Search

Background/purpose To investigate nerve excitability changes in patients with fibromyalgia and the correlation with clinical severity. Methods We enrolled 20 subjects with fibromyalgia and 22 sex and age-matched healthy subjects to receive nerve excitability test and nerve conduction study to evaluate the peripheral axonal function. Results In the fibromyalgia cohort, the sensory axonal excitability test revealed increased superexcitability (%) (P = 0.029) compared to healthy control. Correlational study showed a negative correlation between increased subexcitability (%) (r = −0.534, P = 0.022) with fibromyalgia impact questionnaire (FIQ) score. Computer modeling confirmed that the sensory axon excitability pattern we observed in fibromyalgia cohort was best explained by increased Barrett–Barrett conductance, which was thought to be attributed to paranodal fast K+ channel dysfunction. Conclusion The present study revealed that paranodal sensory K+ conductance was altered in patients with fibromyalgia. The altered conductance indicated dysfunction of paranodal fast K+ channels, which is known to be associated with the generation of pain.

Perioperative pain control for hip arthroscopy procedures represents a significant challenge for both surgeons and anesthetists. In light of the opioid crisis, greater emphasis has been placed on multimodal pain control techniques. There is considerable debate regarding regional nerve blockade for hip arthroscopy. Although regional anesthesia has a significant role in perioperative pain management strategies, many of the most common techniques present their own risks and limitations. In particular, the less desirable effects of postoperative weakness in the lower extremity and difficulty with ambulation are commonly produced with standard regional blockades. We present a technique for performing a targeted, sensory nerve block that can be done efficiently and safely in the immediate preoperative period. This block can potentially lower the intraoperative and postoperative opioid requirements without the risks of muscle blockade and falls from other regional anesthesia modalities., Technique Video Video 1 This video demonstrates the pericapsular nerve group (PENG) block done before surgery for regional anesthesia and postoperative pain control in a patient undergoing a right hip arthroscopy. The patient is in the supine position with the right hip exposed. The anesthetist is seated to the side of the patient, with the probe in his right hand the needle in his left. The block is performed with ultrasound guidance using a SonoSite X-Porte HFL50xp (15-6MHz) linear ultrasound probe. The ultrasound screen is placed on the opposite side of the patient for easy viewing. The video includes the labeled corresponding ultrasound video performed during the block.

Highlights • In Berrettinni anastomosis, frequently a sensory communicating branch from ulnar nerve supplies digit 3. • Despite anatomical evidence of ulnar communicating branch providing sensory supply to digit 2, there are no electrodiagnostic descriptions of the same. • Electrodiagnostic findings in a patient with median nerve laceration were suggestive of ulnar sensory innervation of digit 2. • Knowledge of existence of these communications and their electrodiagnostic features can prevent misdiagnosis and iatrogenic injuries., Introduction Berrettini Anastomosis is a common purely sensory anastomosis between ulnar and median nerves in palm. Here, via a communicating branch, ulnar nerve can provide sensory supply to digits 3 and 2.There have been electrodiagnostic (EDX) descriptions of the former. However, till date, to the best of our knowledge, there have been no EDX descriptions of the latter. Here, in our case report we would like to describe first instance of the same. Presentation of case During an assault with a knife a 25-year-old male sustained laceration injury of right median nerve and flexor tendons which were repaired surgically. During rehabilitation, a nerve conduction study (NCS) was performed which incidentally revealed that ulnar nerve was responsible for sensory innervation of digit 2. Discussion Until recently, it was generally believed that EDX of BA was not possible. However, recent studies on EDX features in BA, have recorded small sensory nerve action potentials (SNAP) from digit 3 on distal ulnar nerve stimulation. But there are no published reports where SNAP from digit 2 on ulnar nerve stimulation were studied, even though anatomical evidence of the same exists. In our patient, we incidentally recorded the same. Conclusion Although our patient had a complete laceration of median nerve, he did not have major sensory disturbances. NCS findings suggested sensory supply of digits 5, 4, 3 and 2 were by ulnar nerve. Without adequate knowledge of communicating branch crossovers in palm, there is a possibility that clinical findings can be misdiagnosed and NCS features can be misinterpreted. For surgeons, awareness of these communicating branches can prevent iatrogenic injuries during surgical interventions.

Highlights • Tendon areflexia may be observed in otherwise asymptomatic lower limbs, in patients with Multifocal Motor Neuropathy. • Sensory afferent pathways can be assessed electrophysiologically by recording T (tendon) and H (Hoffmann) waves. • Hypo-/areflexia may relate to Ia afferent impairment in Multifocal Motor Neuropathy., Objectives To report the clinical and electrophysiological findings in two patients with multifocal motor neuropathy (MMN) and bilateral absent patellar and Achilles tendon reflexes despite normal strength of quadriceps and calf muscles. Methods The medical history and clinical evaluation were completed by electrophysiological tests: sensory and motor nerve conduction studies, needle electromyography, motor-evoked potentials (MEPs) after transcranial magnetic stimulation, patellar T (tendon) responses, quadriceps and soleus H (Hoffman) reflex recordings. Results In the two patients, history, clinical evaluation, nerve conduction studies, favorable response to intravenous immunoglobulins, and positive anti-GM1 antibodies fulfilled the diagnosis of MMN. The lower limbs were asymptomatic, except for a unilateral weakness of foot dorsiflexion. The patellar and Achilles tendon reflexes disappeared during the course of the disease. The sensory nerve conduction studies were normal or minimally modified, M-wave and MEP/M amplitude ratio to the quadriceps were normal, patellar T (tendon) responses were virtually absent, and H-reflex to the quadriceps and soleus muscles were absent. Conclusions These observations, which show the interruption of the reflex afferent pathway, raise the question of Ia afferent involvement in the lower limbs of these two patients with MMN. Further investigations should determine the frequency and significance of these findings in this disorder.

The sural sensory nerve, which innervates the lower extremities, is a useful model for studying the structural and functional characteristics of peripheral sensory nerves. Its development and myelination extends across the early postnatal through to the juvenile stage. Myelination of the sural nerve depends on interactions between axons and Schwann cells and requires a variety of factors including hormones, neurotrophic factors, nerve impulses, and transcription factors. Maternal deprivation or malnutrition during early life reduces the thickness of myelin and decreases the area and amplitude of the compound action potential of the sural nerve. Importantly, the replacement of tactile or social stimuli during experimental maternal isolation in rats prevents such effects. Electrical stimulation or neurotrophic factors favor the remyelination and regeneration of nerves damaged by crushing or neuropathies derived from genetic, infectious, or metabolic diseases such as diabetes mellitus.

Cancer-induced bone pain (CIBP) is a refractory form of pain that has a high incidence in advanced tumors. Src protein tyrosine kinase is mainly composed of six domains, with two states of automatic inhibition and activation. The modular domain allows Src to conveniently regulate by and communicate with a variety of proteins, directly or indirectly participate in each step of the CIBP process. Src is beneficial to the growth and proliferation of tumor cells, and it can promote the metastases of primary tumors to bone. In the microenvironment of bone metastasis, it mainly mediates bone resorption, activates related peripheral receptors to participate in the formation of pain signals, and may promote the generation of pathological sensory nerve fibers. In the process of pain signal transmission, it mainly mediates NMDAR and central glial cells to regulate pain signal intensity and central sensitization, but it is not limited to these two aspects. Both basic experimentation and clinical research have shown encouraging potential, providing new ideas and inspiration for the prevention and treatment of CIBP.

Highlights • Sural-sparing pattern is an electrodiagnostic footprint of Guillain-Barré Syndrome. • Sural-sparing pattern helps in diagnosis of GBS, including regional subtypes. • It is likely due to predilection of upper limb nerves for subclinical entrapment., Objective We present an exemplar patient, illustrating utility of the sural-sparing pattern in diagnosis of Guillain-Barré Syndrome (GBS). We then present data that sheds light on the pathophysiology of sural-sparing. Method and results We describe a case of complex ophthalmoplegia that exemplifies the challenge of diagnosing regional subtypes of Guillain-Barré Syndrome, and the value of scrutinizing sensory nerve action potentials for the sural-sparing pattern. We also demonstrate, in a series of GBS patients, how serial nerve conduction studies can reveal “covert” sural-sparing in patients without sural-sparing on the initial study. Finally, by studying the median and radial sensory nerve action potentials at digit I in GBS patients, we demonstrate that the likely pathology of sural-sparing is related to the predilection of median nerve for subclinical entrapment; where the blood-nerve barrier is deficient and therefore more exposed to the immunopathology of GBS. Conclusion Incorporating sural-sparing would improve the specificity of GBS electrodiagnosis; especially in difficult to diagnose regional subtypes of GBS.

Mechanosensory transduction (MST) in proprioceptors, and other low threshold mechanosensory nerve terminals (LTMT), has been debated intensely for decades. MST in muscle spindles produces a receptor potential that encodes stimulus speed and duration, is predominantly due to Na+, a little Ca2+, plus some transient, non-mechanically-gated K+ ion fluxes. The abundant, multiple Na+-selective DEG/ENaC channel isoforms present in all LTMTs seemed obvious Na+ sources, perhaps supplemented with Ca2+-selective TRPs, and Ca2+-activated K+ channels. However, genetic deletions of even multiple DEG/ENaC genes produces only mild functional perturbation. Conversely, deleting the more recently discovered Piezo2 mechanosensory protein profoundly impairs LTMT responses, including in muscle spindles. Yet its transient opening, non-Na+-selectivity and its pharmacology do not reflect known receptor potential and response properties. A Ca2+-dependent recycling vesicle pool that we have shown is essential for mechanosensitivity, plus other recent DEG/ENaC discoveries, may reconcile these conflicting observations. We propose the abundance of axolemmal MST complexes, comprising untested DEG/ENaC combinations, is controlled by Piezo2-gated Ca2+ influx that regulates their vesicular insertion and retrieval.

SUMMARY The flat bones of the skull are densely innervated during development, but little is known regarding their role during repair. We describe a neurotrophic mechanism that directs sensory nerve transit in the mouse calvaria. Patent cranial suture mesenchyme represents an NGF (nerve growth factor)-rich domain, in which sensory nerves transit. Experimental calvarial injury upregulates Ngf in an IL-1β/TNF-α-rich defect niche, with consequent axonal ingrowth. In calvarial osteoblasts, IL-1β and TNF-α stimulate Ngf and downstream NF-κB signaling. Locoregional deletion of Ngf delays defect site re-innervation and blunted repair. Genetic disruption of Ngf among LysM-expressing macrophages phenocopies these observations, whereas conditional knockout of Ngf among Pdgfra-expressing cells does not. Finally, inhibition of TrkA catalytic activity similarly delays re-innervation and repair. These results demonstrate an essential role of NGF-TrkA signaling in bone healing and implicate macrophage-derived NGF-induced ingrowth of skeletal sensory nerves as an important mediator of this repair., In Brief Meyers et al. describe the role of skeletal sensory nerves in cranial bone repair. The authors demonstrate several necessary aspects of membranous bone healing, including influx of nerve growth factor (NGF)-expressing macrophages after injury, followed by skeletal sensory nerve ingrowth to positively regulate bone repair., Graphical Abstract

Publisher Summary This chapter describes clinical neurophysiological tests of functional integrity of the sacral neuromuscular system used for diagnostic purposes. The functions involving the genitourinary and anorectal systems are uniquely controlled by the complex interaction of the vegetative and the somatic nervous system. Insofar as it is the sacral parasympathetic and somatic systems that constitute the most important peripheral nervous structures controlling these functions, they may also be referred to as sacral functions. The lower urinary tract (LUT) is innervated by three sets of peripheral nerves. The pelvic parasympathetic nerves arise at the sacral level of the spinal cord. The sympathetic nerves arise from the upper lumbar segments and inhibit the bladder body, modulate transmission in bladder parasympathetic ganglia, and excite the bladder base and urethra. Touch, pin-pricks, and hot and cold stimuli can be perceived in the anal canal to a level of up to 15 mm above the anal valves. The epithelium in the area from about 10–15 mm above the valves has a rich sensory nerve supply made up of both free and organized nerve endings.

The nervous system consists of four kinds of nerves: the somatic sensory nerve from receptor around the skeletal muscle (e.g., receptor in the skin), the somatic motor nerve to the skeletal muscle (voluntary muscle), the visceral sensory nerve from the receptor around the smooth or cardiac muscle (e.g., receptor in the gastrointestinal tract), and the visceral motor nerve (autonomic nerve) to the smooth or cardiac muscle (involuntary muscle). This chapter explores two pathways of the somatic sensory nerve (spinothalamic tract and medial lemniscus pathway), one pathway of the somatic motor nerve (corticospinal tract). Additional content is two components of the visceral motor nerve (sympathetic and parasympathetic nerves). Comprehension of the pathways is enhanced by practice with stained slices of the brainstem and spinal cord (or their photos).

Highlights • Detecting signs of neuropathy helps therapeutic decisions in familial amyloidosis. • Psychophysical thermal testing may be the only test showing damage in small fibers. • Quantitative signs of improvement may remain a few years after liver transplantation., Introduction Small fiber polyneuropathy (SFP) is a common heralding clinical manifestation of damage to the nervous system in patients with familial amyloidosis. The diagnosis of SFP is a significant factor in the decision to treat a previously asymptomatic gene carrier, as treatment would prevent irreversible nerve damage. This requires detection of the earliest but unequivocal signs of peripheral nerve involvement. Case report We present the case of a young female who was diagnosed of SFP, supported by data from quantitative sensory testing. She had preserved sensory nerve action potentials in the distalmost nerves of her feet and recordable nociceptive evoked potentials. She was successfully transplanted the liver from a previously healthy donor, and recovered fully of her symptoms and signs. Improvement was documented with repeated psychophysical and electrodiagnostic testing in the course of 4 years after transplantation. Significance This case illustrates the utility of psychophysical testing to support the diagnosis of SFP.

Atopic dermatitis (AD) displays different clinical symptoms, progress, and response to treatment during early infancy and after childhood. After the childhood period, itch appears first, followed by formation of well-circumscribed plaque or polymorphous dermatoses at the same site. When accompanied with dermatitis and dry skin, treatment of skin lesions should be prioritized. When itch appears first, disease history, such as causes and time of appearance of itch should be obtained by history taking. In many cases, itch increases in the evening when the sympathetic nerve activity decreased. Treatment is provided considering that hypersensitivity to various external stimulations can cause itch. Heat and sweating are thought to especially exacerbate itch. Factors causing itch, such as cytokines and chemical messengers, also induce itch mainly by stimulating the nerve. Scratching further aggravates dermatitis. Skin hypersensibility, where other non-itch senses, such as pain and heat, are felt as itch, sometimes occurs in AD. Abnormal elongation of the sensory nerve into the epidermis, as well as sensitizing of the peripheral/central nerve, are possible causes of hypersensitivity, leading to itch. To control itch induced by environmental factors such as heat, treatment for dermatitis is given priority. In the background of itch exacerbated by sweating, attention should be given to the negative impact of sweat on skin homeostasis due to 1) leaving excess sweat on the skin, and 2) heat retention due to insufficient sweating. Excess sweat on the skin should be properly wiped off, and dermatitis should be controlled so that appropriate amount of sweat can be produced. Not only stimulation from the skin surface, but also visual and auditory stimulation can induce new itch. This “contagious itch” can be notably observed in patients with AD. This article reviews and introduces causes of aggravation of itch and information regarding how to cope with such causes.

While nerve conduction studies are an important part of the electrodiagnostic examination (EDX), the diagnosis of a radiculopathy rests mainly on the needle electrode examination (NEE) findings. Myotomal spontaneous activity and neurogenic motor unit potential (MUP) changes are the key abnormalities seen. To optimize the rate of identifying a radiculopathy, selection of appropriate muscles for the NEE is paramount. Myotomal charts derived from anatomic, radiographic, and EDX studies may help guide development of the NEE protocol for radiculopathy and increase the diagnostic yield. As recommended by a number of studies, the suggested minimum NEE protocol should consist of at least five proximal and distal limb muscles. NEE of paraspinal muscles should also be included routinely, but several limitations preclude reliance on isolated findings for establishing a diagnosis of radiculopathy. In addition to the NEE, the preservation of sensory nerve action potentials is also important in localizing the lesion to the nerve root. In some cases, they may be absent due to age or technical factors, confounding the diagnosis. Finally, various patterns of EDX findings may be seen in specific nerve root disorders that can help expedite diagnosis and clinical management.

The trigeminal sensory nerve fiber branches supply afferent information from the skin and mucous membranes of the face and head and the oral cavity regarding information on temperature, touch, and pain. Under normal conditions, the trigeminal nerve serves to provide important information from nerve fibers and tissues using specialized receptors sensitive for irritant and painful stimuli. The current scientific consensus indicates that nerve endings responsible for chemical and thermal sensitivity of the skin and mucous membranes are the same nerves responsible for nociception. This “chemesthetic sense” allows many vertebrates to detect chemical agonists that induce sensations such as touch, burning, stinging, tingling, or changes in temperature. Research has been under way for many years to determine how exposure of the oral and/or nasal cavity to compounds that elicit pungent or irritant sensations can produce these sensations. In addition, these chemicals can alter other sensory information such as taste and smell to affect the flavor of foods and beverages. We now know that these ‘chemesthetic molecules’ are agonists of molecular receptors, which exist on primary afferent nerve fibers that innervate the orofacial area. However, under pathophysiologic conditions, over- or underexpression or activity of these receptors may lead to painful orotrigeminal syndromes. Some of these individual receptors are discussed in detail, including transient receptor potential channels and acid sensing ion channels, among others.

The electrodiagnostic tests performed in a patient with suspected muscle disease should provide reliable answers to the addressed questions: (1) differentiate a myopathic disorder from a neuropathic one and (2) precise the nature and cause of the myopathy. Answer to the first question mainly requires needle electromyography (EMG) of 4–6 muscles. Recordings may include extraction and measurements of motor unit potentials (MUPs). Reduced MUP spike duration indicates a lack of active muscle fibers within the motor units, and is the most reliable sign of myopathy. Needle EMG will also guide toward the etiology of the myopathy through the topographical distribution (proximal, distal, etc.) of abnormal EMG tracings and the identification of electrical activity at rest, especially fibrillation and myotonic discharges which guide toward evolutive myopathies and myotonic syndromes, respectively. The study of sensory nerve conduction should involve two to three nerves in order to disclose the coexistence of a sensory neuropathy (particularly in mitochondrial myopathies). If the diagnosis remains uncertain, functional provocative tests should be performed: 3 Hz repetitive nerve stimulation to search for a myasthenic syndrome, repeated short exercise (combined with cooling if necessary) in the case of myotonic syndrome; long exercise test if periodic paralysis is suspected.

Nerve conduction studies (NCSs) are an essential tool in the evaluation of the peripheral nervous system. The sensory nerve action potential (SNAP) provides information on the sensory nerve axon and its pathway from the distal receptors in the skin to the dorsal root ganglia, while the compound muscle action potential (CMAP) is an assessment of the motor nerve fibers from their origins in the anterior horn cell to their termination along muscle fibers. Various parameters of the SNAP and CMAP waveforms are used to determine the number of functioning nerve fibers and the speed of conduction. Similarly, specific electrodiagnostic patterns involving SNAP and CMAP amplitudes, latencies and other measurements can help discern the underlying nerve pathophysiology as either axon loss or demyelinating in nature. Numerous technical and environmental factors can affect the NCS and should be recognized and corrected if possible. Finally, while basic NCSs are a noninvasive and low-risk procedure, safety issues for patients with implanted electrical devices should be considered.

The posterior femoral cutaneous nerve is a small sensory nerve that innervates the posterior thigh. This nerve can be blocked near the gluteal crease as a supplement to other blocks of the lower extremity.

Objective Metabolic challenges, such as a cold environment, stimulate sympathetic neural efferent activity to white adipose tissue (WAT) to drive lipolysis, thereby increasing the availability of free fatty acids as one source of fuel for brown adipose tissue (BAT) thermogenesis. WAT is also innervated by sensory nerve fibers that network to metabolic brain areas; moreover, activation of these afferents is reported to increase sympathetic nervous system outflow. However, the endogenous stimuli sufficient to drive WAT afferents during metabolic challenges as well as their functional relation to BAT thermogenesis remain unknown. Method We tested if local WAT lipolysis directly activates WAT afferent nerves, and then assessed whether this WAT sensory signal affected BAT thermogenesis in Siberian hamsters (Phodopus sungorus). Results 2-deoxyglucose, a sympathetic nervous system stimulant, caused β-adrenergic receptor dependent increases in inguinal WAT (IWAT) afferent neurophysiological activity. In addition, direct IWAT injections of the β3-AR agonist CL316,243 dose-dependently increased: 1) phosphorylation of IWAT hormone sensitive lipase, an indicator of SNS-stimulated lipolysis, 2) expression of the neuronal activation marker c-Fos in dorsal root ganglion neurons receiving sensory input from IWAT, and 3) IWAT afferent neurophysiological activity, an increase blocked by antilipolytic agent 3,5-dimethylpyrazole. Finally, we demonstrated that IWAT afferent activation by lipolysis triggers interscapular BAT thermogenesis through a neural link between these two tissues. Conclusions These data suggest IWAT lipolysis activates local IWAT afferents triggering a neural circuit from WAT to BAT that acutely induces BAT thermogenesis., Highlights • Glucoprivation-induced lipolysis activates sensory nerves from white fat via β-adrenoreceptors. • Lipolysis sensation by local afferent nerves innervating white fat is proposed. • Lipid products of lipolysis are sufficient to activate sensory nerves from white fat. • Stimulation of white fat afferents by lipolysis increases brown fat temperature. • Findings illustrate functional neural connectivity between white and brown fat.

The somatosensory system is comprised of a variety of sensory receptors located in the skin, muscle tendons, and visceral organs that are innervated by myelinated and nonmyelinated axons of the peripheral nervous system. These peripheral sensory nerve fibers in turn communicate somatosensory information to spinal reflex pathways and to the ascending sensory tracts and integration centers of the central nervous system. The consequences of somatosensory toxicity may appear as abnormal paresthesia, tingling or burning sensations, or deficits in sensitivity to touch, vibration, pain, temperature, or position sense. The evaluation of somatosensory function may be accomplished through a variety of behavioral and neurophysiological procedures. Somatosensory toxicity may follow exposure to industrial chemicals, natural toxins, or therapeutic agents. For example, somatosensory neurotoxicity may be an important dose-limiting side effect for several chemotherapeutic drugs. This article provides an overview of the anatomy and physiology of the somatosensory system, behavioral and neurophysiological assessment techniques, and selected chemicals or chemical classes that can produce somatosensory toxicity.

The greater occipital nerve (GON) is the main sensory nerve to the occipital area and has been associated with various pain syndromes such as occipital neuralgia, cervicogenic headaches, and migraines. GON derives most of its fibers from the C2 dorsal root, and blocks of this peripheral nerve can provide substantial pain relief.

Chemosensitive afferent nerves expressing the capsaicin/TRPV1 receptor are not only involved in the transmission of nociceptive impulses toward the central nervous system, but also play pivotal roles in the initiation and modulation of vascular, inflammatory, and immune reactions in a variety of organs, including the skin. These sensory nerves exert their efferent/local regulatory functions primarily via the release of vasoactive neuropeptides such as calcitonin gene-related peptide and substance P from their terminals upon antidromic or orthodromic stimulation. The chemical changes induced in the neural microenvironment by tissue injury or inflammation may promote the release of proinflammatory sensory neuropeptides and lead to the augmentation of inflammatory response. In turn, the release of anti-inflammatory peptides from sensory nerves or from inflammatory cells may result in an inhibition of cutaneous vascular reactions. The available experimental evidence shows that capsaicin-sensitive sensory nerves are involved in the pathogenesis of certain skin diseases and maladies with cutaneous manifestations. The development of potent nonpeptide antagonists of sensory neuropeptides, the capsaicin/TRPV1 receptor and proteinase-activated receptors may offer new possibilities for the management of certain skin diseases, and the itch and pain associated with altered sensory nerve functions. Nerve growth factor (NGF) shares tyrosine kinase receptors with other neurotrophic factors. These receptors belong to the TNF receptor superfamily, and are present in the lymphoid cells and cells of the nervous system. In general, NGF stimulates immune responses with the exception of IgE production, which is inhibited. Nerve growth factor is stimulatory for mast cells and neutrophilic leukocytes. It locally exerts a proinflammatory effect. However, systematically applied NGF suppresses inflammation. During inflammatory reactions, lymphocyte-derived NGF protects the nervous system and other tissues from damage.

Introduction The clinical utility of nerve conduction study (NCS) for the distal medial branch of the superficial radial nerve (SRN) has not yet been clarified. Therefore, we investigated the clinical utility of NCS in patients with suspected SRN injury and compared the results with those in healthy control subjects. Methods Bilateral NCS of the medial branch of the SRN was performed in two patients with suspected injury of the medial branch of the SRN, and in 20 healthy control subjects. A surface recording electrode was placed at the medial side of the metacarpophalangeal joint of the thumb. The SRN was then stimulated at a location 12 cm proximal from the recording electrode. Results The mean sensory nerve action potential in the two patients was significantly lower than that of the controls (6.75 ± 0.92 vs. 23.8 ± 8.2 μV, P, Highlights • Nerve conduction was studied in the medial branch of the superficial radial nerve. • The subjects were two patients with suspected medial branch injury and 20 controls. • A recording electrode was placed at the medial side of the thumb. • Mean sensory nerve action potential was lower in patients than controls. • Nerve conduction study may be useful for diagnosing injury of the medial branch.

Charcot–Marie–Tooth neuropathies are frequent hereditary disorders of the nervous system and most cases remain without a molecular definition. Mutations in transcription factors have been previously associated to various types of this disease. Mice carrying a null mutation in Ebf2 transcription factor present peripheral nerve abnormalities. To get insight into Ebf2 function in peripheral nervous system, here we characterize the peripheral neuropathy affecting these mice. We first show that Ebf2 is largely expressed in peripheral nerve throughout postnatal development, its expression being not only restricted to non-myelin forming Schwann cells, but also involving myelin forming Schwann cells and the perineurium. As a consequence, the onset of myelination is delayed and Schwann cell differentiation markers are downregulated in Ebf2−/− mice. Later in development, myelin pathology appears less severe and characterized by isolated clusters of hypomyelinated fibers. However, we find defects in the nerve architecture, such as abnormalities of the nodal region and shorter internodal length. Furthermore, we demonstrate a significant decrease in axonal calibre, with a lack of large calibre axons, and a severe impairment of motor nerve conduction velocity and amplitude, whereas the sensory nerve parameters are less affected. Interestingly, a clinical case with peripheral motor neuropathy and clinical features similar to Ebf2−/− mice phenotype was associated with a deletion encompassing EBF2 human genomic locus. These findings demonstrate that Ebf2 is a new molecule implicated in peripheral nerve development and a potential candidate gene for peripheral nerve disorders.

TREK belongs to a subfamily of tandem pore domain K + channels, and consists of three subunits, TREK-1, TREK-2 and TRAAK. We examined the distribution of TREK-1, TREK-2 and TRAAK immunoreactive neurons in rat trigeminal sensory neurons. In the trigeminal ganglia, 31%, 43% and 60% of neurons were immunoreactive for TREK-1, TREK-2 and TRAAK, respectively. Mean sizes of TREK-1, TREK-2 and TRAAK immunoreactive trigeminal ganglion neurons were 447 ± 185, 445 ± 23 and 492 ± 12 mm 2 , respectively. Furthermore, TREK channels were colocalized with cationic TRP channels, TRPV1, TRPV2 and TRPM8. TREK-1 immunoreactive neurons were colocalized with TRPV1 (57%), TRPV2 (11%) and TRPM8 (33%). TREK-2-immunoreactive neurons were colocalized with TRPV1 (33%), TRPV2 (9%) and TRPM8 (19%). TRAAK immunoreactive neurons were colocalized with TRPV1 (47%), TRPV2 (10%) and TRPM8 (22%). The present results revealed that TREK-1, TREK-2 and TRAAK channels colocalized with thermosensitive TRP channels in some small trigeminal ganglion neurons.

Clinical studies suggest that impaired glucose tolerance (IGT) is associated with the development of neuropathy. The aim of the current study was to determine if neuropathy developed in the female Zucker Diabetic Fatty (ZDF) rat, an animal model of IGT and type 2 diabetes. The ZDF rat develops impaired glucose tolerance (IGT) when fed a control diet, and frank diabetes when fed a high fat diet. Following 10 weeks of hyperglycemia, sensory nerve action potentials (SNAP) and compound motor action potentials (CMAP) were reduced and sensory conduction velocities were slowed (distal > proximal) in the tail and hind limb in ZDF animals with IGT and frank diabetes (p

The chapter provides a detailed analysis of all of the key nerves of the lower limb. First, an overview will be provided about the general layout of the lower limb. This will enable the reader to gain a greater understanding of the main anatomical regions of the lower limb, and will also detail the embryological development of the lower limb. Then an overview of the main muscles in each region will be given along with an account of the nervous innervation of the major areas. Following the orientation of the lower limb anatomy, a detailed account of the main sensory nerve and motor and sensory nerves together will be given. The chapter will provide greater in-depth analysis of the cutaneous innervation examining the subcostal nerve, iliohypogastric nerve, ilioinguinal nerve, genitofemoral nerve, lateral cutaneous nerve of thigh, anterior cutaneous branches, cutaneous nerve of obturator nerve, posterior cutaneous nerve of thigh, saphenous nerve, superficial fibular nerve, deep fibular nerve, sural nerve, medial and lateral plantar nerves, and the cluneal nerve in various sections. Further, the motor and sensory nerves namely the superior gluteal nerve, inferior gluteal nerve, nerve to quadratus femoris, pudendal nerve, nerve to obturator internus, femoral nerve, sciatic nerve, obturator nerve, tibial nerve, common peroneal nerve, superficial peroneal nerve, and deep peroneal nerve will be examined in great detail. Clinical examination of these nerves in terms of how to approach the patient, and hints and tips on how to effectively examine each of these nerves will be discussed. In addition, to place it into clinical context, related pathologies and findings on clinical examination would be given, as relevant.

The trigeminal nerve is the largest sensory nerve in the body with representation of the majority of the sensory cortex. The sensory input from the trigeminal nerve underpins our identity, underpinning pleasure from socializing, eating, drinking, expression, and sexual interaction. When feedback is altered from this domain, particularly with elicited pain or discomfort, the patient’s life can be significantly changed for the worse. Unfortunately, many of these nerve injuries are permanent with lifelong consequences. Dental treatments related to nerve injuries include local anesthetic injections, wisdom tooth surgery, endodontic (root canal), and dental implants. Prevention of these nerve injuries is possible and this chapter aims to address the issues related to trigeminal nerve injuries caused by dental surgery with regard to: • Patient impact • Prevention • Assessment • Prognosis • Management

The glossopharyngeal nerve is a lower cranial nerve arising in the posterior cranial fossa. Although this nerve has multiple branches and functional components, it is often overlooked clinically. This ninth cranial nerve has a close relation to the vagus nerve both structurally and functionally. Although the glossopharyngeal nerve is primarily a sensory nerve, it also carries autonomic and somatic motor fibers. This chapter will review the detailed anatomy of the glossopharyngeal nerve.

This chapter introduces the vagus nerve, which contains both motor and sensory nerve fibers related to digestion, particularly the feeling of hunger and fullness and how Vagal Blocking Therapy (VBLOC) can be used in the treatment of obesity by suppressing the sensation of hunger and promoting the feeling of fullness using the Maestro (EnteroMedics) system.

Tendinopathy is a disorder increasing in prevalence and its treatment involves a huge effort from patient and therapist. Despite the extent of the disorder-targeted therapies has been limited due to lack of knowledge of the underlying pathophysiology. Repetitive loading and intrinsic risk factors, such as genetic variants of matrix proteins, neuronal dysregulation, and metabolic disorders contribute to the development of tendinopathy. Tendinosis is a fibrotic, failed healing response associated with pathological vessel and sensory nerve ingrowth. Aberrant sensory nerve sprouting may partly cause nociception and partly, by release of neuronal mediators contribute to causing the fibrosis. Eccentric exercise should be the basis of treatment, and can be combined with other modalities of treatment with less scientific evidence. Novel targeted therapies are emerging, for example, mini-operative procedures, but multicenter trials are needed to prove their clinical effectiveness.

The presence and effects of nociceptin (N/OFQ) and nocistatin (NST) in the central nervous system have been reasonably well described, but less data are available on their peripheral functions. Besides their presence in several peripheral organs (white blood cells, airway, liver, skin, vascular and intestinal smooth muscles, ovary, and testis), they have been found in the pregnant myometrium in both rat and human. The level of their precursor prepronociceptin is elevated in the preterm human myometrium as compared with full-term samples, whereas it gradually increases toward term in the pregnant rat uterus. Both N/OFQ and NST inhibit myometrial contractions, an effect which can be enhanced by naloxone and blocked by Ca2 +-dependent K+ channel (BKCa) inhibitors. Both compounds increase the myometrial cAMP level which may be responsible for the activation of this channel and subsequent intracellular hyperpolarization. NST releases calcitonin gene-related peptide from the sensory nerve ends, which explains its cAMP-elevating effect. In contrast with the nervous system, where they behave as antagonists, N/OFQ and NST are able to potentiate the uterine-relaxing effect of each other in both rat and human tissues. Further studies are required to clarify the roles of N/OFQ and NST in the regulation of the myometrial contractions and the perception of pain during delivery.

Schindler disease is an autosomal disorder resulting from the deficient activity of α-N-acetylgalactosaminidase (α-galactosidase B). The enzymatic defect leads to the cellular accumulation and increased urinary excretion of ­glycopeptides and oligosaccharides containing α-N-acetylgalactosaminyl residues. The disease is clinically heterogeneous, with three major subtypes. Patients with type I disease have early-onset neuroaxonal dystrophy with the characteristic neuropathology, whereas type II patients have angiokeratoma corporis diffusum, mild intellectual impairment, and sensory nerve involvement with neuroaxonal degeneration of peripheral nerves. Patients with type III disease have an intermediate and variable phenotype with manifestations ranging from seizures and moderate psychomotor retardation in infancy to a milder autistic presentation. All three subtypes have very low levels of α-N-acetylgalactosaminidase activity, have essentially the same patterns of glycoconjugate accumulation in the urine, and are inherited as autosomal recessive traits. Here, the clinical, pathologic, biochemical, and molecular findings in the severe infantile and milder later-onset forms of this metabolic disease are described.

The effects of 2,4,4-trimethyl-3-(15-hydroxypentadecyl)-2-cyclohexen-1-one (tCFA15) on diabetic hypoalgesia and neuropathic hyperalgesia were examined. Treatments of streptozotocin (STZ)-pretreated mice with tCFA15 (8 – 40 mg/kg, i.p.) for 7 days significantly reversed the depressed inflammatory nociceptive licking response in the formalin test. In addition, similar drug treatments and dosing in 7-day postoperative neuropathic pain model rats (prepared by the method of Bennett and Xie) yielded a similarly favorable outcome by significantly reversing decreased nociceptive thresholds in the paw pressure test. These results suggest that tCFA15 may have the potential to normalize sensory nerve abnormalities induced in experimental diabetes and nerve injury. Keywords:: diabetic hypoalgesia, long-chain fatty alcohol, chronic constriction injury

Small-diameter sensory nerves innervating the skin are responsive to noxious stimuli, and an injury to these nerves is presumably related to neuropathic pain. Injury-induced neuropathic pain in animals can be produced by laser irradiation, which usually requires concomitant use of photosensitive dyes, known as the photochemical approach. It is not clear whether laser irradiation alone can induce neuropathic pain. In addition, two issues are important to apply these approaches: the relationship between the extent of laser irradiation and the occurrence of neuropathic pain, and the susceptibility of small-diameter sensory nerves in the skin to laser-induced neuropathic pain. To address these issues, we designed a new model of focal neuropathy by applying a diode laser of 532 nm (100 mW) to the sciatic nerve and evaluated small-diameter nerves by quantifying skin innervation and large-diameter nerves by measuring amplitudes of the compound muscle action potential (CMAP). Immediately after laser irradiation, epineurial vessels were occluded due to the formation of thrombi, and the blood flow through these vessels was markedly reduced. On postoperative day (POD) 2, animals developed characteristic manifestations of neuropathic pain, including spontaneous pain behaviors, thermal hyperalgesia, and mechanical allodynia. These phenomena peaked during PODs 7-21, and lasted for 3-6 weeks. The neuropathology at the irradiated site of the sciatic nerve included a focal area of axonal degeneration surrounded by demyelination and endoneurial edema. The extent of damage to large-diameter motor and sensory nerves after laser irradiation was evaluated by nerve conduction studies. On the irradiated sides, amplitudes of the compound muscle action potentials and sensory nerve action potentials (SNAPs) were reduced to 65.0% (P < 0.0001) and 42.5% (P < 0.01) of those on the control sides, respectively. Motor innervation of the neuromuscular junctions (NMJs) on plantar muscles was examined by combined cholinesterase histochemistry and immunohistochemistry. The ratio of innervated NMJs on the operated sides decreased to 76.3% of that on the control side. Skin innervation in the territory of the irradiated sciatic nerves was evaluated by immunohistochemistry with neuronal markers. Among these markers, epidermal nerve densities for protein gene product (PGP) 9.5, calcitonin gene-related peptide (CGRP), and substance P (SP) were significantly lower on the irradiated sides than the control sides with a different degree of loss for each marker (42.1-53.1%, P < 0.05). Results suggest that laser-induced focal neuropathy provides a new system for studying neuropathic pain. With this approach, the extent of nerve injury can be quantified. Both small-diameter epidermal nerves and large-diameter sensory and motor nerves are susceptible to laser-induced injury of different degrees.

The mutilated-foot rat ( mf rat) is an autosomal recessive mutant with characteristic digit deformities in adult animals, and this phenotype mimics many aspects of human sensory neuropathy. The genetics of mf rats was recently elucidated. To understand whether the genotype is responsible for cutaneous denervation before clinically overt mutilation in adult mf rats, we investigated skin innervation in postnatal day 7 (P7) mf rats and compared the patterns with P7 wild-type rats. The mf rat carries a G→A mutation in the gene encoding the delta subunit of the cytosolic chaperonin-containing t-complex peptide-1 ( Cct4 ). In the footpad skin of P7 mf rats, there was a >90% loss of epidermal nerves (0.7–7.9% of P7 wild-type rats) as indicated by neuronal markers including protein gene product 9.5 (PGP 9.5), growth-associated protein 43 (GAP43), calcitonin gene-related peptide (CGRP), and substance P (SP). The epidermis of hairy skin in hind feet was completely denervated in mf rats as well. Compared with an approximately 80% reduction in the size of dermal nerve fascicles and a parallel loss of nerve fibers, the nearly complete absence of epidermal innervation suggests further sensory nerve degeneration at the level of nerve terminals in the epidermis. In contrast, the loss of epidermal nerves in the abdominal skin of mf rats was less extensive than that in the footpad skin of mf rats; CGRP (+) and SP (+) fibers were moderately reduced (28.3–56.4% of levels of wild-type rats) with normal amounts of PGP 9.5 (+) and GAP43 (+) nerves. Sympathetic innervation as assessed by tyrosine hydroxylase immunoreactivity was absent from the footpad and abdominal skin of mf rats. In conclusion, there is regional skin denervation with diffuse sympathetic denervation in P7 mf rats. These results suggest that the mutation in Cct4 underlies cutaneous nerve degeneration in mf rats.

We examined whether azelastine would inhibit itch-associated responses of mice to mosquito allergy. Repeated injections of mosquito salivary gland extract increased scratching and sensory nerve activity. Azelastine inhibited the increased scratching and nerve activity, while terfenadine was without effects. Dexamethasone did not affect the increased scratching. Azelastine suppressed high K(+)-induced increase in intracellular free Ca(2+) in primary cultures of mouse sensory neurons. Direct inhibition by azelastine of sensory neurons may be at least involved in the anti-pruritic effect of azelastine. Histamine, substance P, and leukotriene B(4) may not play a key role in the itching of mosquito allergy.

Here, we provide a detailed account of how to denervate white and brown adipose tissue (WAT and BAT) and how to measure sympathetic nervous system (SNS) activity to these and other tissues neurochemically. The brain controls many of the functions of WAT and BAT via the SNS innervation of the tissues, especially lipolysis and thermogenesis, respectively. There is no clearly demonstrated parasympathetic innervation of WAT or the major interscapular BAT (IBAT) depot. WAT and BAT communicate with the brain neurally via sensory nerves. We detail the surgical denervation (eliminating both innervations) of several WAT pads and IBAT. We also detail more selective chemical denervation of the SNS innervation via intra-WAT/IBAT 6-hydroxy-dopamine (a catecholaminergic neurotoxin) injections and selective chemical sensory denervation via intra-WAT/IBAT capsaicin (a sensory nerve neurotoxin) injections. Verifications of the denervations are provided (HPLC-EC detection for SNS, ELIA for calcitonin gene-related peptide (proven sensory nerve marker)). Finally, assessment of the SNS drive to WAT/BAT or other tissues is described using the alpha-methyl-para-tyrosine method combined with HPLC-EC, a direct neurochemical measure of SNS activity. These methods have proven useful for us and for other investigators interested in innervation of adipose tissues. The chemical denervation approach has been extended to nonadipose tissues as well.

The eighth cranial nerve is the vestibulocochlear nerve. Arising from the brainstem between the pons and medulla, it comprises two nerves responsible for different functions. The vestibular component deals with information related to balance, with the cochlear nerve relaying information related to hearing. Therefore, it is classified as a special sensory nerve. On exiting the brainstem, it then passes into the petrous temporal bone via the internal auditory meatus, very closely related to the facial nerve. Testing of the vestibulocochlear nerve involves assessing both components of it via hearing assessment and the Weber and Rinne tests before progressing onto more advanced formal testing. A variety of pathologies may affect the vestibulocochlear nerve and result in hearing and balance problems for the patient. If there is a pathology affecting the vestibulocochlear nerve where it enters the petrous temporal bone, it can press on the facial nerve resulting in problems with that nerve too.

Riot control agents (RCAs) cause disabling physiological effects when they come into contact with the eyes or skin, or when inhaled by unprotected individuals, by interacting with sensory nerve receptors in the skin and mucosal surfaces at the site of contamination, resulting in local pain and discomfort with associated reflexes. The Kratschmer reflex causes apnea, bradycardia, and a biphasic fall and rise in aortic blood pressure, which is mediated via the olfactory, trigeminal, and glossopharyngeal cranial nerves. This reflex has been demonstrated in both animals and humans following exposure to inhaled RCAs. The US military has developed a basic military classification of class indices for chemical and biological warfare agents. The class indices divides RCAs into incapacitating agents (fentanyl); tear agents – halogenated (CN and CS); tear agents – nonhalogenated (CR); tear agents in solvents (OC, capsaicin, and PAVA); and vomiting agents (DM). While the acute physiological impacts from the various agents within each of these classes are essentially the same, there are variations in the physical/chemical properties and decomposition products.

The ninth cranial nerve is the glossopharyngeal nerve. On emerging from the brainstem it passes through the cranial cavity to exit at the jugular foramen. It is primarily a sensory nerve but also contains motor and parasympathetic fibers. It supplies the posterior one-third of the tongue for taste and sensation, stylopharyngeus for its motor innervation, parasympathetic supply for the parotid gland, and receives sensory information from several neck structures as well as the ear. Clinically, testing for the integrity of the glossopharyngeal nerve is simple. By asking the patient to say “ahhh” and testing the gag reflex should suffice. Isolated ninth-nerve palsies are extremely rare, and they tend to occur when a pathology affects several cranial nerves found in close proximity like the facial, vagus, spinal accessory, and perhaps also the hypoglossal nerve.

Tarsal tunnel syndrome (TTS) causes pain and paresthesias in the foot and ankle and is due to entrapment of the tibial nerve in the fibro-osseous tarsal tunnel under the flexor retinaculum. The most helpful diagnostic criteria are a positive Tinel's sign at the ankle and objective sensory loss in the territory of any of the terminal branches of the posterior tibial nerve. The diagnosis of TTS is confirmed by the nerve conduction study: prolonged terminal latency in 44% of cases and abnormal mixed and sensory nerve conduction in 86% and 94% of cases, respectively. Better surgical outcome was noted in symptomatic cases due to ‘mass.’

The optic nerve is the second cranial nerve and is one of the more unusual cranial nerves as it develops from the diencephalon. It is a special sensory nerve responsible for vision. The information received from the external environment passes to the rods and cones on the retina, and then to bipolar cells, ganglion cells, and ultimately to the optic nerve. The nerve contains layers of meninges as it is viewed as a direct extension of the brain. Therefore, clinically an increase in intracranial pressure, for whatever reason, can be assessed using an ophthalmoscope. The optic nerve then passes through the optic canal, onward to the optic chiasma, and then to terminate in the occipital lobes. At the optic chiasma, some information crosses to the opposite side aiding binocular vision. A wide variety of tests can be performed to assess the function of the nerve.

Diabetic neuropathy is a major complication of diabetes that involves the sensory and autonomic nervous systems and leads to significant morbidity and impact on quality of life of patients. Mitochondrial stress has been proposed as a major mediator of insulin sensitivity in skeletal muscle in type 2 diabetes and a trigger of diabetic complications such as nephropathy and cardiomyopathy in humans and animal models. Recent studies in the peripheral nervous system in type 1 and type 2 diabetic animal models suggest a role for mitochondrial dysfunction in neurodegeneration in diabetes. This chapter focuses on the nature of sensory nerve dysfunction in diabetes and presents these findings in the context of diabetes-induced nerve degeneration mediated by alterations in mitochondrial physiology. Diabetes-induced dysfunction in calcium homeostasis is discussed and causative associations with suboptimal mitochondrial physiology are developed. Comparisons are made with mitochondrial-dependent dysfunction in muscle and cardiac tissue in diabetes. It is clear that across a range of complications of diabetes mitochondrial physiology is impaired; in general, a reduction in respiratory chain capability is apparent. Where appropriate, we provide clinical evidence for mitochondrial dysfunction in the pathogenesis of complications in patients with diabetes. This abnormal activity may predispose mitochondria to generate elevated reactive oxygen species (ROS), although experimental proof remains lacking, but more importantly will deleteriously alter the bioenergetic status of neurons.