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Diabetic neuropathic pain treatment

Nirupa D Jayaraj, Bula J Bhattacharyya, Abdelhak A Belmadani, Dongjun Ren, Craig A Rathwell, Sandra Hackelberg, Brittany E Hopkins, Herschel R Gupta, Richard J Miller, Daniela M Menichella
Painful diabetic neuropathy (PDN) is an intractable complication of diabetes that affects 25% of patients. PDN is characterized by neuropathic pain and small-fiber degeneration, accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability and loss of their axons within the skin. The molecular mechanisms underlying DRG nociceptor hyperexcitability and small-fiber degeneration in PDN are unknown. We hypothesize that chemokine CXCL12/CXCR4 signaling is central to this mechanism, as we have shown that CXCL12/CXCR4 signaling is necessary for the development of mechanical allodynia, a pain hypersensitivity behavior common in PDN...
March 13, 2018: Journal of Clinical Investigation
Ji-Yuan Zhao, Li Yang, Hu-Hu Bai, Jiang-Ping Liu, Zhan-Wei Suo, Xian Yang, Xiao-Dong Hu
Protein tyrosine phosphatase 1B (PTP1B) has been shown to dephosphorylate and inactivate insulin receptors, which contributes to the pathogenesis of diabetes. Neuropathic pain is one of the severe complications that results from diabetic neuropathy. However, whether PTP1B was involved in the development of diabetic neuropathic pain is largely unknown. The current study illustrated that PTP1B was located in spinal cord dorsal horn neurons of Sprague-Dawley rats. Western blot analysis demonstrated that the diabetic neuropathic pain induced by intraperitoneal injection of streptozotocin was associated with an increased protein expression and a dynamic redistribution of spinal PTP1B into excitatory glutamatergic synapses...
March 8, 2018: European Journal of Pharmacology
Evangelos Agathos, Anastasios Tentolouris, Ioanna Eleftheriadou, Panagiota Katsaouni, Ioannis Nemtzas, Alexandra Petrou, Christina Papanikolaou, Nikolaos Tentolouris
Objective To examine the effect of α-lipoic acid on neuropathic symptoms in patients with diabetic neuropathy (DN). Methods Patients with painful DN were treated with 600 mg/day α-lipoic acid, orally, for 40 days. Neuropathy Symptom Score (NSS), Subjective Peripheral Neuropathy Screen Questionnaire (SPNSQ) and douleur neuropathique (DN)4 questionnaire scores were assessed at baseline and day 40. Quality-of-life treatment effects were assessed by Brief Pain Inventory (BPI), Neuropathic Pain Symptom Inventory (NPSI) and Sheehan Disability Scale (SDS)...
January 1, 2018: Journal of International Medical Research
Cristina Carrasco, Mustafa Naziroǧlu, Ana B Rodríguez, José A Pariente
Currently, neuropathic pain is an underestimated socioeconomic health problem affecting millions of people worldwide, which incidence may increase in the next years due to chronification of several diseases, such as cancer and diabetes. Growing evidence links neuropathic pain present in several disorders [i.e., spinal cord injury (SCI), cancer, diabetes and alcoholism] to central sensitization, as a global result of mitochondrial dysfunction induced by oxidative and nitrosative stress. Additionally, inflammatory signals and the overload in intracellular calcium ion could be also implicated in this complex network that has not yet been elucidated...
2018: Frontiers in Physiology
Claudia Sommer, Christian Geber, Peter Young, Raimund Forst, Frank Birklein, Benedikt Schoser
BACKGROUND: Polyneuropathies (peripheral neuropathies) are the most common type of disorder of the peripheral nervous system in adults, and specifically in the elderly, with an estimated prevalence of 5-8%, depending on age. The options for treatment depend on the cause, which should therefore be identified as precisely as possible by an appropriate diagnostic evaluation. METHODS: This review is based on the current guidelines and on large-scale cohort studies and randomized, controlled trials published from 2000 to 2017, with an emphasis on non-hereditary types of polyneuropathy, that were retrieved by a selective search in PubMed...
February 9, 2018: Deutsches Ärzteblatt International
Hans-Georg Schaible
PURPOSE OF REVIEW: Osteoarthritis is one of the most frequent causes of chronic pain. Because there is no causal treatment of osteoarthritis, sufficient pain control is of uppermost importance but often not met. The review reports recent advances and controversies in our understanding of osteoarthritis pain and its treatment. RECENT FINDINGS: Osteoarthritis pain is determined by processes at different levels. An important local factor of pain generation in the joint is inflammation such as synovitis, and neuropathic components of osteoarthritis pain are being discussed...
February 12, 2018: Current Opinion in Supportive and Palliative Care
Yulin Shen, Shu Guan, Huixiang Ge, Wei Xiong, Lingkun He, Lijuan Liu, Cancan Yin, Hui Liu, Guilin Li, Changshui Xu, Hong Xu, Shuangmei Liu, Guodong Li, Shangdong Liang, Yun Gao
Diabetic neuropathic pain (DNP) is one of the common complications of diabetes. Depression (DP) is also one of the common complications of diabetes. P2X7 receptors play an important role in the transmission of nociceptive signal and are associated with depressive illness. In the study, the hyperalgesia, allodynia and depressive behaviours of rats with comorbidity of DNP and DP were confirmed by the thermal withdrawal latency (TWL) test, mechanical withdrawal threshold (MWT) test, sucrose preference test (SPT), immobility time of forced swimming test (IMFST) and open-field test (OFT)...
February 7, 2018: Brain Research Bulletin
Xiaolei Wang, Chang Feng, Yong Qiao, Xin Zhao
No study has been conducted to examine the interactions of sigma-1 receptor (Sigma-1R) and high mobility group box 1 protein (HMGB1) in the development of diabetic peripheral neuropathy. Thus, we examined the effects of streptozotocin (STZ) treatment on expression of HMGB1 in subcellular levels in the dorsal root ganglion (DRG) in both wild-type and Sigma-1R-/- mice and evaluated the effects of repeated intrathecal administrations of selective Sigma-1R antagonists BD1047, agonist PRE-084, or HMGB1 inhibitor glycyrrhizin on peripheral neuropathy in wild-type mice...
February 5, 2018: Neuroscience Letters
Yasaman Safarpour, Bahman Jabbari
This review evaluates the existing level of evidence for efficacy of BoNTs in different pain syndromes using the recommended efficacy criteria from the Assessment and Therapeutic Subcommittee of the American Academy of Neurology. There is a level A evidence (effective) for BoNT therapy in post-herpetic neuralgia, trigeminal neuralgia, and posttraumatic neuralgia. There is a level B evidence (probably effective) for diabetic neuropathy, plantar fasciitis, piriformis syndrome, pain associated with total knee arthroplasty, male pelvic pain syndrome, chronic low back pain, male pelvic pain, and neuropathic pain secondary to traumatic spinal cord injury...
January 31, 2018: Toxicon: Official Journal of the International Society on Toxinology
Diana Erasso, Gabriel C Tender, Qin Li, Jiusheng Yan, Frank Culicchia, Salahadin Abdi, JianGuo Cui
BACKGROUND: Diabetes mellitus affects 9.3% of the US population and increases risks of surgery and complications. Diabetic neuropathic pain (DNP), one of the main consequences of diabetes mellitus, is extremely difficult to treat. Current medications yield limited benefits and/or have severe adverse effects. Therefore, new, effective treatment is needed. METHODS: Streptozotocin at 55 mg/kg was injected intraperitoneally in rats to induce diabetes mellitus. Diabetic rats exhibiting neuropathic pain underwent intrathecal injection of purified agrin proteins at various doses and were then tested for tactile allodynia to evaluate whether DNP was inhibited...
January 23, 2018: Anesthesia and Analgesia
Corinne Lee-Kubli, Andrew G Marshall, Rayaz A Malik, Nigel A Calcutt
PURPOSE OF REVIEW: Neuropathic pain may arise from multiple mechanisms and locations. Efficacy of current treatments for painful diabetic neuropathy is limited to an unpredictable subset of patients, possibly reflecting diversity of pain generator mechanisms, and there is a lack of targeted treatments for individual patients. This review summarizes preclinical evidence supporting a role for spinal disinhibition in painful diabetic neuropathy, the physiology and pharmacology of rate-dependent depression (RDD) of the spinal H-reflex and the translational potential of using RDD as a biomarker of spinally mediated pain...
January 23, 2018: Current Diabetes Reports
Joanne Dixon, Joshua Coulter, Michele Garrett, Rick Cutfield
AIMS: To review the characteristics, management and outcomes one year after diagnosis in patients with diabetes related charcot neuropathic osteoarthropathy (CN) treated at the Diabetes Podiatry service, Waitemata District Health Board (WDHB) between 2000-2014. METHODS: Patients with diabetes and recorded diagnosis of CN were identified from the podiatry service records. Clinical details were retrospectively obtained from WDHB databases and patient medical records...
December 15, 2017: New Zealand Medical Journal
Youngrak Choi, Young-Woo Kwon, Young-Suk Sim, Taeho Kim, Dayoung Song, Soohyun Lee
BACKGROUND: Calcaneal insufficiency avulsion (CIA) fractures often present with neuropathic etiology, such as Charcot neuroarthropathy (CN). Under the same surgical procedures, the outcomes of CIA fractures are less desirable, compared to the outcomes of the traumatic calcaneal avulsion fractures. Here, the study suggests Achilles tenodesis technique using suture anchor after resection of the CIA fracture fragments could provide satisfactory clinical results in the cases of surgically indicated CIA fractures...
December 13, 2017: Journal of Orthopaedic Surgery and Research
Chenglong Liu, Jia Tao, Hui Wu, Yixin Yang, Qiang Chen, Zeyu Deng, Jiandi Liu, Changshui Xu
Diabetic neuropathic pain (DNP), one of the early symptoms of diabetic neuropathy, relates to metabolic disorders induced by high blood glucose, neurotrophic vascular ischemia and hypoxia, and autoimmune factors. This study was aimed at exploring the effects of long noncoding RNA (lncRNA) BC168687 siRNA on DNP mediated by P2X7 receptor on SGCs in DRG of rats. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats, the expression levels of P2X7 mRNA and protein in the DRG, and nitric oxide (NO) in the serum were, respectively, detected in our study...
2017: BioMed Research International
Muke Zhou, Ning Chen, Li He, Mi Yang, Cairong Zhu, Fengbo Wu
BACKGROUND: Several anticonvulsant drugs are used in the management of neuropathic pain. Oxcarbazepine is an anticonvulsant drug closely related to carbamazepine. Oxcarbazepine has been reported to be efficacious in the treatment of neuropathic pain, but evidence from randomised controlled trials (RCTs) is conflicting. Oxcarbazepine is reportedly better tolerated than carbamazepine. This is the first update of a review published in 2013. OBJECTIVES: To assess the benefits and harms of oxcarbazepine for different types of neuropathic pain...
December 2, 2017: Cochrane Database of Systematic Reviews
Iulia Blesneac, Andreas C Themistocleous, Carl Fratter, Linus J Conrad, Juan D Ramirez, James J Cox, Solomon Tesfaye, Pallai R Shillo, Andrew S C Rice, Stephen J Tucker, David L H Bennett
Diabetic peripheral neuropathy (DPN) is a common disabling complication of diabetes. Almost half of the patients with DPN develop neuropathic pain (NeuP) for which current analgesic treatments are inadequate. Understanding the role of genetic variability in the development of painful DPN is needed for improved understanding of pain pathogenesis for better patient stratification in clinical trials and to target therapy more appropriately. Here, we examined the relationship between variants in the voltage-gated sodium channel NaV1...
March 2018: Pain
Lalit Kishore, Navpreet Kaur, Randhir Singh
Generation of excessive reactive oxygen species (ROS) and advanced glycation end products (AGEs), and cellular apoptosis are implicated in the pathogenesis of diabetic neuropathy. Present study was aimed to explore the effect of Eruca sativa and Kaempferol (KP) on hyperalgesia (thermal and mechanical); tactile allodynia, motor nerve conduction velocity (MNCV) and oxidative-nitrosative stress in streptozotocin (STZ) induced experimental diabetes. Neuropathy developed in diabetic rats was evident from a marked hyperalgesia and allodynia; reduced MNCV associated with excess formation of AGEs and ROS...
November 20, 2017: Inflammopharmacology
Yee Fun Lee, Chou-Ching Lin, Jung-Sung Cheng, Gin-Shin Chen
Nerve conduction block with a high intensity-focused ultrasound (HIFU) transducer has been performed in normal and diabetic animal models recently. HIFU can reversibly block the conduction of peripheral nerves without damaging the nerves while using an appropriate ultrasonic parameter. Temporary and partial block of the action potentials of nerves shows that HIFU has the potential to be a useful clinical treatment for pain relief. This work demonstrates the procedures for suppressing the action potentials of neuropathic nerves in diabetic rats in vivo using an HIFU transducer...
October 20, 2017: Journal of Visualized Experiments: JoVE
Damien Sène
Small fiber neuropathy, which affects the sensory Aδ and C fibers, is now a major diagnostic and therapeutic challenge. Nearly 7% of the general population have chronic neuropathic pain responsible for severe quality-of-life impairments. Awareness must therefore be raised among clinicians of the somatosensory and autonomic symptoms that can reveal small fiber neuropathy, appropriate diagnostic investigations, most common causes, and best treatment options for each patient profile. To help achieve this goal, the present review article discusses the clinical presentation of neuropathic pain and paresthesia and/or autonomic dysfunction due to involvement of nerves supplying exocrine glands and smooth muscle; normal findings from standard electrophysiological investigations; most informative diagnostic tests (epidermal nerve fiber density in a skin biopsy, laser-evoked potentials, heat- and cold-detection thresholds, electrochemical skin conductance); main causes, which consist chiefly of metabolic diseases (diabetes mellitus, glucose intolerance), dysimmunity syndromes (Sjögren's syndrome, sarcoidosis, monoclonal gammopathy), and genetic abnormalities (familial amyloidosis due to a transthyretin mutation, Fabry disease, sodium channel diseases); and the available symptomatic and etiological treatments...
November 16, 2017: Joint, Bone, Spine: Revue du Rhumatisme
Abhilasha Ahlawat, Saurabh Sharma
In view of the pathologic basis for the treatment of diabetic neuropathy, it is important to enhance nerve regeneration as well as prevent nerve degeneration. So, in the present study, we have investigated the effect of S-Methylisothiourea Sulfate (selective iNOS inhibitor) and Citicoline, alone and in combination, on Type II diabetes mellitus induced neuropathic pain in wistar rats. Type II diabetes was induced by providing high fat diet and low dose of Streptozotocin for 35 days in rats. Type II diabetes mellitus was assessed in terms of increased glucose, triglycerides, cholesterol, LDL levels, glucose tolerance and decrease in HDL levels...
January 5, 2018: European Journal of Pharmacology
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