Is numbness the absence of one or all touch sensations?

Is numbness the absence of one or all touch sensations?

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I am studying the effects of tetrodotoxin and its symptoms when consumed. Numbness is one of the first sensations reported.

But I googled numbness and I couldn't find information about whether this means all touch sensations (e.g. thermal, mechano, etc) have to be absent for numbness or just one specific kind.

My Question:

Can someone

  1. Define numbness
  2. Explain whether numbness is the absence of one or more than one or all touch sensations.

The definition of numbness has been answered by yourself, and I will focus on the second part of the question.

In terms of the underlying physiological mechanism behind numbness I think it's good to narrow the question down and focus on local anesthetics, which numb a local area of the body for minor surgical procedures. Cocaine and related compounds have been shown to block not only pain, but also warmth, cold and touch perception, as well as blocking motor function. Cocain and related compounds are basically voltage-gated Na+ channel blockers, but also block K+ channels to some extent. Their affinity to various different channels differs, explaining the differential effects. E.g., pain is blocked more effectively than motor functions (Scholz, 2002).

We all know the feeling of numbness when our limbs are asleep due to restriction of blood flow. Likely all neural activity is blocked here too, as the cutting off of oxygen affects all neurons.

Given the broad range of effects of local anesthetics and restriction of blood flow, I would tentatively conclude that numbness can be interpreted as a reduction of sensitivity of all the senses.

- Scholz, Br J Anaesth (2002); 89; 52-61

An Initial clarification of what "loss of sensation" means:

The history in the patient with “numbness” is extremely important. First of all, as with most neurologic complaints, you must determine what the patient means by “numbness.” Some patients are describing loss of sensitivity (anesthesia or hypesthesia) or distorted sensations (paresthesia), which is often described as tingling. Actual loss of sensitivity is more likely to represent true damage to sensory pathways in the nervous system, while paresthesia has a much broader differential. Dysesthesia, that is the perception of an unpleasant (often burning) sensation or allodynia (the perception of innocuous stimuli as being painful) may result from damage to the nervous system or, more commonly, be the manifestation of an underlying painful condition.

Some properties of numbness

The pattern of numbness may help define its origin. Numbness confined to a specific nerve or nerve root distribution (see the maps of dermatomes and peripheral nerve sensory innervation) lead to consideration of peripheral nerve or nerve root damage. Loss of sensation on one side of the body is more likely to result from central nervous system damage and if the sensory loss also involves the same side of the face, you can be sure that the cause is located above the level of the pons.

When there is a clear sensory level (a line on the body, below which sensations are lost), a spinal cord lesion must be suspected. Loss of sensation over the upper limbs or upper part of the trunk bilaterally, with preservation over the lower limbs and buttocks, suggests an expanding intraspinal mass. This so-called “sacral sparing” is seen with intraspinal tumors or syrinxes. Numbness over one side of the face, while being a relatively common presentation of psychiatric disease, can also be caused by damage to the lateral part of the brain stem, or upper spinal cord (spinal tract of the trigeminal). Lateral brain stem damage can also produce a picture of sensory decrease on one side of the head and on the opposite side of the body.

But the article concludes

In summary, the evaluation of numbness can be quite frustrating due to its subjective nature.

So it is in essence a term that can have specific meanings uncertain contexts, but one must be careful to clarify exactly how the term is being used since there isn't one single meaning.

This is all from this link here


A sense is a biological system used by an organism for sensation, the process of gathering information about the world and responding to stimuli. (For example, in the human body, the brain receives signals from the senses, which continuously receive information from the environment, interprets these signals, and causes the body to respond, either chemically or physically.) Although traditionally around five human senses were known (namely sight, smell, touch, taste, and hearing), it is now recognized that there are many more. [1] Senses used by other non-human organisms are even greater in variety and number. During sensation, sense organs collect various stimuli (such as a sound or smell) for transduction, meaning transformation into a form that can be understood by the brain. Sensation and perception are fundamental to nearly every aspect of an organism's cognition, behavior and thought.

In organisms, a sensory organ consists of a group of interrelated sensory cells that respond to a specific type of physical stimulus. Via cranial and spinal nerves (nerves of the Central and Peripheral nervous systems that relay sensory information to and from the brain and body), the different types of sensory receptor cells (such as mechanoreceptors, photoreceptors, chemoreceptors, thermoreceptors) in sensory organs transduct sensory information from these organs towards the central nervous system, finally arriving at the sensory cortices in the brain, where sensory signals are processed and interpreted (perceived).

Sensory systems, or senses, are often divided into external (exteroception) and internal (interoception) sensory systems. Human external senses are based on the sensory organs of the eyes, ears, skin, nose, and mouth. Internal sensation detects stimuli from internal organs and tissues. Internal senses possessed by humans include the vestibular system (sense of balance) sensed by the inner ear, as well as others such as spatial orientation, proprioception (body position) and nociception (pain). Further internal senses lead to signals such as hunger, thirst, suffocation, and nausea, or different involuntary behaviors, such as vomiting. [2] [3] [4] Some animals are able to detect electrical and magnetic fields, air moisture, or polarized light, while others sense and perceive through alternative systems, such as echolocation. Sensory modalities or sub modalities are different ways sensory information is encoded or transduced. Multimodality integrates different senses into one unified perceptual experience. For example, information from one sense has the potential to influence how information from another is perceived. [5] Sensation and perception are studied by a variety of related fields, most notably psychophysics, neurobiology, cognitive psychology, and cognitive science.


Symptoms of CMT usually begin in early childhood or early adulthood, but can begin later. Some people do not experience symptoms until their early 30s or 40s. Usually, the initial symptom is foot drop early in the course of the disease. This can also cause hammer toe, where the toes are always curled. Wasting of muscle tissue of the lower parts of the legs may give rise to a "stork leg" or "inverted champagne bottle" appearance. Weakness in the hands and forearms occurs in many people as the disease progresses.

Loss of touch sensation in the feet, ankles, and legs, as well as in the hands, wrists, and arms occurs with various types of the disease. Early- and late-onset forms occur with 'on and off' painful spasmodic muscular contractions that can be disabling when the disease activates. High-arched feet (pes cavus) or flat-arched feet (pes planus) are classically associated with the disorder. [3] Sensory and proprioceptive nerves in the hands and feet are often damaged, while unmyelinated pain nerves are left intact. Overuse of an affected hand or limb can activate symptoms including numbness, spasm, and painful cramping.

Symptoms and progression of the disease can vary. Involuntary grinding of teeth and squinting are prevalent, and often go unnoticed by the person affected. Breathing can be affected in some, as can hearing, vision, and neck and shoulder muscles. Scoliosis is common, causing hunching and loss of height. Hip sockets can be malformed. Gastrointestinal problems can be part of CMT, [4] [5] as can difficulty chewing, swallowing, and speaking (due to atrophy of vocal cords). [6] A tremor can develop as muscles waste. Pregnancy has been known to exacerbate CMT, as well as severe emotional stress. Patients with CMT must avoid periods of prolonged immobility such as when recovering from a secondary injury, as prolonged periods of limited mobility can drastically accelerate symptoms of CMT. [7]

Pain due to postural changes, skeletal deformations, muscle fatigue, and cramping is fairly common in people with CMT. It can be mitigated or treated by physical therapies, surgeries, and corrective or assistive devices. Analgesic medications may also be needed if other therapies do not provide relief from pain. [8] Neuropathic pain is often a symptom of CMT, though, like other symptoms of CMT, its presence and severity vary from case to case. For some people, pain can be significant to severe and interfere with daily life activities. However, pain is not experienced by all people with CMT. When neuropathic pain is present as a symptom of CMT, it is comparable to that seen in other peripheral neuropathies, as well as postherpetic neuralgia and complex regional pain syndrome, among other diseases. [9]

Charcot–Marie–Tooth disease is caused by genetic mutations that cause defects in neuronal proteins. Nerve signals are conducted by an axon with a myelin sheath wrapped around it. Most mutations in CMT affect the myelin sheath, but some affect the axon.

Classification Edit

CMT is a heterogeneous disease and the mutations linked to it may occur in a number of different genes. [10] Based on the affected gene, CMT is categorized into several types and subtypes. [11]

Chromosome 17 Edit

The most common cause of CMT (70–80% of the cases) is the duplication of a large region on the short arm of chromosome 17 that includes the gene PMP22.

Some mutations affect the gene MFN2, on chromosome 1, which codes for a mitochondrial protein. Mutated MFN2 causes the mitochondria to form large clusters, or clots, which are unable to travel down the axon towards the synapses. This prevents the synapses from functioning. [12]

X-linked CMT and Schwann cells Edit

CMT can also be produced by X-linked mutations, and is named X-linked CMT (CMTX). In CMTX, mutated connexons create non-functional gap junctions that interrupt molecular exchange and signal transport. [13] [14] [15]

The mutation can appear in GJB1 coding for connexin 32, a gap junction protein expressed in Schwann cells. Because this protein is also present in oligodendrocytes, demyelination can appear in the CNS. [16]

Schwann cells create the myelin sheath, by wrapping its plasma membrane around the axon. [13]

Neurons, Schwann cells, and fibroblasts work together to create a functional nerve. Schwann cells and neurons exchange molecular signals by gap junctions that regulate survival and differentiation.

Demyelinating Schwann cells causes abnormal axon structure and function. They may cause axon degeneration, or they may simply cause axons to malfunction. [1]

The myelin sheath allows nerve cells to conduct signals faster. When the myelin sheath is damaged, nerve signals are slower, and this can be measured by a common neurological test, electromyography. When the axon is damaged, though, this results in a reduced compound muscle action potential. [17]

CMT can be diagnosed through three different forms of tests: measurement of the speed of nerve impulses (nerve conduction studies), a biopsy of the nerve, and DNA testing. DNA testing can give a definitive diagnosis, but not all the genetic markers for CMT are known. CMT is first most noticed when someone develops lower leg weakness, such as foot drop, or foot deformities, including hammertoes and high arches, but signs alone do not lead to diagnosis. Patients must be referred to a physician specialising in neurology or rehabilitation medicine. To see signs of muscle weakness, the neurologist may ask patients to walk on their heels or to move part of their leg against an opposing force. To identify sensory loss, the neurologist tests for deep-tendon reflexes, such as the knee jerk, which are reduced or absent in CMT. The doctor may also ask the patient's family history since CMT is hereditary. The lack of family history does not rule out CMT, but is helpful to rule out other causes of neuropathy, such as diabetes or exposure to certain chemicals or drugs. [18]

In 2010, CMT was one of the first diseases where the genetic cause of a particular patient's disease was precisely determined by sequencing the whole genome of an affected individual. This was done by the scientists employed by the Charcot Marie Tooth Association (CMTA) [19] [11] Two mutations were identified in a gene, SH3TC2, known to cause CMT. Researchers then compared the affected patient's genome to the genomes of the patient's mother, father, and seven siblings with and without the disease. The mother and father each had one normal and one mutant copy of this gene, and had mild or no symptoms. The offspring who inherited two mutant genes presented fully with the disease.

Histology Edit

The constant cycle of demyelination and remyelination, which occurs in CMT, can lead to the formation of layers of myelin around some nerves, termed an "onion bulb". These are also seen in chronic inflammatory demyelinating polyneuropathy. [20] Muscles show fiber type grouping, a similarly nonspecific finding that indicates a cycle of denervation/reinnervation. Normally, type I and type II muscle fibers show a checkerboard-like random distribution. However, when reinnervation occurs, the group of fibers associated with one nerve are of the same type. The standard for indicating fiber type is histoenzymatic adenosine triphosphatase (ATPase at pH 9.4). [21]

Often, the most important goal for patients with CMT is to maintain movement, muscle strength, and flexibility. Therefore, an interprofessional team approach with occupational therapy (OT), physical therapy (PT), orthotist, podiatrist, and or orthopedic surgeon is recommended. [22] PT typically focuses on muscle-strength training, muscle stretching, and aerobic exercise, while OT can provide education on energy conservation strategies and activities of daily living. Physical therapy should be involved in designing an exercise program that fits a person's personal strengths and flexibility. Bracing can also be used to correct problems caused by CMT. An orthotist may address gait abnormalities by prescribing the use of ankle-foot orthoses. These orthoses help control foot drop and ankle instability and often provide a better sense of balance for patients.

Appropriate footwear is also very important for people with CMT, but they often have difficulty finding well-fitting shoes because of their high arched feet and hammer toes. Due to the lack of good sensory reception in the feet, CMT patients may also need to see a podiatrist for assistance in trimming nails or removing calluses that develop on the pads of the feet. Lastly, patients can also decide to have surgery performed by a podiatrist or an orthopedic surgeon. Surgery may help to stabilize the patients' feet or correct progressive problems. These procedures include straightening and pinning the toes, lowering the arch, and sometimes, fusing the ankle joint to provide stability. [7] CMT patients must take extra care to avoid falling as fractures take longer to heal in someone with an underlying disease process. Additionally, the resulting inactivity may cause the CMT to worsen. [7] The Charcot–Marie–Tooth Association classifies the chemotherapy drug vincristine as a "definite high risk" and states, "vincristine has been proven hazardous and should be avoided by all CMT patients, including those with no symptoms." [23] Several corrective surgical procedures can be done to improve the physical condition of the affected individuals. [24]

The severity of symptoms varies widely even for the same type of CMT. Cases of monozygotic twins with varying levels of disease severity have been reported, showing that identical genotypes are associated with different levels of severity (see penetrance). Some patients are able to live a normal life and are almost or entirely asymptomatic. [25] A 2007 review stated that, "life expectancy is not known to be altered in the majority of cases." [26]

Severe Guillain-Barré Syndrome Following Shingrix ® Vaccine Administration

Citation: Yadav R, Hundley D, Cation L (2019) Severe Guillain-Barré Syndrome Following Shingrix ® Vaccine Administration. J Neurol Neurosci Vol.10 No.4:301. DOI: 10.36648/2171-6625.10.4.301


Guillain-Barré syndrome (GBS) is a rare life threatening acute polyradiculoneuropathy with variable clinical presentations, including weakness, paresthesias, diminished deep tendon reflexes, hyponatremia, dysautonomia, and a cytoalbuminological dissociation on cerebral spinal fluid (CSF) analysis. The exact etiology remains unknown but is thought to occur as a post-infective immunemediated process. Vaccines and illnesses, including H1N1 Swine Flu vaccine, pneumococcal vaccine, Campylobacter jejuni bacteria, cytomegalovirus, and herpes zoster virus, have been associated with GBS. One vaccine that has not been identified to cause GBS is the newly released Shingrix ® vaccine for herpes zoster infection prevention. We present a case of severe GBS following Shingrix ® vaccine immunization.


Guillain Barre Syndrome Shingrix vaccine Polyradiculoneuropathy Cytoalbuminogenic dissociation


Guillain-Barré syndrome (GBS) is a rare life threatening acute polyradiculoneuropathy with variable clinical presentations [1]. GBS has been documented to most commonly occur as a post-infective immune-mediated process. GBS has been associated with many vaccines and illnesses H1N1 Swine Flu vaccine, pneumococcal vaccine, Campylobacter jejuni bacteria, cytomegalovirus, and herpes zoster virus [2-4]. One vaccine that has yet to be identified to cause GBS is the newly released Shingrix ® vaccine. Shingrix ® aims to prevent herpes zoster infection and the associated post-herpetic neuralgia. Here, we report a case of severe GBS after recent Shingrix ® vaccine immunization.

Case Report

A 76-year-old female with a past medical history of hyperlipidemia, asthma, macular degeneration, and two previous episodes of pancreatitis of unknown origin, presented with a two-day history of bilateral proximal lower extremity weakness. The Patient denied recent camping, hiking, insect bites, and prior neuropathy/myopathy. However, the patient did report a mild upper respiratory tract infection ten weeks prior to admission. The Patient stated that she had received the new Shingrix ® (Recombinant Zoster) vaccine ten days before hospitalization. The Patient reported that she had progressive weakness that initially started with inability to ascend stairs. This progressed to difficulty with standing and a subsequent non-traumatic fall. These described symptoms deviated significantly from her baseline. The Patient&rsquos baseline consisted of independence with mobility and activities of daily living. The patient did not require any assistive devices.

On presentation, the patient was afebrile (98.4°F), had a normal respiratory rate (17 breaths/minute), had an oxygen saturation of 98% on room air, and was normotensive (136/76 mmHg). The Patient reported paresthesias and numbness on the dorsal region of her right lower extremity and difficulty lifting both legs. On examination, the Patient was alert and oriented, cranial nerves II-XII were intact, there was 5/5 bilateral upper extremity strength, and 5/5 bilateral lower extremity strength with dorsiflexion. The Patient had normal sensation bilaterally in upper and lower extremities. However, the Patient had 3/5 lower bilateral extremity strength with hip flexion. Furthermore, that Patient had bilateral absent Patellar and Achilles tendon reflexes.

On further assessment, the Patient&rsquos labs were unremarkable. A computed tomography scan of the brain was performed, which revealed no evidence of acute intracranial abnormalities. The report did endorse microvascular ischemic disease involving the white matter. These results were found to be secondary to aging. Magnetic resonance imaging scan of the brain and lumbar spinal cord was only positive for degenerative antegrade spondylolisthesis deformity at L5-S1. Over the next 24 hours, the Patient reported worsening lower extremity paresthesias and weakness. The Patient could no longer stand without assistance. The Patient also stated that she was having neuropathic pain in bilateral lower extremities burning, tingling, and electrical shock sensations. Furthermore, the Patient described new difficulties with swallowing. An endoscopy was performed, and the Patient was described to have esophageal dysmotility because she was unable to pass the barium pill during the examination. Consequently, a lumbar puncture was performed due to concern for disease progression. Lumbar cerebral spinal fluid studies revealed an elevated protein level (61 mg/dL), a normal white blood cell count (0 CUMM), and a cytoalbuminogenic dissociation. These results indicated acute inflammatory demyelinating polyneuropathy (GBS). Neurologic consultation was obtained. No electrodiagnostic studies were performed.

The Patient was diagnosed with Guillen Barre Syndrome likely secondary to Shingrix ® vaccine. Treatment with intravenous immunoglobulin (2 g/kg divided over five days) was initiated. The Patient showed gradual improvements with five days of treatment and was transferred to an acute rehabilitation facility (Hospital day 5). At discharge, the Patient&rsquos bilateral Patellar and Achilles tendon reflexes remained absent. However, the Patient was able to stand and ambulate with a walker.

Five days after discharge to the rehab facility, the patient reported worsening of bilateral lower extremity pain (per Patient, this pain was worse than her prior admission). The patient was therefore readmitted to the hospital. On examination, the patient had 5/5 bilateral upper extremity strength, 5/5 bilateral strength on lower extremity dorsiflexion, normal bilateral sensation in upper and lower extremities, and 3/5 bilateral lower extremity hip flexion strength. This strength assessment was consistent with the Patient&rsquos previous presentation. Furthermore, light touch sensation was intact in all four extremities. There was no apparent sensory loss. Bilateral Achilles and Patellar tendon reflexes remained absent. However, the Patient could no longer stand with and without assistance and therefore could no longer ambulate. This presentation significantly deviated from her prior discharge appearance.

Initially the patient described neuropathic pain and therefore, she was treated with Gabapentin and amitriptyline. However, the patient became hyponatremic (133 mmol/L on admission to 122 mmol/L after treatment) and had significant fluctuations in her blood pressure (ranging from 110/67 mmHg to 182/88 mmHg). Additionally, the Patient unfortunately feels due to weakness while attempting to walk with assistance. She suffered a nondisplaced spiral fracture through the distal fibular metaphysis and had a large ankle joint effusion. The Patient was seen by Orthopedic Surgery and was placed in a CAM boot. Plasma exchange was initiated because the Patient&rsquos muscular strength continued to decline, and her lower extremity pain was increasing.

After undergoing three plasma exchange treatments, the Patient showed remarkable improvement with lower extremity strength and power. The Patient was then able to ambulate the hospital halls with the use of a walker and some assistance after five treatments of plasma exchange. Additionally, the Patient&rsquos neuropathic pain improved. She was then discharged to an acute rehabilitation center with scheduled physical therapy (Figures 1 and 2).

Figure 1: Mechanism of action of Guillian-Barré syndrome, a proposed antibody mediated pathologic process.

Figure 2: Typical time course of Guillan-Barré syndrome.


We present a case of Guillian-Barré syndrome that occurred 10 days after Shingrix ® vaccine administration. We identified no other possible etiology of the Patient&rsquos symptoms. The Patient displayed several key features of GBS established by the Brighton Criteria of weakness paresthesias, diminished Patellar and Achilles deep tendon reflexes, hyponatremia secondary to Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH), dysautonomia, and cytoalbuminological dissociation on cerebral spinal fluid analysis. We believe that this is an example of post-vaccine related Guillain-Barré Syndrome, given the timing of the presentation and when she received her vaccine [2-6].

While electrodiagnostic studies have been used to help diagnose GBS secondary to bacterial, viral, and vaccination origins, these results are not necessary. The diagnosis of GBS is confirmed with the elevated CSF protein level and absence of deep tendon reflexes (found in 90% of GBS affected patients) [2]. Additionally, it can take up to four weeks before electrodiagnostic studies show loss of motor and sensory response secondary to GBS [7]. GBS is a rapidly progressing disease and if not treated in a timely fashion can result in paralysis of the diaphragm and even death [7].

There have been numerous vaccines connected to GBS, including the H1N1 swine flu vaccine and the pneumococcal vaccine. However, the newly release Shingrix ® vaccine has yet to be reported to be associated with this potentially life threatening polyradiculoneuropathy [3]. Shingrix ® is a non-live recombinant vaccine containing the varicella-zoster virus glycoprotein E in combination with an adjuvant ASO1B suspension component [8]. This immunization was FDA approved and released to the public in 2017 to prevent latent activation of varicella zoster virus (Chickenpox) as herpes zoster virus (Shingles) in patients 50 plus years old [9]. This vaccination presents in a two-dose series and is administered intramuscularly 2-6 months apart (Table 1).

H1N1 Swine Flu Vaccine Pneumococcal Vaccine Cytomegalovirus
Campylobacter jejuni bacteria Herpes Zoster Virus Zika Virus

Table 1: Previously documented causes of GBS.

Before Shingrix ® was released the Zoster vaccine was used to inhibit varicella zoster virus reactivation [10]. However, Shingrix ® has been found to be superior. Shingrix ® not only prevents latent herpes zoster virus reactivation within the dorsal root ganglia of a dermatome after primary infection, but also prevents the subsequent post-herpetic neuralgia [9-11]. Post-herpetic neuralgia affects 10-13% of infected individuals. Following the resolution of shingles, post-herpetic neuralgia consists of persistent pain for at least 90 days [11]. Documented adverse reactions to the Shingrix ® vaccination from eight high quality randomized control trials, include local injection site rash or irritation, disseminated rash, herpes zoster infection in immunocompetent patients, and life-threatening complications in immunocompromised recipients [9-13]. However, none of these studies demonstrated a relationship between Shingrix ® , nor the previous Zoster vaccine, to GBS. As a result, GBS likely secondary to the Shingrix ® vaccine could not have been expected in this patient after receiving this immunization.

Interestingly, there have been multiple cases of GBS secondary to herpes zoster infection. The first documented case was in 1924. Since then, there have been over 50 cases described [14]. It is thought that the mechanism by which GBS results from herpes zoster infection is similar to that of GBS secondary to Campylobacter jejuni [4]. It has been hypothesized that GBS results from C. jejuni infection because the bacteria&rsquos lipopolysaccharide contains epitopes that resemble human peripheral nerve ganglioside epitopes [4,9]. Consequently, the human body generates antibodies against these bacterial lipopolysaccharide epitopes. These antibodies then also target the patient&rsquos peripheral nerve gangliosides because they cannot distinguish between the ganglioside epitope and the bacterial epitope. In summary, the bacterial lipopolysaccharide epitope acts as a molecular mimicker [4]. The precise nature by which this occurs is still unclear. Therefore, the mechanism by which GBS may result from Shingrix ® vaccine remains unknown. If further cases reveal a similar association, this should be further explored. Per this case report and prior documentation of GBS secondary to herpes zoster, there is now evidence to state that antibodies generated in a lab against herpes zoster and then given intramuscularly via vaccination (Shingrix ® ) may be a sufficient nidus for Guillain-Barré syndrome (Table 2).

Brighton Diagnostic Criteria for GBS Level of Diagnostic Certainty
Symptoms 1 2 3 4
Bilateral and flaccid weakness of limbs + + + +/-
Decreased or absent deep tendon reflexes in weak limbs + + + +/-
Monophasic course and time between onset-nadir = 12 hours to 28 days + + + +/-
Absence of alternative diagnosis for weakness + + + +/-
CSF cell count <50/ml + +/-a - +/-
CSF protein concentration > 60 mg/dL + +/-a - +/-
Nerve conduction study findings consistent with one of
the subtypes of GBS
+ +/-a - +/-

Table 2: Level of diagnostic certainty in brighton diagnostic criteria for GBS.


In summary, we present a case of GBS that occurred shortly after Shingrix ® vaccination. Our case is consistent with other vaccine and herpes zoster related cases of GBS. Clinicians should be cognizant of the possible association between Guillain-Barré syndrome and the new Shingrix ® vaccine.

All of the worst possible causes of back pain and their major features

None of these are common. All of them usually cause serious symptoms that are easy to take seriously. Some of them can “fly under the radar” in early stages, but usually not for long. The names of the conditions link to carefully chosen articles from good sources.

The worst possible causes of back pain
what is it? major features
cancer a tumor in or near the spine Many kinds of cancer can cause many kinds of back pain, but some strong themes are: the pain grows steadily and is mostly unaffected by position and activity, worse with weight bearing and at night, and comes with other signs of being unwell.
cauda equina syndrome pinching of the lowest part of the spinal cord Hard to mistake for anything else: hard to pee, fecal incontinence, numb groin, weak legs. Caused by ruptured discs, trauma, cancer, infection.
spinal infection infection in or near spinal structures Hard to detect, often for a long time. Usually there’s a well-defined tender spot and then, eventually, deep constant pain, a rigid spine, sometimes fever and illness but not always.
abdominal aneurysm ballooning of a large artery next to the spine Pain may throb in sync with pulse. Mostly occcurs in people at risk of heart disease: older, heavier, hypertensive smokers and diabetes patients.
ankylosing spondylitis inflammatory arthritis of spine and pelvis, mostly Long term back pain starting well before middle age and progressing slowly and erratically, improves with activity but not rest, prolonged morning stiffness, possible involvement of other areas. More common in men.

Highly recommended reading for professionals — peek at the infographic to start — and a key source for this article:

How is an epidural abscess treated?

Typically, your healthcare provider will give you antibiotics to fight the infection that caused the abscess. A surgeon may need to drain the fluid from the abscess with a needle, to help relieve the pressure. Sometimes, your surgeon may remove it entirely. You will most likely require surgery to drain or remove the abscess if you have difficulty moving or are unable to move at all, or if you have sensation problems, such as numbness, somewhere in the body.

To flourish or perish: evolutionary TRiPs into the sensory biology of plant-herbivore interactions

The interactions between plants and their herbivores are highly complex systems generating on one side an extraordinary diversity of plant protection mechanisms and on the other side sophisticated consumer feeding strategies. Herbivores have evolved complex, integrative sensory systems that allow them to distinguish between food sources having mere bad flavors from the actually toxic ones. These systems are based on the senses of taste, olfaction and somatosensation in the oral and nasal cavities, and on post-ingestive chemosensory mechanisms. The potential ability of plant defensive chemical traits to induce tissue damage in foragers is mainly encoded in the latter through chemesthetic sensations such as burning, pain, itch, irritation, tingling, and numbness, all of which induce innate aversive behavioral responses. Here, we discuss the involvement of transient receptor potential (TRP) channels in the chemosensory mechanisms that are at the core of complex and fascinating plant-herbivore ecological networks. We review how “sensory” TRPs are activated by a myriad of plant-derived compounds, leading to cation influx, membrane depolarization, and excitation of sensory nerve fibers of the oronasal cavities in mammals and bitter-sensing cells in insects. We also illustrate how TRP channel expression patterns and functionalities vary between species, leading to intriguing evolutionary adaptations to the specific habitats and life cycles of individual organisms.

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Why MSG Has a Bad Rap (But Doesn't Deserve It)

The Internet is abuzz with chatter about MSG. Perhaps you&rsquove heard it&rsquos perfectly safe. Or that it causes mild problems for people who have a sensitivity to it. Or even that it&rsquos a toxic chemical that&rsquos slowly killing us all.

To set the record straight, we&rsquove taken a close look at the large body of scientific research and spoken with the U.S. Food and Drug Administration and Ajinomoto (the original producer of MSG) to learn the essentials about MSG: what it is, why it&rsquos used, and whether or not it&rsquos safe.

What is MSG?

Like its name suggests, monosodium glutamate (MSG) is the product of two smaller components: sodium and glutamate. (Both of which are present in foods we eat every day.) Sodium is part of table salt and glutamate can be found in high concentrations in Parmesan cheese and soy sauce. Glutamate is also naturally abundant in our own bodies and is vital to a wide range of biological functions Metabolic fate and function of dietary glutamate in the gut. Burrin DG, Stoll B. The American Journal of Clinical Nutrition. 2009 Sep90(3):850S-856S. . Because the human body produces its own glutamate, consuming glutamate in your diet isn&rsquot necessary&mdashthough it may be difficult to avoid, since it&rsquos a natural component of nearly every food protein.

When sodium (a positively charged molecule) is combined with a negatively charged molecule, the result is called a sodium salt. MSG is the sodium salt of the amino acid glutamate.

Discovery and Production

MSG was first isolated in 1908 by Japanese scientist Kikunae Ikeda as the compound that gave dashi (a Japanese soup base made from seaweed and fish) its distinct flavor. Ikeda successfully crystallized MSG and described its unique taste as &ldquoumami,&rdquo which roughly translates to &ldquodelicious taste.&rdquo In the year following his discovery, Ikeda and his partner founded Ajinomoto and began producing MSG for use in food.

Ajinomoto and other manufacturers produce MSG by fermenting corn, sugar cane, and tapioca. To meet Food Chemical Codex regulations, the glutamate in MSG must be 99 percent pure. This is so pure that the body can&rsquot distinguish the manmade glutamate from the kind that naturally occurs in things like meat and cheese, says Dr. Eyassu Abegaz, director of scientific and regulatory affairs at Ajinomoto North America. MSG manufacturers also add sodium to the glutamate because it creates a powder that is easy to store, ship, and use, Abegaz, said.

Note: In the rest of this article the terms glutamate, L-glutamate, glutamic acid, monosodium glutamate, monosodium L-glutamate, and umami will be used interchangeably to describe MSG.

The Fifth Taste

Human tastebuds are primed to distinguish between at least four basic tastes: salty, sour, bitter, and sweet. It&rsquos long been suspected that we also have taste receptors specifically designed to detect umami. In 2000, researchers at the University of Miami School of Medicine finally pinpointed the receptors A metabotropic glutamate receptor variant functions as a taste receptor. Chaudhari N, Landin AM, Roper SD. Nature Neuroscience. 2000 Feb3(2):113-9. . The researchers found that our mouths have L-glutamate receptors (just like we have sweet and bitter receptors), which allow us to recognize umami whenever free glutamate molecules touch our tongues. This has solidified umami&rsquos classification as the fifth basic taste The discovery of umami. Lindemann B, Ogiwara Y, Ninomiya Y. Chemical Senses. 2002 Nov27(9):843-4. Gustatory system: the finer points of taste. Trivedi BP. Nature. 2012 Jun 20486(7403):S2-3. .

Although the taste sensation of umami is unique, most people find it vague and difficult to describe because it tends to serve a supporting role when combined with other flavors. Umami, however, is perhaps best described as a meaty, mouth-filling, richly savory taste Taste receptors for umami: the case for multiple receptors. Chaudhari N, Pereira E, Roper SD. The American Journal of Clinical Nutrition. 2009 Sep90(3):738S-742S .

Scientists have also discovered glutamate receptors in our gut Glutamate. Its applications in food and contribution to health. Jinap S, Hajeb P. Appetite. 2010 Aug55(1):1-10. . It&rsquos presumed these receptors signal the brain to prepare for the digestion of protein-rich food, which supports the theory of taste as an indicator of nutrition. It goes like this: Humans tend to like sweet tastes because they signal to our body that we&rsquore consuming carbohydrate energy. It may follow that we tend to like umami because it sends asignal to our body that we&rsquore consuming the protein our bodies need The discovery of umami. Lindemann B, Ogiwara Y, Ninomiya Y. Chemical Senses. 2002 Nov27(9):843-4. .

Why Is MSG Added to Food?

MSG is typically added as a flavor enhancer. It tends to enhance salty and savory flavors while muting bitterness and sourness. MSG can also unify and balance the flavors of a dish while causing them to linger longer on the tongue. Because of these properties, MSG is often added to soups, snack foods, and prepared entrees. But it&rsquos rarely added in large quantity to any food. In fact, the amount of MSG added to processed foods is similar to the concentration of free glutamate that naturally occurs in tomatoes or Parmesan cheese Glutamate. Its applications in food and contribution to health. Jinap S, Hajeb P. Appetite. 2010 Aug55(1):1-10. .

From a food production standpoint, MSG is a popular additive because it offers an affordable way to enhance the flavor of a wide variety of savory foods. MSG can also be used to reduce the amount of sodium in foods&mdashit contains 30 percent less sodium than table salt, but its flavor-boosting ability keeps low-sodium foods palatable.

Other glutamate-rich seasonings, such as yeast extract and hydrolyzed vegetable protein (HVP), can achieve the effects of umami without using granulated MSG. These ingredients might add notes of cheese, chicken, or beer, depending on the strain of yeast or type of vegetable protein used during production. The choice between using MSG and one of the alternative flavor enhancers is often based on the flavor profile, cost (MSG is often the cheapest option), and labeling&mdashfood producers know MSG is unpopular with some consumers, and these alternatives might not trigger the same negative reaction.

Labeling of MSG and Other Flavor Enhancers

Critics of MSG often refer to yeast extracts and HVPs as &ldquohidden MSG&rdquo because these flavor enhancers contain significant levels of MSG, but don&rsquot have to be labeled as such on food packaging. The FDA requires companies to list all the ingredients in a product, but producers don&rsquot need to detail the components of a single ingredient. And since the glutamates in yeast extracts and HVPs is a component of the yeast or vegetable protein&mdashno crystallized MSG is added&mdashthe glutamate doesn&rsquot have to be listed on the label.

The most common exception to this FDA rule is if ingredient is of the &ldquobig eight&rdquo allergens: milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat, and soybeans. In that case, food producers are required by law to mention the ingredient by its common name on the label at least once.

The FDA doesn&rsquot require this kind of labeling for MSG because MSG sensitivity is not an allergy Monosodium glutamate &lsquoallergy&rsquo: menace or myth? Williams AN, Woessner KM. Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology. 2009 May39(5):640-6. . The symptoms generally attributed to MSG are mild and temporary, unlike some severe allergic reactions, which can require swift medical attention Executive summary from the report: analysis of adverse reactions to monosodium glutamate (MSG). Federation of American Societies for Experimental Biology. The Journal of Nutrition. 1995 Nov125(11):2891S-2906S. .

Additionally, the FDA classifies MSG as Generally Recognized as Safe (GRAS). Dr. Marianna Naum, a FDA spokesperson, explained the steps to achieve GRAS status: &ldquoThere must be evidence of expert consensus that its use in food is safe, and the information relied on to establish its safe use must be publicly available.&rdquo MSG has been classified as GRAS since the list&rsquos inception in 1958. But MSG&rsquos GRAS status hasn&rsquot saved it from considerable controversy over the years.

Even with the FDA&rsquos general approval of MSG, the organization still strongly discourages false advertising, Dr. Naum said. &ldquoClaims such as &lsquoNo MSG&rsquo or &lsquoNo added MSG,&rsquo could potentially be considered false or misleading on foods that contain sources of MSG or substantial amounts of naturally occurring free glutamate,&rdquo Dr. Naum said.

MSG Symptom Complex

In 1968, Dr. Robert Ho Man Kwok wrote a letter to the New England Journal of Medicine where he described feeling sensations of numbness, tingling, warmth, and tightness after eating Chinese food. Dr. Ho Man Kwok acknowledged there were many potential causes for his symptoms, including MSG sensitivity. He called these symptoms Chinese Restaurant Syndrome, though it is often referred to today as &ldquoMSG Symptom Complex.&rdquo His letter sparked a flurry of follow-up letters that specifically called out MSG in Chinese food.

Due to growing consumer concern at the time, the FDA and Center for Food Safety and Applied Nutrition commissioned an independent review of all scientific findings on MSG to offer a conclusive answer to the question: Is MSG dangerous?

The Federation of American Societies for Experimental Biology (FASEB) conducted the study and published its findings in 1995 as a supplement to The Journal of Nutrition Executive summary from the report: analysis of adverse reactions to monosodium glutamate (MSG). Federation of American Societies for Experimental Biology. The Journal of Nutrition. 1995 Nov125(11):2891S-2906S. .

&ldquoThe FASEB report did identify temporary and generally mild symptoms that may occur in some individuals after consuming 3 grams of MSG without food,&rdquo said Dr. Naum, spokesperson at the FDA. &ldquoHowever, to date, scientists have not been able to consistently trigger these temporary reactions in studies where MSG was provided with food.&rdquo

Three grams of MSG is more than five times the amount of MSG an average adult consumes in a day. When MSG is consumed with food, even mild symptoms become less apparent and repeatable.

FASEB&rsquos findings have been confirmed by more recent MSG research, including a large multicenter, double-blind, placebo-controlled, multiple challenge test. Researchers on this study concluded: &ldquoNeither persistent, nor serious effects from MSG ingestion are observed, and the responses were not consistent on retesting&rdquo Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study. Geha RS, Beiser A, Ren C, et al. The Journal of Nutrition. 2000 Apr130(4S Suppl):1058S-62S. .

MSG and Asthma

A decade ago, the derogatory phrase Chinese Restaurant Syndrome was coined in a letter to the editor in The New England Journal of Medicine. Another series of letters in the same journal detailed stories of individuals experiencing asthmatic symptoms after eating food with high levels of MSG. A study prompted by these letters found that 13 of the 32 test subjects had asthma attacks after taking pills of MSG Monosodium L-glutamate-induced asthma. Allen DH1, Delohery J, Baker G. The Journal of Allergy and Clinical Immunology. 1987 Oct80(4):530-7. .

This study was heavily criticized, however, because it gave patients up to five grams of MSG in capsule form, significantly more than the half gram an average person consumes daily. Since the 1980s, studies have repeatedly and consistently shown no link between asthma attacks and eating MSG Monosodium L-glutamate-induced asthma. Allen DH1, Delohery J, Baker G. The Journal of Allergy and Clinical Immunology. 1987 Oct80(4):530-7. Monosodium glutamate sensitivity in asthma. Woessner KM, Simon RA, Stevenson DD. The Journal of Alergy and Clinical Immunology. 1999 Aug104(2 Pt 1):305-10. The effects of monosodium glutamate in adults with asthma who perceive themselves to be monosodium glutamate-intolerant. Woods RK, Weiner JM, Thien F, et al. The Journal of Allergy and Clinical Immunology. 1998 Jun101(6 Pt 1):762-71. Monosodium glutamate and asthma. Stevenson DD. The Journal of Nutrition. 2000 Apr130(4S Suppl):1067S-73S. Food allergy and asthma&ndashwhat is the link? Roberts G, Lack G. Pediatric Respiratory Reviews. 2003 Sep4(3):205-12. Food Intolerance and childhood asthma: what is the link? Beausoleil JL, Fiedler J, Spergel JM. Pediatric Drugs. 20079(3):157-63. Effects of oral monosodium glutamate in mouse models of asthma. Yoneda J, Chin K, Torii K, et al. Food and Chemical Toxicology. 2011 Jan49(1):299-304. .

MSG and Migraines

In recent years, there&rsquos been an increasing number of anecdotes of MSG inducing migraines in people with a sensitivity. Migraines are fundamentally different from the MSG symptom complex symptoms, so determining if MSG causes migraines requires its own research.

A review of MSG research published in Appetite, a peer-reviewed journal, states, &ldquoIn the absence of clinical data, we cannot make any conclusions about glutamate as a potential trigger for migraine headaches. Therefore, with no consistent data to suggest that glutamate causes any type of headache, much more extensive clinical research would be required to establish a link between glutamate and migraine headaches&rdquo Glutamate. Its applications in food and contribution to health. Jinap S, Hajeb P. Appetite. 2010 Aug55(1):1-10. .

Are You Sensitive to MSG?

In the world of science, causality is a tricky thing to prove. Even if your results do indicate causality, they&rsquore only considered reliable if you have a large number of test subjects, unimpeachable methods, and (this one&rsquos the kicker) the results are repeatable. If another scientist repeats the experiment but gets different results, it suggests that chance (or some other factor) came into play in the initial results. Repeatability has been the main problem for those seeking to establish that MSG is the cause of MSG symptom complex.

The best studies I found on MSG found that any adverse reactions were inconsistent and not repeatable. The lack of scientific evidence behind the claim that MSG triggers certain symptoms doesn&rsquot necessarily mean that the syndrome (or something like it) isn&rsquot real&mdashit just means that MSG isn&rsquot causing it in a scientifically measurable way.

If you think you&rsquore sensitive to MSG, here are some possible scenarios as to what&rsquos causing your symptoms:

  1. You may be sensitive to some part of the food you eat, but not specifically to MSG.
  2. You may be mildly allergic to something in your food. Mild allergic reactions to the soy or fish common in Chinese food are sometimes misattributed to MSG sensitivity Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study. Geha RS, Beiser A, Ren C, et al. The Journal of Nutrition. 2000 Apr130(4S Suppl):1058S-62S. .
  3. You may be sensitive to the high histamine levels present in many Chinese foods, which can mimic an allergic reaction Monosodium glutamate &lsquoallergy&rsquo: menace or myth? Williams AN, Woessner KM. Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology. 2009 May39(5):640-6.Executive summary from the report: analysis of adverse reactions to monosodium glutamate (MSG). Federation of American Societies for Experimental Biology. The Journal of Nutrition. 1995 Nov125(11):2891S-2906S. .
  4. You have a pre-existing vitamin B6 deficiency, which some researchers have speculated is the true cause of MSG symptom complex symptoms The biochemistry of vitamin B6 is basic to the cause of the Chinese restaurant syndrome. Folkers K, Shizukuishi S, Willis R. Hoppe-Seyler&rsquos Zeitschrift Fuer Physiologische Chemie. 1984 Mar365(3):405-14.Executive summary from the report: analysis of adverse reactions to monosodium glutamate (MSG). Federation of American Societies for Experimental Biology. The Journal of Nutrition. 1995 Nov125(11):2891S-2906S. .
  5. You may be experiencing pain due to irritation of the esophagus Glutamic acid, twenty years later. Garattini S. The Journal Nutrition. 2000 Apr130(4S Suppl):901S-9S. .
  6. You have a true sensitivity to MSG.

If you&rsquore experiencing symptoms after eating Chinese food or other food containing MSG, your best course of action is to see a doctor, who can then refer you to an allergist, registered dietitian, or other specialist for further testing. A healthcare specialist might recommend that you try an elimination diet, where you systematically avoid certain foods in order to identify the root cause of a symptom.

The Source of MSG&rsquos Bad Rap

Most of the research against MSG stems from two sources.

The first: Dr. Russell L. Blaylock&rsquos 1996 book Excitotoxins: The Taste That Kills, which argues that nerve cells in the brain and elsewhere are killed by excessive stimulation of neurotransmitters, including glutamate.

The argument for brain damage originates in a 1969 article about MSG injections in young mice Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Olney JW. Science. 1969 May 9164(3880):719-21. . The newborn mice were injected with heavy doses of MSG under the skin, which can&rsquot be fairly compared to amount and manner in which humans typically consume MSG Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study. Geha RS, Beiser A, Ren C, et al. The Journal of Nutrition. 2000 Apr130(4S Suppl):1058S-62S. .

Glutamate is an excitotoxin that can cause brain cell death, but that role is actually essential for normal brain function. Every paper I&rsquove come across on the topic of exicitotoxicy refers to endogenous glutamate (the type made by our bodies), or glutamate that&rsquos been injected or administered in a way that completely circumvents the digestive system. I couldn&rsquot find any papers arguing that dietary MSG has any effect on brain chemistry. In fact, recent studies have found that 95 percent of dietary glutamate is metabolized in the digestive tract and turned into fuel or other amino acids Metabolic fate and function of dietary glutamate in the gut. Burrin DG, Stoll B. The American Journal of Clinical Nutrition. 2009 Sep90(3):850S-856S. Intestinal glutamate metabolism. Reeds PJ, Burrin DG, Stoll B, et al. The Journal of Nutrition. 2000 Apr130(4S Suppl):978S-82S. . What little glutamate does make it into the bloodstream is prevented from entering our brains in any significant quantity by the blood brain barrier The blood-brain barrier and glutamate. Hawkins RA. The American Journal of Clinical Nutrition. 2009 Sep90(3):867S-874S. . Given this information, the idea that the MSG we eat somehow travels to the brain and causes damage is a stretch.

Perhaps the best-researched and written criticism of MSG I could find comes from Adrienne Samuels, a self-proclaimed advocate against MSG who first became interested in the topic after her husband developed symptoms related to consuming MSG.

In her review of MSG research and legislation, she clearly documents the history of the food industry&rsquos influence on research studies, FDA rulings, and suppression of others&rsquo results The toxicity/safety of processed free glutamic acid (MSG): a study in suppression of information. Samuels A. Accountability in Research. 19996(4):259-310. . It&rsquos a story we saw when researching nonnutritive sweeteners too. Whenever large corporations have a stake in research, there&rsquos bound to be influence and politics involved.

But, just because the history of MSG is clouded with politics and agendas doesn&rsquot mean it&rsquos unsafe. I think Samuels makes a compelling argument that the industry has more to do with MSG research than we should feel comfortable with, but I don&rsquot think she makes a compelling argument that MSG actually causes harm.

If you come across sites or stories that are anti-MSG, check to see whether the arguments stem from either Dr. Blaylock&rsquos book or Samuels&rsquos website, and then see if they take into account other publicly-available published research.

Slow Changing Opinions

So why do people continue to condemn MSG after 40 years of science has failed to show that consuming MSG causes harm? Once fear is ingrained, it&rsquos difficult to completely remove.

Adding to this consumer uncertainty is the fact that the true cause of MSG symptom complex is still a mystery. Many people are left wondering, &ldquoWhy do some people feel ill after eating food containing MSG?&rdquo Some researchers speculate that the symptoms are caused by referred pain due to irritation of the esophagus The Chinese restaurant syndrome: an anecdote revisited. Kenney RA. Food and Chemical Toxicology. 1986 Apr24(4):351-4. . Others suspect it could involve a Vitamin B6 deficiency or the high histamine levels present in many Chinese foods The biochemistry of vitamin B6 is basic to the cause of the Chinese restaurant syndrome. Folkers K, Shizukuishi S, Willis R. Hoppe-Seyler&rsquos Zeitschrift Fuer Physiologische Chemie. 1984 Mar365(3):405-14.Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study. Geha RS, Beiser A, Ren C, et al. The Journal of Nutrition. 2000 Apr130(4S Suppl):1058S-62S.Executive summary from the report: analysis of adverse reactions to monosodium glutamate (MSG). Federation of American Societies for Experimental Biology. The Journal of Nutrition. 1995 Nov125(11):2891S-2906S. .

No matter where you stand on the topic, it&rsquos important to investigate where information is coming from and how valid it is. And if you ever experience symptoms you think may be related to an MSG allergy, consult a doctor.

This article was originally produced as part of 75toGo, a project to publish research-intensive health and fitness stories for twentysomethings looking to create good practices and habits for the decades ahead.

Is numbness the absence of one or all touch sensations? - Biology

Mutations in a protein called dynein, required for the proper functioning of sensory nerve cells, can cause defects in mice that may provide crucial clues leading to better treatments for a human nerve disorder known as peripheral neuropathy, which affects about three percent of all those over age 60.

Peripheral neuropathy results from damage to the nerves and nerve processes that are located outside the brain and spinal cord. Symptoms include pain in the hands and arms, legs and feet--sometimes constant and quite severe--as well as progressive numbness and weakness in the arms and legs. Despite its prevalence, little is known about the precise causes of the disease or how to prevent or treat it.

In the December 26, 2007, issue of the Journal of Neuroscience, however, researchers at the University of Chicago Medical Center show that mice with mutations in only one copy of a gene coding for one part of dynein protein have severe defects in proprioception, the ability to perceive the spatial orientation of body parts.

These defects caused a significant reduction in the number of sensory nerve cells in affected mice. They also caused early-onset locomotion problems in the mice's hind legs, a defect that appears to be quite similar to some human neuropathies.

"This gene codes for part of a multi-protein complex," said study author Brian Popko, PhD, Jack Miller Professor in Neurological Diseases at the University of Chicago Medical Center. "So a mutation in any of these proteins, or disruption in the function of this multi-protein complex through some other mechanism, could also lead to very similar abnormalities" in human patients with sensory neuropathies.

Mutations in the gene for dynein heavy chain 1, Dync1h, led to movement defects in the hind legs of mice. These defect resembled human neuropathies, said Popko, particularly some forms of Charcot-Marie-Tooth disease and hereditary sensory neuropathy.

Charcot-Marie-Tooth disease is one of the most common inherited neurological disorders, affecting approximately 1 in 2,500 people in the United States. It is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs. In CMT, both the sensory nerves that carry signals from receptors in the extremities to the brain and spinal cord, as well as motor nerves that relay signals from the brain and spinal cord to the limbs and internal organs are affected.

Hereditary sensory neuropathy affects predominantly sensory nerves. Symptoms included sensation loss, decreased or absent reflexes, foot deformities and various anatomic features.

Dynein appears to be a likely suspect, the authors report. Although it is found throughout the body, Dynein plays an important role in the transport of cargo within axons, the elongated extension of nerve cells that transmit signals from one neuron to another. Dynein is crucial for survival, because mice that lack dynein or have mutations in both Dync1h copies die before birth.

Although dynein is important for the whole body, defects are found only in sensory neurons, and predominantly in hind limbs.

The key question is why" said Popko. This mutation may affect transport proteins in all neurons, but perhaps the region that is mutated is more important for the proteins that it transports in sensory neurons, whereas other regions could play a role in motor neurons. Also, mutations in different regions of this protein seem to have different effects. That may be due to differences in the cargo-binding domains.

Affected neurons in mice and in patients with sensory neuropathies have very long axons. Such neurons that transmit signals over huge distances depend on dynein, the "cargo-transporter" to carry molecules from the tip of the axon to the neurons cell bodies. If the cargo-transporter is somehow disturbed, Popko said, like in the case of mutations in Dync1h gene, neurons that transmit signals over long distances will suffer more.

Its very common for neuropathies to affect neurons with the longer axons, for example those that innervate the legs and feet, says Popko. It has been previously suggested that hereditary sensory neuropathy might be connected with disabled trafficking along the axons. There have been mutations found in two genes that form a complex essential for survival of sensory neurons, and this complex is thought to be transported along the neurons by dynein.

This study lays the groundwork for the search for disruptions of this cargo transporting complex in human patients with sensory neuropathy, write the authors in their paper.

They are already looking at human patients for similar mutations. And theyre working further on answering new questions, including: what are the binding partners of dynein that are disrupted in diseases, and why does this affect sensory and not motor neurons"

Researchers finds hidden sensory system in the skin

December 15, 2009 - (Albany, N.Y., USA) The human sensory experience is far more complex and nuanced than previously thought, according to a groundbreaking new study published in the December 15 issue of the journal Pain (http://www. painjournalonline. com/ article/ S0304-3959%2809%2900526-0/ abstract). In the article, researchers at Albany Medical College, the University of Liverpool and Cambridge University report that the human body has an entirely unique and separate sensory system aside from the nerves that give most of us the ability to touch and feel. Surprisingly, this sensory network is located throughout our blood vessels and sweat glands, and is for most people, largely imperceptible.

"It's almost like hearing the subtle sound of a single instrument in the midst of a symphony," said senior author Frank Rice, PhD, a Neuroscience Professor at Albany Medical College (AMC), who is a leading authority on the nerve supply to the skin. "It is only when we shift focus away from the nerve endings associated with normal skin sensation that we can appreciate the sensation hidden in the background."

The research team discovered this hidden sensory system by studying two unique patients who were diagnosed with a previously unknown abnormality by lead author David Bowsher, M.D., Honorary Senior Research Fellow at the University of Liverpool's Pain Research Institute. These patients had an extremely rare condition called congenital insensitivity to pain, meaning that they were born with very little ability to feel pain. Other rare individuals with this condition have excessively dry skin, often mutilate themselves accidentally and usually have severe mental handicaps. "Although they had a few accidents over their lifetimes, what made these two patients unique was that they led normal lives. Excessive sweating brought them to the clinic, where we discovered their severe lack of pain sensation," said Dr. Bowsher. "Curiously, our conventional tests with sensitive instruments revealed that all their skin sensation was severely impaired, including their response to different temperatures and mechanical contact. But, for all intents and purposes, they had adequate sensation for daily living and could tell what is warm and cold, what is touching them, and what is rough and smooth."

The mystery deepened when Dr. Bowsher sent skin biopsies across the ocean to Dr. Rice's laboratory, which focuses on multi-molecular microscopic analyses of nerve endings in the skin, especially in relation to chronic pain conditions such as those caused by nerve injuries, diabetes, and shingles. These unique analyses were pioneered by Dr. Rice at Albany Medical College (AMC) along with collaborators at the Karolinska Institute in Stockholm, Sweden. "Under normal conditions, the skin contains many different types of nerve endings that distinguish between different temperatures, different types of mechanical contact such as vibrations from a cell phone and movement of hairs, and, importantly, painful stimuli," said Dr. Rice. "Much to our surprise, the skin we received from England lacked all the nerve endings that we normally associated with skin sensation. So how were these individuals feeling anything?"

The answer appeared to be in the presence of sensory nerve endings on the small blood vessels and sweat glands embedded in the skin. "For many years, my colleagues and I have detected different types of nerve endings on tiny blood vessels and sweat glands, which we assumed were simply regulating blood flow and sweating. We didn't think they could contribute to conscious sensation. However, while all the other sensory endings were missing in this unusual skin, the blood vessels and sweat glands still had the normal types of nerve endings. Apparently, these unique individuals are able to 'feel things' through these remaining nerve endings," said Dr. Rice. "What we learned from these unusual individuals is that there's another level of sensory feedback that can give us conscious tactile information. Problems with these nerve endings may contribute to mysterious pain conditions such as migraine headaches and fibromyalgia, the sources of which are still unknown, making them very difficult to treat."

In addition to international collaborations such as this one, Dr. Rice and his principle AMC colleague, Dr. Philip Albrecht, in the Center for Neuropharmacology and Neuroscience, collaborate extensively with neurologists Dr. Charles Argoff at AMC and Dr. James Wymer of Upstate Clinical Research Associates, who also holds a joint AMC appointment. All are co-authors on the study, which included normal subjects from the Albany, N.Y. area. Several studies on chronic pain are being conducted by this team with support from National Institutes of Heath (NIH) and several pharmaceutical companies.

About Integrated Tissue Dynamics (INTIDYN)

To facilitate these collaborations, Dr. Rice and Dr. Albrecht, recently founded a new biotechnology company, Integrated Tissue Dynamics, LLC, also known as Intidyn ( Intidyn provides flexible and scalable research capabilities on behalf of pharmaceutical companies to detect chemical and structural changes in the skin that may cause the chronic numbness, pain and itch associated with a wide variety of afflictions such as diabetes, shingles, complex regional pain syndrome, carpal tunnel syndrome, sciatica, fibromyalgia, psoriasis, chemotherapy and even the unintended side effects caused by many drugs. Such afflictions and the associated neurological problems respond poorly to existing treatments. The preclinical and clinical research conducted by AMC and Intidyn facilitates biomarker identification and the evaluation of potential therapeutic strategies to prevent or treat these naturally-occurring afflictions and drug-induced side effects that harm the skin and nerves.

"By looking carefully at genomics and the structural and chemical differences between normal and diseased skin, we can better determine if a treatment is working or if it's even targeting the right problem," said Dr. Rice. "For example, in cases of 'unexplained' pain that's unresponsive to conventional treatment, it's important to know if nerve receptors in the vascular and sweat gland tissue are involved, and if so, whether a given treatment is targeting those nerves. We can also see if a pain treatment is damaging vascular tissue, for example, and make inferences about what the impact of that damage might mean clinically."

Most recently, Intidyn has partnered with neurologists and fellow co-authors, Drs. Argoff and Wymer to study a mysterious condition called fibromyalgia. They suspect the unrelenting pain may be related to the sensory nerve endings on blood vessels deep in the skin.

About Albany Medical College

At Albany Medical College, one of the nation's oldest medical schools, basic research scientists work to facilitate discoveries that translate into medical innovations at patients' bedsides. NIH-funded scientists are conducting research in many exciting areas including infectious disease, biodefense, addiction, cancer, pain, and more. Albany Medical Center is northeastern New York's only academic health sciences center. It consists of Albany Medical College, Albany Medical Center Hospital and the Albany Medical Center Foundation, Inc. Additional information about Albany Medical Center can be found at

Bowsher D, Geoffrey Woods C, Nicholas AK, Carvalho OM, Haggett CE, Tedman B, Mackenzie JM, Crooks D, Mahmood N, Aidan Twomey J, Hann S, Jones D, Wymer JP, Albrecht PJ, Argoff CE, Rice FL. Absence of pain with hyperhidrosis: A new syndrome where vascular afferents may mediate cutaneous sensation. PAIN. 2009 Dec 15147(1-3):287-98.

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