scholarly journals Impaired sensory nerve function and axon morphology in mice with diabetic neuropathy

2011 ◽  
Vol 106 (2) ◽  
pp. 905-914 ◽  
Author(s):  
Richard C. Lennertz ◽  
Karen A. Medler ◽  
James L. Bain ◽  
Douglas E. Wright ◽  
Cheryl L. Stucky
Keyword(s):  
Diabetic Neuropathy ◽  
Nerve Fiber ◽  
Sensory Nerve ◽  
The United States ◽  
Sensory Nerves ◽  
Sensory Function ◽  
Diabetic Patients ◽  
Fiber Morphology ◽  
C Fibers ◽  
Aβ Fibers

Diabetes is the most prevalent metabolic disorder in the United States, and between 50% and 70% of diabetic patients suffer from diabetes-induced neuropathy. Yet our current knowledge of the functional changes in sensory nerves and their distal terminals caused by diabetes is limited. Here, we set out to investigate the functional and morphological consequences of diabetes on specific subtypes of cutaneous sensory nerves in mice. Diabetes was induced in C57Bl/6 mice by a single intraperitoneal injection of streptozotocin. After 6–8 wk, mice were characterized for behavioral sensitivity to mechanical and heat stimuli followed by analysis of sensory function using teased nerve fiber recordings and histological assessment of nerve fiber morphology. Diabetes produced severe functional impairment of C-fibers and rapidly adapting Aβ-fibers, leading to behavioral hyposensitivity to both mechanical and heat stimuli. Electron microscopy images showed that diabetic nerves have axoplasm with more concentrated organelles and frequent axon-myelin separations compared with control nerves. These changes were restricted to the distal nerve segments nearing their innervation territory. Furthermore, the relative proportion of Aβ-fibers was reduced in diabetic skin-nerve preparations compared with nondiabetic control mice. These data identify significant deficits in sensory nerve terminal function that are associated with distal fiber loss, morphological damage, and behavioral hyposensitivity in diabetic C57Bl/6 mice. These findings suggest that diabetes damages sensory nerves, leading to functional deficits in sensory signaling that underlie the loss of tactile acuity and pain sensation associated with insensate diabetic neuropathy.

TRPA1 in bradykinin-induced mechanical hypersensitivity of vagal C fibers in guinea pig esophagus

2009 ◽  
Vol 296 (2) ◽  
pp. G255-G265 ◽  
Author(s):  
Shaoyong Yu ◽  
Ann Ouyang
Keyword(s):  
Guinea Pig ◽  
Action Potentials ◽  
Transient Receptor Potential ◽  
Ex Vivo ◽  
Sensory Nerve ◽  
Sensory Nerves ◽  
Peripheral Sensitization ◽  
Nerve Terminals ◽  
Mechanical Hypersensitivity ◽  
C Fibers

Bradykinin (BK) activates sensory nerves and causes hyperalgesia. Transient receptor potential A1 (TRPA1) is expressed in sensory nerves and mediates cold, mechanical, and chemical nociception. TRPA1 can be activated by BK. TRPA1 knockout mice show impaired responses to BK and mechanical nociception. However, direct evidence from sensory nerve terminals is lacking. This study aims to determine the role of TRPA1 in BK-induced visceral mechanical hypersensitivity. Extracellular recordings of action potentials from vagal nodose and jugular neurons are performed in an ex vivo guinea pig esophageal-vagal preparation. Peak frequencies of action potentials of afferent nerves evoked by esophageal distension and chemical perfusion are recorded and compared. BK activates most nodose and all jugular C fibers. This activation is repeatable and associated with a significant increase in response to esophageal distension, which can be prevented by the B2 receptor antagonist WIN64338. TRPA1 agonist allyl isothiocyanate (AITC) activates most BK-positive nodose and jugular C fibers. This is associated with a transient loss of response to mechanical distensions and desensitization to a second AITC perfusion. Desensitization with AITC and pretreatment with TRPA1 inhibitor HC-030031 both inhibit BK-induced mechanical hypersensitivity but do not affect BK-evoked activation in nodose and jugular C fibers. In contrast, esophageal vagal afferent Aδ fibers do not respond to BK or AITC and fail to show mechanical hypersensitivity after BK perfusion. This provides the first evidence directly from visceral sensory afferent nerve terminals that TRPA1 mediates BK-induced mechanical hypersensitivity. This reveals a novel mechanism of visceral peripheral sensitization.

scholarly journals Role of Electro-Diagnostic Tests In Early Detection of Diabetic Neuropathy

1970 ◽  
Vol 24 (1) ◽  
pp. 34-44
Author(s):  
Zahed Ali ◽  
Maliha Hakim ◽  
Monirul Islam ◽  
Nirmalendu Bikash Bhowmik ◽  
Shamsun Nahar ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Action Potential ◽  
Median Nerve ◽  
Conduction Velocity ◽  
Nerve Conduction ◽  
Sensory Nerve ◽  
Diabetic Patients ◽  
Sensory Nerve Action Potential ◽  
Nerve Action ◽  
Sensory Nerve Action

Since the peripheral nerve has the ability to regenerate, therapeutic intervention at earlier stages expected to have a better result in the treatment of diabetic neuropathy. So early detection of diabetic neuropathy is one of the major goals in its management. Purpose: The purpose of present study is to evaluate the efficacy of the electrodiagnostic tests to detect diabetic neuropathy at an early stage (before development of the signs of neuropathy). Method: 30 diabetic patients with or without symptoms of diabetic neuropathy were included in the test group. Diabetic patients with signs of neuropathy and with other complications, like stroke, peripheral vascular diseases were excluded. Twenty six control subjects (non-diabetic with no family history of diabetes) were included. Both the groups were matched for age. To see the functional status of peripheral nerves motor nerve conduction velocity (NCV), compound muscle action potentials (CAMP) of median nerve were studied. Sensory nerve conduction velocities (NCV), and sensory nerve action potential (SNAP) of median and sural nerves were also measured. Results: Sensory nerve conduction velocity of sural nerve was significantly slowed (43.84±8.23 vs 48.23±5.03 m/sec, p < .05) in diabetic patients. Sural sensory nerve action potential has lower in amplitude (13.31±7.03 vs 14.24±4.714 mv, p<.3) in diabetic patients. Median sensory nerve conduction velocity did show difference (50.89+8.23 vs 57.17±6.67 m/s, p < .01) and median sensory nerve action potential has significantly lower in amplitude (3.86±1.016 vs 7.39±4.79, p < .001) in diabetic patients. No significant difference was found in median nerve motor conduction velocity between the two groups of subjects. Amplitude of compound muscle action potential of median nerve also shows no significant variations.Considering mean±SD value of conduction parameter as the cut off value, sural nerve sensory conduction velocity was found slowed in 8 diabetic subjects (26%). Sural nerve sensory action potential was of lower amplitude in 12 diabetic subjects (40%). Eleven diabetic subjects (36%) had lower amplitude for median sensory nerve action potential (SNAP). For compound muscle action potential (CAMP) and sensory nerve action potential (SNAP) half the mean value of control was the cut off point. Conclusion: The result suggests that in diabetic patients of Bangladesh with or without symptoms of neuropathy, abnormalities of nerve conduction parameters can be detected early by routine electrodiagnostic monitoring. Sensory nerve conduction parameters are affected more than motor ones. Amplitude abnormalities are slightly more common than conduction velocity or latency abnormalities for sensory studies. Lower extremity nerves were affected more. Sural median nerve has the highest abnormalities in diabetic patients with early neuropathy. DOI: http://dx.doi.org/10.3329/bjn.v24i1.3038 Bangladesh Journal of Neuroscience 2008; Vol. 24 (1) :34-44

scholarly journals Prenylated quinolinecarboxylic acid compound-18 prevents sensory nerve fiber outgrowth through inhibition of the interleukin-31 pathway

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246630
Author(s):  
Masato Ogura ◽  
Kumiko Endo ◽  
Toshiyuki Suzuki ◽  
Yoshimi Homma
Keyword(s):  
Neurite Outgrowth ◽  
Nerve Fiber ◽  
Sensory Nerve ◽  
Skin Lesions ◽  
Janus Kinase ◽  
Sensory Nerves ◽  
Fiber Density ◽  
Stat3 Phosphorylation ◽  
Sensory Nerve Fiber ◽  
Quinolinecarboxylic Acid

Interleukin-31 (IL-31) is involved in excessive development of cutaneous sensory nerves in atopic dermatitis (AD), leading to severe pruritus. We previously reported that PQA-18, a prenylated quinolinecarboxylic acid (PQA) derivative, is an immunosuppressant with inhibition of p21-activated kinase 2 (PAK2) and improves skin lesions in Nc/Nga mice as an AD model. In the present study, we investigate the effect of PQA-18 on sensory nerves in lesional skin. PQA-18 alleviates cutaneous nerve fiber density in the skin of Nc/Nga mice. PQA-18 also inhibits IL-31-induced sensory nerve fiber outgrowth in dorsal root ganglion cultures. Signaling analysis reveals that PQA-18 suppresses phosphorylation of PAK2, Janus kinase 2, and signal transducer and activator of transcription 3 (STAT3), activated by IL-31 receptor (IL-31R), resulting in inhibition of neurite outgrowth in Neuro2A cells. Gene silencing analysis for PAK2 confirms the requirement for STAT3 phosphorylation and neurite outgrowth elicited by IL-31R activation. LC/MS/MS analysis reveals that PQA-18 prevents the formation of PAK2 activation complexes induced by IL-31R activation. These results suggest that PQA-18 inhibits the IL-31 pathway through suppressing PAK2 activity, which suppresses sensory nerve outgrowth. PQA-18 may be a valuable lead for the development of a novel drug for pruritus of AD.

scholarly journals Plasma total homocysteine is not associated with peripheral neuropathy in a groups Bangladeshi type 2 diabetic subjects

2012 ◽  
Vol 11 (4) ◽  
pp. 335-342
Author(s):  
MM Rahman ◽  
Z Hassan ◽  
KB Biswas ◽  
NB Bhowmik ◽  
L Ali
Keyword(s):  
Diabetic Neuropathy ◽  
Nerve Conduction ◽  
Sensory Nerve ◽  
Plasma Homocysteine ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Conduction Velocities ◽  
Total Homocysteine ◽  
Type 2 Diabetic

Aims: The present study was undertaken to explore the relationship of plasma homocysteine in the pathogenesis of neuropathy in diabetic patients.Subjects and Methods: Forty two type 2 diabetic patients [22 with neuropathy (DN group) and 20 without neuropathy (DNN group)], age range between 35-70 years had relatively controlled glycemia and duration of diabetes 7-15 years, were studied. Motor and sensory nerve conduction velocities and action potential amplitudes of peripheral nerves were determined by following standard protocol. HbA1c was estimated by modified HPLC (BIO-RAD Variant, USA). Serum C-peptide was measured by enzyme linked immunosorbentassay (ELISA), plasma total homocysteine by Fluorescent Polarization Immunoassay (FPIA). Results: Age, BMI and blood pressure of the study subjects were. Duration of diabetes between DN and DNN groups was comparable. DN group had significantly higher fasting glucose levels (9.8±3.8, mmol/l) compared to the DNN group (6.9±1.8, p=0.004). This trend was also reflected in the HbA1c level: 8.7± 2.1 vs 7.2±1.6 in DN group and DNN group respectively (p=0.009). The two diabetic groups had relatively higher absolute C-peptide level compared to the controls (p=ns). DN and DNN groups had significantly higher plasma homocysteine level compared to the Controls. But between the two diabetic groups no significant difference was observed. Ulnar and peroneal motor nerve conduction velocities and compound muscle action potentials in the diabetic neuropathy group significantly lower compared to diabetic counterpart and the controls. Ulnar and sural sensory nerve conduction velocities and action potentials were significantly lower in the diabetic neuropathy group compared to the diabetic counterpart and the controls. Plasma homocysteine did not show any correlation with nerve conduction velocities  and action potential amplitudes.Conclusions: The data concluded that (i) Diabetic neuropathy may not  be related to hyperhomocysteinemia in type 2 diabetic patients of Bangladeshi origin; (ii) Hyperglycemia, even at milder level, is related to neuronal dysfunction in these subjects; and (ii) Hyperinsulinemia don't seem to be prerequisite for neuropathy in these subjects. DOI: http://dx.doi.org/10.3329/bjms.v11i4.12607 Bangladesh Journal of Medical Science Vol. 11 No. 04 Oct’12  

scholarly journals Challenges in Diabetic Micro-Complication Management: Focus on Diabetic Neuropathy

2021 ◽  
Vol 1 (3) ◽  
pp. 175-186
Author(s):  
Prawej Ansari ◽  
J.M.A. Hannan ◽  
Shofiul Azam ◽  
Md. Jakaria
Keyword(s):  
Diabetic Neuropathy ◽  
Current Knowledge ◽  
Microvascular Complications ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Underlying Mechanism ◽  
Sensory Function ◽  
Diabetic Patients ◽  
Type I ◽  
Substantial Morbidity

The progression of diabetes leads to macro and microvascular complications, including diabetic neuropathy, which is the most prevalent microvascular complication with diabetes. Clinical manifestations of diabetic neuropathy begin with the loss of distal sensory function, pain, and substantial morbidity. It has been evident that ~50% of diabetic patients develop neuropathy at a certain stage in their lifetime. Interestingly, two major subtypes (type I and II) of diabetes do not share the same epidemiology and pathophysiology of diabetic neuropathy; thus, their management or treatment strategies may vary from each other. The past few decades of research suggest that many etiological features, diagnosis, and management complexities depend on the type of diabetes. However, the underlying mechanism of neuropathy in type I and type II diabetes remains unclear. This review provides the current knowledge on successful assessment, management, and pharmacological biomarkers to explore the treatment and surpass current challenges in diabetic neuropathy.

scholarly journals Itch and Cough – Similar Role of Sensory Nerves in Their Pathogenesis

2020 ◽  
pp. S43-S54
Author(s):  
T. Pecova ◽  
I. Kocan ◽  
R. Vysehradsky ◽  
R. Pecova
Keyword(s):  
Sensory Nerve ◽  
Small Diameter ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Upper Respiratory Tract ◽  
C Fibers ◽  
Afferent Nerves ◽  
Sensory Fibers ◽  
Peripheral Sensory

Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all three of which are host actions trying to clear noxious stimuli. The pathomechanisms of these symptoms are not completely determined. The itch can originate from a variety of etiologies. Itch originates following the activation of peripheral sensory nerve endings following damage or exposure to inflammatory mediators. More than one sensory nerve subtype is thought to subserve pruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Aδ nerve fibers. There are a lot of mediators capable of stimulating these afferent nerves leading to itch. Cough and itch pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. The inflammation is involved in the development of chronic conditions of itch and cough. The aim of this review is to point out the role of sensory nerves in the pathogenesis of cough and itching. The common aspects of itch and cough could lead to new thoughts and perspectives in both fields.

scholarly journals Asymptomatic Neuropathy in Recently Diagnosed Diabetic Patients: Electrophysiological Evaluation

2014 ◽  
Vol 30 (1) ◽  
pp. 16-22
Author(s):  
Abu Saleh Md Badrul Hasan ◽  
Biplob Kumar Roy ◽  
Kazi Giasuddin Ahmed ◽  
Md Rafiqul Islam ◽  
AKM Anwaullah ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Median Nerve ◽  
Ulnar Nerve ◽  
Nerve Conduction ◽  
Motor Nerve ◽  
Sensory Nerves ◽  
Case Group ◽  
Diabetic Patients ◽  
Significant Difference ◽  
And Control

Aim & background: As significant electrophysiological changes are found in asymptomatic neuropathy in diabetes mellitus and electrophysiological studies of nerve conduction velocity are our most sensitive tools to quantify early abnormalities, therefore, we tried to find out status of asymptomatic peripheral nerve dysfunction in recently diagnosed diabetic patients in Bangladesh perspective. Method :This study was carried out at BSMMU and BIRDEM during November 2005 and April 2006. The study included 60 subjects, 30 recently diagnosed diabetic subjects (14 male, 16 female). None had neuropathic symptoms or signs. All cases were selected randomly diagnosed by ADA criteria accepted by WHO. Thirty healthy controls with mean age comparable to that of diabetic subject were selected from the friends of the subjects and patients attending neurology outdoor of BSMMU. Result:Findings (mean±SD) were (case and control, respectively): Tibial nerve, DML 4.05±0.81 and 3.84±0.70 msec (P>0.10), CMAP 16.90±5.14 and 19.49±4.73 mV (P<0.05), MCV 45.43±4.55 and 48.24±4.72 m/ s (P<0.05), and F latency 45.09±12.43 and 42.50±8.93 msec (P>0.10); peroneal nerve, DML 4.12±1.10 and 4.03±0.67 msec (P>0.50), CMAP 5.80±2.89 and 6.97±1.79 mV (P>0.05), MCV 43.10±8.89 and 48.27±3.56 m/s (P<0.01), and F latency 50.27±10.81 and 41.32±3.05 msec (P<0.001); median nerve, DML 3.57±0.46 and 3.55±0.52 msec (P>0.50), CMAP 16.33±4.24 and 17.84±3.73 mV (P>0.10) and MCV 55.16±5.33 and 57.70±4.33 m/s (P<0.05), and F latency 25.08±5.28 and 24.39±4.83 msec (P>0.50); and ulnar nerve DML 2.57±0.33 an 3.17±0.61 msec (P<0.001), CMAP 14.65±3.32 and 17.29±6.83 mV (P>0.05), MCV 55.74±5.00 and 58.50±5.13 m/s (P<0.05), F latency 25.09±5.35 and 25.82±3.33 msec (P>0.50); sural nerve, DSL 2.46±0.68 and 3.12±0.45 msec (P<0.001), SNAP 19.44±10.25 and 25.32±7.88 ìV (P<0.05), SCV 49.95±10.22 and 52.46±3.96 m/s (P>0.10); median nerve, DSL 2.52±0.39 and 2.77±0.49 msec (P<0.05), SNAP 30.23±12.79 and 31.69±11.02 ìV (P>0.50), and SCV 56.90±6.77 and 57.41±5.85 m/s (P>0.50); and ulnar nerve, DSL 2.03±0.39 and 2.48±0.49 msec (P<0.001), SNAP 29.30±14.36 and 30.72±10.76 ìV (P>0.50), and SCV 60.96±8.38 and 57.93±7.15 m/s (P>0.10). Mean (±SD) HbA1c was significantly high (P<0.001) in case group (7.10±0.80%) compared to control (5.51±0.65%). Mean (±SD) SGPT showed no significant difference between case (36.10±13.02 u/L) and control (36.20±7.94 u/L). Similarly, mean (±SD) total cholesterol also showed no significant difference between case (201.57±37.56 mg/dl) and control (191.00±17.17 mg/dl). Conclusion: Motor nerve conduction parameters are affected more than sensory nerves and F-wave latencies are more frequently and early involved in these subjects. Abnormalities on nerve conduction was started in the feet rather than the hands.Clinical spectrum of diabetic neuropathy is variable and may be asymptomatic, but once established as polyneuropathy, it is irreversible and may finally be disabling. Early detection of diabetic neuropathy is one of the major goals in the management of diabetes since timely intervention may substantially reduce mortality and morbidity. Bangladesh Journal of Neuroscience 2014; Vol. 30 (1): 16-22

Mast cell-nerve fiber interaction: Ultrastructural studies

1990 ◽  
Vol 48 (3) ◽  
pp. 428-429
Author(s):  
E.Y. Chi ◽  
M.L. Su ◽  
Y.T. Tien ◽  
W.R. Henderson
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Substance P ◽  
Nerve Fiber ◽  
Sensory Nerves ◽  
Ultrastructural Studies ◽  
Morphological Studies ◽  
Granulocyte Infiltration ◽  
Intracutaneous Injection ◽  
Recent Attention

Recent attention has been directed to the interaction of the nerve and immune systems. The neuropeptide substance P, a tachykinnin which is a neurotransmitter in the central and peripheral nervous systems produces tissue swelling, augemntation of intersitial fibrin deposition and leukocyte infiltration after intracutaneous injection. There is a direct correlation reported between the extent of mast cell degranulation at the sites of injection and the tissue swelling or granulocyte infiltration. It has previously been demonstrated that antidromic electrical stimulation of sensory nerves induces degranulation of cutaneous mast cells, cutaneous vasodilation and augmented vascular permeability. Morphological studies have documented a close anatiomical association between mast cells and nonmyelinated nerves, that contain substance P and other neuropeptides. However, the presence of mast cells within nerve fasicles has not been previously examined ultrastructurally. In this study, we examined ultrastructurally the distribution of mast cells in the nerve fiber bundles located in the muscular connective tissue of rat tongues (n=20).

Awareness of diabetic patients regarding diabetic neuropathy in Saudi Arabia

2020 ◽  
pp. 1715-1720
Author(s):  
Amnah Basharheel ◽  
Somayh Khawaji ◽  
Alaa Mawkili ◽  
Yahya Alddarb ◽  
Asmaa Moafa ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Diabetic Neuropathy ◽  
Diabetic Patients
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