Pathophysiology Of Diabetic Neuropathy Research Articles

Exploring the role of miRNA in diabetic neuropathy: from diagnostics to therapeutics.

Diabetic neuropathy (DN) is one of the major microvascular complications of diabetes mellitus affecting 50% of the diabetic population marred by various unmet clinical needs. There is a need to explore newer pathological mechanisms for designing futuristic regimens for the management of DN. There is a need for post-transcriptional regulation of gene expression by non-coding RNAs (ncRNAs) to finetune different cellular mechanisms with significant biological relevance. MicroRNAs (miRNAs) are a class of small ncRNAs (~ 20 to 24 nucleotide length) that are known to regulate the activity of ~ 50% protein-coding genes through repression of their target mRNAs. Differential expression of these miRNAs is associated with the pathophysiology of diabetic neuropathy via regulating various pathways such as neuronal hyperexcitability, inflammation, axonal growth, regeneration, and oxidative stress. Of note, the circulating and extracellular vesicular miRNAs serve as potential biomarkers underscoring their diagnostic potential. Recent pieces of evidence highlight the potential of miRNAs in modulating the initiation and progression of DN and the possibility of developing miRNAs as treatment options for DN. In this review, we have elaborated on the role of different miRNAs as potential biomarkers and emphasized their druggable aspects for promising future therapies for the clinical management of DN.

The emerging role of autophagy in the pathophysiology of diabetic neuropathy

The emerging role of autophagy in the pathophysiology of diabetic neuropathy

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

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.

Diabetic neuropathy: an insight on the transition from synthetic drugs to herbal therapies.

The global pandemic of prediabetes and diabetes has led to a severe corresponding complication of these disorders. Neuropathy is one of the most prevalent complication of diabetes is, affecting blood supply of the peripheral nervous system that may eventually results into loss of sensations, injuries, diabetic foot and death. The utmost identified risk of diabetic neuropathy is uncontrolled high blood glucose levels. However, aging, body mass index (BMI), oxidative stress, inflammation, increased HbA1c levels and blood pressure are among the other key factors involved in the upsurge of this disease. The so far treatment to deal with diabetic neuropathy is controlling metabolic glucose levels. Apart from this, drugs like reactive oxygen species (ROS) inhibitors, aldose reductase inhibitors, PKC inhibitors, Serotonin-norepinephrine reuptake inhibitors (SNRIs), anticonvulsants, N-methyl-D-aspartate receptor (NMDAR) antagonists, are the other prescribed medications. However, the related side-effects (hallucinations, drowsiness, memory deficits), cost, poor pharmacokinetics and drug resistance brought the trust of patients down and thus herbal renaissance is occurring all over the word as the people have shifted their intentions from synthetic drugs to herbal remedies. Medicinal plants have widely been utilized as herbal remedies against number of ailments in Indian medicinal history. Their bioactive components are very much potent to handle different chronic disorders and complications with lesser-known side effects. Therefore, the current article mainly concludes the etiology and pathophysiology of diabetic neuropathy. Furthermore, it also highlights the important roles of medicinal plants and their naturally occurring bioactive compounds in addressing this disease.

Mechanisms of Diabetic Neuropathies and Antioxidant Therapy

Background: Diabetic neuropathy is very common and affects half of patients with either type 1 or type 2 diabetes mellitus. It is the leading cause of diabetes-related hospital admissions and nontraumatic amputations. Currently, the keys to management are maintaining blood glucose concentration within the normal range and treatment of symptoms. Despite many studies of chronic pain associated with diabetic neuropathy, few improvements have been made.
 Main Finding: This is a review of the classification of diabetic neuropathy, molecular mechanisms, and treatment options focusing on antioxidants.
 Conclusion: As oxidative stress may play a significant role in the pathophysiology of diabetic neuropathy, the study of molecular mechanisms by which hyperglycemia induces oxidative stress is important. New targets for disease-modifying drugs could be elucidated.

Statins and Neuropathic Pain: A Narrative Review.

The frequently prescribed drug class of statins have pleiotropic effects and have been implicated in neuropathic pain syndromes. This narrative review examines studies of statin-induced neuropathic pain which to date have been conducted only in animal models. However, the pathophysiology of diabetic neuropathy in humans may shed some light on the etiology of neuropathic pain. Statins have exhibited a paradoxical effect in that statins appear to reduce neuropathic pain in animals but have been associated with neuropathic pain in humans. While there are certain postulated mechanisms offering elucidation as to how statins might be associated with neuropathic pain, there is, as the American Heart Association stated, to date no definitive association between statins and neuropathic pain. Statins are important drugs that reduce cardiovascular risk factors and should be prescribed to appropriate patients with these risk factors but some of this population is also at elevated risk for neuropathic pain from other causes.

P1-4-01. Evaluation of small fiber involvement using pain-related evoked potentials in patients with type 1 and type 2 diabetes

The pathophysiology of diabetic neuropathy presumably differs between type1 and type 2 diabetes mellitus (T1DM and T2DM), and neuropathic pain is more frequent in patients with T2DM than T1DM. To investigate difference in small fiber involvement, we studied painrelated evoked potentials (PREPs) using intraepidermal electrical stimulation (IES) selective to A-delta-fibers and C-fibers in patients with T1DM (n = 20) and T2DM (n = 20). IES was applied in the back of hand and foot, and PREPs were recorded from the Cz electrode referenced to the linked earlobes. We evaluated the thresholds, and PREP latencies and amplitudes. Nerve conduction studies were performed in the ipsilateral limbs. There were no significant differences in age and hemoglobin A1c levels between the groups, but disease duration was significantly longer in T1DM. In nerve conduction study, patients with T1DM showed significantly more severe large fiber dysfunction in the lower extremity, however less pain/paresthesia than T2DM patients. PREPs study showed no significant differences in all the parameters between T1DM and T2DM. Diabetic neuropathy in T1DM showed relatively mild small fiber involvement compared with large fiber dysfunction, and this characteristic pattern might be related to the difference in the pathophysiology or neuropathic symptoms.

Nrf2: a potential therapeutic target for diabetic neuropathy.

Different aspects involved in pathophysiology of diabetic neuropathy are related to inflammatory and apoptotic pathways. This article summarizes evidence that Nrf2 acts as a bridging link in various inflammatory and apoptotic pathways impacting progression of diabetic neuropathy. Nrf2 is involved in expression of various antioxidant proteins (such as detoxifying enzymes) via antioxidant response element (ARE) binding site. Under normal conditions, Nrf2 is inactive and remains in the cytosol. Hyperglycemia is a strong stimulus for oxidative stress and inflammation that downregulates the activity of Nrf2 through various neuroinflammatory pathways. Acute hyperglycemia increases the expression of Nrf2, but persistent hyperglycemia decreases its expression. This downregulation of Nrf2 causes various microvascular changes, which result in diabetic neuropathy. The key contribution of Nrf2 in progression of diabetic neuropathy has been summarized in the article. Despite involvement of Nrf2 in progression of diabetic neuropathy, targeting Nrf2 activators as a therapeutic potential will provide important new insights into the ways that influence treatment of diabetic neuropathy.

Diabetes mellitus influences the expression of NPY and VEGF in neurons of rat trigeminal ganglion

BackgroundDiabetes mellitus (DM) influences the trigeminal nerve function by changing the pain response and transduction of the orofacial sensory pathways. It affects the inflammatory response via neuropeptide Y (NPY) and vascular endothelial growth factor (VEGF), which could potentially have a relevant role in the pathophysiology of diabetic neuropathy. The aim was to investigate expression of VEGF and NPY in subpopulations of trigeminal ganglion (TG) neurons in rat models of early DM1 and DM2. MethodsDM1 model was induced by an intraperitoneal (i.p.) injection of streptozotocin (STZ) (55mg/kg). DM2 rats were fed with a high fat diet (HFD) for two weeks and then received 35mg/kg of STZ i.p. Two weeks and 2months after the STZ-diabetes induction, rats were sacrificed and TG was immunohistochemically analyzed for detection of VEGF and NPY expression, and also double immunofluorescence labeling with isolectin (IB4) was completed. ResultsAn increased percentage of NPY+ neurons was observed 2weeks after DM1 and 2months post DM2 induction. NPY immunoreactivity was restricted to IB4-negative small-diameter and IB4+ neurons. Two weeks post induction, DM1 rats showed an increased percentage of VEGF/IB4− large neurons and DM2 rats showed an increased percentage of VEGF/IB4+ neurons. Two months after DM induction, the DM1 group showed a reduced percentage of VEGF/IB4− small neurons. ConclusionThe observed changes may play a critical role in the modulation of nociceptor activity and plasticity of primary sensory trigeminal neurons. The results contribute to the understanding of the basic pathophysiology of trigeminal diabetic neuropathy.

Efficient Transdermal Delivery of Benfotiamine in an Animal Model

We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake. Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-epithelial layers. In this proof of concept study in guinea pigs, we found that a single topical application of either a solubilized form of benfotiamine (15 mg) or a microcrystalline suspension form (25 mg) resulted in considerable increases of the dephosphorylated benfotiamine (S-benzoylthiamine) in the skin tissue as well as in significant increases in the thiamine and thiamine phosphate pools compared to control animals. The presence of a ~8000x increase in thiamine and increases in its phosphorylated derivatives in the epidermis and dermis tissue of the test animals gives a strong indication that the topical treatment with benfotiamine works very well for the desired outcome of producing an intracellular increase of the activating cofactor pool for transketolase enzyme, which is implicated in the pathophysiology of diabetic neuropathy.

THE BENEFICIAL EFFECT OF ASIATICOSIDE ON EXPERIMENTAL NEUROPATHY IN DIABETIC RATS

Though diabetic neuropathy produces high impact on quality of life, annual cost and morbidities, the therapeutic efficacy is still not in a satisfaction level. Based on the crucial role of oxidative stre ss on the pathophysiology of diabetic neuropathy and the impr ovement of this condition induced by antioxidant, w e hypothesized that asiaticoside, a substance possess ing antioxidant activity, could provide beneficial effect. Therefore, we aimed to determine the effect of asia ticoside on the recovery of sciatic nerve in experi mental neuropathy in diabetic rats. Young adult male Wist ar rats at 8 weeks old, weighing approximate 180-22 0 g, were orally given asiaticoside at doses of 0.1 and 1 mg kg -1 BW at a period of 5 days before and 3 weeks after sciatic nerve crush injury. Motor and sensory functions were observed every 3 day until the end of the experiment by using Deminacelli method, walking pattern, muscle power and foot reflex withdrawal test, respectively. Our results showed that both doses of asiaticoside could significantly reverse the enhan ced withdrawal threshold intensity elicited by electric al stimuli. However, the rats received asiaticoside at dose of 1 mg kg -1 BW provided optimum benefit. However, no other significant effects were observed. Asiaticoside administration in an experimental mode l of neuropathy in diabetic rats mitigates some functional impairment of sciatic nerve. Though our data show only the beneficial effect of asiaticosid e on the foot withdrawal reflex, it is very much importa nt because it involve the protective mechanism agai nst painful stimuli. Therefore, it is worth for further investigation in order to confirm the improvement of sensori-motor functions and determined the both the rapeutic window and possible underlying mechanism.

Novel systems for in vivo monitoring and microenvironmental investigations of diabetic neuropathy in a murine model

Peripheral neuropathy is a devastating complication of diabetes conferring vast morbidity and mortality. Despite prolonged efforts to elucidate the mechanisms underlying diabetic related neuropathic phenomena and develop effective therapies, current treatment is for the most part glycemic control and symptomatic care. This is partially due to the intricate pathophysiology of diabetic neuropathy and the scarcity of valid experimental models. The aim of the study was to establish novel systems enabling monitoring and dissection of significant processes in the development of diabetic neuropathy. In a non-invasive in vivo model, two-photon microscopy is applied to evaluate mechanoreceptors (Meissner corpuscles) within an intact footpad of transgenic mice expressing a fluorescent neuronal tracer. By applying this advanced technology, which couples potent tissue penetration with superb resolution, we documented qualitative and quantitative diabetes-specific alterations in these sensory structures. Detection of such changes previously required laborious invasive histopathological techniques. In parallel, we present an ex vivo system that mimics the native microenvironment of the nerve ending via a unique co-culture of primary sensory neurons and thin skin slices. In conjunction with innovative high-throughput digital axonal measurements and computerized quantification tools, this method enables an unbiased exploration of neuronal autonomous and non-autonomous malfunctions. Using this setup we demonstrate that while the diabetic nerve retains a near-normal growth and regeneration capacities, the diabetic skin exhibits a decreased ability to support axonal outgrowth. Thus, an early target organ failure rather than intrinsic neuronal failure may initiate the neuropathy. Overall, the illustrated experimental platforms may greatly facilitate the holistic investigation of diabetic neuropathy.

Suppression of NF-κB and NF-κB regulated oxidative stress and neuroinflammation by BAY 11-7082 (IκB phosphorylation inhibitor) in experimental diabetic neuropathy

Inflammation is an emerging patho-mechanism of diabetes and its complications. NF-κB pathway is one of the central machinery initiating and propagating inflammatory responses. The present study envisaged the involvement of NF-κB inflammatory cascade in the pathophysiology of diabetic neuropathy using BAY 11-7082, an IκB phosphorylation inhibitor. Streptozotocin was used to induce diabetes in Sprauge Dawley rats. BAY 11-7082 (1 & 3 mg/kg) was administered to diabetic rats for 14 days starting from the end of six weeks post diabetic induction. Diabetic rats developed deficits in nerve functions and altered nociceptive parameters and also showed elevated expression of NF-κB (p65), IκB and p-IκB along with increased levels of IL-6 & TNF-α and inducible enzymes (COX-2 and iNOS). Furthermore, there was an increase in oxidative stress and decrease in Nrf2/HO-1 expression. We observed that BAY 11-7082 alleviated abnormal sensory responses and deficits in nerve functions. BAY 11-7082 also ameliorated the increase in expression of NF-κB, IκB and p-IκB. BAY 11-7082 curbed down the levels of IL-6, TNF-α, COX-2 and iNOS in the sciatic nerve. Lowering of lipid peroxidation and improvement in GSH levels was also seen along with increased expression of Nrf2/HO-1. Thus it can be concluded that NF-κB expression and downstream expression of proinflammatory mediators are prominent features of nerve damage leading to inflammation and oxidative stress and BAY 11-7082 was able to ameliorate experimental diabetic neuropathy by modulating neuroinflammation and improving antioxidant defence.

The identification of gene expression profiles associated with progression of human diabetic neuropathy

Diabetic neuropathy is a common complication of diabetes. While multiple pathways are implicated in the pathophysiology of diabetic neuropathy, there are no specific treatments and no means to predict diabetic neuropathy onset or progression. Here, we identify gene expression signatures related to diabetic neuropathy and develop computational classification models of diabetic neuropathy progression. Microarray experiments were performed on 50 samples of human sural nerves collected during a 52-week clinical trial. A series of bioinformatics analyses identified differentially expressed genes and their networks and biological pathways potentially responsible for the progression of diabetic neuropathy. We identified 532 differentially expressed genes between patient samples with progressing or non-progressing diabetic neuropathy, and found these were functionally enriched in pathways involving inflammatory responses and lipid metabolism. A literature-derived co-citation network of the differentially expressed genes revealed gene subnetworks centred on apolipoprotein E, jun, leptin, serpin peptidase inhibitor E type 1 and peroxisome proliferator-activated receptor gamma. The differentially expressed genes were used to classify a test set of patients with regard to diabetic neuropathy progression. Ridge regression models containing 14 differentially expressed genes correctly classified the progression status of 92% of patients (P < 0.001). To our knowledge, this is the first study to identify transcriptional changes associated with diabetic neuropathy progression in human sural nerve biopsies and describe their potential utility in classifying diabetic neuropathy. Our results identifying the unique gene signature of patients with progressive diabetic neuropathy will facilitate the development of new mechanism-based diagnostics and therapies.

Oxidative stress and Nrf2 in the pathophysiology of diabetic neuropathy: Old perspective with a new angle

Long-standing diabetes and complications thereof particularly, neuropathy stands for one of the major causes of morbidity across the globe. It is postulated that excessive production of reactive oxygen species is a key component in the development and progression of diabetic neuropathy. Oxidative damage is the most common concluding pathway for various pathogenetic mechanisms of neuronal injury in diabetic neuropathy. However despite optimistic preclinical data, it is still very ambiguous that why antioxidants have failed to demonstrate significant neuroprotection in humans. A growing body of evidences now suggests that strategies utilizing a more targeted approach like focusing on Nrf2 (a transcription factor modulating oxidative stress) may provide an enthralling avenue to optimize neuroprotection in diabetes and diabetic neuropathy. This review presents an emerging concept of Nrf2 in diabetic neuropathy; thus looking forward to newer strategies for combating the oxidant induced damage.

NF-κB inhibitory action of resveratrol: A probable mechanism of neuroprotection in experimental diabetic neuropathy

Resveratrol has shown array of biological actions, and is under clinical development for various disease conditions. The etiology of diabetic neuropathy revolves around oxidative stress, AGE formation, lipid peroxidation etc. All these stimulate inflammatory processes and NF-κB cascade is considered as one of the major players of inflammatory response. Activation of NF-κB results in elevated levels of inflammatory mediators. COX-2 and TNF-α activity have also been correlated with inflammatory damage in the pathophysiology of diabetic neuropathy (DN). Therefore we investigated the effect of resveratrol on NF-κB inflammatory cascade, COX-2, TNF-α and IL-6 levels in experimental DN. We found that resveratrol protected against various functional and behavioral deficits in diabetic neuropathy in line with our earlier published reports. In this study we found that the resveratrol treatment decreased the expression of p65 and IκB-α in treated rats. Treatment also ameliorated the elevated levels of TNF-α, IL-6 and COX-2. Resveratrol treatment produced significant decrease in nerve MDA levels in treated animals which may also be contributing to reduction in neuro-inflammation. This study confirms the NF-κB inhibitory activity and anti-inflammatory activity of resveratrol which may contribute to neuroprotection in diabetic neuropathy apart from its antioxidant effect.

Effects of resveratrol on nerve functions, oxidative stress and DNA fragmentation in experimental diabetic neuropathy

Oxidative stress has been implicated in pathophysiology of diabetic neuropathy. All the pathways responsible for development of diabetic neuropathy are linked to oxidative stress in one way or the other. In the present study, we have targeted oxidative stress in diabetic neuropathy using resveratrol, a potent antioxidant. Eight weeks streptozotocin-diabetic rats developed neuropathy which was evident from significant reduction in motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and increased thermal hyperalgesia. The 2-week treatment with resveratrol (10 and 20 mg/kg, i.p.) started 6 weeks after diabetes induction significantly ameliorated the alterations in MNCV, NBF, and hyperalgesia. Resveratrol also attenuated enhanced levels of malondialdehyde (MDA), peroxynitrite and produced increase in catalase levels in diabetic rats. There was marked reduction in DNA fragmentation observed after resveratrol treatment in diabetic rats as evident from decrease in Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in sciatic nerve sections. Results of the present study suggest the potential of resveratrol in treatment of diabetic neuropathy and its protective effect may be mediated through reduction in oxidative stress and DNA fragmentation.

Sciatic nerve lipoprotein lipase is reduced in streptozotocin-induced diabetes and corrected by insulin.

The metabolic abnormalities underlying the cause of diabetic neuropathy have been the subject of much debate. Lipoprotein lipase (LPL) is a 56-kDa enzyme produced by several tissues in the body and has recently been shown in vitro to be expressed in cultured Schwann cells, where it is important in phospholipid synthesis. This suggests a role for LPL in myelin biosynthesis in the peripheral nervous system. The aim of this study was to determine if acute streptozotocin (STZ)-induced diabetes reduces the expression and regulation of sciatic nerve LPL in vivo. Adult Sprague Dawley rats were rendered diabetic via an sc injection of STZ. A decrease in sciatic nerve LPL activity was observed in the STZ-treated rats after just 2 d of diabetes and remained significantly reduced for at least 35 d. The decrease in LPL activity coincided temporally with a drop in motor nerve conduction velocity. Treatment with insulin for 4 d showed a normalization of sciatic nerve LPL activity. These results show that STZ-induced diabetes causes a decrease in LPL activity in the sciatic nerve that, as in other tissues, is reversible with insulin treatment. These data may suggest a role for LPL in the pathophysiology of diabetic neuropathy.

Abnormal axonal inward rectifier in streptozocin-induced experimental diabetic neuropathy.

In order to explore the pathophysiology of diabetic neuropathy, we studied serial changes of axonal excitability in 20 adult Wistar rats with streptozocin-induced diabetes using the technique of threshold electrotonus (TE). After persistent hyperglycaemia had developed, rats were divided into two groups: nine were fed a diet containing aldose reductase inhibitor (Epalrestat 30 mg/kg/day) (ARI(+) group) and 11 were fed a diet without the inhibitor (ARI(-) group). Eight normal control rats of similar age (NC group) were also studied. We monitored membrane properties of motor axons in the tail for 3 months using TE to measure the changes in excitability induced by subthreshold polarizing currents while recording compound muscle action potentials (CMAPs) in the tail muscle. The ARI(-) group showed a significant increase in CMAP latency 1 month after streptozocin injection, and by 3 months there was significantly lower excitability after hyperpolarization for 100 ms compared with the NC group. A similar change in TE was reproduced by injection of caesium chloride, an inhibitor of inward rectification. By contrast, the ARI(+) group exhibited no significant change in TE or latency at 3 months, although they showed significant body weight loss and hyperglycaemia. These findings indicate that inward rectification is reduced in an experimental model, as in human diabetes, and that blocking the polyol pathway with an ARI prevents this reduction. Reduced inward rectification potentiates conduction block caused by activity-dependent hyperpolarization and may underlie the decreased vibratory sensation seen in the early stage of diabetic neuropathy.

Taurine Replacement Prevents Apoptosis In Experimental Diabetic Neuropathy

The pathophysiology of diabetic neuropathy (DN) is complex involving both metabolic and vascular deficits. Recent data have implicated a potential role for programmed cell death (PCD) in the development of experimental DN (EDN). Oxidative stress has emerged as a leading candidate in the development of nerve blood flow (NBF) and nerve conduction deficits. We have previously shown that replacement of the endogenous antioxidant taurine in the nerve of streptozotocin‐diabetic (STZ‐D) rats corrects neuro‐vascular dysfunction, prevents deficits in Na,K‐ATPase activity and attenuates motor and sensory NCV slowing. The aims of this study were to examine the hypothesis that oxidative stress‐mediated mitochondrial dysfunction may promote the activation of PCD pathways in STZ‐D rats and to determine whether these effects could be attenuated by taurine. Dorsal root ganglion (DRG) neurons were extracted from perfused control (C), STZ‐D and STZ‐D rats given a 1% taurine supplemented diet for 6 weeks. STZ‐D induced a significant decrease in sensory nerve conduction velocity (SNCV) and NBF vs controls and these deficits were corrected by taurine. Lumbar and sacral DRG were sectioned at 10 mm intervals and slides were prepared from two different sampling sites. Apoptosis was detected by TUNEL staining. 150 or more DRG nuclei were counted per animal. In STZ‐D rats 21.3 ± 4.9% of DRG nuclei were found to be TUNEL positive as compared with 2.9 ± 2.1% in controls (p &lt; 0.05). Taurine replacement markedly attenuated apoptosis since only 6.5 ± 2.9% neurons were TUNEL positive. In summary, 6 weeks of STZ‐D increased apoptosis in DRG neurons of STZ‐D rats. This increase in apoptosis could be prevented by replacement of the endogenous antioxidant taurine, implicating a role of taurine depletion in the development of sensory neuron degeneration.