Painful peripheral neuropathy

Opinion statement  

Painful diabetic mastopathy as a reason for mastectomy

A 34 year old woman with longstanding insulin-dependent diabetes mellitus experienced disabling bilateral breast pain and tenderness associated with the benign breast lesions of diabetic mastopathy. Diabetic mastopathy is typically associated with nontender lesions, however we present a case where disabling pain and tenderness lead to bilateral mastectomy, as requested by the patient. This relieved the patient of her symptoms.     

Peripheral neuropathy in diabetic monkeys

Peripheral neuropathy is a significant complication of human diabetes and a source of morbidity. Appropriate experimental models may aid in understanding its pathogenesis and in developing therapeutic strategies. We sought to determine whether spontaneously diabetic obese adult monkeys developed peripheral neuropathy and whether it occurred early or late in relation to the onset of hyperglycemia. We studied nerve conduction in both motor (peroneal, median, and ulnar) and sensory (median and ulnar) nerves in 13 adult male rhesus monkeys, 4 overtly diabetic and 9 nondiabetic (mean age 21 +/- 2 and 16 +/- 2 yr, respectively, NS; mean fasting plasma glucose 14.5 +/- 3.4 and 4.4 +/- 0.6 mM, P = .001). The diabetic animals had significantly reduced motor conduction velocities and prolonged F-wave latencies. Motor-evoked amplitudes did not differ. In the diabetic monkeys, nerve conduction times were increased in motor fibers, which could be identified as early as 2 yr after the onset of hyperglycemia. These abnormalities are similar to those seen in humans and suggest further study of these animals as a primate model of human diabetic neuropathy.     

糖尿病性周围神经病变与糖尿病足

糖尿病性周围神经病变是引起糖尿病足最重要的原因之一.糖尿病患者肢体局部血供及代谢变化可导致神经节段性脱髓鞘、许旺细胞丢失以及不同程度的轴突变性,使肢体感觉、运动等重要功能丧失,加之物理或机械性刺激等启动因素,最终导致下肢感染、溃疡形成和(或)深部组织破坏.随着近年患者人数不断升高,糖尿病足发病神经机制研究逐渐成为热点....     

Cutaneous thermal sensitivity in diabetic neuropathy

BACKGROUND: The goal of this investigation was to determine if cutaneous thermal sensitivity could be used as a discriminator of peripheral neuropathy in diabetic subjects who were sensate to the Semmes-Weinstein 5.07 monofilament. METHODS: Sixty adult subjects were separated into two groups. The control group (A) was composed of 30 young healthy individuals without a history of diabetes. The focus group (B) was composed of 26 individuals with adult onset diabetes and four with juvenile onset. All of the subjects underwent thermal sensitivity testing in peripheral nerve root dermatomes of their hands and feet. Testing was performed with custom devices fabricated from materials with different thermal conduction capacities (copper, steel, glass, and plastic). Similar tests were performed with glass tubes containing heated or cooled water to develop a range of thermal sensitivity for the subjects. RESULTS: There was a strong relationship between cold perception and stimulation with the copper probe in dermatomes of the radial nerve of the upper limb and the superficial peroneal dermatome of the lower limb. CONCLUSIONS: Thermal sensitivity to copper and cold stimulation may be more discriminative and have a higher threshold than sensitivity to the Semmes-Weinstein monofilament. This simple method may have a role in the early detection of peripheral neuropathy in adult-onset diabetes mellitus.     

Renal transplantation and diabetic autonomic neuropathy

This report describes six episodes of cardiovascular collapse in the perioperative period of a young diabetic woman undergoing general anaesthesia for renal transplantation and a similar episode after a second anaesthetic. She was subsequently found to have an autonomic neuropathy. Recommendations for the management of similar patients are made.     

糖尿病周围神经病变在糖尿病骨病中的发病机制研究进展

糖尿病骨病是指糖尿病患者出现骨质减少、关节病变、骨皮质变薄、骨骼脆性增加甚至骨折的一种全身性、代谢性骨病,是糖尿病的重要并发症之一。随着糖尿病患者生活质量的提高以及病程的延长,患者的肌肉骨骼病变发生率在逐年提高,严重者可导致残疾或死亡。其发病机制目前尚未完全阐明,近年来,随着对糖尿病骨病的深入研究,发现糖尿病周围神经病变在骨骼疾病的发病和进展中起着重要作用。本文就糖尿病骨病、神经病变之间的关系加以综述,旨在探索神经病变导致骨代谢失调、骨密度下降、骨折风险的可能机制,为糖尿病骨病的诊断、预防、治疗提供新思路。     

Painful neuropathy alters the effect of gabapentin on sensory neuron excitability in rats

BACKGROUND: Pain following peripheral nerve injury is associated with increased excitability of sensory neurons. Gabapentin (GBP), a novel anticonvulsant with an uncertain mechanism of action, is an effective treatment for neuropathic pain. We therefore investigated the effect of GBP on dorsal root ganglion (DRG) neurons from normal rats and those with painful peripheral nerve injury. METHODS: Dorsal root ganglions were excised from rats with neuropathic pain behaviour following chronic constriction injury (CCI) of the sciatic nerve, and from normal rats. Intercellular recordings were made from myelinated sensory neuron somata using a microelectrode technique from DRGs bathed in artificial CSF with or without GBP (100 microM). RESULTS: Compared with normal neurons, injury decreased the refractory interval (RI) for repeat action potential (AP) generation increased the number of APs during sustained depolarization, and shortened the after hyperpolarization following an AP. In normal neurons, GBP decreased the RI and increased the AP number during sustained depolarization. In an opposite fashion, the result of GBP application to injured neurons was a decreased number of APs during depolarization and no change in RI. In injured neurons only, GBP increased the time-to-peak for AP depolarization. CONCLUSIONS: Nerve injury by CCI is associated with increased sensory neuron excitability, associated with a decreased AHP. In normal peripheral sensory neurons, GBP has pro-excitatory effects, whereas GBP decreases excitability in injured neurons, possibly on the basis of altered sodium channel function.     

Fuzzy expert system for diagnosing diabetic neuropathy

AIM To design a fuzzy expert system to help detect and diagnose the severity of diabetic neuropathy. METHODS The research was completed in 2014 and consisted of two main phases. In the first phase, the diagnostic parameters were determined based on the literature review and by investigating specialists' perspectives(n= 8). In the second phase, 244 medical records related to the patients who were visited in an endocrinology and metabolism research centre during the first six months of 2014 and were primarily diagnosed with diabetic neuropathy, were used to test the sensitivity, specificity, and accuracy of the fuzzy expert system.RESULTS The final diagnostic parameters included the duration of diabetes, the score of a symptom examination based on the Michigan questionnaire, the score of a sign examination based on the Michigan questionnaire, the glycolysis haemoglobin level, fasting blood sugar, blood creatinine, and albuminuria. The output variable was the severity of diabetic neuropathy which was shown as a number between zero and 10, had been divided into four categories: absence of the disease,(the degree of severity) mild, moderate, and severe. The interface of the system was designed by ASP.Net(Active Server Pages Network Enabled Technology) and the system function was tested in terms of sensitivity(true positive rate)(89%), specificity(true negative rate)(98%), and accuracy(a proportion of true results, both positive and negative)(93%).CONCLUSION The system designed in this study can help specialistsand general practitioners to diagnose the disease more quickly to improve the quality of care for patients.     

Local sympathetic denervation in painful diabetic neuropathy

This study assessed whether painful diabetic neuropathy is associated with abnormal sympathetic nervous function in the affected limbs. Nine patients with diabetes (four men, five women; age 61 +/- 7 years) and painful peripheral neuropathy of the feet, but without evidence of generalized autonomic neuropathy, underwent intravenous infusion of tritiated norepinephrine (NE) and sampling of arterial and venous blood in both feet and in one arm to quantify the rate of entry of NE into the local venous plasma (NE spillover). In the same patients, positron emission tomography (PET) scanning after intravenous injection of the sympathoneural imaging agent 6-[(18)F]fluorodopamine was used to visualize sympathetic innervation and after intravenous [(13)N]ammonia to visualize local perfusion. The results were compared with those in the feet of normal volunteers and in an unaffected foot of patients with unilateral complex regional pain syndrome (CRPS). In addition, neurochemical results obtained in painful diabetic neuropathy were compared with those obtained in diabetic control patients with painless neuropathy and diabetic control patients without neuropathy. Local arteriovenous difference in plasma NE levels (DeltaNE(AV)) and NE spillover in the arms did not differ across the groups. However, DeltaNE(AV) in the feet was significantly less in the group with painful diabetic neuropathy than in the control groups. Also NE spillover in the feet tended to be lower in painful neuropathy. DeltaNE(AV) of diabetic control patients without neuropathy (n = 6) resembled values in the control groups without diabetes, whereas patients with painless diabetic neuropathy (n = 6) had evidence suggesting partial loss of sympathetic innervation. PET scanning revealed decreased flow-corrected 6-[(18)F]fluorodopamine-derived radioactivity in patients with painful diabetic neuropathy, compared with values in normal volunteers and patients with CRPS. The results provide neurochemical and neuroimaging evidence for regionally selective sympathetic denervation in the painful feet of patients with diabetic neuropathy.     

Direct insulin signaling of neurons reverses diabetic neuropathy

Diabetic polyneuropathy is the most common acquired diffuse disorder of the peripheral nervous system. It is generally assumed that insulin benefits human and experimental diabetic neuropathy indirectly by lowering glucose levels. Insulin also provides potent direct support of neurons and axons, and there is a possibility that abnormalities in direct insulin signaling on peripheral neurons relate to the development of this disorder. Here we report that direct neuronal (intrathecal) delivery of low doses of insulin (0.1-0.2 IU daily), insufficient to reduce glycemia or equimolar IGF-I but not intrathecal saline or subcutaneous insulin, improved and reversed slowing of motor and sensory conduction velocity in rats rendered diabetic using streptozotocin. Moreover, insulin and IGF-I similarly reversed atrophy in myelinated sensory axons in the sural nerve. That intrathecal insulin had the capability of signaling sensory neurons was confirmed by observing that fluorescein isothiocyanate-labeled insulin given intrathecally accessed and labeled individual lumbar dorsal root ganglion neurons. Moreover, we confirmed that such neurons express the insulin receptor, as previously suggested by Sugimoto et al. Finally, we sequestered intrathecal insulin in nondiabetic rats using an anti-insulin antibody. Conduction slowing and axonal atrophy resembling the changes in diabetes were generated by anti-insulin but not by an anti-rat albumin antibody infusion. Defective direct signaling of insulin on peripheral neurons through routes that include the cerebrospinal fluid may relate to the development of diabetic peripheral neuropathy.