pain, numbness, tingling, tremors, bladder problems, unsteadiness

Peripheral neuropathy, often shortened to neuropathy, refers to 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. Neuropathies 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 (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 or leprosy), hyperglycemia-induced glycation, vitamin deficiency, medication (e.g., chemotherapy, or commonly prescribed antibiotics including metronidazole and the fluoroquinolone class of antibiotics (such as ciprofloxacin, levofloxacin, moxifloxacin)), traumatic injury, ischemia, radiation therapy, excessive alcohol consumption, immune system disease, celiac disease, non-celiac gluten sensitivity, or viral infection. It can also be genetic (present from birth) or idiopathic (no known cause). In conventional medical usage, 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". 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", "multifocal mononeuropathy", or "multiple mononeuropathy".

Neuropathy may cause painful cramps, 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 (pain from normally nonpainful stimuli, such as light touch); and autonomic neuropathy 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), compression (compression neuropathy), chemotherapy (chemotherapy-induced peripheral neuropathy). 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

See also: Compression neuropathy and Ulnar neuropathy

Mononeuropathy is a type of neuropathy that only affects a single nerve. 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. Carpal tunnel syndrome and axillary nerve palsy are examples. Direct injury to a nerve, interruption of its blood supply resulting in (ischemia), or inflammation also may cause mononeuropathy.

Polyneuropathy

Main article: 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 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 axons are affected in proportion to their length; the longest axons are the most affected. Diabetic neuropathy is the most common cause of this pattern. In demyelinating polyneuropathies, the myelin 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 of neurons directly. This affects the sensory neurons (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, and difficulty controlling urination.

Polyneuropathies usually are caused by processes that affect the body as a whole. Diabetes and impaired glucose tolerance are the most common causes. Hyperglycemia-induced formation of advanced glycation 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, 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 with typical symptoms of tingling, pain, and loss of sensation in the feet and hands were due to glucose intolerance 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.

Mononeuritis multiplex

Mononeuritis multiplex, occasionally termed polyneuritis multiplex, is simultaneous or sequential involvement of individual noncontiguous nerve trunks, 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. 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, mononeuritis multiplex typically is encountered as acute, unilateral, and severe thigh pain followed by anterior muscle weakness and loss of knee reflex.

Electrodiagnostic medicine studies will show multifocal sensory motor axonal neuropathy.

It is caused by, or associated with, several medical conditions:

• Diabetes mellitus
• Vasculitides: polyarteritis nodosa, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis. This results in vasculitic neuropathy.
• Immune-mediated diseases, such as rheumatoid arthritis, systemic lupus erythematosus (SLE)
• Infections: leprosy, lyme disease, parvovirus B19, HIV
• Sarcoidosis
• Cryoglobulinemia
• Reactions to exposure to chemical agents, including trichloroethylene and dapsone
• Rarely, following the sting of certain jellyfish, such as the sea nettle

Autonomic neuropathy

Autonomic neuropathy 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 system, the digestive tract, and the genital 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. 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 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, such as multiple system atrophy, and therefore, may cause similar symptoms to autonomic neuropathy.

The signs and symptoms of autonomic neuropathy include the following:

• Urinary bladder conditions: bladder incontinence or urine retention
• Gastrointestinal tract: dysphagia, abdominal pain, nausea, vomiting, malabsorption, fecal incontinence, gastroparesis, diarrhoea, constipation
• Cardiovascular system: disturbances of heart rate (tachycardia, bradycardia), orthostatic hypotension, inadequate increase of heart rate on exertion
• Respiratory system: impairments in the signals associated with regulation of breathing and gas exchange (central sleep apnea, hypopnea, bradypnea).
• Skin : thermal regulation, dryness through sweat disturbances
• Other areas: hypoglycemia unawareness, genital impotence

Neuritis

Neuritis is a general term for inflammation of a nerve or the general inflammation of the peripheral nervous system. Symptoms depend on the nerves involved, but may include pain, paresthesia (pins-and-needles), paresis (weakness), hypoesthesia (numbness), anesthesia, paralysis, wasting, and disappearance of the reflexes.

Causes of neuritis include:

• Physical injury
• Infection
  • Diphtheria
  • Herpes zoster (shingles)
  • Leprosy
  • Lyme disease
• Chemical injury such as chemotherapy
• Radiation therapy

Types of neuritis include:

• Brachial neuritis
• Cranial neuritis such as Bell's palsy
• Optic neuritis
• Vestibular neuritis
• Wartenberg's migratory sensory neuropathy
• Underlying conditions including:
  • Alcoholism
  • Autoimmune disease, especially multiple sclerosis and Guillain–Barré syndrome
  • Beriberi (vitamin B₁ deficiency)
  • Cancer
  • Celiac disease
  • Non-celiac gluten sensitivity
  • Diabetes mellitus (Diabetic neuropathy)
  • Hypothyroidism
  • Porphyria
  • Vitamin B₁₂ deficiency
  • Vitamin B₆ excess

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, tremor, impairment of balance, and gait abnormality. Gain of function (positive) symptoms include tingling, pain, itching, 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, and muscle twitch (fasciculations).

In the most common form, length-dependent peripheral neuropathy, pain and parasthesia 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 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:

• Ribose-5-Phosphate Isomerase Deficiency
• Surgery: LASIK (corneal neuropathy — 20 to 55% of people).
• Genetic diseases: Friedreich's ataxia, Fabry disease, Charcot-Marie-Tooth disease, hereditary neuropathy with liability to pressure palsy
• Hyperglycemia-induced formation of advanced glycation end products (AGEs)
• Metabolic and endocrine diseases: diabetes mellitus, chronic kidney failure, porphyria, amyloidosis, liver failure, hypothyroidism
• Idiopathic peripheral neuropathy refers to neuropathy with no known cause.
• Toxic causes: drugs (vincristine, metronidazole, phenytoin, nitrofurantoin, isoniazid, ethyl alcohol, statins), organic herbicides TCDD dioxin, organic metals, heavy metals, excess intake of vitamin B₆ (pyridoxine). Peripheral neuropathies also may result from long term (more than 21 days) treatment with linezolid.
• Adverse effects of fluoroquinolones: irreversible neuropathy is a serious adverse reaction of fluoroquinolone drugs
• Inflammatory diseases: Guillain–Barré syndrome, systemic lupus erythematosus, leprosy, Sjögren's syndrome, Babesiosis, Lyme disease, vasculitis, sarcoidosis. Multiple sclerosis may also be causal.
• Vitamin deficiency states: Vitamin B₁₂ (Methylcobalamin), vitamin A, vitamin E, vitamin B₁ (thiamin)
• Physical trauma: compression, automobile accident, sports injury, sports pinching, cutting, projectile injuries (for example, gunshot wound), strokes including prolonged occlusion of blood flow, electric discharge, including lightning strikes
• Effect of chemotherapy – see Chemotherapy-induced peripheral neuropathy
• Exposure to Agent Orange
• Others: Carpal tunnel syndrome, electric shock, HIV, malignant disease, radiation, shingles, MGUS (Monoclonal gammopathy of undetermined significance).

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, specifically a neurological examination, those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, although those with a pathology (problem) of the nerves may be perfectly normal; may show proximal weakness, as in some inflammatory neuropathies, such as Guillain–Barré syndrome; 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. For large fiber neuropathy, an exam will usually show an abnormally decreased sensation to vibration, which is tested with a 128-Hz tuning fork, and decreased sensation of light touch when touched by a nylon monofilament.

Diagnostic tests include electromyography (EMG) and nerve conduction studies (NCSs), which assess large myelinated nerve fibers. Testing for small-fiber peripheral neuropathies often relates to the autonomic nervous system 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 B₁₂ levels, a complete blood count, measurement of thyroid stimulating hormone levels, a comprehensive metabolic panel 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 or prediabetes, 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 or steroids. When peripheral neuropathy results from vitamin deficiencies 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 antidepressants (such as nortriptyline, amitriptyline. imapramine, and desipramine,) serotonin-norepinephrine reuptake inhibitor (SNRI) medications (duloxetine, venlafaxine, and milnacipran) and antiepileptic medications (gabapentin, pregabalin, oxcarbazepine zonisamide levetiracetam, lamotrigine, topiramate, clonazepam, phenytoin, lacosamide, sodium valproate and carbamazepine). Opioid and opiate medications (such as buprenorphine, morphine, methadone, fentanyl, hydromorphone, tramadol and oxycodone) 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 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 large scale 2013 review found opioids to be more effective for intermediate term use than short term use, but couldn't properly assess effectiveness for chronic use because of insufficient data. Most recent guidelines on the pharmacotherapy of neuropathic pain however are in agreement with the results of this review and recommend the use of opioids. A 2017 Cochrane review examining mainly propoxyphene 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 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 drugs 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 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 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 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-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 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 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 inhibitors for the treatment of the pain deriving from diabetic polyneuropathy found it no better than placebo.

Medical devices

Transcutaneous electrical nerve stimulation (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 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 or St John's wort 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 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 (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 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 [celiac disease]) but the presence or absence of an enteropathy does not influence the positive effect of a strict gluten-free diet."

Stem-cell therapy is also being looked at as a possible means to repair peripheral nerve damage, however efficacy has not yet been demonstrated.