Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy.

Science.gov (United States)

Granovsky, Yelena; Nahman-Averbuch, Hadas; Khamaisi, Mogher; Granot, Michal

2017-05-01

Alleviation of pain, by either medical or surgical therapy, is accompanied by transition from less efficient, or pro-nociceptive, to efficient conditioned pain modulation (CPM). Spontaneous decrease or resolution of pain with disease progression is reported for some patients with painful diabetic neuropathy (PDN). To explore whether CPM changes similarly in parallel to spontaneous resolution of pain in PDN patients. In this cross-sectional study, thirty-three patients with PDN underwent psychophysical assessment of pain modulation on the forearm, remote from the clinical pain. Pain duration was not correlated with neuropathic pain intensity, yet, it correlated with CPM efficiency; patients with longer pain duration had same pain level, but more efficient CPM than those with short-pain duration (ρ = -0.417; P = 0.025, Spearman correlation). Patients with pain more than 2 years (median split) expressed efficient CPM that was not different from that of healthy controls. These patients also had lower temporal summation of pain than the short-pain duration patients group ( P < 0.05). The 2 patient groups did not differ in clinical pain characteristics or use of analgesics. Pro-nociception, expressed by less efficient CPM and high temporal summation that usually accompanies clinical painful conditions, seems to "normalize" with chronicity of the pain syndrome. This is despite continuing pain, suggesting that pro-nociceptivity in pain syndromes is multifactorial. Because the pain modulation profile affects success of therapy, this suggests that different drugs might express different efficacy pending on duration of the pain in patients with PDN.

Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomised clinical trial

DEFF Research Database (Denmark)

de Vos, Cecile C; Meier, Kaare; Zaalberg, Paul Brocades

2014-01-01

Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our......D questionnaires also showed that patients in the SCS group, unlike those in the control group, experienced reduced pain and improved health and quality of life after 6 months of treatment. In patients with refractory painful diabetic neuropathy, spinal cord stimulation therapy significantly reduced...

Pain and autonomic dysfunction in patients with sarcoidosis and small fibre neuropathy

NARCIS (Netherlands)

M. Bakkers (Mayienne); C.G. Faber (Carin); M. Drent (Marjolein); M.C.E. Hermans; S.I. van Nes (Sonja); G. Lauria (Giuseppe); M.H. de Baets (Marc); I.S.J. Merkies (Ingemar)

2010-01-01

textabstractSmall fibre neuropathy (SFN) has been demonstrated in sarcoidosis. However, a systematic analysis of neuropathic pain and autonomic symptoms, key features of SFN, has not been performed. Clinimetric evaluation of pain and autonomic symptoms using the neuropathic pain scale (NPS) and the

Protective Effect of a Mitochondria-Targeted Peptide against the Development of Chemotherapy-Induced Peripheral Neuropathy in Mice.

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Toyama, Satoshi; Shimoyama, Naohito; Szeto, Hazel H; Schiller, Peter W; Shimoyama, Megumi

2018-04-18

Several chemotherapeutic agents used for cancer treatment induce dose-limiting peripheral neuropathy that compromises patients' quality of life and limits cancer treatment. Recently, mitochondrial dysfunction has been shown to be involved in the mechanism of chemotherapy-induced peripheral neuropathy. SS-20 is a mitochondria-targeted peptide that promotes mitochondrial respiration and restores mitochondrial bioenergetics. In the present study, we examined the protective effect of SS-20 against the development of chemotherapy-induced peripheral neuropathy utilizing a murine model of peripheral neuropathy induced by oxaliplatin, a first-line chemotherapy agent for colon cancer. Weekly administrations of oxaliplatin induced peripheral neuropathy as demonstrated by the development of neuropathic pain and loss of intraepidermal nerve fibers in the hind paw. Continuous administration of SS-20 protected against the development of oxaliplatin-induced neuropathic pain and mitigated the loss of intraepidermal nerve fibers to normal levels. Our findings suggest that SS-20 may be a drug candidate for the prevention of chemotherapy-induced peripheral neuropathy.

Comparison of topical capsaicin and topical turpentine oil for treatment of painful diabetic neuropathy

International Nuclear Information System (INIS)

Musharraf, M.U.; Ahmed, Z.

2017-01-01

Background: Diabetes Mellitus is a pandemic of the modern era owing to our rapidly deteriorating lifestyle. Painful diabetic neuropathy is one of the costliest and disabling complications of diabetes mellitus. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Topical Capsaicin and Turpentine Oil are found to be effective in treatment of painful diabetic neuropathy. Methods: Patients of either gender with ages between 18 and 70 years having painful diabetic neuropathy already taking one oral drug for painful neuropathy and treatment for diabetes mellitus and an HbA1C less than 8.5% were included while Pregnant or lactating mothers, patients with chronic liver disease and patients with renal insufficiency (creatinine >3.0 mg/dl) and peripheral arterial disease were excluded from study. Patients were randomly divided into two groups (A and B) using computer generated random number table. Group A was given topical application of capsaicin while Group B was given topical application of commercially available turpentine oil over painful site on feet. Results: 300 patients were equally divided in two groups. The patients in group A had a Visual Analog Pain Score of 7.91±5.10 at baseline and 5.10±1.343 after 3 months of treatment (p-value 0.0001). The patients in group B had a Visual Analog Pain Score of 7.83±1.012 at baseline and 5.20±1.187 after 3 months of treatment (p-value 0.0001). Chi Square test was applied to compare efficacy of both groups. It was noted that 71 (53%) had efficacy in group A and 63 (47%) had efficacy in the group B but the difference was not statistically significant. (p-value=0.399). Conclusion: It has been concluded that turpentine oil is effective in managing diabetic neuropathic pain similar to capsaicin cream.

Global inhibition of reactive oxygen species (ROS inhibits paclitaxel-induced painful peripheral neuropathy.

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Mehmet Fidanboylu

Full Text Available Paclitaxel (Taxol® is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS, the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6, the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL were compared. Systemic 100 mg/kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg/kg PBN (days -1 to 13 completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose (250 mg/kg systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL (day -1 to 12 did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals

Pharmacological Modulation of the Mitochondrial Electron Transport Chain in Paclitaxel-Induced Painful Peripheral Neuropathy.

Science.gov (United States)

Griffiths, Lisa A; Flatters, Sarah J L

2015-10-01

Paclitaxel is an effective first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Mitochondrial dysfunction and oxidative stress have been implicated in paclitaxel-induced painful neuropathy. Here we show the effects of pharmacological modulation of mitochondrial sites that produce reactive oxygen species using systemic rotenone (complex I inhibitor) or antimycin A (complex III inhibitor) on the maintenance and development of paclitaxel-induced mechanical hypersensitivity in adult male Sprague Dawley rats. The maximally tolerated dose (5 mg/kg) of rotenone inhibited established paclitaxel-induced mechanical hypersensitivity. However, some of these inhibitory effects coincided with decreased motor coordination; 3 mg/kg rotenone also significantly attenuated established paclitaxel-induced mechanical hypersensitivity without any motor impairment. The maximally tolerated dose (.6 mg/kg) of antimycin A reversed established paclitaxel-induced mechanical hypersensitivity without any motor impairment. Seven daily doses of systemic rotenone or antimycin A were given either after paclitaxel administration or before and during paclitaxel administration. Rotenone had no significant effect on the development of paclitaxel-induced mechanical hypersensitivity. However, antimycin A significantly inhibited the development of paclitaxel-induced mechanical hypersensitivity when given before and during paclitaxel administration but had no effect when given after paclitaxel administration. These studies provide further evidence of paclitaxel-evoked mitochondrial dysfunction in vivo, suggesting that complex III activity is instrumental in paclitaxel-induced pain. This study provides further in vivo evidence that mitochondrial dysfunction is a key contributor to the development and maintenance of chemotherapy-induced painful neuropathy. This work also indicates that selective modulation of the electron transport chain can induce antinociceptive

Neurosteroid 3α-androstanediol efficiently counteracts paclitaxel-induced peripheral neuropathy and painful symptoms.

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Laurence Meyer

Full Text Available Painful peripheral neuropathy belongs to major side-effects limiting cancer chemotherapy. Paclitaxel, widely used to treat several cancers, induces neurological symptoms including burning pain, allodynia, hyperalgesia and numbness. Therefore, identification of drugs that may effectively counteract paclitaxel-induced neuropathic symptoms is crucial. Here, we combined histopathological, neurochemical, behavioral and electrophysiological methods to investigate the natural neurosteroid 3α-androstanediol (3α-DIOL ability to counteract paclitaxel-evoked peripheral nerve tissue damages and neurological symptoms. Prophylactic or corrective 3α-DIOL treatment (4 mg/kg/2 days prevented or suppressed PAC-evoked heat-thermal hyperalgesia, cold-allodynia and mechanical allodynia/hyperalgesia, by reversing to normal, decreased thermal and mechanical pain thresholds of PAC-treated rats. Electrophysiological studies demonstrated that 3α-DIOL restored control values of nerve conduction velocity and action potential peak amplitude significantly altered by PAC-treatment. 3α-DIOL also repaired PAC-induced nerve damages by restoring normal neurofilament-200 level in peripheral axons and control amount of 2',3'-cyclic-nucleotide-3'-phosphodiesterase in myelin sheaths. Decreased density of intraepidermal nerve fibers evoked by PAC-therapy was also counteracted by 3α-DIOL treatment. More importantly, 3α-DIOL beneficial effects were not sedation-dependent but resulted from its neuroprotective ability, nerve tissue repairing capacity and long-term analgesic action. Altogether, our results showing that 3α-DIOL efficiently counteracted PAC-evoked painful symptoms, also offer interesting possibilities to develop neurosteroid-based strategies against chemotherapy-induced peripheral neuropathy. This article shows that the prophylactic or corrective treatment with 3α-androstanediol prevents or suppresses PAC-evoked painful symptoms and peripheral nerve dysfunctions in

Central pain processing in chronic chemotherapy-induced peripheral neuropathy: a functional magnetic resonance imaging study.

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Elaine G Boland

Full Text Available Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN with those from healthy volunteers (HV. Twenty-four participants (n = 12 MM-CIPN, n = 12 HV underwent Blood Oxygen Level-Dependent (BOLD fMRI at 3T whilst noxious heat-pain stimuli were applied to the foot and then thigh. Patients with MM-CIPN demonstrated greater activation during painful stimulation in the precuneus compared to HV (p = 0.014, FWE-corrected. Patients with MM-CIPN exhibited hypo-activation of the right superior frontal gyrus compared to HV (p = 0.031, FWE-corrected. Significant positive correlation existed between the total neuropathy score (reduced version and activation in the frontal operculum (close to insular cortex during foot stimulation in patients with MM-CIPN (p = 0.03, FWE-corrected; adjusted R2 = 0.87. Painful stimuli delivered to MM-CIPN patients evoke differential activation of distinct cortical regions, reflecting a unique pattern of central pain processing compared with healthy volunteers. This characteristic activation pattern associated with pain furthers the understanding of the pathophysiology of painful chemotherapy induced peripheral neuropathy. Functional MRI provides a tool for monitoring cerebral changes during anti-cancer and analgesic treatment.

Recurrent painful ophthalmoplegic neuropathy; A case report

OpenAIRE

Semra Saygi; Tulun Savas; ilknur Erol

2014-01-01

Recurrent painful ophthalmoplegic neuropathy, typically seen as a serious childhood migraine attack which is followed by ptosis and diplopia due to oculomotor nerve palsy. This is regarded as a form of migraine in the previous classifications but according to the latest classification of the International Headache Society has been recognized as cranial neuralgia. Due to the poor pathological and radiological findings of oculomotor nerve during attack, it is difficult to make differential diag...

Treatment of painful diabetic neuropathy

Science.gov (United States)

Petropoulos, Ioannis N.; Alam, Uazman; Malik, Rayaz A.

2015-01-01

Painful diabetic neuropathy (PDN) is a debilitating consequence of diabetes that may be present in as many as one in five patients with diabetes. The objective assessment of PDN is difficult, making it challenging to diagnose and assess in both clinical practice and clinical trials. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Treatment of PDN is based on three major approaches: intensive glycaemic control and risk factor management, treatments based on pathogenetic mechanisms, and symptomatic pain management. Clinical guidelines recommend pain relief in PDN through the use of antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids and topical agents such as capsaicin. Of these medications, duloxetine and pregabalin were approved by the US Food and Drug Administration (FDA) in 2004 and tapentadol extended release was approved in 2012 for the treatment of PDN. Proposed pathogenetic treatments include α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage in diabetes) and aldose-reductase inhibitors (reduces flux through the polyol pathway). There is a growing need for studies to evaluate the most potent drugs or combinations for the management of PDN to maximize pain relief and improve quality of life. A number of agents are potential candidates for future use in PDN therapy, including Nav 1.7 antagonists, N-type calcium channel blockers, NGF antibodies and angiotensin II type 2 receptor antagonists. PMID:25553239

Evidence that spinal astrocytes but not microglia contribute to the pathogenesis of paclitaxel-induced painful neuropathy

OpenAIRE

Zhang, Haijun; Yoon, Seo-Yeon; Zhang, Hongmei; Dougherty, Patrick M.

2012-01-01

Paclitaxel often induces persistent painful neuropathy as its most common treatment limiting side effect. Little is known concerning the underlying mechanisms. Given the prominent role of glial cells in many types of neuropathic pain, we investigated here the morphological and functional changes of spinal astrocytes and microglia in a rat model of paclitaxel-induced neuropathy. Immunohistochemistry, western blotting and real-time polymerase chain reaction (rt-PCR) were performed with samples ...

How diagnostic tests help to disentangle the mechanisms underlying neuropathic pain symptoms in painful neuropathies.

Science.gov (United States)

Truini, Andrea; Cruccu, Giorgio

2016-02-01

Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. Neurophysiological investigation and skin biopsy studies suggest that ongoing burning pain primarily reflects spontaneous activity in nociceptive-fiber pathways. Electrical shock-like sensations presumably arise from high-frequency ectopic bursts generated in demyelinated, nonnociceptive, Aβ fibers. Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.

Involvement of high mobility group box 1 in the development and maintenance of chemotherapy-induced peripheral neuropathy in rats

International Nuclear Information System (INIS)

Nishida, Takeshi; Tsubota, Maho; Kawaishi, Yudai; Yamanishi, Hiroki; Kamitani, Natsuki; Sekiguchi, Fumiko; Ishikura, Hiroyasu; Liu, Keyue; Nishibori, Masahiro; Kawabata, Atsufumi

2016-01-01

Given that high mobility group box 1 (HMGB1), a nuclear protein, once released to the extracellular space, promotes nociception, we asked if inactivation of HMGB1 prevents or reverses chemotherapy-induced painful neuropathy in rats and also examined possible involvement of Toll-like receptor 4 (TLR4) and the receptor for advanced glycation endproduct (RAGE), known as targets for HMGB1. Painful neuropathy was produced by repeated i.p. administration of paclitaxel or vincristine in rats. Nociceptive threshold was determined by the paw pressure method and/or von Frey test in the hindpaw. Tissue protein levels were determined by immunoblotting. Repeated i.p. administration of the anti-HMGB1-neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, prevented the development of hyperalgesia and/or allodynia induced by paclitaxel or vincristine in rats. A single i.p. or intraplantar (i.pl.) administration of the antibody or rhsTM reversed the chemotherapy-induced neuropathy. A single i.pl. administration of a TLR4 antagonist or low molecular weight heparin, known to inhibit RAGE, attenuated the hyperalgesia caused by i.pl. HMGB1 and also the chemotherapy-induced painful neuropathy. Paclitaxel or vincristine treatment significantly decreased protein levels of HMGB1 in the dorsal root ganglia, but not sciatic nerves. HMGB1 thus participates in both development and maintenance of chemotherapy-induced painful neuropathy, in part through RAGE and TLR4. HMGB1 inactivation is considered useful to prevent and treat the chemotherapy-induced painful neuropathy.

Peripheral neuropathy

Science.gov (United States)

... peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy; Chronic pain - peripheral neuropathy ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

Duloxetine in the treatment of chronic pain due to fibromyalgia and diabetic neuropathy

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Alan Wright

2010-12-01

Full Text Available Alan Wright, Kyle E Luedtke, Chad VanDenBergCenter for Clinical Research, Mercer University, Atlanta, Georgia, USAAbstract: Duloxetine is a serotonin-norepinephrine reuptake inhibitor approved by the US Food and Drug Administration for the treatment of fibromyalgia and painful diabetic neuropathy at doses of 60 mg daily. Duloxetine has been shown to significantly improve the symptoms of chronic pain associated with these disorders, as measured by the Fibromyalgia Impact Questionnaire, Brief Pain Inventory scores, the Clinical Global Impressions Scale, and other various outcome measures in several placebo-controlled, randomized, double-blind, multicenter studies. Symptom improvement generally began within the first few weeks, and continued for the duration of the study. In addition, the efficacy of duloxetine was found to be due to direct effects on pain symptoms rather than secondary to improvements in depression or anxiety. Adverse events including nausea, constipation, dry mouth, and insomnia, were mild and transient and occurred at relatively low rates. In conclusion, duloxetine, a selective inhibitor for the serotonin and norepinephrine transporters, is efficacious in the treatment of chronic pain associated with fibromyalgia or diabetic neuropathy, and has a predictable tolerability profile, with adverse events generally being mild to moderate.Keywords: duloxetine, chronic pain, neuropathic pain, fibromyalgia, efficacy, safety

Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia after acute foot trauma

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Tobias Wienemann

2014-11-01

Full Text Available Introduction and objective: Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy. Design and methods: A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture. Cases were 12 patients (11 diabetic subjects with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT and deep pressure pain perception threshold (DPPPT were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®. Results: In the control group, post-traumatic DPPPT (but not CPPPT at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group; CPPPT did not decrease post-operatively. Conclusion: Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking.

Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia) after acute foot trauma

Science.gov (United States)

Wienemann, Tobias; Chantelau, Ernst A.; Koller, Armin

2014-01-01

Introduction and objective Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy). Design and methods A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture). Cases were 12 patients (11 diabetic subjects) with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT) and deep pressure pain perception threshold (DPPPT) were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®). Results In the control group, post-traumatic DPPPT (but not CPPPT) at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal) versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group); CPPPT did not decrease post-operatively. Conclusion Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic) neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking. PMID:25397867

Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia) after acute foot trauma.

Science.gov (United States)

Wienemann, Tobias; Chantelau, Ernst A; Koller, Armin

2014-01-01

Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy). A case-control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture). Cases were 12 patients (11 diabetic subjects) with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT) and deep pressure pain perception threshold (DPPPT) were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II(®)). In the control group, post-traumatic DPPPT (but not CPPPT) at the injured foot was reduced by about 15-25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15-20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal) versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group); CPPPT did not decrease post-operatively. Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic) neuropathy. A degree of post-traumatic hypersensitivity required to 'pull away' from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking.

Spinal cord stimulation in patients with painful diabetic neuropathy: A multicentre randomized clinical trial

NARCIS (Netherlands)

de Vos, Cecilia Cecilia Clementine; Meier, Kaare; Brocades Zaalberg, Paul; Nijhuis, Harold J.A.; Duyvendak, Wim; Vesper, Jan; Enggaard, Thomas P.; Lenders, Mathieu W.P.M.

2014-01-01

Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our

Mexiletine for treatment of chronic painful diabetic neuropathy

DEFF Research Database (Denmark)

Dejgard, A; Kastrup, J; Petersen, P

1988-01-01

Sixteen of nineteen patients completed a randomised double-blind crossover trial to assess the effect of oral mexiletine (10 mg/kg bodyweight daily) on the symptoms and signs of chronic painful diabetic neuropathy. The median age of the sixteen patients was 50 years (range 30-64). Assessment...... threshold levels, beat-to-beat variation in heart rate during deep breathing, and postural blood pressure response. Mild side-effects were seen in three of the sixteen patients during mexiletine treatment....

Recurrent painful ophthalmoplegic neuropathy; A case report

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Semra Saygi

2014-08-01

Full Text Available Recurrent painful ophthalmoplegic neuropathy, typically seen as a serious childhood migraine attack which is followed by ptosis and diplopia due to oculomotor nerve palsy. This is regarded as a form of migraine in the previous classifications but according to the latest classification of the International Headache Society has been recognized as cranial neuralgia. Due to the poor pathological and radiological findings of oculomotor nerve during attack, it is difficult to make differential diagnosis. In this manuscript we report 11-year-old female patient with ophtalmoplegic migraine. [Cukurova Med J 2014; 39(4.000: 938-941

Trigeminal pain and quantitative sensory testing in painful peripheral diabetic neuropathy.

Science.gov (United States)

Arap, Astrid; Siqueira, Silvia R D T; Silva, Claudomiro B; Teixeira, Manoel J; Siqueira, José T T

2010-07-01

To evaluate patients with Diabetes Mellitus type 2 and painful peripheral neuropathy in order to investigate oral complaints and facial somatosensory findings. Case-control study; 29 patients (12 women, mean age 57.86 yo) with Diabetes Mellitus type 2 and 31 age-gender-matched controls were evaluated with a standardized protocol for general characteristics, orofacial pain, research diagnostic criteria for temporomandibular disorders, visual analogue scale and McGill Pain questionnaire, and a systematic protocol of quantitative sensory testing for bilateral facial sensitivity at the areas innervated by the trigeminal branches, which included the thermal detection by ThermoSensi 2, tactile evaluation with vonFrey filaments, and superficial pain thresholds with a superficial algometer (Micromar). Statistical analysis was performed with Wilcoxon, chi-square, confidence intervals and Spearman (ppain was reported by 55.2% of patients, and the most common descriptor was fatigue (50%); 17.2% had burning mouth. Myofascial temporomandibular disorders were diagnosed in 9 (31%) patients. The study group showed higher sensory thresholds of pain at the right maxillary branch (p=0.017) but sensorial differences were not associated with pain (p=0.608). Glycemia and HbA(1c) were positively correlated with the quantitative sensory testing results of pain (ppain thresholds were correlated with higher glycemia and glycated hemoglobin (p=0.027 and p=0.026). There was a high prevalence of orofacial pain and burning mouth was the most common complaint. The association of loss of pain sensation and higher glycemia and glycated hemoglobin can be of clinical use for the follow-up of DM complications. 2010 Elsevier Ltd. All rights reserved.

Role of satellite cell-derived l-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy

OpenAIRE

Kiya, T; Kawamata, T; Namiki, A; Yamakage, M

2011-01-01

Paclitaxel is one of the most commonly used antineoplastic drugs for the treatment of solid tumors. Unfortunately, its use is often associated with dose-limiting painful peripheral neuropathy and subsequent neuropathic pain that is resistant to standard analgesics. However, there are few clinically available drugs or drug classes for the treatment of paclitaxel-induced neuropathy due to a lack of information regarding the mechanisms responsible for it. In this study, we examined the involveme...

Painful Diabetic Peripheral Neuropathy: Consensus Recommendations on Diagnosis, Assessment and Management

DEFF Research Database (Denmark)

Tesfaye, S; Vileikyte, L; Rayman, G

2011-01-01

use of opiates such as the synthetic opioid tramadol, morphine and oxycodone controlled release. There is a limited literature with regard to combination treatment. In extreme cases of painful DPN unresponsive to pharmacotherapy, occasional use of electrical spinal cord stimulation might be indicated......Painful Diabetic peripheral neuropathy (painful DPN) is common, is associated with significant reduction in quality of life and poses major treatment challenges to the practising physician. Although poor glucose control and cardiovascular risk factors are proven to contribute to the aetiology...... of DPN, risk factors specific for painful DPN remain unknown. A number of instruments have been proven to assess the character, intensity and impact of painful DPN on quality of life, activities of daily living and mood. Management of the patient with DPN must be tailored to individual requirements...

MRI-guided cryoablation of the posterior femoral cutaneous nerve for the treatment of neuropathy-mediated sitting pain

International Nuclear Information System (INIS)

Joshi, Dharmdev H.; Thawait, Gaurav K.; Fritz, Jan; Del Grande, Filippo

2017-01-01

Neuropathy of the posterior femoral cutaneous nerve may manifest as pain and paresthesia in the skin over the inferior buttocks, posterior thigh, and popliteal region. Current treatment options include physical and oral pain therapy, perineural injections, and surgical neurectomy. Perineural steroid injections may provide short-term pain relief; however, to our knowledge, there is currently no minimally invasive denervation procedure for sustained pain relief that could serve as an alternative to surgical neurectomy. Percutaneous cryoablation of nerves is a minimally invasive technique that induces a sustained nerve conduction block through temporary freezing of the neural layers. It can result in long-lasting pain relief, but has not been described for the treatment of neuropathy-mediated PFCN pain. We report a technique of MR-guided cryoablation of the posterior femoral cutaneous nerve resulting in successful treatment of PFCN-mediated sitting pain. Cryoablation of the posterior femoral cutaneous nerve seems a promising, minimally invasive treatment option that deserves further investigation. (orig.)

MRI-guided cryoablation of the posterior femoral cutaneous nerve for the treatment of neuropathy-mediated sitting pain

Energy Technology Data Exchange (ETDEWEB)

Joshi, Dharmdev H.; Thawait, Gaurav K.; Fritz, Jan [Johns Hopkins University School of Medicine, Section of Musculoskeletal Radiology, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Del Grande, Filippo [Johns Hopkins University School of Medicine, Section of Musculoskeletal Radiology, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Ospedale Regionale di Lugano, Servizio di Radiologia, Lugano, Ticino (Switzerland)

2017-07-15

Neuropathy of the posterior femoral cutaneous nerve may manifest as pain and paresthesia in the skin over the inferior buttocks, posterior thigh, and popliteal region. Current treatment options include physical and oral pain therapy, perineural injections, and surgical neurectomy. Perineural steroid injections may provide short-term pain relief; however, to our knowledge, there is currently no minimally invasive denervation procedure for sustained pain relief that could serve as an alternative to surgical neurectomy. Percutaneous cryoablation of nerves is a minimally invasive technique that induces a sustained nerve conduction block through temporary freezing of the neural layers. It can result in long-lasting pain relief, but has not been described for the treatment of neuropathy-mediated PFCN pain. We report a technique of MR-guided cryoablation of the posterior femoral cutaneous nerve resulting in successful treatment of PFCN-mediated sitting pain. Cryoablation of the posterior femoral cutaneous nerve seems a promising, minimally invasive treatment option that deserves further investigation. (orig.)

Atypical hereditary sensory and autonomic neuropathy type IV with neither mental retardation nor pain insensitivity.

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Jung, Chae Lim; Ki, Chang-Seok; Kim, Byoung Joon; Lee, Jong-Hyuck; Sung, Ki-Sun; Kim, Jong-Won; Park, Youn-Soo

2013-12-01

Hereditary sensory and autonomic neuropathy type IV is an autosomal recessive disorder characterized by severe mental retardation and self-mutilation-related complications. Recently, we investigated a 16-year-old Korean boy with normal intelligence. He had preserved pain sensation but was suspected of having hereditary sensory and autonomic neuropathy type IV because of the recurrent bone fractures and painless joint destruction in the absence of any predisposing medical conditions. Genetic analysis of the NTRK1 gene revealed compound heterozygous mutations including c.851-33T>A and c.2303C>T (p.Pro768Leu) in the NTRK1 gene. The p.Pro768Leu mutation has been identified in 2 Japanese patients with a mild phenotype. Therefore, although it is rare, hereditary sensory and autonomic neuropathy type IV should be considered in patients with recurrent bone fractures and painless joint destruction who do not have any predisposing conditions even when they do not have typical clinical features such as mental retardation or pain insensitivity.

A case report of congenital sensory neuropathy with anhidrosis

International Nuclear Information System (INIS)

Lee, Won Hyong; Chang, Hae Soon; Han, Man Chung; Lee, Suck Hyun; Lee, Duk Yong

1974-01-01

Congenital sensory neuropathy with anhidrosis is rare disease and may be confused with other cause of pain insensitivity or indifference. Other cause of pain insensitivity include congenital indifference to pain, congenital sensory neuropathy, hereditary sensory radicular neuropathy, nonprogressive sensory radicular neuropathy, syringomyelia, and hysterical analgesia. It is hereditary disease which is transmitted with autosomal recessive trait. The patient is 8 years old Korean male with complaint of swelling and local heat on right knee joint. Generalized analgesia is noted on physical examination. The skin is dry and coarse with no evidence of sweating. Delayed motor development was noted on early children. Mental development is retarded. On past history, patient showed unpredictable rises of temperature, though the general condition remained good. Multiple painless fracture on right humerus and right metatasal bone was occurred. Rt.knee radiograms show marked swelling of soft tissue and periosteal calcification on distal femru,which are resemble with neurotrophic joint

A case report of congenital sensory neuropathy with anhidrosis

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Lee, Won Hyong; Chang, Hae Soon; Han, Man Chung; Lee, Suck Hyun; Lee, Duk Yong [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1974-10-15

Congenital sensory neuropathy with anhidrosis is rare disease and may be confused with other cause of pain insensitivity or indifference. Other cause of pain insensitivity include congenital indifference to pain, congenital sensory neuropathy, hereditary sensory radicular neuropathy, nonprogressive sensory radicular neuropathy, syringomyelia, and hysterical analgesia. It is hereditary disease which is transmitted with autosomal recessive trait. The patient is 8 years old Korean male with complaint of swelling and local heat on right knee joint. Generalized analgesia is noted on physical examination. The skin is dry and coarse with no evidence of sweating. Delayed motor development was noted on early children. Mental development is retarded. On past history, patient showed unpredictable rises of temperature, though the general condition remained good. Multiple painless fracture on right humerus and right metatasal bone was occurred. Rt.knee radiograms show marked swelling of soft tissue and periosteal calcification on distal femru,which are resemble with neurotrophic joint.

The effects of intradermal botulinum toxin type a injections on pain symptoms of patients with diabetic neuropathy

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Majid Ghasemi

2014-01-01

Full Text Available Background: Considering the dramatic increasing rate of diabetes and consequently its related complications, most importantly diabetic peripheral neuropathy (DPN, challenges regarding proper treatment of DPN and its effect on the quality-of-life and care of diabetic patients, the aim of this current study is to evaluate the effect of intradermal botulinum toxin type A (BTX-A injections on pain symptoms of patients with diabetic neuropathic pain. Materials and Methods: In this randomized double-blind placebo-controlled clinical trial study, diabetic patients aged <70 years with neuropathic pain in both feet were enrolled. Diabetic neuropathy (DN in selected patients was diagnosed using DN4 questionnaire and nerve conduction velocity examinations. They randomized in two intervention (BTX-A injection/100 unit, N = 20 and placebo groups (normal saline injection, N = 20. The outcome of injection on diabetic neuropathic pain was assessed using neuropathy pain scale (NPS and visual analog scale (VAS score and compared in two studied groups. Results: There was no significant difference in DN4, NPS and VAS scales of studied population after intervention in the placebo group. Intradermal injection of BTX-A reduced NPS scores for all items except cold sensation (P = 0.05. It reduced DN4 scores for electric shocks, burning, pins and needles and brushing (P < 0.05. According to VAS scale 30% and 0% of patients in intervention and placebo groups have no pain after intervention (P = 0.01. Conclusion: Intradermal injection of BTX-A is a well-tolerated agent that has a significant effect on DPN pain.

Effect and safety of spinal cord stimulation for treatment of chronic pain caused by diabetic neuropathy

NARCIS (Netherlands)

de Vos, C.; de Vos, Cecile C.; Rajan, Vinayakrishnan; Steenbergen, Wiendelt; van der Aa, Hans E.; Buschman, H.P.J.

2009-01-01

Aim: Spinal cord stimulation (SCS) has been shown effective as a therapy for different chronic painful conditions, but the effectiveness of this treatment for pain as a result of peripheral diabetic neuropathy is not well established. The primary objectives of this study were to evaluate the effect

Duloxetine in the treatment of chronic pain due to fibromyalgia and diabetic neuropathy

OpenAIRE

Wright, Alan; Luedtke, Kyle E; VanDenBerg, Chad

2010-01-01

Alan Wright, Kyle E Luedtke, Chad VanDenBergCenter for Clinical Research, Mercer University, Atlanta, Georgia, USAAbstract: Duloxetine is a serotonin-norepinephrine reuptake inhibitor approved by the US Food and Drug Administration for the treatment of fibromyalgia and painful diabetic neuropathy at doses of 60 mg daily. Duloxetine has been shown to significantly improve the symptoms of chronic pain associated with these disorders, as measured by the Fibromyalgia Impact Questionnaire, Brief P...

Randomized, Double-Blind, Crossover Trial of Amitriptyline for Analgesia in Painful HIV-Associated Sensory Neuropathy.

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Natalya Dinat

Full Text Available We conducted a randomized, double-blind, placebo-controlled, crossover study at a single center in South Africa, to ascertain whether amitriptyline is an effective analgesic for painful HIV-associated sensory neuropathy of moderate to severe intensity in: i antiretroviral drug naive individuals, and ii antiretroviral drug users. 124 HIV-infected participants (antiretroviral drug naive = 62, antiretroviral drug users = 62 who met the study criteria for painful HIV-associated sensory neuropathy were randomized to once-daily oral amitriptyline (titrated to a median: interquartile range of 50: 25-50 mg or placebo for six weeks, followed by a three-week washout period and subsequent treatment crossover. The primary outcome measure was change from baseline in worst pain intensity of the feet (measured by participant self-report using an 11-point numerical pain rating scale after six weeks of treatment. 122 of 124 participants completed all study visits and were included in the analysis of the primary outcome. In the antiretroviral drug-naive group (n = 61 there was no significant difference in the mean change in pain score from baseline after six weeks of treatment with placebo or amitriptyline [amitriptyline: 2.8 (SD 3.3 vs. placebo: 2.8 (3.4]. Similarly, there was no significant difference in the change in pain score after six weeks of treatment with placebo or amitriptyline in the antiretroviral drug-user group (n = 61 [amitriptyline: 2.7 (3.3 vs. placebo: 2.1 (2.8]. Controlling for period effects and treatment order effects did not alter the outcome of the analyses. Nor did analyzing the intention-to-treat cohort (missing data interpolated using baseline observation carried forward alter the outcome of the analyses. In summary, amitriptyline, at the doses used here, was no more effective than an inactive placebo at reducing pain intensity in individuals with painful HIV-associated sensory neuropathy of moderate to severe intensity, irrespective of

Increased Interleukin-6 Activity Associated with Painful Chemotherapy-Induced Peripheral Neuropathy in Women after Breast Cancer Treatment

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Angela Starkweather

2010-01-01

Full Text Available Accumulating evidence suggests that neural-immune interactions are involved in the development of painful chemotherapy-induced peripheral neuropathy, particularly through the increased release of proinflammatory cytokines. The purpose of this study was used to evaluate levels of interleukin [IL]-6 and IL-6 receptors in women with breast cancer after the conclusion of chemotherapy who either had painful symptoms of chemotherapy-induced peripheral neuropathy (CIPN group, N=20 or did not experience CIPN symptoms (Comparison group, N=20. CIPN participants had significantly higher levels of IL-6 and soluble IL-6R (sIL-6R compared to women without CIPN symptoms (P<.001 for both. In addition, soluble gp130, which blocks the IL-6/sIL-6R complex from binding to gp130 within the cellular membrane, was significantly lower (P<.01. Circulating concentrations of sIL-6R were inversely correlated with the density of IL-6R on the cell surface of monocytes in the total sample (r=−.614,P=.005. These findings suggest that IL-6 transsignaling may be an important biological mechanism associated with the persistence of painful CIPN symptoms, with potential implications for symptom management and research.

Treatment of neuropathic pain in a patient with diabetic neuropathy using transcutaneous electrical nerve stimulation applied to the skin of the lumbar region.

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Somers, D L; Somers, M F

1999-08-01

Diabetic neuropathy can produce severe pain. The purpose of this case report is to describe the alteration of pain in a patient with severe, painful diabetic neuropathy following application of transcutaneous electrical nerve stimulation (TENS) to the low back. The patient was a 73-year-old woman with pain in the left lower extremity over the lateral aspect of the hip and the entire leg below the knee. The pain prevented sound sleep. The intensity of pain was assessed with a visual analog scale. The TENS (80 Hz) was delivered 1 to 2 hours a day and during the entire night through electrodes placed on the lumbar area of the back. Following 20 minutes of TENS on the first day of treatment, the patient reported a 38% reduction in intensity of pain. After 17 days, the patient reported no pain following 20 minutes of TENS and that she could sleep through the night. Application of TENS to the skin of the lumbar area may be an effective treatment for the pain of diabetic neuropathy.

Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: Evidence for mitochondrial dysfunction

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Flatters, Sarah J.L.; Bennett, Gary J.

2006-01-01

Paclitaxel chemotherapy frequently induces neuropathic pain during and often persisting after therapy. The mechanisms responsible for this pain are unknown. Using a rat model of paclitaxel-induced painful peripheral neuropathy, we have performed studies to search for peripheral nerve pathology. Paclitaxel-induced mechano-allodynia and mechano-hyperalgesia were evident after a short delay, peaked at day 27 and finally resolved on day 155. Paclitaxel- and vehicle-treated rats were perfused on d...

Biomarkers of neuropathic pain in skin nerve degeneration neuropathy: contact heat-evoked potentials as a physiological signature.

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Wu, Shao-Wei; Wang, Yi-Chia; Hsieh, Paul-Chen; Tseng, Ming-Tsung; Chiang, Ming-Chang; Chu, Chih-Pang; Feng, Fang-Ping; Lin, Yea-Huey; Hsieh, Sung-Tsang; Chao, Chi-Chao

2017-03-01

Contact heat-evoked potentials (CHEPs) have become an established method of assessing small-fiber sensory nerves; however, their potential as a physiological signature of neuropathic pain symptoms has not been fully explored. To investigate the diagnostic efficacy in examining small-fiber sensory nerve degeneration, the relationship with skin innervations, and clinical correlates with sensory symptoms, we recruited 188 patients (115 men) with length-dependent sensory symptoms and reduced intraepidermal nerve fiber (IENF) density at the distal leg to perform CHEP, quantitative sensory testing, and nerve conduction study. Fifty-seven age- and sex-matched controls were enrolled for comparison of CHEP and skin innervation. Among patients with neuropathy, 144 patients had neuropathic pain and 64 cases had evoked pain. Compared with quantitative sensory testing and nerve conduction study parameters, CHEP amplitudes showed the highest sensitivity for diagnosing small-fiber sensory nerve degeneration and exhibited the strongest correlation with IENF density in multiple linear regression. Contact heat-evoked potential amplitudes were strongly correlated with the degree of skin innervation in both patients with neuropathy and controls, and the slope of the regression line between CHEP amplitude and IENF density was higher in patients with neuropathy than in controls. Patients with evoked pain had higher CHEP amplitude than those without evoked pain, independent of IENF density. Receiver operating characteristic analysis showed that CHEP had better performance in diagnosing small-fiber sensory nerve degeneration than thermal thresholds. Furthermore, CHEPs showed superior classification accuracy with respect to evoked pain. In conclusion, CHEP is a sensitive tool to evaluate pathophysiology of small-fiber sensory nerve and serves as a physiological signature of neuropathic pain symptoms.

Fibromyalgia and neuropathic pain - differences and similarities. A comparison of 3057 patients with diabetic painful neuropathy and fibromyalgia

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2011-01-01

Background Patients with diabetic neuropathy (DPN) and fibromyalgia differ substantially in pathogenetic factors and the spatial distribution of the perceived pain. We questioned whether, despite these obvious differences, similar abnormal sensory complaints and pain qualities exist in both entities. We hypothesized that similar sensory symptoms might be associated with similar mechanisms of pain generation. The aims were (1) to compare epidemiological features and co-morbidities and (2) to identify similarities and differences of sensory symptoms in both entities. Methods The present multi-center study compares epidemiological data and sensory symptoms of a large cohort of 1434 fibromyalgia patients and 1623 patients with painful diabetic neuropathy. Data acquisition included standard demographic questions and self-report questionnaires (MOS sleep scale, PHQ-9, PainDETECT). To identify subgroups of patients with characteristic combinations of symptoms (sensory profiles) a cluster analysis was performed using all patients in both cohorts. Results Significant differences in co-morbidities (depression, sleep disturbance) were found between both disorders. Patients of both aetiologies chose very similar descriptors to characterize their sensory perceptions. Burning pain, prickling and touch-evoked allodynia were present in the same frequency. Five subgroups with distinct symptom profiles could be detected. Two of the subgroups were characteristic for fibromyalgia whereas one profile occurred predominantly in DPN patients. Two profiles were found frequently in patients of both entities (20-35%). Conclusions DPN and fibromyalgia patients experience very similar sensory phenomena. The combination of sensory symptoms - the sensory profile - is in most cases distinct and almost unique for each one of the two entities indicating aetiology-specific mechanisms of symptom generation. Beside the unique aetiology-specific sensory profiles an overlap of sensory profiles can be

Relapsing Painful Ophthalmoplegic Neuropathy: No longer a "Migraine," but Still a Headache.

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Smith, Stacy V; Schuster, Nathaniel M

2018-06-14

Recurrent painful ophthalmoplegic neuropathy (RPON), formerly known as ophthalmoplegic migraine, is an uncommon disorder with repeated episodes of ocular cranial nerve neuropathy associated with ipsilateral headache. This review discusses the clinical presentation, current understanding of the pathophysiology, key differential diagnoses, and evaluation and treatment of RPON. The literature is limited due to the rarity of the disorder. Recent case reports and series continue to suggest the age of first attack is most often during childhood or adolescence as well as a female predominance. Multiple recent case reports and series demonstrate focal enhancement of the affected cranial nerve, as the nerve root exits the brainstem. This finding contributed to the current classification of the disorder as a neuropathy, with the present understanding that it is due to a relapsing-remitting inflammatory or demyelinating process. The link to migraine remains a cause of disagreement in the literature. RPON is a complex disorder with features of inflammatory neuropathy and an unclear association with migraine. Regardless, the overall prognosis is good for individual episodes, but permanent nerve damage may accumulate with repeated attacks. A better understanding of the pathogenesis is needed to clarify whether it truly represents a single disorder and to guide its treatment. Until that time, a combined approach with acute and preventive therapies can mitigate acute symptoms as well as attempt to limit recurrence of this disabling syndrome.

Profound and persistent painful paclitaxel peripheral neuropathy in a premenopausal patient.

LENUS (Irish Health Repository)

Quintyne, K I

2011-01-01

The authors herein report the case of a 35-year-old woman undergoing adjuvant therapy for node positive breast cancer, who presented with short and rapidly progressive history of bilateral lower limb symptoms of peripheral neuropathy following therapy with paclitaxel. MRI of her neural axis revealed no leptomeningeal enhancement or focal metastatic lesions. Neurophysiological tests favoured toxic sensory axonal polyneuropathy. She remains symptomatic following discontinuation of therapy 20 months ago, and is under review with pain management.

Effect of Transcutaneous Electrical Nerve Stimulation on Sensation Thresholds in Patients with Painful Diabetic Neuropathy: An Observational Study

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Moharic, Metka

2010-01-01

Transcutaneous electrical nerve stimulation (TENS) is one of the therapies for painful neuropathy. Its analgesic mechanisms probably involve the gate control theory, the physiological block and the endogenous pain inhibitory system. The aim of the study was to determine whether TENS improves small fibre function diminished because of painful…

Expression of macrophage migration inhibitory factor in footpad skin lesions with diabetic neuropathy.

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Up Noh, Sun; Lee, Won-Young; Kim, Won-Serk; Lee, Yong-Taek; Jae Yoon, Kyung

2018-01-01

Background Diabetic neuropathy originating in distal lower extremities is associated with pain early in the disease course, overwhelming in the feet. However, the pathogenesis of diabetic neuropathy remains unclear. Macrophage migration inhibitory factor has been implicated in the onset of neuropathic pain and the development of diabetes. Objective of this study was to observe pain syndromes elicited in the footpad of diabetic neuropathy rat model and to assess the contributory role of migration inhibitory factor in the pathogenesis of diabetic neuropathy. Methods Diabetic neuropathy was made in Sprague Dawley rats by streptozotocin. Pain threshold was evaluated using von Frey monofilaments for 24 weeks. On comparable experiment time after streptozotocin injection, all footpads were prepared for following procedures; glutathione assay, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining, immunohistochemistry staining, real-time reverse transcription polymerase chain reaction, and Western blot. Additionally, human HaCaT skin keratinocytes were treated with methylglyoxal, transfected with migration inhibitory factor/control small interfering RNA, and prepared for real-time reverse transcription polymerase chain reaction and Western blot. Results As compared to sham group, pain threshold was significantly reduced in diabetic neuropathy group, and glutathione was decreased in footpad skin, simultaneously, cell death was increased. Over-expression of migration inhibitory factor, accompanied by low expression of glyoxalase-I and intraepidermal nerve fibers, was shown on the footpad skin lesions of diabetic neuropathy. But, there was no significance in expression of neurotransmitters and inflammatory mediators such as transient receptor potential vanilloid 1, mas-related G protein coupled receptor D, nuclear factor kappa B, tumor necrosis factor-alpha, and interleukin-6 between diabetic neuropathy group and sham group. Intriguingly

High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience.

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Filipczak-Bryniarska, Iwona; Krzyzewski, Roger M; Kucharz, Jakub; Michalowska-Kaczmarczyk, Anna; Kleja, Justyna; Woron, Jarosław; Strzepek, Katarzyna; Kazior, Lucyna; Wordliczek, Jerzy; Grodzicki, Tomasz; Krzemieniecki, Krzysztof

2017-08-17

High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m 2 . Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

Efficacy of spinal cord stimulators in treating peripheral neuropathy: a case series.

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Abd-Elsayed, Alaa; Schiavoni, Nick; Sachdeva, Harsh

2016-02-01

Peripheral neuropathy is a common cause of pain, and it is increasing in prevalence. Peripheral neuropathic pain is very hard to treat and can be resistant to multiple pain management modalities. Our series aimed at testing the efficacy of spinal cord stimulators (SCSs) in treating resistant painful peripheral neuropathy. Case 1: A 79-year-old man presented to our clinic with long-standing history of painful peripheral diabetic neuropathy resistant to conservative management. After failure of all possible modalities, we offered the patient an SCS trial that was very successful, and we proceeded with the permanent implant that continued to help with his pain and allowed the patient to wean down his medications. Case 2: A 60-year-old man presented with chronic peripheral neuropathy secondary to HIV, patient failed all conservative and procedural management. Patient then had an SCS trial that relieved his pain significantly. Unfortunately, we did not proceed with the implant due to deterioration of the patient general health. Case 3: A 39-year-old woman presented with painful peripheral neuropathy secondary to chemotherapy for breast cancer. After failure of medication management and procedures, patient had a SCS trial that improved her pain and we then proceeded with performing the permanent implant that controlled her pain. We presented 3 cases with chronic painful peripheral neuropathy secondary to HIV, diabetes mellitus, and chemotherapy that was resistant to conservative pain management and procedures that was successfully treated with neurostimulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Multimodal assessment of painful peripheral neuropathy induced by chronic oxaliplatin-based chemotherapy in mice

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Dorsey Susan G

2011-04-01

Full Text Available Abstract Background A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by in vivo electrophysiological recording of spinal dorsal horn (SDH wide dynamic range neurons in oxaliplatin-treated mice Results We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH. Conclusions Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds.

From genes to pain: nerve growth factor and hereditary sensory and autonomic neuropathy type V.

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Capsoni, Simona

2014-02-01

Hereditary sensory and autonomic neuropathy type V (HSAN V) is an autosomal recessive disorder characterized by the loss of deep pain perception. The anomalous pain and temperature sensations are due to the absence of nociceptive sensory innervation. The neurotrophin nerve growth factor (NGF), by binding to tropomyosin receptor A (TrkA) and p75NTR receptors, is essential for the development and survival of sensory neurons, and for pain perception during adulthood. Recently a homozygous missense mutation (R100W) in the NGF gene has been identified in HSAN V patients. Interestingly, alterations in NGF signalling, due to mutations in the NGF TRKA gene, have also been involved in another congenital insensitivity to pain, HSAN IV, characterized not only by absence of reaction to painful stimuli, but also anhidrosis and mental retardation. These symptoms are absent in HSAN V patients. Unravelling the mechanisms that underlie the differences between HSAN IV and V could assist in better understanding NGF biology. This review highlights the recent key findings in the understanding of HSAN V, including insights into the molecular mechanisms of the disease, derived from genetic studies of patients with this disorder. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Olesoxime (cholest-4-en-3-one, oxime): Analgesic and neuroprotective effects in a rat model of painful peripheral neuropathy produced by the chemotherapeutic agent, paclitaxel

OpenAIRE

Xiao, Wen Hua; Zheng, Felix Y.; Bennett, Gary J.; Bordet, Thierry; Pruss, Rebecca M.

2009-01-01

Olesoxime is a small cholesterol-like molecule that was discovered in a screening program aimed at finding treatment for amyotrophic lateral sclerosis and other diseases where motor neurons degenerate. In addition to its neuroprotective and pro-regenerative effects on motor neurons in vitro and in vivo, it has been shown to have analgesic effects in rat models of painful peripheral neuropathy due to vincristine and diabetes. We used a rat model of painful peripheral neuropathy produced by the...

Heterogeneity in diabetic distal neuropathy and differential approach to its treatment

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Oksana Evgen'evna Khutornaya

2013-06-01

Full Text Available Aims. To determine the prevalence of painful diabetic neuropathy (PDN, to evaluate the composition and efficacy of pharmacotherapy and to develop a differential algorithm for symptomatic treatment of PDN. Materials and Methods. 4494 outpatient subjects participated in this study. Severity of pain syndrome was assessed with DN4 question- naire (supplemented with NTSS-9 scale and visual analogue scale (VAS. After initial examination, a pharmacological evaluation of treatment was performed. Results. Based on our data, prevalence of diabetic neuropathy was estimated at 54%, with painful form reaching 6.4%. Median age was 57.2?12.1, duration of diabetes mellitus ? 16.5?10.6 years. Type 1 / type 2 ratio equaled 32.4% : 67.6%, male/female ? 29.7%: 70.3%. Median HbA1c level was 8.4?1.6%. Ratio of chronic/acute forms of neuropathy was 267 : 20. Pain severity (as measured by VAS distribution was as following: 15.6% ? severe, 40.6% ? moderate, 12.3% ? mild, and 31.3% ? no pain symptoms. We did not find PDN to be associated with any parameters but sensory deficit (NTSS-9 and NDS: r=0.4; p

An update on electrophysiological studies in neuropathy

DEFF Research Database (Denmark)

Krarup, Christian

2003-01-01

The review concentrates on the use of clinical neurophysiology in peripheral nerve disorders covered in the present issue. It is pertinent to distinguish different types of involvement of fibers in diabetic neuropathy, including the involvement of small and large fibers, to outline the diagnostic...... criteria of inflammatory neuropathies, and to describe the spectrum of peripheral nerve pathophysiology in inherited neuropathies. Painful neuropathies represent a particular challenge to clinical neurophysiology since it is mainly small fibers, which are difficult to study, that are affected....

Pregabalin versus oxcarbazepine in painful diabetic neuropathy in elderly population: Efficacy and safety in terms of pain relief, cognitive function, and overall quality of life

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Syed H Amir

2018-01-01

Full Text Available Background and Aims: The treatment of painful diabetic neuropathy (PDN in elderly patients is challenging considering the adverse effects associated with long term use of drugs. Pregabalin has been recommended as the first line therapy for relief of neuropathic pain in such patients. However, the occurrence of side effects especially cognitive dysfunction and peripheral edema raised concerns during long term therapy in elderly population. Recently, few studies have highlighted the role of oxcarbazepine, a second generation antiepileptic, in PDN. This prospective, randomized, single-blind, parallel-group study was done to compare pregabaline and oxcarbazepine monotherapy in patients of PDN. Materials and Methods: 150 elderly patients of painful diabetic neuropathy, for at least 6 months of duration with an average baseline pain score ≥ 4 on 11 point numeric rating scale (NRS, were divided into two groups to receive either pregabalin 150 mg/day or oxcarbazepine 600 mg/day. Assessment of pain scores, cognitive functions and quality of life were performed at different time intervals during the course of treatment. Results: Patients in both the study groups showed significant reduction in pain scores from the baseline; however no significant differences in pain scores were noted between the two groups during the course of treatment. The incidence of cognitive dysfunction as measured by BCRS score was significantly more in pregabalin group while no significant changes were noted in oxcarbazepine group. The overall quality of life as demonstrated by SF12 scores was significantly better in both the study groups as compared to baseline. Conclusion: Oxcarbazepine can be used as an alternative to pregabalin in elderly patients with PDN considering the similar degree of pain relief and better cognitive profile.

Evaluation of pre-existing neuropathy and bortezomib retreatment as risk factors to develop severe neuropathy in a mouse model.

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Bruna, Jordi; Alé, Albert; Velasco, Roser; Jaramillo, Jessica; Navarro, Xavier; Udina, Esther

2011-09-01

Pre-existing neuropathy, a not uncommon feature in oncologic patients, is a potential but non-confirmed risk factor to develop early or severe chemotherapy-induced neuropathy. The main goal of this study is to evaluate the role of pre-existing neuropathy induced by vincristine (VNC) or bortezomib (BTZ) as a risk factor to develop more severe BTZ-induced neuropathy in a mouse model. VNC, at doses of 1 and 1.5 mg/kg given twice per week for 4 weeks, induced a moderate and severe sensory-motor neuropathy, primarily axonal, with predominant involvement of myelinated sensory axons. The neuropathy induced by BTZ at dose of 1 mg/kg given twice per week for 6 weeks was a mild axonal sensory neuropathy involving myelinated and unmyelinated fibers. The neuropathy in mice previously treated and retreated with the same schedule of BTZ after 4 weeks of washout period was similar in profile and severity to the one observed after the first treatment. When basal neuropathy was classified as moderate (most of BTZ-treated animals) or severe (all VNC-treated animals and two BTZ-treated animals), there was a more marked decline in sensory nerve function during BTZ retreatment in the group with basal severe neuropathy (-86%) than in the groups with basal mild (-57%) or without neuropathy (-52%; p < 0.001). Histopathological findings supported the functional results. Therefore, this study shows that the presence of a severe neuropathy previous to treatment with an antitumoral agent, such as BTZ, results in a more marked involvement of peripheral nerves. © 2011 Peripheral Nerve Society.

Peripheral neuropathy in prediabetes and the metabolic syndrome.

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Stino, Amro M; Smith, Albert G

2017-09-01

Peripheral neuropathy is a major cause of disability worldwide. Diabetes is the most common cause of neuropathy, accounting for 50% of cases. Over half of people with diabetes develop neuropathy, and diabetic peripheral neuropathy (DPN) is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. Most patients with non-diabetic neuropathy have cryptogenic sensory peripheral neuropathy (CSPN). A growing body of literature links prediabetes, obesity and metabolic syndrome to the risk of both DPN and CSPN. This association might be particularly strong in type 2 diabetes patients. There are no effective medical treatments for CSPN or DPN, and aggressive glycemic control is an effective approach to neuropathy risk reduction only in type 1 diabetes. Several studies suggest lifestyle-based treatments that integrate dietary counseling with exercise might be a promising therapeutic approach to early DPN in type 2 diabetes and CSPN associated with prediabetes, obesity and metabolic syndrome. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management.

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Watson, James C; Dyck, P James B

2015-07-01

Peripheral neuropathy is one of the most prevalent neurologic conditions encountered by physicians of all specialties. Physicians are faced with 3 distinct challenges in caring for patients with peripheral neuropathy: (1) how to efficiently and effectively screen (in less than 2 minutes) an asymptomatic patient for peripheral neuropathy when they have a disorder in which peripheral neuropathy is highly prevalent (eg, diabetes mellitus), (2) how to clinically stratify patients presenting with symptoms of neuropathy to determine who would benefit from specialty consultation and what testing is appropriate for those who do not need consultation, and (3) how to treat the symptoms of painful peripheral neuropathy. In this concise review, we address these 3 common clinical scenarios. Easily defined clinical patterns of involvement are used to identify patients in need of neurologic consultation, the yield of laboratory and other diagnostic testing is reviewed for the evaluation of length-dependent, sensorimotor peripheral neuropathies (the most common form of neuropathy), and an algorithmic approach with dosing recommendations is provided for the treatment of neuropathic pain associated with peripheral neuropathy. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Imaging of neuropathies about the hip

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Martinoli, Carlo, E-mail: carlo.martinoli@unige.it [Radiologia – DISC, Università di Genova, Largo Rosanna Benzi 8, I-16132 Genoa (Italy); Miguel-Perez, Maribel [Unit of Human Anatomy and Embryology, Department of Pathology and Experimental Therapy, Faculty of Medicine (C Bellvitge), University of Barcelona, Barcelona (Spain); Padua, Luca [Fondazione Don Gnocchi Onlus and Department of Neurology, Policlinico “A. Gemelli”, Università Cattolica del Sacro Cuore, Rome (Italy); Gandolfo, Nicola [IM2S – Institut Monégasque de Médecine and Chirurgie Sportive, Montecarlo (Monaco); Zicca, Anna [Radiologia – DISC, Università di Genova, Largo Rosanna Benzi 8, I-16132 Genoa (Italy); Tagliafico, Alberto [Radiologia – National Institute for Cancer Research, Genoa (Italy)

2013-01-15

Neuropathies about the hip may be cause of chronic pain and disability. In most cases, these conditions derive from mechanical or dynamic compression of a segment of a nerve within a narrow osteofibrous tunnel, an opening in a fibrous structure, or a passageway close to a ligament or a muscle. Although the evaluation of nerve disorders primarily relies on neurological examination and electrophysiology, diagnostic imaging is currently used as a complement to help define the site and aetiology of nerve compression and exclude other disease possibly underlying the patient’ symptoms. Diagnosis of entrapment neuropathies about the hip with US and MR imaging requires an in-depth knowledge of the normal imaging anatomy and awareness of the anatomic and pathologic factors that may predispose or cause a nerve injury. Accordingly, the aim of this article is to provide a comprehensive review of hip neuropathies with an emphasis on the relevant anatomy, aetiology, clinical presentation, and their imaging appearance. The lateral femoral cutaneous neuropathy (meiralgia paresthetica), femoral neuropathy, sciatic neuropathy, obturator neuropathy, superior and inferior gluteal neuropathies and pudendal neuropathy will be discussed.

The Therapeutic Potential of Monocyte/Macrophage Manipulation in the Treatment of Chemotherapy-Induced Painful Neuropathy

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Karli Montague

2017-11-01

Full Text Available In cancer treatments a dose-limiting side-effect of chemotherapeutic agents is the development of neuropathic pain, which is poorly managed by clinically available drugs at present. Chemotherapy-induced painful neuropathy (CIPN is a major cause of premature cessation of treatment and so a greater understanding of the underlying mechanisms and the development of novel, more effective therapies, is greatly needed. In some cases, only a weak correlation between chemotherapy-induced pain and neuronal damage is observed both clinically and preclinically. As such, a critical role for non-neuronal cells, such as immune cells, and their communication with neurons in CIPN has recently been appreciated. In this mini-review, we will discuss preclinical evidence for the role of monocytes/macrophages in the periphery in CIPN, with a focus on that which is associated with the chemotherapeutic agents vincristine and paclitaxel. In addition we will discuss the potential mechanisms that regulate monocyte/macrophage–neuron crosstalk in this context. Informed by preclinical data, we will also consider the value of monocytes/macrophages as therapeutic targets for the treatment of CIPN clinically. Approaches that manipulate the signaling pathways discussed in this review show both promise and potential pitfalls. Nonetheless, they are emerging as innovative therapeutic targets with CX3CL1/R1-regulation of monocyte/macrophage–neuron communication currently emerging as a promising front-runner.

Pain in Patients with Pancreatic Cancer: Prevalence, Mechanisms, Management and Future Developments.

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Koulouris, Andreas I; Banim, Paul; Hart, Andrew R

2017-04-01

Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients' quality of life and survival.

Identification, prevalence, and treatment of painful diabetic neuropathy in patients from a rural area in South Carolina

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Pruitt III J

2017-04-01

Full Text Available Jimmy Pruitt III,1 Carolina Moracho-Vilrriales,1,2 Tiffaney Threatt,3 Sarah Wagner,3 Jun Wu,1 E Alfonso Romero-Sandoval1 1Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, Clinton, SC, USA; 2Department of Biochemistry and Biotechnology, University of Alcalá de Henares, Madrid, Spain; 3Department of Pharmacy Practice, Presbyterian College School of Pharmacy, Clinton, SC, USA Abstract: Diabetic peripheral neuropathy (DPN represents significant burdens to many patients and the public health-care system. Patients with diabetes in rural areas have higher risk of developing complications and having less access to proper treatment. We studied a rural population of patients with diabetes who attended a pharmacist-led free clinic for a diabetic education program. Our objectives were to 1 determine the prevalence of DPN and painful diabetic neuropathy (p-DN in patients with type 2 diabetes; 2 assess the proportion of patients with DPN and p-DN left undocumented upon physician referral to a pharmacist-led free clinic; and 3 determine the appropriateness of pain medication regimen. We performed a retrospective analysis of clinical records of patients from the Presbyterian College School of Pharmacy (PCSP Wellness Center located in Clinton, SC. Diagnoses of DPN and/or p-DN were obtained from referral notes in the clinical records and compared with results from foot examinations performed in the free clinic and clinical features. Medication regimens were also obtained and compared using American Academy of Neurology (AAN treatment guidelines. Within our study population (n=111, the prevalence of DPN was 62.2% (national average of 28%–45% and that of p-DN was 23.4% (national average of 11%–24%. In p-DN patients (n=26, 53.8% (n=14 had a documented diagnosis of p-DN by the referring physician, and 46.2% (n=12 were identified by the pharmacists. A total of 95% (19 of 20 of the patients treated for p

Whole-body vibration as a modality for the rehabilitation of peripheral neuropathies: implications for cancer survivors suffering from chemotherapy-induced peripheral neuropathy

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Anna L.J. Verhulst

2015-02-01

Full Text Available The objective was to study the effect of whole-body vibration (WBV on strength, balance and pain in patients with peripheral neuropathies and to consider its significance for the rehabilitation of patients suffering from chemotherapy-induced peripheral neuropathy (CIPN. Using a broad search strategy, PubMed was searched for clinical trials on WBV interventions aimed at improving strength, balance or pain in patients with peripheral neuropathies, which were published in English until 5th June 2014. The search was performed by the first author and generated a total of 505 results, which yielded 5 articles that met the inclusion criteria, being studies: i published in English; ii involving adult human subjects’ peripheral neuropathies; iii evaluating the effect of WBV as a therapeutic intervention; and iv reporting findings for at least one of the following outcomes: strength, balance or pain. Methodological quality of included studies was assessed independently by first and second author, using the physiotherapy evidence database scale. The overall methodological quality of included studies was low. Two studies found a beneficial effect of WBV on neuropathic pain, but another study failed to find the same effect. One study found significant improvements in both muscle strength and balance, while another study found improvements only in some, but not all, of the applied tests to measure muscle strength and balance. The results of this literature search suggest insufficient evidence to assess the effectiveness for the effects of WBV on neuropathic pain, muscle strength and balance in patients with peripheral neuropathies. More high-quality trials are needed to guide the optimization of rehabilitation programs for cancer survivors with CIPN in particular.

Delayed ethylene glycol poisoning presenting with abdominal pain and multiple cranial and peripheral neuropathies: a case report

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Sran Hersharan

2010-07-01

Full Text Available Abstract Introduction Ethylene glycol poisoning may pose diagnostic difficulties if the history of ingestion is not volunteered, or if the presentation is delayed. This is because the biochemical features of high anion-gap metabolic acidosis and an osmolar gap resolve within 24 to 72 hours as the ethylene glycol is metabolized to toxic metabolites. This case illustrates the less well-known clinical features of delayed ethylene glycol poisoning, including multiple cranial and peripheral neuropathies, and the clinical findings which may point towards this diagnosis in the absence of a history of ingestion. Case presentation A 53-year-old Afro-Caribbean man presented with vomiting, abdominal pain and oliguria, and was found to have acute renal failure requiring emergency hemofiltration, and raised inflammatory markers. Computed tomography imaging of the abdomen revealed the appearance of bilateral pyelonephritis, however he failed to improve with broad-spectrum antibiotics, and subsequently developed multiple cranial neuropathies and increasing obtundation, necessitating intubation and ventilation. Computed tomography of the brain showed no focal lesions, and a lumbar puncture revealed a raised cerebrospinal fluid opening pressure and cyto-albuminological dissociation. Nerve conduction studies revealed a sensorimotor radiculoneuropathy mimicking a Guillain-Barre type lesion with an atypical distribution. It was only about two weeks after presentation that the history of ethylene glycol ingestion one week before presentation was confirmed. He had a slow recovery on the intensive care unit, requiring renal replacement therapy for eight weeks, and complicated by acute respiratory distress syndrome, neuropathic pain and a slow neurological recovery requiring prolonged rehabilitation. Conclusions Although neuropathy as a result of ethylene glycol poisoning has been described in a few case reports, all of these were in the context of a known history of

[Diabetic neuropathy: therapeutic nihilism is no longer acceptable].

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Haslbeck, Manfred

2007-05-21

The repeatedly expressed doubts about the value of an effective therapy for diabetic neuropathies are no longer acceptable. Today a number of excellent longitudinal and cross-sectional studies, i.e. DCCT, Steno 2, DCCT/EDIC, European Diabetes Prospective Complications Study, are available. The attending physician should make every effort to diagnose diabetic neuropathies as soon as possible with all their multivarious manifestations. Treatment must be promptly, aggressively and multifactorially as described in evidence-based guidelines. In principle, the same risk factors apply to neuropathy in type 1 and type 2 diabetes as for macro-angiopathy and microangiopathy. Therapy focuses on establishing near-normal diabetes and blood pressure control, lipid management, intensive patient education, avoidance of exogenous noxae such as alcohol and nicotine and if necessary, an effective therapy of neuropathic pain. The objective of all diagnostic and preventive efforts must be always to avoid the development of the diabetic neuropathic foot syndrome, which is the most important end stage of somatic and autonomic diabetic neuropathy.

CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy.

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Huang, Zhen-Zhen; Li, Dai; Liu, Cui-Cui; Cui, Yu; Zhu, He-Quan; Zhang, Wen-Wen; Li, Yong-Yong; Xin, Wen-Jun

2014-08-01

Painful peripheral neuropathy is a dose-limiting side effect of paclitaxel therapy, which hampers the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms remain largely unknown. Here we showed that the clinically relevant dose of paclitaxel (3×8mg/kg, cumulative dose 24mg/kg) induced significant upregulation of the chemokine CX3CL1 in the A-fiber primary sensory neurons in vivo and in vitro and infiltration of macrophages into the dorsal root ganglion (DRG) in rats. Paclitaxel treatment also increased cleaved caspase-3 expression, induced the loss of primary afferent terminal fibers and decreased sciatic-evoked A-fiber responses in the spinal dorsal horn, indicating DRG neuronal apoptosis induced by paclitaxel. In addition, the paclitaxel-induced DRG neuronal apoptosis occurred exclusively in the presence of macrophage in vitro study. Intrathecal or systemic injection of CX3CL1 neutralizing antibody blocked paclitaxel-induced macrophage recruitment and neuronal apoptosis in the DRG, and also attenuated paclitaxel-induced allodynia. Furthermore, depletion of macrophage by systemic administration of clodronate inhibited paclitaxel-induced allodynia. Blocking CX3CL1 decreased activation of p38 MAPK in the macrophage, and inhibition of p38 MAPK activity blocked the neuronal apoptosis and development of mechanical allodynia induced by paclitaxel. These findings provide novel evidence that CX3CL1-recruited macrophage contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluating the Measurement Properties of the Self-Assessment of Treatment Version II, Follow-Up Version, in Patients with Painful Diabetic Peripheral Neuropathy

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Floortje van Nooten

2017-01-01

Full Text Available Background. The Self-Assessment of Treatment version II (SAT II measures treatment-related improvements in pain and impacts and impressions of treatment in neuropathic pain patients. The measure has baseline and follow-up versions. This study assesses the measurement properties of the SAT II. Methods. Data from 369 painful diabetic peripheral neuropathy (PDPN patients from a phase III trial assessing capsaicin 8% patch (Qutenza® efficacy and safety were used in these analyses. Reliability, convergent validity, known-groups validity, and responsiveness (using the Brief Pain Inventory-Diabetic Neuropathy [BPI-DN] and Patient Global Impression of Change [PGIC] analyses were conducted, and minimally important differences (MID were estimated. Results. Exploratory factor analysis supported a one-factor solution for the six impact items. The SAT II has good internal consistency (Cronbach’s alpha: 0.96 and test-retest reliability (intraclass correlation coefficients: 0.62–0.88. Assessment of convergent validity showed moderate to strong correlations with change in other study endpoints. Scores varied significantly by level of pain intensity and sleep interference (p<0.05 defined by the BPI-DN. Responsiveness was shown based on the PGIC. MID estimates ranged from 1.2 to 2.4 (pain improvement and 1.0 to 2.0 (impact scores. Conclusions. The SAT II is a reliable and valid measure for assessing treatment improvement in PDPN patients.

Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain.

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Labuz, Dominika; Celik, Melih Ö; Zimmer, Andreas; Machelska, Halina

2016-09-08

Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment.

Heterogeneity in diabetic distal neuropathy and differential approach to its treatment

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O E Khutornaya

2013-06-01

Full Text Available Aims. To determine the prevalence of painful diabetic neuropathy (PDN, to evaluate the composition and efficacy of pharmacotherapy and to develop a differential algorithm for symptomatic treatment of PDN.Materials and Methods. 4494 outpatient subjects participated in this study. Severity of pain syndrome was assessed with DN4 question- naire (supplemented with NTSS-9 scale and visual analogue scale (VAS. After initial examination, a pharmacological evaluation of treatment was performed.Results. Based on our data, prevalence of diabetic neuropathy was estimated at 54%, with painful form reaching 6.4%. Median age was 57.2±12.1, duration of diabetes mellitus – 16.5±10.6 years. Type 1 / type 2 ratio equaled 32.4% : 67.6%, male/female – 29.7%: 70.3%. Median HbA1c level was 8.4±1.6%. Ratio of chronic/acute forms of neuropathy was 267 : 20. Pain severity (as measured by VAS distribution was as following: 15.6% – severe, 40.6% – moderate, 12.3% – mild, and 31.3% – no pain symptoms. We did not find PDN to be associated with any parameters but sensory deficit (NTSS-9 and NDS: r=0.4; p <0.001. 21% of patients with chronic painful neuropathy (CPN demonstrated allodynia and hyperalgesia besides typical symptoms. 97.9% of patients were previ- ously treated with “pathogenetic” agents, 2.1% received anticonvulsants; overall efficiency was estimated at 22%. Patients with CPN and allodynia did not respond to treatment with alpha-lipoic acid (ALA, but pregabalin was efficient. After the examination treatment composition was adjusted as follows: treatment was ceased in 23% of patients, 11.9% received ALA, 53.6% – anticonvulsants, and11.5% – antidepressants; overall efficiency was estimated at 75%.Conclusion. Prevalence of PDN is relatively low. 15.6% of patients suffer from severe pain. Neuropathic pain intensity correlates only with sensory deficit and is not dependent on any other parameters. CPN consists of two forms with higher and lower

Ophthalmople gic cranial neuropathy: clinical case

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N. S. Dozorova; A. S. Kotov; E. V. Mukhina

2018-01-01

Ophthalmoplegic cranial neuropathy (OCN) is a disease with unknown etiology, which manifests itself by episodes of intense headache, accompanied by completely or partially reversible dysfunction of the oculomotor nerve: ptosis, mydriasis and ophthalmoplegia. It is assumed that the pathology is demyelinating in nature, therefore in the International classification of headaches OCN excluded from rubric migraine and related to the painful cranial neuropathies. The question of the prevention and ...

An integrated perspective on diabetic, alcoholic, and drug-induced neuropathy, etiology, and treatment in the US

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Zeng L

2017-01-01

efforts to develop additional treatments for NeuP. Keywords: small-fiber neuropathy, pain, alcohol use disorder, diabetes mellitus, chemotherapy, opioid receptors

Topiramate-induced Neuropathy Mimicking Carpal Tunnel Syndrome: A Case Report

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Jigar S. Gandhi

2018-01-01

Full Text Available Carpel tunnel syndrome (CTS is a condition in which median nerve compression results in paresthesias and pain in thewrist and hand. We are going to report a rare case of topiramate-induced neuropathy which clinically resembles CTS.Discontinuation of topiramate resulted in spontaneous resolution of numbness, paresthesia and pain in a few days. Highclinical suspicion is advised in patients who are on topiramate and present with signs of compressive neuropathy.

Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy.

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Winkler, G; Pál, B; Nagybéganyi, E; Ory, I; Porochnavec, M; Kempler, P

1999-03-01

The therapeutic effectiveness of a benfotiamine (CAS 22457-89-2)-vitamin B combination (Milgamma-N), administered in high (4 x 2 capsules/day, = 320 mg benfotiamine/day) and medium doses (3 x 1 capsules/day), was compared to a monotherapy with benfotiamine (Benfogamma) (3 x 1 tablets/day, = 150 mg benfotiamine/day) in diabetic patients suffering from painful peripheral diabetic neuropathy (DNP). In a 6-week open clinical trial, 36 patients (aged 40 to 70 yrs) having acceptable metabolic control (HbA1c benfotiamine (p benfotiamine is most effective in large doses, although even in smaller daily dosages, either in combination or in monotherapy, it is effective.

Inherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy.

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Chance, Phillip F

2006-01-01

Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers. The histopathological changes observed in peripheral nerves of HNPP patients include segmental demyelination and tomaculous or "sausage-like" formations. Mild overlap of clinical features with Charcot-Marie-Tooth (CMT) disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed as having CMT1. HNPP and CMT1 are both demyelinating neuropathies, however, their clinical, pathological, and electrophysiological features are quite distinct. HNPP is most frequently associated with a 1.4-Mb pair deletion on chromosome 17p12. A duplication of the identical region leads to CMT1A. Both HNPP and CMT1A result from a dosage effect of the PMP22 gene, which is contained within the deleted/duplicated region. This is reflected in reduced mRNA and protein levels in sural nerve biopsy samples from HNPP patients. Treatment for HNPP consists of preventative and symptom-easing measures. Hereditary neuralgic amyotrophy (HNA; also called familial brachial plexus neuropathy) is an autosomal-dominant disorder causing episodes of paralysis and muscle weakness initiated by severe pain. Individuals with HNA may suffer repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb. The onset of HNA is at birth or later in childhood with prognosis for recovery usually favorable; however, persons with HNA may have permanent residual neurological dysfunction following attack(s). Episodes are often

Peripheral Neuropathy and Nerve Compression Syndromes in Burns.

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Strong, Amy L; Agarwal, Shailesh; Cederna, Paul S; Levi, Benjamin

2017-10-01

Peripheral neuropathy and nerve compression syndromes lead to substantial morbidity following burn injury. Patients present with pain, paresthesias, or weakness along a specific nerve distribution or experience generalized peripheral neuropathy. The symptoms manifest at various times from within one week of hospitalization to many months after wound closure. Peripheral neuropathy may be caused by vascular occlusion of vasa nervorum, inflammation, neurotoxin production leading to apoptosis, and direct destruction of nerves from the burn injury. This article discusses the natural history, diagnosis, current treatments, and future directions for potential interventions for peripheral neuropathy and nerve compression syndromes related to burn injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute nutritional axonal neuropathy.

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Hamel, Johanna; Logigian, Eric L

2018-01-01

This study describes clinical, laboratory, and electrodiagnostic features of a severe acute axonal polyneuropathy common to patients with acute nutritional deficiency in the setting of alcoholism, bariatric surgery (BS), or anorexia. Retrospective analysis of clinical, electrodiagnostic, and laboratory data of patients with acute axonal neuropathy. Thirteen patients were identified with a severe, painful, sensory or sensorimotor axonal polyneuropathy that developed over 2-12 weeks with sensory ataxia, areflexia, variable muscle weakness, poor nutritional status, and weight loss, often with prolonged vomiting and normal cerebrospinal fluid protein. Vitamin B6 was low in half and thiamine was low in all patients when obtained before supplementation. Patients improved with weight gain and vitamin supplementation, with motor greater than sensory recovery. We suggest that acute or subacute axonal neuropathy in patients with weight loss or vomiting associated with alcohol abuse, BS, or dietary deficiency is one syndrome, caused by micronutrient deficiencies. Muscle Nerve 57: 33-39, 2018. © 2017 Wiley Periodicals, Inc.

Intravenous Lidocaine Infusion to Treat Chemotherapy-Induced Peripheral Neuropathy.

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Papapetrou, Peter; Kumar, Aashish J; Muppuri, Rudram; Chakrabortty, Shushovan

2015-11-01

Chemotherapy-induced peripheral neuropathy is a debilitating side effect of chemotherapy, which manifests as paresthesias, dysesthesias, and numbness in the hands and feet. Numerous chemoprotective agents and treatments have been used with limited success to treat chemotherapy-induced peripheral neuropathy. We report a case in which a patient presenting with chemotherapy-induced peripheral neuropathy received an IV lidocaine infusion over the course of 60 minutes with complete symptomatic pain relief for a prolonged period of 2 weeks.

77 FR 59930 - Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public...

Science.gov (United States)

2012-10-01

...] Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public Workshop... to the clinical development of disease-modifying agents for the treatment of peripheral neuropathy... disease-modifying products for the management of peripheral neuropathy. Date and Time: The public workshop...

The relationship between numbness, tingling and shooting/burning pain in patients with chemotherapy-induced peripheral neuropathy (CIPN) as measured by the EORTC QLQ-CIPN20 instrument, N06CA

NARCIS (Netherlands)

Wolf, S.L.; Barton, D.L.; Qin, R.; Wos, E.J.; Sloan, J.A.; Liu, H.; Aaronson, N.K.; Satele, D.V.; Mattar, B.I.; Green, N.B.; Loprinzi, C.L.

2012-01-01

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is characterized by numbness, tingling, and shooting/burning pain. This analysis was performed to describe the relationship between numbness, tingling, and shooting/burning pain in patients with CIPN, as reported using the EORTC

Polaprezinc reduces paclitaxel-induced peripheral neuropathy in rats without affecting anti-tumor activity

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Kuniaki Tsutsumi; Takanori Kaname; Haruka Shiraishi; Takehiro Kawashiri; Nobuaki Egashira

2016-01-01

Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily) inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7) and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect th...

Definition and diagnosis of small fiber neuropathy: consensus from the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology

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Francisco de Assis Aquino Gondim

Full Text Available ABSTRACT The aim of this study was to describe the results of a Brazilian Consensus on Small Fiber Neuropathy (SFN. Fifteen neurologists (members of the Brazilian Academy of Neurology reviewed a preliminary draft. Eleven panelists got together in the city of Fortaleza to discuss and finish the text for the manuscript submission. Small fiber neuropathy can be defined as a subtype of neuropathy characterized by selective involvement of unmyelinated or thinly myelinated sensory fibers. Its clinical picture includes both negative and positive manifestations: sensory (pain/dysesthesias/pruritus or combined sensory and autonomic complaints, associated with an almost entirely normal neurological examination. Standard electromyography is normal. A growing list of medical conditions is associated with SFN. The classification of SFN may also serve as a useful terminology to uncover minor discrepancies in the normal values from different neurophysiology laboratories. Several techniques may disclose sensory and/or autonomic impairment. Further studies are necessary to refine these techniques and develop specific therapies.

Polaprezinc reduces paclitaxel-induced peripheral neuropathy in rats without affecting anti-tumor activity

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Kuniaki Tsutsumi

2016-06-01

Full Text Available Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7 and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect the anti-tumor activity of paclitaxel in cultured cell lines or tumor-bearing mice. These results suggest a clinical indication for polaprezinc in the prevention of paclitaxel-induced neuropathy.

A cross-sectional study examining the psychometric properties of the painDETECT measure in neuropathic pain

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Cappelleri JC

2015-04-01

Full Text Available Joseph C Cappelleri,1 Vijaya Koduru,2 E Jay Bienen,3 Alesia Sadosky41Pfizer Inc, Groton, CT, USA; 2Eliassen Group, New London, CT, USA; 3Outcomes Research Consultant, New York, NY, USA; 4Pfizer Inc, New York, NY, USABackground: Similarities and differences on the nine-item and seven-item versions of painDETECT, a patient-reported screener to identify neuropathic pain (NeP, have not been psychometrically explored across NeP conditions.Methods: Scores on the nine-item painDETECT (seven pain symptom items, one pain course pattern item, one pain radiation item range from -1 to 38; scores ≥19 indicate NeP is likely (>90% probability. The seven-item version (only pain symptoms score range is 0 to 35. painDETECT was administered to subjects with confirmed diagnoses of human immunodeficiency virus-related peripheral NeP (HIVP (n=103, spinal cord injury-related NeP (SCI (n=103, small fiber neuropathy (n=100, painful diabetic peripheral neuropathy (n=112, posttrauma/postsurgical NeP (n=100, and NeP in chronic low back pain (n=106 identified during office visits to US community-based physicians. Analysis of covariance compared mean scores (adjusted for age, sex, race, ethnicity, time since NeP diagnosis, and number of comorbidities on the nine-item and seven-item versions of painDETECT. Cronbach's alpha assessed internal consistency reliability, and corrected item-to-total correlations assessed item-level discrimination.Results: The adjusted mean nine-item scores ranged from 21.0 (SCI to 24.3 (small fiber neuropathy. Differences between conditions were either trivial or small-to-medium in magnitude. Cronbach's alpha gave overall internal consistency reliability of 0.76, with a range of 0.63 (SCI to 0.82 (HIVP. Mean scores and Cronbach's alphas for the seven-item version were generally similar to the nine-item version. Corrected item-to-total correlations adequately discriminated all pain symptom items on both painDETECT versions for each condition (0.3�

Cold therapy to prevent paclitaxel-induced peripheral neuropathy.

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Griffiths, Claire; Kwon, Nancy; Beaumont, Jennifer L; Paice, Judith A

2018-04-21

This case-control study was designed to assess the efficacy of cryotherapy to prevent paclitaxel-induced painful peripheral neuropathy in women with breast cancer. Participants served as their own paired control, with randomization of the cooled glove/sock to either the dominant or the non-dominant hand/foot, worn for 15 min prior to, during, and 15 min after completion of the paclitaxel infusion. Outcome measures included the Neuropathic Pain Symptom Inventory, the Brief Pain Inventory, and quantitative sensory testing. Data were measured at each of six time points-baseline, post-treatment (approximately 2 weeks after the last paclitaxel infusion), and at the first, fifth, ninth, and final weekly paclitaxel treatments. Of 29 randomized participants, 20 (69%) received at least one cryotherapy treatment, and 11 (38%) received all four cryotherapy treatments. Ten (34%) participants could not tolerate the cryotherapy, and six (21%) declined further participation at some point during the trial. Only seven participants (24%) were available for the final post-chemotherapy QST and questionnaires. There were no significant differences in measures of neuropathy or pain between treated and untreated hands or feet. Strategies to prevent painful peripheral neuropathy are urgently needed. In this current trial, dropout due to discomfort precluded adequate power to fully understand the potential benefits of cryotherapy. Much more research is needed to discover safe and effective preventive strategies that can be easily implemented within busy infusion centers.

Paraneoplastic neuropathies.

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Antoine, Jean-Christophe; Camdessanché, Jean-Philippe

2017-10-01

To review recent advances in paraneoplastic neuropathies with emphasis on their definition, different forms and therapeutic development. A strict definition of definite paraneoplastic neuropathies is necessary to avoid confusion. With carcinoma, seronegative sensory neuronopathies and neuronopathies and anti-Hu and anti-CV2/Contactin Response Mediator Protein 5 antibodies are the most frequent. With lymphomas, most neuropathies occur with monoclonal gammopathy including AL amyloidosis, Polyneuropathy-Organomegaly-Endocrinopathy-M component-Skin changes (POEMS) syndrome, type I cryoglobulinemia and antimyelin-associated glycoprotein (MAG) neuropathies and Waldenström's disease. Neuropathies improving with tumor treatment are occasional, occur with a variety of cancer and include motor neuron disease, chronic inflammatory demyelinating neuropathy and nerve vasculitis. If antibodies toward intracellular antigens are well characterized, it is not the case for antibodies toward cell membrane proteins. Contactin-associated protein-2 antibodies occur with neuromyotonia and thymoma with the Morvan's syndrome in addition to Netrin 1 receptor antibodies but may not be responsible for peripheral nerve hyperexcitability. The treatment of AL amyloidosis, POEMS syndrome, anti-MAG neuropathy and cryoglobulinemia is now relatively well established. It is not the case with onconeural antibodies for which the rarity of the disorders and a short therapeutic window are limiting factors for the development of clinical trials. A strict definition of paraneoplastic neuropathies helps their identification and is necessary to allow an early diagnosis of the underlying tumor.

Cardiac arrest after anesthetic management in a patient with hereditary sensory autonomic neuropathy type IV

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Yakup Ergül

2011-01-01

Full Text Available Hereditary sensory autonomic neuropathy type IV is a rare disorder with an autosomal recessive transmission and characterized by self-mutilation due to a lack in pain and heat sensation. Recurrent hyperpyrexia and anhydrosis are seen in patients as a result of a lack of sweat gland innervation. Self-mutilation and insensitivity to pain result in orthopedic complications and patients undergone recurrent surgical interventions with anesthesia. However, these patients are prone to perioperative complications such as hyperthermia, hypothermia, and cardiac complications like bradycardia and hypotension. We report a 5-year-old boy with hereditary sensory autonomic neuropathy type IV, developing hyperpyrexia and cardiac arrest after anesthesia.

Cardiac arrest after anesthetic management in a patient with hereditary sensory autonomic neuropathy type IV.

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Ergül, Yakup; Ekici, Bariş; Keskin, Sabiha

2011-01-01

Hereditary sensory autonomic neuropathy type IV is a rare disorder with an autosomal recessive transmission and characterized by self-mutilation due to a lack in pain and heat sensation. Recurrent hyperpyrexia and anhydrosis are seen in patients as a result of a lack of sweat gland innervation. Self-mutilation and insensitivity to pain result in orthopedic complications and patients undergone recurrent surgical interventions with anesthesia. However, these patients are prone to perioperative complications such as hyperthermia, hypothermia, and cardiac complications like bradycardia and hypotension. We report a 5-year-old boy with hereditary sensory autonomic neuropathy type IV, developing hyperpyrexia and cardiac arrest after anesthesia.

Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy

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Couture Réjean

2010-06-01

Full Text Available Abstract Background The pro-nociceptive kinin B1 receptor (B1R is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ-diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. Methods Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p., and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p. were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I-HPP-desArg10-Hoe 140 were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK and antagonists (SSR240612 and R-715 were measured on neuropathic pain manifestations. Results STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1β, TNF-α, TRPV1 and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. Conclusion The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats.

Diagnostic approach to peripheral neuropathy

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Misra Usha

2008-01-01

Full Text Available Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG. EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG. Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them.

Peripheral neuropathy in HIV: an analysis of evidence-based approaches.

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Nicholas, Patrice K; Corless, Inge B; Evans, Linda A

2014-01-01

Peripheral neuropathy is a common and vexing symptom for people living with HIV infection (PLWH). Neuropathy occurs in several different syndromes and is identified in the literature as distal sensory polyneuropathy or distal sensory peripheral neuropathy. More recently, the HIV literature has focused on the syndrome as painful HIV-associated sensory neuropathy, addressing the symptom rather than the underlying pathophysiology. Assessment of neuropathy in PLWH is critical and must be incorporated into nursing practice for each visit. Neuropathy has been attributed to the direct effects of HIV, exposure to antiretroviral medications (particularly the nucleoside reverse transcriptase inhibitors), advanced immune suppression, and comorbid tuberculosis infection and exposure to antituberculosis medications. Evidence supports the importance of addressing neuropathy in PLWH with pharmacologic treatment regimens and complementary/alternative approaches. This paper examines the pathophysiology, evidence, and approaches to managing peripheral neuropathy. A case study has been included to illustrate a patient's experience with neuropathy symptoms. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments

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Tesfaye, Solomon; Boulton, Andrew J M; Dyck, Peter J

2010-01-01

Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13-18 October 2009, expert panels were convened to provide updates on cla...... on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs.......Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13-18 October 2009, expert panels were convened to provide updates...

Approach to Peripheral Neuropathy for the Primary Care Clinician.

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Doughty, Christopher T; Seyedsadjadi, Reza

2018-02-02

Peripheral neuropathy is commonly encountered in the primary care setting and is associated with significant morbidity, including neuropathic pain, falls, and disability. The clinical presentation of neuropathy is diverse, with possible symptoms including weakness, sensory abnormalities, and autonomic dysfunction. Accordingly, the primary care clinician must be comfortable using the neurologic examination-including the assessment of motor function, multiple sensory modalities, and deep tendon reflexes-to recognize and characterize neuropathy. Although the causes of peripheral neuropathy are numerous and diverse, careful review of the medical and family history coupled with limited, select laboratory testing can often efficiently lead to an etiologic diagnosis. This review offers an approach for evaluating suspected neuropathy in the primary care setting. It will describe the most common causes, suggest an evidence-based workup to aid in diagnosis, and highlight recent evidence that allows for selection of symptomatic treatment of patients with neuropathy. Copyright © 2018 Elsevier Inc. All rights reserved.

Hereditary sensory neuropathy type I

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Auer-Grumbach Michaela

2008-03-01

Full Text Available Abstract Hereditary sensory neuropathy type I (HSN I is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7 identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN, especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra

Hereditary sensory neuropathy type I.

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Auer-Grumbach, Michaela

2008-03-18

Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin

The impact of bodyweight and body condition on behavioral testing for painful diabetic neuropathy in the streptozotocin rat model.

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Hoybergs, Yves M J J; Biermans, Ria L V; Meert, Theo F

2008-05-02

The streptozotocin (STZ)-induced diabetes model is widely used for the induction of neuropathy in the rat. In this model, diabetic animals often display chronic illness, which raises objections not only on ethical but also on scientific grounds. In this study, the investigators set out to determine the impact of bodyweight and body condition (BC) on behavioral testing in the rat. Animals were allocated to four different groups as a function of their bodyweight, in particular one control group and three experimental groups with different starting weights (low bodyweight [LBW], medium bodyweight [MBW] and high bodyweight [HBW]), the groups having been rendered diabetic with an intraperitoneal injection of STZ (65mg/kg). Bodyweight, blood glucose, body condition and thresholds for mechanical hyperalgesia and tactile allodynia were measured or evaluated over a 68-day period. Animals with a LBW at the start of the experiment showed a gradual increase in BW with a decrease in mechanical nociceptive thresholds, while MBW and HBW animals presented a decrease in both thresholds and BW. The body condition score (BCS) decreased in all STZ-treated groups over time. Since correlations between mechanical thresholds and BW were similar between the control group and the HBW and MBW groups, the loss in BW clearly contributed to the decrease in thresholds. In the LBW group, thresholds and BW correlated negatively, so that the decrease in thresholds was mainly caused by the development of a painful neuropathy. From an ethical and a scientific point of view, in the STZ-induced diabetic neuropathy model, animals should be chosen on the basis of bodyweight and it must also be ensured that STZ is correctly dosed.

Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy

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Yelena Granovsky

2017-06-01

Conclusion:. Pro-nociception, expressed by less efficient CPM and high temporal summation that usually accompanies clinical painful conditions, seems to “normalize” with chronicity of the pain syndrome. This is despite continuing pain, suggesting that pro-nociceptivity in pain syndromes is multifactorial. Because the pain modulation profile affects success of therapy, this suggests that different drugs might express different efficacy pending on duration of the pain in patients with PDN.

Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

International Nuclear Information System (INIS)

Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh

2017-01-01

Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

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Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh, E-mail: ashutosh.niperhyd@gov.in

2017-05-01

Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

Bilateral Ischemic Optic Neuropathy Developed under Interferon Therapy

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Fatih Selcukbiricik

2012-01-01

Full Text Available Introduction. Interferon is a glycoprotein produced by assigned cells of immune system. It has been used in many different diseases. Although flu-like syndrome, myalgia, rash, hypotension, thrombocytopenia and peripheral neuropathy due to interferon use are encountered frequently, ocular side effects are rare, generally mild and transient. Case Report. 47-year-old female patient, presented with a mass lesion in right renal pelvis. Right radical nephrectomy was applied and the histopathological examination was consistent with papillary renal cell carcinoma. Interferon alpha treatment was started subcutaneously at the dose of 5 MIU/3 times in a week. Four weeks after the interferon therapy, suddenly bilateral visual loss developed. We discussed the diagnosis, followup, and treatment of the patient who developed irreversible ischemic optic neuropathy and had no previous known primary systemic disease to cause this condition. Conclusion. We suggest that patients should be screened for risk factors causing optic ischemic neuropathy, before interferon therapy. Although there was no adequate information in the literature for the followup, patients should be monitorized before, 1 month after, and 2 months after the treatment. And if there is no complication, we suggest that they should be followed up at 3-month intervals.

Text Messaging to Improve Disease Management in Patients With Painful Diabetic Peripheral Neuropathy.

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Bauer, Victoria; Goodman, Nancy; Lapin, Brittany; Cooley, Camille; Wang, Ed; Craig, Terri L; Glosner, Scott E; Juhn, Mark S; Cappelleri, Joseph C; Sadosky, Alesia B; Masi, Christopher

2018-06-01

Purpose The purpose of the study was to determine the impact of educational text messages on diabetes self-management activities and outcomes in patients with painful diabetic peripheral neuropathy (pDPN). Methods Patients with pDPN identified from a large integrated health system who agreed to participate were randomized to 6 months of usual care (UC) or UC plus twice-daily diabetes self-management text messages (UC+TxtM). Outcomes included the Pain Numerical Rating Scale, Summary of Diabetes Self-Care Activities (SDSCA), questions on diabetes health beliefs, and glycated hemoglobin (A1C). Changes from baseline were evaluated at 6 months and compared between groups. Results Demographic characteristics were balanced between groups (N = 62; 53% female, mean age = 63 years, 94% type 2 diabetes), as were baseline measures. After 6 months, pain decreased with UC+TxtM from 6.3 to 5.5 and with UC from 6.5 to 6.0, with no difference between groups. UC+TxtM but not UC was associated with significant improvements from baseline on all SDSCA subscales. On diabetes health beliefs, UC+TxtM patients reported significantly increased benefits and reduced barriers and susceptibility relative to UC at 6 months. A1C declined in both groups, but neither change was significant relative to baseline. Conclusions Patients with pDPN who receive twice-daily text messages regarding diabetes management reported reduced pain relative to baseline, although this change was not significant compared with usual care. In addition, text messaging was associated with increased self-management activities and improved diabetes health beliefs and total self-care. These results warrant further investigation.

Diagnostic imaging of compression neuropathy

International Nuclear Information System (INIS)

Weishaupt, D.; Andreisek, G.

2007-01-01

Compression-induced neuropathy of peripheral nerves can cause severe pain of the foot and ankle. Early diagnosis is important to institute prompt treatment and to minimize potential injury. Although clinical examination combined with electrophysiological studies remain the cornerstone of the diagnostic work-up, in certain cases, imaging may provide key information with regard to the exact anatomic location of the lesion or aid in narrowing the differential diagnosis. In other patients with peripheral neuropathies of the foot and ankle, imaging may establish the etiology of the condition and provide information crucial for management and/or surgical planning. MR imaging and ultrasound provide direct visualization of the nerve and surrounding abnormalities. Bony abnormalities contributing to nerve compression are best assessed by radiographs and CT. Knowledge of the anatomy, the etiology, typical clinical findings, and imaging features of peripheral neuropathies affecting the peripheral nerves of the foot and ankle will allow for a more confident diagnosis. (orig.) [de

Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy.

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Maryam Ferdousi

Full Text Available There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04 and warm sensation (P = 0.03 thresholds with a significantly reduced sural sensory (P<0.01 and peroneal motor (P<0.01 nerve conduction velocity, corneal nerve fibre density (CNFD, nerve branch density (CNBD and nerve fibre length (CNFL (P<0.0001. Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02, and CNFL (r = -0.8, P<0.0001 and CNBD (r = 0.63, P = 0.003 were related to the severity of lymph node involvement. After the 3rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003. Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.

Habitual physical activity, peripheral neuropathy, foot deformities ...

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joint or leg pain), lack of equipment, and exercise partner(s).20. Yet, many of these ... peripheral neuropathy and lower limb functions among a group of Nigerian .... scale for inpatients of an orthopaedic rehabilitation ward found that interclass ...

The influence of μ-opioid and noradrenaline reuptake inhibition in the modulation of pain responsive neurones in the central amygdala by tapentadol in rats with neuropathy

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Gonçalves, Leonor; Friend, Lauren V.; Dickenson, Anthony H.

2015-01-01

Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. These two components interact synergistically, resulting in levels of analgesia similar to opioid analgesics such as oxycodone and morphine, but with more tolerable side effects. The right central nucleus of the amygdala (CeA) is critical for the lateral spinal ascending pain pathway, regulates descending pain pathways and is key in the emotional-affective components of pain. Few studies have investigated the pharmacology of limbic brain areas in pain models. Here we determined the actions of systemic tapentadol on right CeA neurones of animals with neuropathy and which component of tapentadol contributes to its effect. Neuronal responses to multimodal peripheral stimulation of animals with spinal nerve ligation or sham surgery were recorded before and after two doses of tapentadol. After the higher dose of tapentadol either naloxone or yohimbine were administered. Systemic tapentadol resulted in dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both naloxone and yohimbine reversed this effect to an extent that was modality selective. The interactions of the components of tapentadol are not limited to the synergy between the MOR and α2-adrenoceptors seen at spinal levels, but are seen at this supraspinal site where suppression of responses may relate to the ability of the drug to alter affective components of pain. PMID:25576174

Trench Foot or Non-Freezing Cold Injury As a Painful Vaso-Neuropathy: Clinical and Skin Biopsy Assessments

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Praveen Anand

2017-09-01

Full Text Available BackgroundTrench foot, or non-freezing cold injury (NFCI, results from cold exposure of sufficient severity and duration above freezing point, with consequent sensory and vascular abnormalities which may persist for years. Based on observations of Trench foot in World War II, the condition was described as a vaso-neuropathy. While some reports have documented nerve damage after extreme cold exposure, sensory nerve fibres and vasculature have not been assessed with recent techniques in NFCI.ObjectiveTo assess patients with chronic sensory symptoms following cold exposure, in order to diagnose any underlying small fibre neuropathy, and provide insight into mechanisms of the persistent pain and cold hypersensitivity.MethodsThirty soldiers with cold exposure and persistent sensory symptoms (>4 months were assessed with quantitative sensory testing, nerve conduction studies, and skin biopsies. Immunohistochemistry was used to assess intraepidermal (IENF and subepidermal (SENF nerve fibres with a range of markers, including the pan-neuronal marker protein gene product 9.5 (PGP 9.5, regenerating fibres with growth-associated protein 43 (GAP43, and nociceptor fibres with transient receptor potential cation channel subfamily V member 1 (TRPV1, sensory neuron-specific receptor (SNSR, and calcitonin gene-related peptide (CGRP. von Willebrand factor (vWF, endothelial nitric oxide synthase (eNOS, and vascular endothelial growth factor (VEGF were used for assessing blood vessels, and transient receptor potential cation channel, subfamily A member 1 (TRPA1 and P2X purinoceptor 7 (P2X7 for keratinocytes, which regulate nociceptors via release of nerve growth factor.ResultsClinical examination showed pinprick sensation was abnormal in the feet of 20 patients (67%, and between 67 and 83% had abnormalities of thermal thresholds to the different modalities. 7 patients (23% showed reduced sensory action potential amplitude of plantar nerves. 27 patients (90% had

Ulnar neuropathy and medial elbow pain in women's fastpitch softball pitchers: a report of 6 cases.

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Smith, Adam M; Butler, Thomas H; Dolan, Michael S

2017-12-01

Elite-level women's fastpitch softball players place substantial biomechanical strains on the elbow that can result in medial elbow pain and ulnar neuropathic symptoms. There is scant literature reporting the expected outcomes of the treatment of these injuries. This study examined the results of treatment in a series of these patients. We identified 6 female softball pitchers (4 high school and 2 collegiate) with medial elbow pain and ulnar neuropathic symptoms. Trials of conservative care failed in all 6, and they underwent surgical treatment with subcutaneous ulnar nerve transposition. These patients were subsequently monitored postoperatively to determine outcome. All 6 female pitchers had early resolution of elbow pain and neuropathic symptoms after surgical treatment. Long-term follow-up demonstrated that 1 patient quit playing softball because of other injuries but no longer reported elbow pain or paresthesias. One player was able to return to pitching at the high school level but had recurrent forearm pain and neuritis 1 year later while playing a different sport and subsequently stopped playing competitive sports. Four patients continued to play at the collegiate level without further symptoms. Medial elbow pain in women's softball pitchers caused by ulnar neuropathy can be treated effectively with subcutaneous ulnar nerve transposition if nonsurgical options fail. Further study is necessary to examine the role of overuse, proper training techniques, and whether pitching limits may be necessary to avoid these injuries. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Subacute peripheral and optic neuropathy syndrome with no evidence of a toxic or nutritional cause.

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Allen, D; Riordan-Eva, P; Paterson, R W; Hadden, R D M

2013-08-01

The syndrome of subacute simultaneous peripheral neuropathy and bilateral optic neuropathy is known to occur in tropical countries, probably due to malnutrition or toxicity, but not often seen in developed countries. We report seven patients in London who were not malnourished or alcoholic, and in whom no clear cause was found. We retrospectively reviewed the case notes and arranged some further investigations. All patients developed peripheral and bilateral optic neuropathy within 6 months. Patients were aged 30-52, and all of Jamaican birth and race but lived in the UK. Most had subacute, painful ataxic sensory axonal neuropathy or neuronopathy, some with myelopathy. Nerve conduction studies revealed minor demyelinating features in two cases. The optic neuropathy was symmetrical, subacute and monophasic, usually with marked reduction in visual acuity. CSF protein concentration was usually elevated but other laboratory investigations were normal. Patients showed only modest improvement at follow-up. These patients share a common clinical and electrophysiological phenotype, age, ethnicity and elevated CSF protein, but otherwise normal laboratory investigations. The syndrome is a cause of significant morbidity in young people. The cause remains uncertain despite thorough investigation. Copyright © 2013 Elsevier B.V. All rights reserved.

Role of microglia in neuropathic pain, postoperative pain, and morphine tolerance

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Wen, Yeong-Ray; Tan, Ping-Heng; Cheng, Jen-Kun; Liu, Yen-Chin; Ji, Ru-Rong

2011-01-01

Management of chronic pain such as nerve injury-induced neuropathic pain associated with diabetic neuropathy, viral infection, and cancer is a real clinical challenge. Major surgeries such as breast and thoracic surgery, leg amputation, and coronary artery bypass surgery also lead to chronic pain in 10–50% of individuals after acute postoperative pain, in part due to surgery-induced nerve injury. Current treatments mainly focus on blocking neurotransmission in the pain pathway and have only resulted in limited success. Ironically, chronic opioid exposure may lead to paradoxical pain. Development of effective therapeutic strategies requires a better understanding of cellular mechanisms underlying the pathogenesis of neuropathic pain. An important progress in pain research points to important role of microglial cells in the development of chronic pain. Spinal cord microglia are strongly activated after nerve injury, surgical incision, and chronic opioid exposure. Increasing evidence suggests that under all these conditions the activated microglia not only exhibit increased expression of microglial markers CD11b and Iba1 but also display elevated phosphorylation of p38 MAP kinase. Inhibition of spinal cord p38 has been shown to attenuate neuropathic pain and postoperative pain, as well as morphine-induced antinociceptive tolerance. Activation of p38 in spinal microglia results in increased synthesis and release of the neurotrophin BDNF and the proinflammatory cytokines IL-1β, IL-6, and TNF-α. These microglia-released mediators can powerfully modulate spinal cord synaptic transmission, leading to increased excitability of dorsal horn neurons, i.e. central sensitization, in part via suppressing inhibitory synaptic transmission. We review the studies that support the pronociceptive role of microglia in conditions of neuropathic pain, post-surgical pain, and opioid tolerance. Some of these studies have been accomplished by four Taiwanese anesthesiologists who are also

Treatment of diabetic neuropathy in the lower limb

African Journals Online (AJOL)

Diabetic peripheral neuropathy (DPN) is defined as 'the presence of symptoms and/or ... painful, paralytic and ataxic), type of fibres affected (motor, sensory, ... alcohol abuse and smoking. In fact, ... prevents or slows the progression of diabetic ...

Clinical spectrum of Castleman disease-associated neuropathy.

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Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay; Mauermann, Michelle L

2016-12-06

To define the peripheral neuropathy phenotypes associated with Castleman disease. We conducted a retrospective chart review for patients with biopsy-proven Castleman disease evaluated between January 2003 and December 2014. Patients with associated peripheral neuropathy were identified and divided into 2 groups: those with Castleman disease without POEMS syndrome (CD-PN) and those with Castleman disease with POEMS syndrome (CD-POEMS). We used a cohort of patients with POEMS as controls. Clinical, electrodiagnostic, and laboratory characteristics were collected and compared among patient subgroups. There were 7 patients with CD-PN, 20 with CD-POEMS, and 122 with POEMS. Patients with CD-PN had the mildest neuropathy characterized by predominant sensory symptoms with no pain and mild distal sensory deficits (median Neuropathy Impairment Score of 7 points). Although both patients with CD-POEMS and patients with POEMS had a severe sensory and motor neuropathy, patients with CD-POEMS were less affected (median Neuropathy Impairment Score of 33 and 66 points, respectively). The degree of severity was also reflected on electrodiagnostic testing in which patients with CD-PN demonstrated a mild degree of axonal loss, followed by patients with CD-POEMS and then those with POEMS. Demyelinating features, defined by European Federation of Neurologic Societies/Peripheral Nerve Society criteria, were present in 43% of the CD-PN, 78% of the CD-POEMS, and 86% of the POEMS group. There is a spectrum of demyelinating peripheral neuropathies associated with Castleman disease. CD-PN is sensory predominant and is the mildest phenotype, whereas CD-POEMS is a more severe sensory and motor neuropathy. Compared to the POEMS cohort, those with CD-POEMS neuropathy have a similar but less severe phenotype. Whether these patients respond differently to treatment deserves further study. © 2016 American Academy of Neurology.

Clinical spectrum of Castleman disease–associated neuropathy

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Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay

2016-01-01

Objective: To define the peripheral neuropathy phenotypes associated with Castleman disease. Methods: We conducted a retrospective chart review for patients with biopsy-proven Castleman disease evaluated between January 2003 and December 2014. Patients with associated peripheral neuropathy were identified and divided into 2 groups: those with Castleman disease without POEMS syndrome (CD-PN) and those with Castleman disease with POEMS syndrome (CD-POEMS). We used a cohort of patients with POEMS as controls. Clinical, electrodiagnostic, and laboratory characteristics were collected and compared among patient subgroups. Results: There were 7 patients with CD-PN, 20 with CD-POEMS, and 122 with POEMS. Patients with CD-PN had the mildest neuropathy characterized by predominant sensory symptoms with no pain and mild distal sensory deficits (median Neuropathy Impairment Score of 7 points). Although both patients with CD-POEMS and patients with POEMS had a severe sensory and motor neuropathy, patients with CD-POEMS were less affected (median Neuropathy Impairment Score of 33 and 66 points, respectively). The degree of severity was also reflected on electrodiagnostic testing in which patients with CD-PN demonstrated a mild degree of axonal loss, followed by patients with CD-POEMS and then those with POEMS. Demyelinating features, defined by European Federation of Neurologic Societies/Peripheral Nerve Society criteria, were present in 43% of the CD-PN, 78% of the CD-POEMS, and 86% of the POEMS group. Conclusion: There is a spectrum of demyelinating peripheral neuropathies associated with Castleman disease. CD-PN is sensory predominant and is the mildest phenotype, whereas CD-POEMS is a more severe sensory and motor neuropathy. Compared to the POEMS cohort, those with CD-POEMS neuropathy have a similar but less severe phenotype. Whether these patients respond differently to treatment deserves further study. PMID:27807187

Treatment strategies for chemotherapy-induced peripheral neuropathy: potential role of exercise

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Karen Y. Wonders

2011-12-01

Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN is a common, dose-limiting effect of cancer therapy that often has negative implications on a patient’s quality of life. The pain associated with CIPN has long been recognized as one of the most difficult types of pain to treat. Historically, much effort has been made to explore pharmacological therapies aimed at reducing symptoms of CIPN. While many of these agents provide a modest relief in the symptoms of peripheral neuropathy, many have been shown to have additional negative side effects for cancer patients. Therefore, the authors suggest exercise rehabilitation as one lifestyle modification that may positively impact the lives of patients with CIPN. To our knowledge, there are currently no published clinical trials examining the role of exercise in preserving neurological function following chemotherapy. However, investigations using low-to-moderate intensity exercise as an intervention in patients with diabetic peripheral neuropathy and hereditary motor and sensory neuropathies have produced promising results. Given that cancer patients appear to tolerate exercise, it seems plausible that exercise rehabilitation could be used as an effective strategy to minimize CIPN-induced detriments to quality of life.

Guidelines in the management of diabetic nerve pain clinical utility of pregabalin

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Vinik AI

2013-02-01

Full Text Available Aaron I Vinik, Carolina M Casellini Strelitz Diabetes Center for Endocrine and Metabolic Disorders, Eastern Virginia Medical School, Norfolk, VA, USA Abstract: Diabetic peripheral neuropathy is a common complication of diabetes. It presents as a variety of syndromes for which there is no universally accepted unique classification. Sensorimotor polyneuropathy is the most common type, affecting about 30% of diabetic patients in hospital care and 25% of those in the community. Pain is the reason for 40% of patient visits in a primary care setting, and about 20% of these have had pain for greater than 6 months. Chronic pain may be nociceptive, which occurs as a result of disease or damage to tissue with no abnormality in the nervous system. In contrast, neuropathic pain is defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.” Persistent neuropathic pain interferes significantly with quality of life, impairing sleep and recreation; it also significantly impacts emotional well-being, and is associated with depression, anxiety, and noncompliance with treatment. Painful diabetic peripheral neuropathy is a difficult-to-manage clinical problem, and patients with this condition are more apt to seek medical attention than those with other types of diabetic neuropathy. Early recognition of psychological problems is critical to the management of pain, and physicians need to go beyond the management of pain per se if they are to achieve success. This evidence-based review of the assessment of the patient with pain in diabetes addresses the state-of-the-art management of pain, recognizing all the conditions that produce pain in diabetes and the evidence in support of a variety of treatments currently available. A search of the full Medline database for the last 10 years was conducted in August 2012 using the terms painful diabetic peripheral neuropathy, painful diabetic peripheral polyneuropathy

Long-term consequences of upper extremity peripheral neuropathy in former Vietnam prisoners of war.

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Holmboe, Eric S; Wang, Yun; Brass, Lawrence M

2002-09-01

At the time of repatriation in 1973, a substantial number of Vietnam prisoners of war (POWs) were diagnosed with upper extremity peripheral neuropathy (UEPN). To assess the long-term functional consequences of UEPN among former Vietnam POWs diagnosed with UEPN at repatriation. Former POWs with an International Classification of Diseases, Eighth Revision, code of peripheral neuropathy identified from a central database registry. Cross-sectional survey. Standardized survey instruments and the SF-12 questionnaire were mailed to all subjects. A subsample of subjects completing the mailed survey was contacted by telephone to complete a semistructured questionnaire on current symptoms and physical limitations attributable to peripheral neuropathy. Seventy-nine percent of POWs diagnosed with peripheral neuropathy at repatriation currently experience some numbness or tingling more than 25 years after repatriation, and 63% currently experience pain in one or both hands. Although the average severity rating for numbness and pain was mild, 23% of the POWs still have moderate to severe pain. Ulnar neuropathy was present in more than 30% of the POWs. SF-12 physical composite scores were substantially lower among this group of POWs compared with an age-matched group from the Medical Outcomes Study. For those POWs diagnosed with UEPN at repatriation, nearly 80% continue to experience symptoms of numbness, tingling, and pain, with nearly 25% reporting a moderate or greater degree of symptoms. The low physical function scores of this cohort are particularly troubling. More research concerning physical symptoms and conditions among former POWs is needed, and this research should also investigate what causes are responsible for the significantly lower physical functional status.

Challenges Evaluating Chemotherapy-Induced Peripheral Neuropathy in Childhood Cancer Survivors.

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Mohrmann, Caroline; Armer, Jane; Hayashi, Robert J

Children treated for cancer are exposed to a variety of chemotherapeutic agents with known toxicity to the peripheral nervous system. The side effect of peripheral neuropathy can cause changes in sensation, function, and even cause pain. Although peripheral neuropathy is recognized by pediatric oncology nurses as an important and significant side effect, measuring neuropathy can be quite complex for clinical care and research efforts. With more children surviving a cancer diagnosis today, this issue is increasingly important for childhood cancer survivors. This article has reviewed existing literature examining peripheral neuropathy in childhood cancer survivors with particular interest paid to measurement tools available and needs for future research. It is important for nurses to choose appropriate measures for clinical care and research methods in order to have an impact on patients experiencing this condition.

Rationale and design of a randomized double-blind clinical trial in breast cancer: dextromethorphan in chemotherapy-induced peripheral neuropathy.

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Martin, Elodie; Morel, Véronique; Joly, Dominique; Villatte, Christine; Delage, Noémie; Dubray, Claude; Pereira, Bruno; Pickering, Gisèle

2015-03-01

Anti-cancer chemotherapy often induces peripheral neuropathy and consequent cognitive and quality of life impairment. Guidelines recommend antiepileptics or antidepressants but their efficacy is limited.Dextromethorphan, a N-methyl-D-aspartate receptor antagonist, has shown its efficacy in painful diabetic neuropathy and in post-operative pain but has not been studied in chemotherapy-induced peripheral neuropathy. This clinical trial evaluates the effect of dextromethorphan on pain, cognition and quality of life in patients who suffer from neuropathic pain induced by chemotherapy for breast cancer. It also assesses the impact of dextromethorphan genetic polymorphism on analgesia. This trial is a randomized, placebo-controlled, double-blind clinical study in two parallel groups (NCT02271893). It includes 40 breast cancer patients suffering from chemotherapy-induced peripheral neuropathy. They are randomly allocated to dextromethorphan (maximal dose 90 mg/day) or placebo for 4 weeks. The primary endpoint is pain intensity measured after 4 weeks of treatment on a (0-10) Numeric Pain Rating Scale. Secondary outcomes include assessment of neuropathic pain, cognitive function, anxiety/depression, sleep and quality of life. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at α=0.05. Considering the poor efficacy of available drugs in chemotherapy-induced neuropathic pain, dextromethorphan may be a valuable therapeutic option. Pharmacogenetics may provide predictive factors of dextromethorphan response in patients suffering from breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Gasoline sniffing multifocal neuropathy.

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Burns, T M; Shneker, B F; Juel, V C

2001-11-01

The polyneuropathy caused by chronic gasoline inhalation is reported to be a gradually progressive, symmetric, sensorimotor polyneuropathy. We report unleaded gasoline sniffing by a female 14 years of age that precipitated peripheral neuropathy. In contrast with the previously reported presentation of peripheral neuropathy in gasoline inhalation, our patient developed multiple mononeuropathies superimposed on a background of sensorimotor polyneuropathy. The patient illustrates that gasoline sniffing neuropathy may present with acute multiple mononeuropathies resembling mononeuritis multiplex, possibly related to increased peripheral nerve susceptibility to pressure in the setting of neurotoxic components of gasoline. The presence of tetraethyl lead, which is no longer present in modern gasoline mixtures, is apparently not a necessary factor in the development of gasoline sniffer's neuropathy.

Results of conservative, surgical treatment and rehabilitation of entrapment neuropathies in elderly patients in geriatric practice

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Jadwiga Główczewska

2017-03-01

Full Text Available Entrapment neuropahies of upper limbs can cause mainly nocturnal neuropathic pain and impaired manual dexterity. The most common entrapment neuropathy is carpal tunnel syndrome and ulnar groove syndrome - ulnar nerve entrapment at the elbow. Treatment of entrapment neuropathies is both analgetic therapy and physiotherapy. In the cases of conservative treatment inefficiencies surgical decompression of nerves is performed. Authors of this oublication present results of both conservative  and surgical of entrapment neuropathies in patients over 65 years old. Among the 17 patients with entraoment neuropathies 12 of them underwent surgical treatment. Achieved partial improvement in pain, mostly nocturnal and improving the quality of life and dexterity. In comparison, however, a group of younger patients who underwent surgery for the improvement was less spectacular, which may testify advancement and irreversibility of changes in older patients.

Genetics Home Reference: small fiber neuropathy

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... IS, Cheng X, Han C, Ahn HS, Persson AK, Hoeijmakers JG, Gerrits MM, Pierro T, Lombardi R, Kapetis D, Dib-Hajj SD, Waxman SG. Gain-of-function Nav1.8 mutations in painful neuropathy. Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19444-9. doi: 10.1073/pnas.1216080109. Epub ...

Presence of neuropathic pain may explain poor performances on olfactory testing in diabetes mellitus patients.

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Brady, Shauna; Lalli, Paul; Midha, Nisha; Chan, Ayechen; Garven, Alexandra; Chan, Cynthia; Toth, Cory

2013-07-01

Olfactory dysfunction in neurodegenerative conditions such as Parkinson's syndrome and Alzheimer's disease can hallmark disease onset. We hypothesized that patients with diabetes mellitus, a condition featuring peripheral and central neurodegeneration, would have decreased olfaction abilities. We examined participants with diabetic peripheral neuropathy, participants with diabetes without diabetic peripheral neuropathy, and control participants in blinded fashion using standardized Sniffin' Sticks. Diabetic peripheral neuropathy severity was quantified using the Utah Early Neuropathy Scale. Further subcategorization of diabetic peripheral neuropathy based on presence of neuropathic pain was performed with Douleur Neuropathique 4 Questionnaires. Participants with diabetes had decreased olfactory sensitivity, impaired olfactory discrimination abilities, and reduced odor identification skills when compared with controls. However, loss of olfaction ability was, at least partially, attributed to presence of neuropathic pain on subcategory assessment, although pain severity was not associated with dysfunction. Those participants with diabetes without diabetic peripheral neuropathy and those with diabetic peripheral neuropathy without neuropathic pain had similar olfactory function as controls in general. The presence of neuropathic pain, associated with limited attention and concentration, may explain at least a portion of the olfactory dysfunction witnessed in the diabetic patient population.

Peripheral Glial Cells in the Development of Diabetic Neuropathy

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Gonçalves, Nádia Pereira; Vægter, Christian Bjerggaard; Pallesen, Lone Tjener

2018-01-01

The global prevalence of diabetes is rapidly increasing, affecting more than half a billion individuals within the next few years. As diabetes negatively affects several physiological systems, this dramatic increase represents not only impaired quality of life on the individual level but also a huge socioeconomic challenge. One of the physiological consequences affecting up to half of diabetic patients is the progressive deterioration of the peripheral nervous system, resulting in spontaneous pain and eventually loss of sensory function, motor weakness, and organ dysfunctions. Despite intense research on the consequences of hyperglycemia on nerve functions, the biological mechanisms underlying diabetic neuropathy are still largely unknown, and treatment options lacking. Research has mainly focused directly on the neuronal component, presumably from the perspective that this is the functional signal-transmitting unit of the nerve. However, it is noteworthy that each single peripheral sensory neuron is intimately associated with numerous glial cells; the neuronal soma is completely enclosed by satellite glial cells and the length of the longest axons covered by at least 1,000 Schwann cells. The glial cells are vital for the neuron, but very little is still known about these cells in general and especially how they respond to diabetes in terms of altered neuronal support. We will discuss current knowledge of peripheral glial cells and argue that increased research in these cells is imperative for a better understanding of the mechanisms underlying diabetic neuropathy. PMID:29770116

Evaluation of Peripheral Neuropathy of Unknown Origin in an Outpatient Foot and Ankle Practice.

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Klein, Sandra E; Chu, Jennifer; McCormick, Jeremy J; Johnson, Jeffrey E

2015-09-01

The foot and ankle surgeon can see peripheral neuropathy in the treatment of foot and ankle conditions. The purpose of this study was (1) to evaluate the demographics and presenting complaints of patients diagnosed with idiopathic peripheral neuropathy during an examination by a foot and ankle surgeon and (2) to identify the type and frequency of subsequent diagnosis of medical causes of neuropathy. This was a retrospective study of patients diagnosed with idiopathic peripheral neuropathy in our practice between January 1997 and December 2008. Ninety-five patients were identified, and demographic data, presenting complaints, and medical comorbidities were extracted from the medical record. Examination findings of decreased sensation to Semmes Weinstein 5.07 monofilament testing were documented, and electromyogram and nerve conduction study results were reviewed when available. Laboratory values were noted, as were neurologic evaluations performed to diagnose medical conditions associated with peripheral neuropathy. The most common presentation was foot pain, in 36 patients (38%). Ninety-one patients had Semmes Weinstein 5.07 monofilament testing, with loss of protective sensation reported in 75 of the 91 tested (82%). Only 30 of the 95 patients had electromyogram and nerve conduction study results available, with a test positive for peripheral neuropathy in 20 of the 30 tested. Thirty-two patients were evaluated by a neurologist. A specific cause was identified in 12 of the 32 seen by a neurologist. Of the total group of 95 patients, 31 patients (33%) were diagnosed with a condition that may be associated with peripheral neuropathy. Thirty-three percent of the patients presenting to our clinic and given a diagnosis of idiopathic peripheral neuropathy were ultimately diagnosed with a medical cause of neuropathy-most commonly, diabetes. For those patients with idiopathic neuropathy, a spectrum of disease was encountered, including pain, ulcer, infection, and Charcot

Effect of curcumin in mice model of vincristine-induced neuropathy.

Science.gov (United States)

Babu, Anand; Prasanth, K G; Balaji, Bhaskar

2015-06-01

Curcumin exhibits a wide spectrum of biological activities which include neuroprotective, antinociceptive, anti-inflammatory, and antioxidant activity. The present study evaluates the effect of curcumin in vincristine-induced neuropathy in a mice model. Vincristine sulfate (0.1 mg/kg, i.p. for 10 consecutive days) was administered to mice to induce neuropathy. Pain behavior was assessed at different days, i.e., 0, 7, 10, and 14 d. Sciatic nerve total calcium, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), nitric oxide (NO), and lipid peroxidation (LPO) were also estimated after the 14th day of study. Pregabalin (10 mg/kg, p.o.) and curcumin (15, 30, and 60 mg/kg, p.o.) were administered for 14 consecutive days. Curcumin at 60 mg/kg significantly attenuated the vincristine-induced neuropathic pain manifestations in terms of thermal hyperalgesia (p Curcumin at 30 and 60 mg/kg exhibited significant changes (p Curcumin at 30 and 60 mg/kg dose levels significantly attenuated vincristine-induced neuropathy which may be due to its multiple actions including antinociceptive, calcium inhibitory, and antioxidant effect.

Guidelines in the management of diabetic nerve pain: clinical utility of pregabalin.

Science.gov (United States)

Vinik, Aaron I; Casellini, Carolina M

2013-01-01

Diabetic peripheral neuropathy is a common complication of diabetes. It presents as a variety of syndromes for which there is no universally accepted unique classification. Sensorimotor polyneuropathy is the most common type, affecting about 30% of diabetic patients in hospital care and 25% of those in the community. Pain is the reason for 40% of patient visits in a primary care setting, and about 20% of these have had pain for greater than 6 months. Chronic pain may be nociceptive, which occurs as a result of disease or damage to tissue with no abnormality in the nervous system. In contrast, neuropathic pain is defined as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system." Persistent neuropathic pain interferes significantly with quality of life, impairing sleep and recreation; it also significantly impacts emotional well-being, and is associated with depression, anxiety, and noncompliance with treatment. Painful diabetic peripheral neuropathy is a difficult-to-manage clinical problem, and patients with this condition are more apt to seek medical attention than those with other types of diabetic neuropathy. Early recognition of psychological problems is critical to the management of pain, and physicians need to go beyond the management of pain per se if they are to achieve success. This evidence-based review of the assessment of the patient with pain in diabetes addresses the state-of-the-art management of pain, recognizing all the conditions that produce pain in diabetes and the evidence in support of a variety of treatments currently available. A search of the full Medline database for the last 10 years was conducted in August 2012 using the terms painful diabetic peripheral neuropathy, painful diabetic peripheral polyneuropathy, painful diabetic neuropathy and pain in diabetes. In addition, recent reviews addressing this issue were adopted as necessary. In particular, reports from the American Academy of Neurology

Antinociceptive interaction of gabapentin with minocycline in murine diabetic neuropathy.

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Miranda, H F; Sierralta, F; Jorquera, V; Poblete, P; Prieto, J C; Noriega, V

2017-02-01

Diabetic neuropathy (DN) is the most common complication of diabetes and pain is one of the main symptoms of diabetic neuropathy, however, currently available drugs are often ineffective and complicated by adverse events. The purpose of this research was to evaluate the antinociceptive interaction between gabapentin and minocycline in a mice experimental model of DN by streptozocin (STZ). The interaction of gabapentin with minocycline was evaluated by the writhing and hot plate tests at 3 and 7 days after STZ injection or vehicle in male CF1 mice. STZ (150 mg/kg, i.p.) produced a marked increase in plasma glucose levels on day 7 (397.46 ± 29.65 mg/dL) than on day 3 (341.12 ± 35.50 mg/dL) and also developed neuropathic pain measured by algesiometric assays. Gabapentin produced similar antinociceptive activity in both writhing and hot plate tests in mice pretreated with STZ. However, minocycline was more potent in the writhing than in the hot plate test in the same type of mice. The combination of gabapentin with minocycline produced synergistic interaction in both test. The combination of gabapentin with minocycline in a 1:1 proportion fulfills all the criteria of multimodal analgesia and this finding suggests that the combination provide a therapeutic alternative that could be used for human neuropathic pain management.

Antinociceptive effects of topical mepivacaine in a rat model of HIV-associated peripheral neuropathic pain

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Sagen J

2016-06-01

Full Text Available Jacqueline Sagen, Daniel A Castellanos,† Aldric T Hama The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA †Daniel A Castellanos passed away on April 14, 2010 Background: A consequence of HIV infection is sensory neuropathy, a debilitating condition that degrades the quality of life of HIV patients. Furthermore, life-extending antiretroviral treatment may exacerbate HIV sensory neuropathy. Analgesics that relieve other neuropathic pains show little or no efficacy in ameliorating HIV sensory neuropathy. Thus, there is a need for analgesics for people with this particular pain. While lidocaine is used in the management of painful peripheral neuropathies, another local anesthetic mepivacaine, with a potentially improved bioavailability, could be utilized for the management of HIV neuropathic pain.Methods: The efficacy of topical anesthetics was evaluated in a preclinical rodent model of painful peripheral neuropathy induced by epineural administration of the HIV envelope protein gp120 delivered using saturated oxidized cellulose implanted around the sciatic nerve. Beginning at 2 weeks following gp120 administration, the effects of local anesthetics topically applied via gauze pads were tested on heat and mechanical hyperalgesia in the hind paw. Rats were tested using several concentrations of mepivacaine or lidocaine during the following 2 weeks.Results: By 2 weeks following epineural gp120 implantation, the ipsilateral hind paw developed significant hypersensitivity to noxious pressure and heat hyperalgesia. A short-lasting, concentration-dependent amelioration of pressure and heat hyperalgesia was observed following topical application of mepivacaine to the ipsilateral plantar hind paw. By contrast, topical lidocaine ameliorated heat hyperalgesia in a concentration-dependent manner but not pressure hyperalgesia. Equipotent concentrations of mepivacaine and lidocaine applied topically to the

A rare cause of forearm pain: anterior branch of the medial antebrachial cutaneous nerve injury: a case report.

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Yildiz, Necmettin; Ardic, Füsun

2008-04-21

Medial antebrachial cutaneous nerve (MACN) neuropathy is reported to be caused by iatrogenic reasons. Although the cases describing the posterior branch of MACN neuropathy are abundant, only one case caused by lipoma has been found to describe the anterior branch of MACN neuropathy in the literature. As for the reason for the forearm pain, we report the only case describing isolated anterior branch of MACN neuropathy which has developed due to repeated minor trauma. We report a 37-year-old woman patient with pain in her medial forearm and elbow following the shaking of a rug. Pain and symptoms of dysestesia in the distribution of the right MACN were found. Electrophysiological examination confirmed the normality of the main nerve trunks of the right upper limb and demonstrated abnormalities of the right MACN when compared with the left side. Sensory action potential (SAP) amplitude on the right anterior branch of the MACN was detected to be lower in proportion to the left. In the light of these findings, NSAI drug and physical therapy was performed. Dysestesia and pain were relieved and no recurrence was observed after a follow-up of 14 months. MACN neuropathy should be taken into account for the differential diagnosis of the patients with complaints of pain and dysestesia in medial forearm and anteromedial aspect of the elbow.

A rare cause of forearm pain: anterior branch of the medial antebrachial cutaneous nerve injury: a case report

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Ardic Füsun

2008-04-01

Full Text Available Abstract Introduction Medial antebrachial cutaneous nerve (MACN neuropathy is reported to be caused by iatrogenic reasons. Although the cases describing the posterior branch of MACN neuropathy are abundant, only one case caused by lipoma has been found to describe the anterior branch of MACN neuropathy in the literature. As for the reason for the forearm pain, we report the only case describing isolated anterior branch of MACN neuropathy which has developed due to repeated minor trauma. Case presentation We report a 37-year-old woman patient with pain in her medial forearm and elbow following the shaking of a rug. Pain and symptoms of dysestesia in the distribution of the right MACN were found. Electrophysiological examination confirmed the normality of the main nerve trunks of the right upper limb and demonstrated abnormalities of the right MACN when compared with the left side. Sensory action potential (SAP amplitude on the right anterior branch of the MACN was detected to be lower in proportion to the left. In the light of these findings, NSAI drug and physical therapy was performed. Dysestesia and pain were relieved and no recurrence was observed after a follow-up of 14 months. Conclusion MACN neuropathy should be taken into account for the differential diagnosis of the patients with complaints of pain and dysestesia in medial forearm and anteromedial aspect of the elbow.

"Mitochondrial neuropathies": A survey from the large cohort of the Italian Network.

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Mancuso, Michelangelo; Orsucci, Daniele; Angelini, Corrado; Bertini, Enrico; Carelli, Valerio; Comi, Giacomo Pietro; Federico, Antonio; Minetti, Carlo; Moggio, Maurizio; Mongini, Tiziana; Tonin, Paola; Toscano, Antonio; Bruno, Claudio; Ienco, Elena Caldarazzo; Filosto, Massimiliano; Lamperti, Costanza; Diodato, Daria; Moroni, Isabella; Musumeci, Olimpia; Pegoraro, Elena; Spinazzi, Marco; Ahmed, Naghia; Sciacco, Monica; Vercelli, Liliana; Ardissone, Anna; Zeviani, Massimo; Siciliano, Gabriele

2016-01-01

Involvement of the peripheral nervous system in mitochondrial disorders has been previously reported. However, the prevalence of peripheral neuropathy in mitochondrial disorders is still unclear. Based on the large database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases", we reviewed the clinical data of 1200 patients, with special regard to peripheral neuropathy (mean age at onset 24.3 ± 20.1 years; age at last evaluation 39.8 ± 22.3 years; females 52.7%; childhood onset [before age 16 years] 43.1%). Peripheral neuropathy was present in 143/1156 patients (12.4%), being one of the ten most common signs and symptoms. POLG mutations cause a potentially painful, axonal/mixed, mainly sensory polyneuropathy; TYMP mutations lead to a demyelinating sensory-motor polyneuropathy; SURF1 mutations are associated with a demyelinating/mixed sensory-motor polyneuropathy. The only mtDNA mutation consistently associated with peripheral neuropathy (although less severely than in the above-considered nuclear genes) was the m.8993T > G (or the rarer T > C) changes, which lead to an axonal, mainly sensory polyneuropathy. In conclusion, peripheral neuropathy is one of the most common features of a mitochondrial disorder, and may negatively impact on the quality of life of these patients. Furthermore, the presence or absence of peripheral neuropathy, as well as its specific forms and the association with neuropathic pain (indicative of a POLG-associated disease) can guide the molecular analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

ARA290 : a novel treatment for neuropathic pain in sarcoidosis

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Heij, L.

2016-01-01

The general aim of this thesis is to investigate small fiber neuropathy in sarcoidosis and to asses whether ARA290 is a possible new agent to treat the neuropathic complaints in sarcoidosis population. The results of the various ARA290 trials in painful sarcoidosis are discussed. Painful neuropathy

DRG Voltage-Gated Sodium Channel 1.7 Is Upregulated in Paclitaxel-Induced Neuropathy in Rats and in Humans with Neuropathic Pain.

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Li, Yan; North, Robert Y; Rhines, Laurence D; Tatsui, Claudio Esteves; Rao, Ganesh; Edwards, Denaya D; Cassidy, Ryan M; Harrison, Daniel S; Johansson, Caj A; Zhang, Hongmei; Dougherty, Patrick M

2018-01-31

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect experienced by cancer patients receiving treatment with paclitaxel. The voltage-gated sodium channel 1.7 (Na v 1.7) plays an important role in multiple preclinical models of neuropathic pain and in inherited human pain phenotypes, and its gene expression is increased in dorsal root ganglia (DRGs) of paclitaxel-treated rats. Hence, the potential of change in the expression and function of Na v 1.7 protein in DRGs from male rats with paclitaxel-related CIPN and from male and female humans with cancer-related neuropathic pain was tested here. Double immunofluorescence in CIPN rats showed that Na v 1.7 was upregulated in small DRG neuron somata, especially those also expressing calcitonin gene-related peptide (CGRP), and in central processes of these cells in the superficial spinal dorsal horn. Whole-cell patch-clamp recordings in rat DRG neurons revealed that paclitaxel induced an enhancement of ProTx II (a selective Na v 1.7 channel blocker)-sensitive sodium currents. Bath-applied ProTx II suppressed spontaneous action potentials in DRG neurons occurring in rats with CIPN, while intrathecal injection of ProTx II significantly attenuated behavioral signs of CIPN. Complementarily, DRG neurons isolated from segments where patients had a history of neuropathic pain also showed electrophysiological and immunofluorescence results indicating an increased expression of Na v 1.7 associated with spontaneous activity. Na v 1.7 was also colocalized in human cells expressing transient receptor potential vanilloid 1 and CGRP. Furthermore, ProTx II decreased firing frequency in human DRGs with spontaneous action potentials. This study suggests that Na v 1.7 may provide a potential new target for the treatment of neuropathic pain, including chemotherapy (paclitaxel)-induced neuropathic pain. SIGNIFICANCE STATEMENT This work demonstrates that the expression and function of the voltage-gated sodium channel Na

Vincristine-induced neuropathy in pediatric patients with acute lymphoblastic leukemia in Oman: Frequent autonomic and more severe cranial nerve involvement.

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Nazir, Hanan F; AlFutaisi, Amna; Zacharia, Mathew; Elshinawy, Mohamed; Mevada, Surekha T; Alrawas, Abdulhakim; Khater, Doaa; Jaju, Deepali; Wali, Yasser

2017-12-01

Vincristine (VCR) induced peripheral neuropathy is a common complication in children with acute lymphoblastic leukemia (ALL). A retrospective data analysis over an interval of 10 years (2006-2016) of all children with ALL seen at Sultan Qaboos University Hospital was carried out. Electronic medical records of eligible patients were reviewed. Patients with clinical evidence of neuropathy and abnormal nerve conduction studies (NCSs) were included in the study. Nineteen (nine females and 10 males) out of 103 pediatric patients developed VCR-related neuropathy, and their age ranged between 2.5 and 14 years. Symptoms started after 2-11 doses of VCR. All 19 patients had documented peripheral neuropathy on NCSs. The autonomic nervous system and cranial nerves affection was relatively common in our patients; two presented with bradycardia, two patients with unexplained tachycardia, and five had abdominal pain and constipation, complicated by typhlitis in two patients. One patient developed unilateral hearing loss. Two patients developed severe life-threatening cranial nerve involvement with bilateral ptosis and recurrent laryngeal nerve involvement presented as vocal cord paralysis, hoarseness of voice, frequent chocking, and aspiration episodes. Peripheral neuropathy was the commonest form of VCR-related neuropathy. Autonomic neuropathy was relatively common in our patients. Cranial neuropathy is a serious side effect of VCR that can be severe, involving multiple cranial nerves and needs prompt recognition and management. Concomitant administration of pyridoxine and pyridostigmine does not seem to protect against further neurological damage in some patients. © 2017 Wiley Periodicals, Inc.

Pharmacological Treatment of Painful HIV-Associated Sensory Neuropathy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

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Phillips, Tudor J. C.; Cherry, Catherine L.; Cox, Sarah; Marshall, Sarah J.; Rice, Andrew S. C.

2010-01-01

Background Significant pain from HIV-associated sensory neuropathy (HIV-SN) affects ∼40% of HIV infected individuals treated with antiretroviral therapy (ART). The prevalence of HIV-SN has increased despite the more widespread use of ART. With the global HIV prevalence estimated at 33 million, and with infected individuals gaining increased access to ART, painful HIV-SN represents a large and expanding world health problem. There is an urgent need to develop effective pain management strategies for this condition. Method and Findings Objective: To evaluate the clinical effectiveness of analgesics in treating painful HIV-SN. Design: Systematic review and meta-analysis. Data sources: Medline, Cochrane central register of controlled trials, www.clinicaltrials.gov, www.controlled-trials.com and the reference lists of retrieved articles. Selection criteria: Prospective, double-blinded, randomised controlled trials (RCTs) investigating the pharmacological treatment of painful HIV-SN with sufficient quality assessed using a modified Jadad scoring method. Review methods: Four authors assessed the eligibility of articles for inclusion. Agreement of inclusion was reached by consensus and arbitration. Two authors conducted data extraction and analysis. Dichotomous outcome measures (≥30% and ≥50% pain reduction) were sought from RCTs reporting interventions with statistically significant efficacies greater than placebo. These data were used to calculate RR and NNT values. Results Of 44 studies identified, 19 were RCTs. Of these, 14 fulfilled the inclusion criteria. Interventions demonstrating greater efficacy than placebo were smoked cannabis NNT 3.38 95%CI(1.38 to 4.10), topical capsaicin 8%, and recombinant human nerve growth factor (rhNGF). No superiority over placebo was reported in RCTs that examined amitriptyline (100mg/day), gabapentin (2.4g/day), pregabalin (1200mg/day), prosaptide (16mg/day), peptide-T (6mg/day), acetyl-L-carnitine (1g/day), mexilitine (600mg

Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials.

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Tudor J C Phillips

Full Text Available BACKGROUND: Significant pain from HIV-associated sensory neuropathy (HIV-SN affects ∼40% of HIV infected individuals treated with antiretroviral therapy (ART. The prevalence of HIV-SN has increased despite the more widespread use of ART. With the global HIV prevalence estimated at 33 million, and with infected individuals gaining increased access to ART, painful HIV-SN represents a large and expanding world health problem. There is an urgent need to develop effective pain management strategies for this condition. METHOD AND FINDINGS: OBJECTIVE: To evaluate the clinical effectiveness of analgesics in treating painful HIV-SN. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Cochrane central register of controlled trials, www.clinicaltrials.gov, www.controlled-trials.com and the reference lists of retrieved articles. SELECTION CRITERIA: Prospective, double-blinded, randomised controlled trials (RCTs investigating the pharmacological treatment of painful HIV-SN with sufficient quality assessed using a modified Jadad scoring method. REVIEW METHODS: Four authors assessed the eligibility of articles for inclusion. Agreement of inclusion was reached by consensus and arbitration. Two authors conducted data extraction and analysis. Dichotomous outcome measures (≥ 30% and ≥ 50% pain reduction were sought from RCTs reporting interventions with statistically significant efficacies greater than placebo. These data were used to calculate RR and NNT values. RESULTS: Of 44 studies identified, 19 were RCTs. Of these, 14 fulfilled the inclusion criteria. Interventions demonstrating greater efficacy than placebo were smoked cannabis NNT 3.38 95%CI(1.38 to 4.10, topical capsaicin 8%, and recombinant human nerve growth factor (rhNGF. No superiority over placebo was reported in RCTs that examined amitriptyline (100mg/day, gabapentin (2.4 g/day, pregabalin (1200 mg/day, prosaptide (16 mg/day, peptide-T (6 mg/day, acetyl-L-carnitine (1g

Comparative efficacy and safety of six antidepressants and anticonvulsants in painful diabetic neuropathy: a network meta-analysis.

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Rudroju, Neelima; Bansal, Dipika; Talakokkula, Shiva Teja; Gudala, Kapil; Hota, Debasish; Bhansali, Anil; Ghai, Babita

2013-01-01

Anticonvulsants and antidepressants are mostly used in management of painful diabetic neuropathy (PDN). However there are few direct comparisons between drugs of these classes, making evidence-based decision-making in the treatment of painful diabetic neuropathy difficult. This study aimed to perform a network meta-analysis and benefit-risk analysis to evaluate the comparative efficacy and safety of these drugs in PDN treatment. Comparative effectiveness study. Medical Education and Research facility in India. A comprehensive data search was done in PubMed, Cochrane, and Embase up to August 2012. We then systematically reviewed the studies which compared any of 6 drugs for the management of PDN: amitriptyline, duloxetine, gabapentin, pregabalin, valproate, and venlafaxine or any of their combinations. We performed a random-effects network meta-analysis to rank treatments in terms of efficacy and safety. We chose the number of patients experiencing = 50% reduction in pain and number of patient withdrawals due to adverse events (AE) as primary outcomes for efficacy and safety, respectively. We also performed benefit-risk analysis, taking efficacy outcome as benefit and safety outcome as risk. Analysis was intention-to-treat. We included 21 published trials in the analysis. Duloxetine, gabapentin, pregabalin, and venlafaxine were shown to be significantly efficacious compared to placebo with odds ratios (OR) of 2.12, 3.98, 2.78, and 4.43, respectively. Amitriptyline (OR: 7.03, 95% confidence interval [CI]: 1.87, 29.05) and duloxetine (OR: 3.26, 95% CI: 1.04, 9.97) caused more withdrawals than gabapentin. The ranking order of efficacy was gabapentin, venlafaxine, pregabalin, duloxetine/gabapentin, duloxetine, amitriptyline, and placebo and the ranking order of safety was placebo, gabapentin, pregabalin, venlafaxine, duloxetine/gabapentin combination, duloxetine, and amitriptyline. Benefit-risk balance favored the order: gabapentin, venlafaxine, pregabalin, duloxetine

Investigation of depression in Greek patients with diabetic peripheral neuropathy.

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Rekleiti, Maria; Sarafis, Pavlos; Saridi, Maria; Toska, Aikaterini; Melos, Chrysovaladis; Souliotis, Kyriakos; Tsironi, Maria

2013-06-16

Considerable studies directly connect the complications in diabetic patients, and especially peripheral neuropathy, with the emergence of depression. Neuropathetic pain may deteriorate the general health status of the diabetic patient and glycaemic regulation. The purpose of this study was to investigate the appearance and degree of diabetic peripheral neuropathy and its correlation with depression, with other parameters of the disease and also duration. 57 diabetic patients participated with diagnosed diabetic peripheral neuropathy (male n=27, female n= 30, mean of age 72.7±6.35 years). The first part of Michigan Neuropathy Screening Instrument and the Zung Depression Rating Scale were used as tools for our study. Data was analysed with the SPSS 18.0 statistic program. 57.9% of the patients were overweight, 35.1% were obese and only 7% were within normal weight range. The BMI findings between the two genders indicate that male participants are more often obese than females. Women surpassed men in the category of overweight patients (p depression, it derives that a high degree of diabetic neuropathy is related with high score of depression [F(3.160)=9.821, p=0.001]. Moderate and severe neuropathy was found with almost the same levels of depression. The correlation between diabetic neuropathy and depression is confirmed, while a very high depression rate was found in patients with severe neuropathy. The issue needs further study by using common instruments to obtain comparative results from the scientific community.

The vasculitic neuropathies: an update.

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Collins, Michael P

2012-10-01

Vasculitic neuropathy is a heterogeneous disorder that usually occurs in systemic diseases, but less commonly appears as nonsystemic vasculitic neuropathy (NSVN). This review is intended to highlight recent developments in the field of vasculitic neuropathies. A Peripheral Nerve Society guideline provides data-driven consensus recommendation on classification of vasculitic neuropathies and diagnosis/treatment of NSVN. NSVN is sometimes accompanied by subclinical inflammation of adjacent skin. Amyotrophic lateral sclerosis with sensory involvement can mimic NSVN. Systemic vasculitides with neuropathy include polyarteritis nodosa, microscopic polyangiitis (MPA), rheumatoid vasculitis, Churg-Strauss syndrome (CSS), and hepatitis C-related mixed cryoglobulinemic vasculitis (MCV). At autopsy, MPA affects limb nerves diffusely, with maximal damage in proximal/middle segments. CSS can be accompanied by antineutrophil cytoplasmic antibodies (ANCAs), but most patients with neuropathy lack ANCAs. Cryoglobulinemic neuropathies are usually caused by vasculitis, irrespective of phenotype. Two randomized trials revealed rituximab to be noninferior to cyclophosphamide for inducing remission in ANCA-associated vasculitis. Many reports also document efficacy of rituximab in MCV. Consensus guidelines on NSVN should be evaluated prospectively. MPA-associated vasculitic neuropathy results from vasculitic lesions distributed diffusely throughout peripheral extremity nerves. Rituximab is effective for ANCA-associated and cryoglobulinemic vasculitis with neuropathy.

CR4056, a new analgesic I2 ligand, is highly effective against bortezomib-induced painful neuropathy in rats

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Meregalli C

2012-06-01

Full Text Available Cristina Meregalli,1 Cecilia Ceresa,1 Annalisa Canta,1 Valentina Alda Carozzi,1 Alessia Chiorazzi,1 Barbara Sala,1 Norberto Oggioni,1 Marco Lanza,2 Ornella Letar,i2 Flora Ferrari,2 Federica Avezza,1 Paola Marmiroli,1 GianFranco Caselli,2 Guido Cavaletti11Department of Neuroscience and Biomedical Technologies, University of Milan-Bicocca, 2Pharmacology and Toxicology Department, Rottapharm | Madaus Research Center, Monza, ItalyAbstract: Although bortezomib (BTZ is the frontline treatment for multiple myeloma, its clinical use is limited by the occurrence of painful peripheral neuropathy, whose treatment is still an unmet clinical need. Previous studies have shown chronic BTZ administration (0.20 mg/kg intravenously three times a week for 8 weeks to female Wistar rats induced a peripheral neuropathy similar to that observed in humans. In this animal model of BTZ-induced neurotoxicity, the present authors evaluated the efficacy of CR4056, a novel I2 ligand endowed with a remarkable efficacy in several animal pain models. CR4056 was administered in a wide range of doses (0.6–60 mg/kg by gavage every day for 2–3 weeks in comparison with buprenorphine (Bupre (28.8 µg/kg subcutaneously every day for 2 weeks and gabapentin (Gaba (100 mg/kg by gavage every day for 3 weeks. Chronic administration of BTZ reduced nerve conduction velocity and induced allodynia. CR4056, Bupre, or Gaba did not affect the impaired nerve conduction velocity. Conversely, CR4056 dose-dependently reversed BTZ-induced allodynia (minimum effective dose 0.6 mg/kg. The optimal dose found, 6 mg/kg, provided a constant pain relief throughout the treatment period and without rebound after suspension, being effective when coadministered with BTZ, starting before or after allodynia was established, or when administered alone after BTZ cessation. A certain degree of tolerance was seen after 7 days of administration, but only at the highest doses (20 and 60 mg/kg. Bupre was effective

[Hereditary sensory and autonomic neuropathy type II A: early neurological and skeletal findings].

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Esmer, C; Díaz Zambrano, S; Santos Díaz, M A; González Huerta, L M; Cuevas Covarrubias, S A; Bravo Oro, A

2014-04-01

The hereditary sensory and autonomic neuropathies are genetic disorders characterized by the loss of sensation including pain, tactile and temperature. Its clinical and molecular features vary widely; the symptoms may begin from birth or be noticed in the first or second decade, with different types of complications of trauma to the extremities such as ulcers, mutilations and acral amputations. They are classified into six groups from I to VI, determined by the abnormality in eleven genes leading to phenotypic variations in the age of onset and the presence or absence of dysautonomia signs. With the exception of type I, all are autosomal recessive. The type II of these neuropathies is characterized by insensitivity to pain, heat and proprioception. We describe three members of a Mexican family with WNK1 gene mutation that caused hereditary neuropathy IIA. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Phenotyping animal models of diabetic neuropathy

DEFF Research Database (Denmark)

Biessels, G J; Bril, V; Calcutt, N A

2014-01-01

NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy...... with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence...

A3 adenosine receptor agonist prevents the development of paclitaxel-induced neuropathic pain by modulating spinal glial-restricted redox-dependent signaling pathways.

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Janes, Kali; Esposito, Emanuela; Doyle, Timothy; Cuzzocrea, Salvatore; Tosh, Dillip K; Jacobson, Kenneth A; Salvemini, Daniela

2014-12-01

Chemotherapy-induced peripheral neuropathy accompanied by chronic neuropathic pain is the major dose-limiting toxicity of several anticancer agents including the taxane paclitaxel (Taxol). A critical mechanism underlying paclitaxel-induced neuropathic pain is the increased production of peroxynitrite in spinal cord generated in response to activation of the superoxide-generating enzyme, NADPH oxidase. Peroxynitrite in turn contributes to the development of neuropathic pain by modulating several redox-dependent events in spinal cord. We recently reported that activation of the Gi/Gq-coupled A3 adenosine receptor (A3AR) with selective A3AR agonists (ie, IB-MECA) blocked the development of chemotherapy induced-neuropathic pain evoked by distinct agents, including paclitaxel, without interfering with anticancer effects. The mechanism or mechanisms of action underlying these beneficial effects has yet to be explored. We now demonstrate that IB-MECA attenuates the development of paclitaxel-induced neuropathic pain by inhibiting the activation of spinal NADPH oxidase and two downstream redox-dependent systems. The first relies on inhibition of the redox-sensitive transcription factor (NFκB) and mitogen activated protein kinases (ERK and p38) resulting in decreased production of neuroexcitatory/proinflammatory cytokines (TNF-α, IL-1β) and increased formation of the neuroprotective/anti-inflammatory IL-10. The second involves inhibition of redox-mediated posttranslational tyrosine nitration and modification (inactivation) of glia-restricted proteins known to play key roles in regulating synaptic glutamate homeostasis: the glutamate transporter GLT-1 and glutamine synthetase. Our results unravel a mechanistic link into biomolecular signaling pathways employed by A3AR activation in neuropathic pain while providing the foundation to consider use of A3AR agonists as therapeutic agents in patients with chemotherapy-induced peripheral neuropathy. Copyright © 2014

Improved foot sensitivity and pain reduction in patients with peripheral neuropathy after treatment with monochromatic infrared photo energy--MIRE.

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Harkless, Lawrence B; DeLellis, Salvatore; Carnegie, Dale H; Burke, Thomas J

2006-01-01

The medical records of 2239 patients (mean age=73 years) with established peripheral neuropathy (PN) were examined to determine whether treatment with MIRE was, in fact, associated with increased foot sensitivity to the Semmes Weinstein monofilament (SWM) 5.07 and a reduction in neuropathic pain. The PN in 1395 of these patients (62%) was due to diabetes. Prior to treatment with MIRE, of the 10 tested sites (5 on each foot), 7.1+/-2.9 were insensitive to the SWM 5.07, and 2078 patients (93%) exhibited loss of protective sensation defined by Medicare as a loss of sensation at two or more sites on either foot. After treatment, the number of insensate sites on both feet decreased to 2.4+/-2.6, an improvement of 66%. Of the 2078 (93%) patients initially presenting with loss of protective sensation, 1106 (53%) no longer had loss of protective sensation after treatment (P<.0001); 1563 patients (70%) also exhibited neuropathic pain in addition to sensory impairment. Prior to treatment with MIRE, pain measured on the 11-point visual analogue scale (VAS) was 7.2+/-2.2 points, despite the use of a variety of pain-relieving therapeutic agents. After treatment with MIRE, pain was reduced by 4.8+/-2.4 points, a 67% reduction. Therefore, MIRE appears to be associated with significant clinical improvement in foot sensation and, simultaneously, a reduction in neuropathic pain in a large cohort of primarily Medicare aged, community-dwelling patients, initially diagnosed with PN. The quality of life associated with these two outcomes cannot be underappreciated.

Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes

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Cazzato, Daniele; Castori, Marco; Lombardi, Raffaella; Caravello, Francesca; Bella, Eleonora Dalla; Petrucci, Antonio; Grammatico, Paola; Dordoni, Chiara; Colombi, Marina

2016-01-01

Objective: To investigate the involvement of small nerve fibers in Ehlers-Danlos syndrome (EDS). Methods: Patients diagnosed with EDS underwent clinical, neurophysiologic, and skin biopsy assessment. We recorded sensory symptoms and signs and evaluated presence and severity of neuropathic pain according to the Douleur Neuropathique 4 (DN4) and ID Pain questionnaires and the Numeric Rating Scale (NRS). Sensory action potential amplitude and conduction velocity of sural nerve was recorded. Skin biopsy was performed at distal leg and intraepidermal nerve fiber density (IENFD) obtained and referred to published sex- and age-adjusted normative reference values. Results: Our cohort included 20 adults with joint hypermobility syndrome/hypermobility EDS, 3 patients with vascular EDS, and 1 patient with classic EDS. All except one patient had neuropathic pain according to DN4 and ID Pain questionnaires and reported 7 or more symptoms at the Small Fiber Neuropathy Symptoms Inventory Questionnaire. Pain intensity was moderate (NRS ≥4 and <7) in 8 patients and severe (NRS ≥7) in 11 patients. Sural nerve conduction study was normal in all patients. All patients showed a decrease of IENFD consistent with the diagnosis of small fiber neuropathy (SFN), regardless of the EDS type. Conclusions: SFN is a common feature in adults with EDS. Skin biopsy could be considered an additional diagnostic tool to investigate pain manifestations in EDS. PMID:27306637

Unilateral Optic Neuropathy and Acute Angle-Closure Glaucoma following Snake Envenomation

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Osman Okan Olcaysu

2015-01-01

Full Text Available Purpose. We aimed to describe a unique case in which a patient developed unilateral optic neuritis and angle-closure glaucoma as a result of snake envenomation. Case Report. Approximately 18 hours after envenomation, a 67-year-old female patient described visual impairment and severe pain in her left eye (LE. The patient’s best corrected visual acuity was 10/10 in the RE and hand motion in the LE. Cranial magnetic resonance imaging showed signs of neuropathy in the left optic nerve. In the LE, corneal haziness, closure of the iridocorneal angle, and mild mydriasis were observed and pupillary light reflex was absent. Intraocular pressure was 25 mmHg and 57 mmHg in the RE and LE, respectively. The patient was diagnosed with acute angle-closure glaucoma in the LE. Optic neuropathy was treated with intravenous pulse methylprednisolone. Left intraocular pressure was within normal range starting on the fourth day. One month after the incident, there was no sign of optic neuropathy; relative afferent pupillary defect and optic nerve swelling disappeared. Conclusions. Patients with severe headache and visual loss after snake envenomation must be carefully examined for possible optic neuropathy and angle-closure glaucoma. Early diagnosis and treatment of these cases are necessary to prevent permanent damage to optic nerves.

Radiation-induced neuropathies: collateral damage of improved cancer prognosis

International Nuclear Information System (INIS)

Pradat, Pierre-Francois; Maisonobe, Thierry; Psimaras, Dimitri; Lenglet, Timothee; Porcher, Raphael; Lefaix, J.L.; Delenian, S.

2012-01-01

Because of the improvement of cancer prognosis, long-term damages of treatments become a medical and public health problem. Among the iatrogenic complications, neurological impairment is crucial to consider since motor disability and pain have a considerable impact on quality of life of long cancer survivors. However, radiation-induced neuropathies have not been the focus of great attention. The objective of this paper is to provide an updated review about the radiation-induced lesions of the peripheral nerve system. Radiation-induced neuropathies are characterized by their heterogeneity in both symptoms and disease course. Signs and symptoms depend on the affected structures of the peripheral nerve system (nerve roots, nerve plexus or nerve trunks). Early-onset complications are often transient and late complications are usually progressive and associated with a poor prognosis. The most frequent and well known is delayed radiation-induced brachial plexopathy, which may follow breast cancer irradiation. Radiation-induced lumbosacral radiculoplexopathy is characterized by pure or predominant lower motor neuron signs. They can be misdiagnosed, confused with amyotrophic lateral sclerosis (ALS) or with leptomeningeal metastases since nodular MRI enhancement of the nerve roots of the cauda equina and increased cerebrospinal fluid protein content can be observed. In the absence of specific markers of the link with radiotherapy, the diagnosis of post-radiation neuropathy may be difficult. Recently, a posteriori conformal radiotherapy with 3D dosimetric reconstitution has been developed to link a precise anatomical site to unexpected excess irradiation. The importance of early diagnosis of radiation-induced neuropathies is underscored by the emergence of new disease-modifying treatments. Although the pathophysiology is not fully understood, it is already possible to target radiation-induced fibrosis but also associated factors such as ischemia, oxidative stress and

Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats

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Shota Yamamoto

2015-09-01

Full Text Available Bortezomib, an effective anticancer drug for multiple myeloma, often causes peripheral neuropathy which is mainly characterized by numbness and painful paresthesia. Nevertheless, there is no effective strategy to escape or treat bortezomib-induced peripheral neuropathy (BIPN, because we have understood few mechanism of this side effect. In this study, we evaluated behavioral and pathological characteristics of BIPN, and investigated pharmacological efficacy of various analgesic drugs and adjuvants on mechanical allodynia induced by bortezomib treatment in rats. The repeated administration of bortezomib induced mechanical and cold allodynia. There was axonal degeneration of sciatic nerve behind these neuropathic symptoms. Furthermore, the exposure to bortezomib shortened neurite length in PC12 cells. Finally, the result of evaluation of anti-allodynic potency, oral administration of tramadol (10 mg/kg, pregabalin (3 mg/kg, duloxetine (30 mg/kg or mexiletine (100 mg/kg, but not amitriptyline or diclofenac, transiently relieved the mechanical allodynia induced by bortezomib. These results suggest that axonal degeneration of the sciatic nerve is involved in BIPN and that some analgesic drugs and adjuvants are effective in the relief of painful neuropathy.

Efficiencies of Low-Level Laser Therapy (LLLT) and Gabapentin in the Management of Peripheral Neuropathy: Diabetic Neuropathy.

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Abdel-Wahhab, Khaled G; Daoud, Eitedal M; El Gendy, Aliaa; Mourad, Hagar H; Mannaa, Fathia A; Saber, Maha M

2018-03-12

Diabetic neuropathy (DN) is the highly occurred complication of diabetes mellitus; it has been defined as an event of peripheral nerve dysfunction characterized by pain, allodynia, hyperalgesia, and paraesthesia. The current study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) in the management of neuropathy in diabetic rats. The used animals were divided into the following groups: negative control, streptozotocin-induced diabetic rats, and diabetic rats with peripheral neuropathy (DNP) and DNP treated with gabapentin or with LLLT. Behavioral tests were carried out through hotplate test for the determination of pain sensations and the Morris water maze test for spatial reference memory evaluation. Blood samples were collected at the end of treatment for biochemical determinations. In the current study, the latency of hind-paw lick decreased significantly when DNP are treated with gabapentin or LLLT. The Morris water maze test showed that LLLT treatment improved memory that deteriorated in DNP more than gabapentin do. The results of the biochemical study revealed that LLLT could not affect the level of beta-endorphin that decreased in DNP but significantly decreased S100B that rose in DNP. PGE2 and cytokines IL-1β, IL-10, and TNF-α showed significant increase in DNP compared with control group. The gabapentin administration or LLLT application significantly reversed the levels of the mentioned markers towards the normal values of the controls. Levels of serum MDA and nitric oxide increased significantly in the DNP but rGSH showed significant decrease. These markers were improved significantly when the DNP were treated with gabapentin or LLLT. The treatment with gabapentin or LLLT significantly decreased the raised level in total cholesterol in DNP but could not decrease the elevated level of triglycerides, while LDL cholesterol decreased significantly in DNP treated with gabapentin but not affected by LLLT. Values of serum alanine

Protective effect of oryzanol isolated from crude rice bran oil in experimental model of diabetic neuropathy

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Somsuvra B. Ghatak

2012-09-01

Full Text Available Several studies have implicated the involvement of poor glycemic control and oxidative/nitrosative stress in the development of diabetic neuropathic pain, an important microvascular complication affecting more than 50% of diabetic patients. However, lack of understanding of the underlying etiology, development of tolerance, inadequate relief and possible toxicity associated with classical analgesics warrant the investigation of the novel agents. Therefore, the present study was carried out to investigate the effect of oryzanol (OZ, a commercially-important potent antioxidant component isolated from from crude rice bran oil (cRBO, in streptozotocin (STZ-induced diabetic neuropathy in rats. After eight weeks, diabetic rats developed neuropathy which was evident from decreased tail-flick latency (thermal hyperalgesia and increased nociceptive behavior during the formalin test. This was accompanied by decreased motor coordination based on the evaluation of neuromuscular strength. Na+ K+ ATPase, a biochemical marker associated with the development of diabetic neuropathy, was significantly inhibited in the sciatic nerve of diabetic animals. The activities of antioxidant enzymes and lipid peroxidation levels were significantly elevated in diabetic rats, indicating the involvement of oxidative stress in diabetic neuropathy. Chronic treatment with oryzanol (OZ (50 and 100 mg/kg per oral (p.o. and standard drug glibenclamide (Gl (10 mg/kg, p.o. significantly attenuated the behavioral as well as biochemical changes associated with diabetic neuropathy. The findings provide experimental evidence to the protective effects of OZ on hyperglycemia-induced thermal hyperalgesia and oxidative stress which might be responsible for diabetes induced nerve damage.

The development and validation of a neuropathy- and foot ulcer-specific quality of life instrument.

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Vileikyte, Loretta; Peyrot, Mark; Bundy, Christine; Rubin, Richard R; Leventhal, Howard; Mora, Pablo; Shaw, Jonathan E; Baker, Paul; Boulton, Andrew J M

2003-09-01

The purpose of this study was to develop a questionnaire that measures patients' perceptions of the impact of diabetic peripheral neuropathy and foot ulcers on their quality of life and to assess the psychometric properties of this instrument in a sample of patients with varying severity and symptomatology of diabetic peripheral neuropathy. The neuropathy- and foot ulcer-specific quality of life instrument (NeuroQoL), generated from interviews with patients with (n = 47) and without (n = 15) diabetic peripheral neuropathy, was administered to 418 consecutive patients with diabetic peripheral neuropathy (35% with foot ulcer history) attending either U.K. (n = 290) or U.S. (n = 128) diabetes centers. Psychometric tests of NeuroQoL included factor analyses and internal consistency of scales; a series of multivariate analyses were performed to establish its criterion, construct, and incremental validity. Results were compared with those obtained using the Short Form (SF)-12 measure of health-related functioning. Factor analyses of NeuroQoL revealed three physical symptom measures and two psychosocial functioning measures with good reliability (alpha = 0.86-0.95). NeuroQoL was more strongly associated with measures of neuropathic severity than SF-12, more fully mediated the relationship of diabetic peripheral neuropathy with overall quality of life, and significantly increased explained variance in overall quality of life over SF-12. NeuroQoL reliably captures the key dimensions of the patients' experience of diabetic peripheral neuropathy and is a valid tool for studying the impact of neuropathy and foot ulceration on quality of life.

Improvement in Neuropathy Specific Quality of Life in Patients with Diabetes after Vitamin D Supplementation

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Uazman Alam

2017-01-01

Full Text Available Objective. To assess the effect of vitamin D supplementation on neuropathy specific quality of life (NeuroQoL in patients with painful diabetic neuropathy. Methods. This prospective, open label study was conducted between June 2012 and April 2013. Patients with symptomatic diabetic neuropathy were given a single dose of 600,000 IU intramuscular vitamin D, and NeuroQol was assessed at baseline and at five follow-up visits every 4 weeks. Results. Of 143 participants, 41.3% were vitamin D deficient (vitamin D < 20 ng/ml. Treatment with vitamin D resulted in a significant increase in 25(OHD (P<0.0001 and a significant improvement in the NeuroQoL subscale score for emotional distress (P=0.04, with no significant change in the other NeuroQoL domains of painful symptoms and paresthesia, loss of temperature and touch sensation, unsteadiness, limitation in daily activities, and interpersonal problems. There was a significant reduction in patient perception about foot problems on QoL of “quite a lot” (P<0.05 and “very much” (P<0.0001 with a significant reduction in the baseline response of having a “poor” QoL from 5.2% to 0.7% (P<0.0001 and an increase in the response of an “excellent QoL” from 1.5% to 7.4% (P<0.0001. Conclusion. Vitamin D is effective in improving quality of life in patients with painful diabetic neuropathy.

Trigeminal nerve anatomy in neuropathic and non-neuropathic orofacial pain patients.

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Wilcox, Sophie L; Gustin, Sylvia M; Eykman, Elizabeth N; Fowler, Gordon; Peck, Christopher C; Murray, Greg M; Henderson, Luke A

2013-08-01

Trigeminal neuralgia, painful trigeminal neuropathy, and painful temporomandibular disorders (TMDs) are chronic orofacial pain conditions that are thought to have fundamentally different etiologies. Trigeminal neuralgia and neuropathy are thought to arise from damage to or pressure on the trigeminal nerve, whereas TMD results primarily from peripheral nociceptor activation. This study sought to assess the volume and microstructure of the trigeminal nerve in these 3 conditions. In 9 neuralgia, 18 neuropathy, 20 TMD, and 26 healthy controls, the trigeminal root entry zone was selected on high-resolution T1-weighted magnetic resonance images and the volume (mm(3)) calculated. Additionally, using diffusion-tensor images (DTIs), the mean diffusivity and fractional anisotropy values of the trigeminal nerve root were calculated. Trigeminal neuralgia patients displayed a significant (47%) decrease in nerve volume but no change in DTI values. Conversely, trigeminal neuropathy subjects displayed a significant (40%) increase in nerve volume but again no change in DTI values. In contrast, TMD subjects displayed no change in volume or DTI values. The data suggest that the changes occurring within the trigeminal nerve are not uniform in all orofacial pain conditions. These structural and volume changes may have implications in diagnosis and management of different forms of chronic orofacial pain. This study reveals that neuropathic orofacial pain conditions are associated with changes in trigeminal nerve volume, whereas non-neuropathic orofacial pain is not associated with any change in nerve volume. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Herbal Remedies: A Boon for Diabetic Neuropathy.

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Tiwari, Reshu; Siddiqui, Mohd Haris; Mahmood, Tarique; Bagga, Paramdeep; Ahsan, Farogh; Shamim, Arshiya

2018-03-26

Diabetic neuropathy is a chronic complication of diabetes mellitus affecting about 50% of patients. Its symptoms include decreased motility and severe pain in peripheral parts. The pathogenesis involved is an abnormality in blood vessels that supply the peripheral nerves, metabolic disorders such as myo-inositol depletion, and increased nonenzymatic glycation. Moreover, oxidative stress in neurons results in activation of multiple biochemical pathways, which results in the generation of free radicals. Apart from available marketed formulations, extensive research is being carried out on herbal-based natural products to control hyperglycemia and its associated complications. This review is focused to provide a summary on diabetic neuropathy covering its etiology, types, and existing work on herbal-based therapies, which include pure compounds isolated from plant materials, plant extracts, and Ayurvedic preparations.

Vasculitic Neuropathies.

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Naddaf, Elie; Dyck, P James Bonham

2015-10-01

From pathological standpoint, we divide vasculitic neuropathies in two categories: nerve large arteriole vasculitides and nerve microvasculitis. It is also important to determine whether a large arteriole vasculitis has an infectious etiology as it entails different treatment approach. Treatment of non-infectious large arteriole vasculitides consists initially of induction therapy with corticosteroids. Adding an immunosuppressant, mainly cyclophosphamide, is often needed. Treatment of infectious large arteriole vasculitides needs a multidisciplinary approach to target both the underlying infection and the vasculitis. Corticosteroids are the first-line therapy for classic non-systemic vasculitic neuropathy. Stable or improving patients without biopsy evidence of active vasculitis can be either observed or treated. Currently, adding an immunosuppressant is only indicated for patients who continue to progress on corticosteroids alone or patients with a rapidly progressive course. The treatment of the radiculoplexus neuropathies such as diabetic lumbosacral radiculoplexus neuropathy, lumbosacral radiculoplexus neuropathy (in non-diabetic patients), and diabetic cervical radiculoplexus neuropathy, as well as painless diabetic motor neuropathy, is not well established yet. We treat patients, if they present early on in the disease course or if they have severe disabling symptoms, with IV methylprednisolone 1 g once a week for 12 weeks.

AAPT Diagnostic Criteria for Chronic Cancer Pain Conditions.

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Paice, Judith A; Mulvey, Matt; Bennett, Michael; Dougherty, Patrick M; Farrar, John T; Mantyh, Patrick W; Miaskowski, Christine; Schmidt, Brian; Smith, Thomas J

2017-03-01

Chronic cancer pain is a serious complication of malignancy or its treatment. Currently, no comprehensive, universally accepted cancer pain classification system exists. Clarity in classification of common cancer pain syndromes would improve clinical assessment and management. Moreover, an evidence-based taxonomy would enhance cancer pain research efforts by providing consistent diagnostic criteria, ensuring comparability across clinical trials. As part of a collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) and the American Pain Society (APS), the ACTTION-APS Pain Taxonomy initiative worked to develop the characteristics of an optimal diagnostic system. After the establishment of these characteristics, a working group consisting of clinicians and clinical and basic scientists with expertise in cancer and cancer-related pain was convened to generate core diagnostic criteria for an illustrative sample of 3 chronic pain syndromes associated with cancer (ie, bone pain and pancreatic cancer pain as models of pain related to a tumor) or its treatment (ie, chemotherapy-induced peripheral neuropathy). A systematic review and synthesis was conducted to provide evidence for the dimensions that comprise this cancer pain taxonomy. Future efforts will subject these diagnostic categories and criteria to systematic empirical evaluation of their feasibility, reliability, and validity and extension to other cancer-related pain syndromes. The ACTTION-APS chronic cancer pain taxonomy provides an evidence-based classification for 3 prevalent syndromes, namely malignant bone pain, pancreatic cancer pain, and chemotherapy-induced peripheral neuropathy. This taxonomy provides consistent diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms for these potentially serious cancer pain conditions that can be extended and applied with other cancer

Inflammation and neuropathic attacks in hereditary brachial plexus neuropathy

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Klein, C; Dyck, P; Friedenberg, S; Burns, T; Windebank, A; Dyck, P

2002-01-01

Objective: To study the role of mechanical, infectious, and inflammatory factors inducing neuropathic attacks in hereditary brachial plexus neuropathy (HBPN), an autosomal dominant disorder characterised by attacks of pain and weakness, atrophy, and sensory alterations of the shoulder girdle and upper limb muscles. Methods: Four patients from separate kindreds with HBPN were evaluated. Upper extremity nerve biopsies were obtained during attacks from a person of each kindred. In situ hybridisation for common viruses in nerve tissue and genetic testing for a hereditary tendency to pressure palsies (HNPP; tomaculous neuropathy) were undertaken. Two patients treated with intravenous methyl prednisolone had serial clinical and electrophysiological examinations. One patient was followed prospectively through pregnancy and during the development of a stereotypic attack after elective caesarean delivery. Results: Upper extremity nerve biopsies in two patients showed prominent perivascular inflammatory infiltrates with vessel wall disruption. Nerve in situ hybridisation for viruses was negative. There were no tomaculous nerve changes. In two patients intravenous methyl prednisolone ameliorated symptoms (largely pain), but with tapering of steroid dose, signs and symptoms worsened. Elective caesarean delivery did not prevent a typical postpartum attack. Conclusions: Inflammation, probably immune, appears pathogenic for some if not all attacks of HBPN. Immune modulation may be useful in preventing or reducing the neuropathic attacks, although controlled trials are needed to establish efficacy, as correction of the mutant gene is still not possible. The genes involved in immune regulation may be candidates for causing HBPN disorders. PMID:12082044

Neuropathy in a petrol sniffer.

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Hall, D M; Ramsey, J; Schwartz, M S; Dookun, D

1986-09-01

A 4 year old boy developed a profound motor neuropathy after repeated deliberate inhalation of petroleum vapour. The condition was characterised by extreme slowing of the nerve conduction velocity. He made a gradual recovery over six months. The neuropathy was attributed to the N-hexane component of petroleum.

Internal and external factors affecting the development of neuropathic pain in rodents. Is it all about pain?

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Vissers, K; De Jongh, R; Hoffmann, V; Heylen, R; Crul, B; Meert, T

2003-12-01

It is important to know the factors that will influence animal models of neuropathic pain. A good reproducibility and predictability in different strains of animals for a given test increases the clinical relevance and possible targeting. An obligatory requirement for enabling comparisons of results of different origin is a meticulous definition of the specific sensitivities of a model for neuropathic pain and a description of the test conditions. Factors influencing neuropathic pain behavior can be subdivided in external and internal factors. The most important external factors are; timing of the measurement of pain after induction of neuropathy, circadian rhythms, seasonal influences, air humidity, influence of order of testing, diet, social variables, housing and manipulation, cage density, sexual activity, external stress factors, and influences of the experimenter. The internal factors are related to the type of animal, its genetic background, gender, age, and the presence of homeostatic adaptation mechanisms to specific situations or stress. In practice, the behavioral presentations to pain depend on the combination of genetic and environmental factors such as accepted social behavior. It also depends on the use of genetic manipulation of the animals such as in transgenic animals. These make the interpretation of data even more difficult. Differences of pain behavior between in- and outbred animals will be better understood by using modern analysis techniques. Substrains of animals with a high likelihood for developing neuropathic pain make the unraveling of specific pathophysiological mechanisms possible. Concerning the effect of stress on pain, it is important to differentiate between external and internal stress such as social coping behavior. The individual dealing with this stress is species sensitive, and depends on the genotype and the social learning. In the future, histo-immunological and genetic analysis will highlight similarities of the different

Propylthiouracil and peripheral neuropathy

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Valentina Van Boekel

1992-06-01

Full Text Available Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

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Hana Starobova

2017-05-01

Full Text Available Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches.

The evidence for pharmacological treatment of neuropathic pain

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Finnerup, Nanna Brix; Sindrup, Søren Hein; Jensen, Troels Staehelin

2010-01-01

to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions. One hundred and seventy-four studies were included, representing a 66% increase in published randomized, placebo-controlled trials in the last 5 years. Painful poly-neuropathy (most often due to diabetes......Randomized, double-blind, placebo-controlled trials on neuropathic pain treatment are accumulating, so an updated review of the available evidence is needed. Studies were identified using MEDLINE and EMBASE searches. Numbers needed to treat (NNT) and numbers needed to harm (NNH) values were used......) was examined in 69 studies, postherpetic neuralgia in 23, while peripheral nerve injury, central pain, HIV neuropathy, and trigeminal neuralgia were less often studied. Tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, the anticonvulsants gabapentin and pregabalin, and opioids...

Optic neuropathy following an altitude exposure.

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Steigleman, Allan; Butler, Frank; Chhoeu, Austin; O'Malley, Timothy; Bower, Eric; Giebner, Stephen

2003-09-01

This case report describes a 20-yr-old man who presented with retro-orbital pain and blurred vision in his left eye 3 wk after an altitude exposure in a hypobaric chamber. He was found to have significant deficits in color vision and visual fields consistent with an optic neuropathy in his left eye. The patient was diagnosed with decompression sickness and treated with hyperbaric oxygen with a U.S. Navy Treatment Table VI. All signs and symptoms resolved with a single hyperbaric oxygen treatment but recurred. A head MRI revealed a left frontoethmoid sinus opacity. A concomitant sinusitis was diagnosed. The patient had full resolution of symptoms after a total of four hyperbaric oxygen treatments and antibiotic therapy at 6-wk follow-up. Although a para-infectious etiology for this patient's optic neuropathy cannot be excluded, his history of altitude exposure and significant, rapid response to hyperbaric oxygen treatment strongly implies decompression sickness in this case.

Neuropathic pain in the orofacial region: The role of pain history. A retrospective study.

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Dieb, W; Moreau, N; Chemla, I; Descroix, V; Boucher, Y

2017-06-01

Orofacial neuropathic pain is often difficult to treat, mostly because of still unclear underlying mechanisms. The occurrence of such neuropathic pain varies depending on different factors, of which preexisting preoperative pain seems to be of high importance. The aim of this study was thus to test the hypothesis that prior history of pain could indeed be considered a risk factor for the development of orofacial neuropathic pain in the same region. The study was performed in the dental department of the Groupe Hospitalier Pitié-Salpêtrière (GHPS) in Paris, France. We investigated the presence of prior inflammatory pain before development of orofacial neuropathic pain in 56 patients. For each patient file, the following items were collected: age, gender; medical history; diagnosis; description of the pain (at time of consultation); presence or absence of prior dental treatment; date and type of dental treatment received. 41 patients (73%) of orofacial neuropathic pain patients had a history of pain compatible with an inflammatory condition; 4% (n=2) did not report any prior pain and 23% (n=13) could not remember. Among the patients with documented history of pain prior to neuropathy, 88% (n=36) received surgical treatment; 61%, (n=25) endodontic treatment and 22%, (n=9) restorative treatment. All eventually received endodontic treatment or tooth extraction. These dental treatments are compatible with the hypothesis of prior inflammatory pain in these patients. These results support the hypothesis that prior inflammatory pain could favor the development of orofacial neuropathic pain. Prevention and treatment of inflammatory trigeminal pain may therefore play a key role in preventing future neuropathic pain development. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Epalrestat, an aldose reductase inhibitor, in diabetic neuropathy: An Indian perspective

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Sharma S

2008-01-01

Full Text Available Background: A number of diabetic patients with diabetic neuropathy, in India, were treated with epalrestat, an aldose reductase inhibitor. In this study, more than 2000 patients with diabetic neuropathy, who were treated with epalrestat for 3-12 months, were analyzed to assess the efficacy and the adverse reactions of the drug. Method: We analyzed the subjective symptoms (spontaneous pain, numbness, coldness and hypoesthesia and the nerve function tests (motor nerve conduction velocity, sensory nerve conduction velocity and vibration threshold. Result: The improvement rate of the subjective symptoms was 75% (slightly improved or better and that of the nerve function tests 36%. Adverse drug reactions were encountered in 52 (2.5% of the 2190 patients, none of which was severe. Conclusion: Although data are limited, it is strongly suggested that epalrestat is a highly effective and safe agent for the treatment of diabetic neuropathy.

Intravenous lidocaine infusion--a new treatment of chronic painful diabetic neuropathy?

DEFF Research Database (Denmark)

Kastrup, J; Petersen, P; Dejgård, A

1987-01-01

after lidocaine infusion compared to after saline infusion (P less than 0.05 and P less than 0.02, respectively). The duration of the individual effect ranged from 3 to 21 days. Lidocaine infusion had no effect on the objective measurements of neuropathy. Intravenous lidocaine infusion seems to be a new...

Autonomic Neuropathy

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... risk of autonomic neuropathy. Other diseases. Amyloidosis, porphyria, hypothyroidism and cancer (usually due to side effects from treatment) may also increase the risk of autonomic neuropathy. ...

Neuropathic pain: is quantitative sensory testing helpful?

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Krumova, Elena K; Geber, Christian; Westermann, Andrea; Maier, Christoph

2012-08-01

Neuropathic pain arises as a consequence of a lesion or disease affecting the somatosensory system and is characterised by a combination of positive and negative sensory symptoms. Quantitative sensory testing (QST) examines the sensory perception after application of different mechanical and thermal stimuli of controlled intensity and the function of both large (A-beta) and small (A-delta and C) nerve fibres, including the corresponding central pathways. QST can be used to determine detection, pain thresholds and stimulus-response curves and can thus detect both negative and positive sensory signs, the second ones not being assessed by other methods. Similarly to all other psychophysical tests QST requires standardised examination, instructions and data evaluation to receive valid and reliable results. Since normative data are available, QST can contribute also to the individual diagnosis of neuropathy, especially in the case of isolated small-fibre neuropathy, in contrast to the conventional electrophysiology which assesses only large myelinated fibres. For example, detection of early stages of subclinical neuropathy in symptomatic or asymptomatic patients with diabetes mellitus can be helpful to optimise treatment and identify diabetic foot at risk of ulceration. QST assessed the individual's sensory profile and thus can be valuable to evaluate the underlying pain mechanisms which occur in different frequencies even in the same neuropathic pain syndromes. Furthermore, assessing the exact sensory phenotype by QST might be useful in the future to identify responders to certain treatments in accordance to the underlying pain mechanisms.

Effectiveness of gabapentin pharmacotherapy in chemotherapy-induced peripheral neuropathy.

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Magnowska, Magdalena; Iżycka, Natalia; Kapoła-Czyż, Joanna; Romała, Anna; Lorek, Jakub; Spaczyński, Marek; Nowak-Markwitz, Ewa

2018-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a common chemotherapy side effect, but its prevention and treatment remains a challenge. Neurotoxicity may lead to dose limitation or even treatment discontinuation, and therefore potentially affect the efficacy of anticancer treatment and long term outcomes. The practice to administer gabapentin for neuropathy may be applicable, but is limited by insufficient studies. The aim of our study was to assess the presence of chemotherapy-induced peripheral neuropathy in ovarian cancer patients treated with first-line paclitaxel and carboplatin chemotherapy and evaluate the effectiveness of gabapentin in treatment of this condition. 61 ovarian cancer patients treated with first line chemotherapy were included in the study. The first phase of the study was to assess neurological condition of each patient by: neuropathy symptoms scale, McGill's scale, neurological deficit and quality of life, during the chemotherapy. In the second phase of the study we evaluated the response to gabapentin treatment in a group of patients who developed neuropathy. 78.7% of the patients developed chemotherapy related neuropathy. During the course of chemotherapy these patients experienced significant exacerbation of neuropathy symptoms (p peripheral neuropathy.

Integrating data from randomized controlled trials and observational studies to predict the response to pregabalin in patients with painful diabetic peripheral neuropathy

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Joe Alexander

2017-07-01

Full Text Available Abstract Background More patient-specific medical care is expected as more is learned about variations in patient responses to medical treatments. Analytical tools enable insights by linking treatment responses from different types of studies, such as randomized controlled trials (RCTs and observational studies. Given the importance of evidence from both types of studies, our goal was to integrate these types of data into a single predictive platform to help predict response to pregabalin in individual patients with painful diabetic peripheral neuropathy (pDPN. Methods We utilized three pivotal RCTs of pregabalin (398 North American patients and the largest observational study of pregabalin (3159 German patients. We implemented a hierarchical cluster analysis to identify patient clusters in the Observational Study to which RCT patients could be matched using the coarsened exact matching (CEM technique, thereby creating a matched dataset. We then developed autoregressive moving average models (ARMAXs to estimate weekly pain scores for pregabalin-treated patients in each cluster in the matched dataset using the maximum likelihood method. Finally, we validated ARMAX models using Observational Study patients who had not matched with RCT patients, using t tests between observed and predicted pain scores. Results Cluster analysis yielded six clusters (287–777 patients each with the following clustering variables: gender, age, pDPN duration, body mass index, depression history, pregabalin monotherapy, prior gabapentin use, baseline pain score, and baseline sleep interference. CEM yielded 1528 unique patients in the matched dataset. The reduction in global imbalance scores for the clusters after adding the RCT patients (ranging from 6 to 63% depending on the cluster demonstrated that the process reduced the bias of covariates in five of the six clusters. ARMAX models of pain score performed well (R 2 : 0.85–0.91; root mean square errors: 0.53–0

Anterior ischemic optic neuropathy in patients undergoing hemodialysis

NARCIS (Netherlands)

DoorenbosBot, ACC; Geerlings, W; Houtman, IA

Four patients are discussed who underwent hemodialysis and developed anterior ischemic optic neuropathy (AION). Three patients had been treated by hemodialysis for several years. One patient developed bilateral optic neuropathy after the first hemodialysis session, So far, only four hemodialysis

Spinal cord stimulation and modulation of neuropathic pain

NARCIS (Netherlands)

de Vos, Cecilia Cecilia Clementine

2013-01-01

This thesis reports on the opportunities of several new applications of spinal cord stimulation (SCS) for the treatment of neuropathic pain. Our pilot study and consecutively performed international randomised controlled trial on effects of SCS in patients with painful diabetic neuropathy showed

Effect of a polyherbal formulation cream on diabetic neuropathic pain among patients with type 2 diabetes – A pilot study

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Viswanathan, Vijay; Rajsekar, Seena; Selvaraj, Bamila; Kumpatla, Satyavani

2016-01-01

Background & objectives: Painful diabetic neuropathy is a common complication of diabetes and can severely limit patients’ daily functions. The aim of this pilot study was to evaluate the safety and effect of using a polyherbal formulation in reducing the symptoms of diabetic neuropathic pain in comparison with placebo among patients with type 2 diabetes. Methods: A total of 50 (M:F = 33:17) consecutive type 2 diabetes patients with painful diabetic neuropathy were enrolled in this study. All these patients had either two or more symptoms of diabetic neuropathy such as pain, burning and pricking sensations and numbness in their feet. They were randomly assigned to two groups: group 1 (n = 26) patients were treated with polyherbal formulation cream and group 2 (n = 24) patients were administered placebo. The patients were followed up for six months. Changes in the symptoms of painful diabetic neuropathy of each patient were recorded at baseline, third and sixth month using the Diabetic Neuropathic Score. Results: The mean age of the patients, duration of diabetes and glycated haemoglobin (HbA1c) were similar in both groups at baseline. During follow up visits, there was a decrease in the HbA1c levels in the study and control groups. The symptoms of painful diabetic neuropathy were also similar in both groups at baseline. A significant decrease in symptoms of neuropathic pain was observed among the group of patients treated with polyherbal formulation cream (76.9 per cent) compared to the placebo-treated group (12.5 per cent) (P<0.001), at the end of the final follow up. Interpretation & conclusions: In this pilot study polyherbal formulation cream was found to be effective as well as safe to treat painful diabetic neuropathy. However, its long term use needs to be evaluated for any further effectiveness and side effects. PMID:27934800

Hypertrophic neuropathy in Noonan syndrome with multiple lentigines.

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Maridet, Claire; Sole, Guilhem; Morice-Picard, Fanny; Taieb, Alain

2016-06-01

RASopathies comprise several genetic syndromes with mainly cardio-facial-cutaneous manifestations. We report a patient with Noonan syndrome with multiple lentigines (NSML) due to a PTPN11 (p.Thr468Met) mutation associated with hypertrophic neuropathy of lumbar plexus in an adult woman, initially referred for neuropathic pain. Differential diagnosis of neurofibromatosis type 1 (NF1) and other RASopathies is difficult without molecular testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Spectrum of peripheral neuropathies associated with surgical interventions; A neurophysiological assessment

LENUS (Irish Health Repository)

Saidha, Shiv

2010-04-19

Abstract Background We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them. Methods We retrospectively identified 66 patients diagnosed with post-procedure neuropathies between January 2005 and June 2008. We reviewed their referral cards and medical records for patient demographics, information on procedures, symptoms, as well as clinical and neurophysiological findings. Results Thirty patients (45.4%) had neuropathies remote from procedural sites and 36 patients (54.5%) had neuropathies in close proximity to procedural sites. Half of the remote neuropathies (15\\/30) developed following relatively short procedures. In 27% of cases (8\\/30) remote neuropathies were bilateral. Seven patients developed neuropathies remote from operative sites following hip arthroplasties (7\\/30: 23.3%), making hip arthroplasty the most common procedure associated with remote neuropathies. Sciatic neuropathies due to hip arthroplasty (12\\/36, 33.3%) accounted for the majority of neuropathies occurring in close proximity to operative sites. Five medial cutaneous nerve of forearm neuropathies occurred following arterio-venous fistula (AVF) formation. Conclusions An array of surgical procedures may be complicated by neuropathy. Almost half of post-procedure neuropathies occur remote from the site of procedure, emphasizing the need to try to prevent not just local, but also remote neuropathies. Mechanical factors and patient positioning should be considered in the prevention of post-operative neuropathies. There is a possible association between AVF formation and medial cutaneous nerve of forearm neuropathy, which requires further study for validation.

Acquired neuropathies.

Science.gov (United States)

Lozeron, Pierre; Trocello, Jean-Marc; Kubis, Nathalie

2013-09-01

Acquired neuropathies represent most of the neuropathies encountered in clinical practice. Hundreds of causes have been identified even though up to 41% of patients are still classified as idiopathic (Rajabally and Shah in J Neurol 258:1431-1436, 1). Routine evaluation relies on comprehensive medical history taking, clinical examination, nerve conduction studies and laboratory tests. Other investigations such as nerve biopsy or nerve or muscle imaging are performed in specific settings. This review focuses on recent advances in acquired neuropathies.

PREVALENCE OF PERIPHERAL NEUROPATHY AFTER CHEMOTHERAPY IN PATIENTS TREATED IN A SERVICE OF ONCOLOGY: A RETROSPECTIVE REVIEW

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Simone Yuriko Kameo

2016-07-01

Full Text Available Objective: To perform a clinical-epidemiological analysis of cancer patients who had been treated with chemotherapy and had peripheral neuropathy and relate it to nursing diagnosis chronic pain (00133. Methods: A descriptive, retrospective study and data were collected from medical records of cancer patients in Aracaju, Sergipe, Brazil. Results: 5.6% had peripheral neuropathy resulting from chemotherapy. 50% made use of taxanes, 28.5% of monoclonal antibodies and 21.5% platinum derivatives, antibiotic and antimetabolite. Pain was the main complaint of these patients, and result in nerve damage, chronic use of certain drugs (vincristine, cisplatin and paclitaxel or be associated with some diseases. Conclusion: there was a high frequency of changes in sensitivity, highlighting the presence of neuropathic pain, paresthesia and dysesthesia. Professionals should seek training to be able to contribute effectively to the relief of this uncomfortable symptom to be performed properly.

Ophthalmople gic cranial neuropathy: clinical case

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N. S. Dozorova

2018-01-01

Full Text Available Ophthalmoplegic cranial neuropathy (OCN is a disease with unknown etiology, which manifests itself by episodes of intense headache, accompanied by completely or partially reversible dysfunction of the oculomotor nerve: ptosis, mydriasis and ophthalmoplegia. It is assumed that the pathology is demyelinating in nature, therefore in the International classification of headaches OCN excluded from rubric migraine and related to the painful cranial neuropathies. The question of the prevention and treatment of this disease is still controversial, the issue of the appointment of corticosteroids, calcium channel blockers and β-blockers, methods of surgical correction of strabismus and botulin therapy.The article describes OCN in an 11-year-old boy. In the clinical picture headache attacks were observed. These attacks were with signs of selective lesions of the oculomotor nerve on one side. These functional changes are recurrent, and fully regress between attacks. Laboratory and instrumental examinations revealed no pathology that could cause this symptom, including myasthenia. The described case demonstrates the classical picture of OCN with a favorable course and the partial damage of the oculomotor nerve on one side.

Correlation of Michigan neuropathy screening instrument, United Kingdom screening test and electrodiagnosis for early detection of diabetic peripheral neuropathy.

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Fateh, Hamid R; Madani, Seyed Pezhman; Heshmat, Ramin; Larijani, Bagher

2015-01-01

Almost half of Diabetic Peripheral Neuropathies (DPNs) are symptom-free. Methods including questionnaires and electrodiagnosis (EDx) can be fruitful for easy reach to early diagnosis, correct treatments of diabetic neuropathy, and so decline of complications for instance diabetic foot ulcer and prevention of high costs. The goal of our study was to compare effectiveness of the Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST) and electrophysiological evaluation in confirming diabetic peripheral neuropathy. One hundred twenty five known diabetes mellitus male and female subjects older than 18 with or without symptoms of neuropathy comprised in this research. All of them were interviewed in terms of demographic data, lipid profile, HbA1C, duration of disease, and history of retinopathy, so examined by Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST), and nerve conduction studies (NCS). The collected data were analyzed by SPSS software 18. One hundred twenty five diabetic patients (70 female, 55 male) were recruited in this study with a mean age of 58.7 ± 10.2, and mean duration of diabetes was 10.17 ± 6.9 years. The mean neuropathy score of MNSI and UKST were 2.3 (1.7) and 4.16 (2.9), respectively. Each instrument detected the peripheral neuropathy in 78 (69 %) and 91 (73 %) of patients, respectively. There was a significant relationship between number of neuropathies and mean of diabetes duration and development of retinopathy in both questionnaire evaluations and NCS. By nerve conduction study, neuropathy was detected in 121 (97 %) diabetic patients were reported in order 15 (12 %) mononeuropathy (as 33 % sensory and 67 % motor neuropathy) and 106 (85 %) polyneuropathy (as 31 % motor and 69 % sensorimotor neuropathy). As regards NCS is an objective, simple, and non-invasive tool and also can determine level of damage and regeneration in peripheral nerves, this study

Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.

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Schappacher, Katie A; Styczynski, Lauren; Baccei, Mark L

2017-09-01

Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.

H-reflex amplitude depression as a marker of presynaptic inhibition in Painful Diabetic Neuropathy (PDN.

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Ahmad Asmedi

2016-02-01

Full Text Available ABSTRACT Painful Diabetic Neuropathy (PDN is a common complication of diabetes mellitus (DM. Disruption in presynaptic inhibition in dorsal horn of the spinal cord has been proposed as one of the pathomechanism of PDN. Previous research showed that presynaptic inhibition can be detected by H-reflex examination. The aim of this study was to know whether the reduction of presynaptic inhibition in spinal dorsal horn of PDN patients really exist, and detectable by H-reflex examination. It was cohort prospective involving 141 (58 men, 83 women patients with DM and impaired glucose tolerance (IGT between the ages of 40 and 61 years from several health facilities in Yogyakarta. All patients underwent clinical, laboratory and electrodiagnostic examination. Demographic, clinical and electrodiagnostic data were collected and analyzed. By survival analysis there were 25 new cases of PDN (12.12% cumulative incidence. Using survival Kaplan Meier analysis, the significant hazard ratio for PDN were 12.81 for median motor nerve amplitude, 5.74 for median nerve distal latency, 3.71 for median sensory nerve amplitude, 6.33 for median sensory latency, 3.4 for tibial nerve amplitude, 3.48 for tibial nerve distal latency, 2.29 for sural nerve amplitude, 4.47 for sural nerve latency, 3.99 for H-reflex latency, 5.88 for H-reflex amplitude, and 17.83 for Diabetic Neuropathy (DN status. Using hazard proportional cox analysis, only H amplitude and DN status (DNS score were significantly correlated with PDN (p= 0.026; hazard ratio = 15.450; CI 95%= 1.39 – 171.62 for H amplitude and p= 0.030; hazard ratio = 10.766; CI 95%=1.26 – 92.09 for DN status. This study showed that depression of H-reflex amplitude was correlated with the occurrence of PDN. This result proves that there was presynaptic inhibition process in PDN that manifests as low H-reflex amplitude.

Role of metformin in oxaliplatin-induced peripheral neuropathy in patients with stage III colorectal cancer: randomized, controlled study.

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El-Fatatry, Basma Mahrous; Ibrahim, Osama Mohamed; Hussien, Fatma Zakaria; Mostafa, Tarek Mohamed

2018-06-21

Peripheral sensory neuropathy is the most prominently reported adverse effect of oxaliplatin. The purpose of this study was to evaluate metformin role in oxaliplatin-induced neuropathy. From November 2014 to May 2016, 40 patients with stage III colorectal cancer completed 12 cycles of FOLFOX-4 regimen. Twenty patients in the control arm received FOLFOX-4 regimen only, and 20 patients in the metformin arm, received the same regimen along with metformin 500 mg three times daily. The metformin efficacy was evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0), a12-item neurotoxicity questionnaire (Ntx-12) from the validated Functional Assessment of Cancer Therapy/Gynecologic Oncology Group and, the brief pain inventory short form "worst pain" item. In addition to neurotensin, malondialdehyde and interleukin-6 serum levels assessment. At the end of the 12th cycle, there were less patients with grade 2 and 3 neuropathy in metformin arm as compared to control arm. (60 versus 95%, P = 0.009) In addition, metformin arm showed significantly higher total scores of Ntx-12 questionnaire than control arm (24.0 versus 19.2, P < 0.001). Furthermore, the mean pain score in metformin arm was significantly lower than those of control arm, (6.7 versus 7.3, P = 0.005). Mean serum levels of malondialdehyde and neurotensin were significantly lower in metformin arm after the 6th and the 12th cycles. Metformin may be a promising drug in protecting colorectal cancer patients against oxaliplatin-induced chronic peripheral sensory neuropathy.

Characteristics, treatment, and health care expenditures of Medicare supplemental-insured patients with painful diabetic peripheral neuropathy, post-herpetic neuralgia, or fibromyalgia.

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Johnston, Stephen S; Udall, Margarita; Alvir, Jose; McMorrow, Donna; Fowler, Robert; Mullins, Daniel

2014-04-01

To describe the characteristics, treatment, and health care expenditures of Medicare Supplemental-insured patients with painful diabetic peripheral neuropathy (pDPN), post-herpetic neuralgia (PHN), or fibromyalgia. Retrospective cohort study. United States clinical practice, as reflected within a database comprising administrative claims from 2.3 million older adults participating in Medicare supplemental insurance programs. Selected patients were aged ≥65 years, continuously enrolled in medical and prescription benefits throughout years 2008 and 2009, and had ≥1 medical claim with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for DPN, PHN, or fibromyalgia, followed within 60 days by a medication or pain intervention procedure used in treating pDPN, PHN, or fibromyalgia during 2008-2009. Utilization of, and expenditures on, pain-related and all-cause pharmacotherapy and medical interventions in 2009. The study included 25,716 patients with pDPN (mean age 75.2 years, 51.2% female), 4,712 patients with PHN (mean age 77.7 years, 63.9% female), and 25,246 patients with fibromyalgia (mean age 74.4 years, 73.0% female). Patients typically had numerous comorbidities, and many were treated with polypharmacy. Mean annual expenditures on total pain-related health care and total all-cause health care, respectively, (in 2010 USD) were: $1,632, $24,740 for pDPN; $1,403, $16,579 for PHN; and $1,635, $18,320 for fibromyalgia. In age-stratified analyses, pain-related health care expenditures decreased as age increased. The numerous comorbidities, polypharmacy, and magnitude of expenditures in this sample of Medicare supplemental-insured patients with pDPN, PHN, or fibromyalgia underscore the complexity and importance of appropriate management of these chronic pain patients. Wiley Periodicals, Inc.

Sensory Neuropathy Due to Loss of Bcl-w

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Courchesne, Stephanie L.; Karch, Christoph; Pazyra-Murphy, Maria F.; Segal, Rosalind A.

2010-01-01

Small fiber sensory neuropathy is a common disorder in which progressive degeneration of small diameter nociceptors causes decreased sensitivity to thermal stimuli and painful sensations in the extremities. In the majority of patients, the cause of small fiber sensory neuropathy is unknown, and treatment options are limited. Here, we show that Bcl-w (Bcl-2l2) is required for the viability of small fiber nociceptive sensory neurons. Bcl-w −/− mice demonstrate an adult-onset progressive decline in thermosensation and a decrease in nociceptor innervation of the epidermis. This denervation occurs without cell body loss, indicating that lack of Bcl-w results in a primary axonopathy. Consistent with this phenotype, we show that Bcl-w, in contrast to the closely related Bcl-2 and Bcl-xL, is enriched in axons of sensory neurons and that Bcl-w prevents the dying back of axons. Bcl-w −/− sensory neurons exhibit mitochondrial abnormalities, including alterations in axonal mitochondrial size, axonal mitochondrial membrane potential, and cellular ATP levels. Collectively, these data establish bcl-w −/− mice as an animal model of small fiber sensory neuropathy, and provide new insight regarding the role of bcl-w and of mitochondria in preventing axonal degeneration. PMID:21289171

Cutaneous manifestations of diabetic peripheral neuropathy.

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Dogiparthi, S N; Muralidhar, K; Seshadri, K G; Rangarajan, S

2017-01-01

There is a rise in number of people diagnosed with Diabetes Mellitus. The incidence is rising in modern Indian society because of Industrial development and drastically changing lifestyles. Diabetic neuropathies are microvascular disorders that are usually associated with the duration of Diabetes. Among the various forms, the most common is Diabetic Peripheral Neuropathy. The disease if neglected leads to chronic ulcer formation leading to amputations frequently. Hence the aim of this study is to document the early cutaneous changes and create an early awareness in the importance of controlling Diabetes. The study consisted of 205 patients with Type 2 DM. Participant's neuropathy status was determined based on Neuropathy Disability Score and Diabetic Neuropathy Symptom Score. Among the Skin changes documented, the common changes seen were: Peripheral hair loss in 185 (90.2%), Xerosis in 168 (82%), Anhydrosis in 162 (79%), Plantar Fissures in 136 (66.3%), Plantar Ulcer in 80 (39%), common nail changes documented were Onychomycosis in 165 (80.5%) and Onychauxis in 53 (25.8%) patients in relation to the occupation and duration of Diabetes mellitus. In conclusion, it is important to control glycemic levels in the all stages of Diabetes and institute foot care measures to prevent the complications of neuropathy.

Isolated spinal accessory neuropathy and intracisternal schwannomas of the spinal accessory nerve

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Abdullah M. Al-Ajmi

2015-03-01

Full Text Available We report a 40-year-old female patient presenting with isolated left spinal accessory neuropathy that developed insidiously over 6 years. She complained of ill-defined deep neck and shoulder pain. On examination, prominent sternocleidomastoid and trapezoid muscle weakness and atrophy, shoulder instability, and lateral scapular winging were observed. MRI identified a small mass of the cisternal portion of the spinal accessory nerve. Its appearance was typical of schwannoma. Surgical treatment was not offered because of the small tumor size, lack of mass effect and the questionable functional recovery in the presence of muscular atrophy.

Glucose control and diabetic neuropathy: lessons from recent large clinical trials.

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Ang, Lynn; Jaiswal, Mamta; Martin, Catherine; Pop-Busui, Rodica

2014-01-01

Diabetic peripheral and autonomic neuropathies are common complications of diabetes with broad spectrums of clinical manifestations and high morbidity. Studies using various agents to target the pathways implicated in the development and progression of diabetic neuropathy were promising in animal models. In humans, however, randomized controlled studies have failed to show efficacy on objective measures of neuropathy. The complex anatomy of the peripheral and autonomic nervous systems, the multitude of pathogenic mechanisms involved, and the lack of uniformity of neuropathy measures have likely contributed to these failures. To date, tight glycemic control is the only strategy convincingly shown to prevent or delay the development of neuropathy in patients with type 1 diabetes and to slow the progression of neuropathy in some patients with type 2 diabetes. Lessons learned about the role of glycemic control on distal symmetrical polyneuropathy and cardiovascular autonomic neuropathy are discussed in this review.

Persistent facial pain conditions

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Forssell, Heli; Alstergren, Per; Bakke, Merete

2016-01-01

Persistent facial pains, especially temporomandibular disorders (TMD), are common conditions. As dentists are responsible for the treatment of most of these disorders, up-to date knowledge on the latest advances in the field is essential for successful diagnosis and management. The review covers...... TMD, and different neuropathic or putative neuropathic facial pains such as persistent idiopathic facial pain and atypical odontalgia, trigeminal neuralgia and painful posttraumatic trigeminal neuropathy. The article presents an overview of TMD pain as a biopsychosocial condition, its prevalence......, clinical features, consequences, central and peripheral mechanisms, diagnostic criteria (DC/TMD), and principles of management. For each of the neuropathic facial pain entities, the definitions, prevalence, clinical features, and diagnostics are described. The current understanding of the pathophysiology...

Sweet bee venom pharmacopuncture for chemotherapy-induced peripheral neuropathy.

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Yoon, Jeungwon; Jeon, Ju-Hyun; Lee, Yeon-Weol; Cho, Chong-Kwan; Kwon, Ki-Rok; Shin, Ji-Eun; Sagar, Stephen; Wong, Raimond; Yoo, Hwa-Seung

2012-08-01

Chemotherapy-induced peripheral neuropathy (CIPN) is sensory and motor nerve damage to the peripheral nervous system caused by chemotherapeutic agents. It often causes pain and other varying degrees of neuropathic symptoms accompanied by functional limitations and reduced quality of life. Currently, there is no standard treatment protocol for the treatment of CIPN. In need of more research to develop new therapeutic options focusing on their safety, efficacy, and long-term sustained clinical effects, a pilot study of sweet bee venom pharmacopuncture (SBVP) for CIPN was conducted to build up preliminary efficacy data in the process of preparing for a future larger scale randomized controlled SBVP trial for CIPN. We conducted a prospective case series by analyzing the clinical observations made of CIPN patients treated with SBVP. A total of 11 eligible consecutive CIPN patients who visited East-West Cancer Center from June 1, 2010, to February 28, 2011, were treated with total of six SBVP treatments given within the 3-week period. The outcomes were measured using World Health Organization Common Toxicity Criteria for Peripheral neuropathy (WHO grading system), Patient Neurotoxicity Questionnaire (PNQ), Visual Analogue System (VAS), and Health-Related Quality of Life (HRQOL) collected at the baseline, post-second, fourth, and the final treatment. Patients were followed 3 weeks into no intervention to determine the sustained effects of pharmacopuncture. Both of the WHO CIPN grade and PNQ scores have shown a decrease in the level of neuropathy. VAS pain level has also shown a great decrease and improvement in patients' quality of life have also been detected though modest. Changes in WHO grade, VAS and Total HRQOL scores between the baseline and after the last treatment session were significant. Changes in WHO grade, Total PNQ, PNQ-sensory, VAS, Total HRQOL, and HRQOL-functional scores between the baseline and the 3-week follow-up were significant. The positive result

An open-label, non-randomized comparison of venlafaxine and gabapentin as monotherapy or adjuvant therapy in the management of neuropathic pain in patients with peripheral neuropathy

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William Eardley

2010-04-01

Full Text Available William Eardley, Cory TothDepartment of Clinical Neurosciences and the University of Calgary, Calgary, AB, CanadaAbstract: Although many therapies are used in the management of neuropathic pain (NeP due to polyneuropathy (PN, few comparison studies exist. We performed a prospective, non-randomized, unblended, efficacy comparison of the serotonin-norepinephrine reuptake inhibitor venlafaxine, as either monotherapy or adjuvant therapy, with a first-line medication for NeP, gabapentin, in patients with PN-related NeP. VAS pain scores were assessed after 3 and 6 months in intervention groups and in a cohort of patients receiving no pharmacotherapy. In a total of 223 patients, we analyzed pain quantity and quality (visual analogue scale [VAS] score, Brief Pain Inventory [BPI], quality of life and health status measures [EuroQol 5 Domains, EQ-5D], Medical Outcomes Sleep Study Scale [MOSSS], Hospital Anxiety and Depression Scale [HADS] and Short Form 36 Health Survey [SF-36] after 6 months of therapy. Significant improvements in VAS pain scores occurred for all treatment groups after 6 months. Improvements in aspects of daily life and anxiety were identified in all treatment groups. Our data suggest that monotherapy or adjuvant therapy with venlafaxine is comparable to gabapentin for NeP management. We advocate for head-to-head, randomized, double-blinded studies of current NeP therapies.Keywords: peripheral neuropathy, neuropathic pain, pharmacotherapy, venlafaxine, gabapentin

Duloxetine contributing to a successful multimodal treatment program for peripheral femoral neuropathy and comorbid 'reactive depression' in an adolescent.

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Kachko, Ludmyla; Ben Ami, Shiri; Liberman, Alon; Birk, Einat; Kronenberg, Sefi

2011-01-01

In the United States, duloxetine has been approved for the treatment of major depressive disorder, diabetic peripheral neuropathic pain and fibromyalgia in the adult population. Data regarding the use of duloxetine in the pediatric population, however, are very limited. Femoral nerve injury is a rare complication of cardiac catheterization. In the case described, duloxetine contributed to a successful multimodal treatment program for peripheral neuropathic pain due to femoral neuropathy in an adolescent with 'reactive depression' and conversion symptoms. To the best of the authors' knowledge, the present article is only the third such report on this dual use of duloxetine in children and adolescents, and the first report of such treatment following femoral neuropathy induced by cardiac catheterization.

Electroacupuncture to treat painful diabetic neuropathy: study protocol for a three-armed, randomized, controlled pilot trial.

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Lee, Seunghoon; Kim, Joo-Hee; Shin, Kyung-Min; Kim, Jung-Eun; Kim, Tae-Hun; Kang, Kyung-Won; Lee, Minhee; Jung, So-Young; Shin, Mi-Suk; Kim, Ae-Ran; Park, Hyo-Ju; Hong, Kwon-Eui; Choi, Sun-Mi

2013-07-18

The purpose of this study is to conduct a basic analysis of the effectiveness and safety of electroacupuncture in the treatment of painful diabetic neuropathy (PDN) as compared to placebo and usual care and to evaluate the feasibility of large-scale clinical research. This study is a protocol for a three-armed, randomized, patient-assessor-blinded (to the type of treatment), controlled pilot trial. Forty-five participants with a ≥ six month history of PDN and a mean weekly pain score of ≥ 4 on the 11-point Pain Intensity Numerical Rating Scale (PI-NRS) will be assigned to the electroacupuncture group (n = 15), sham group (n = 15) or usual care group (n = 15). The participants assigned to the electroacupuncture group will receive electroacupuncture (remaining for 30 minutes with a mixed current of 2 Hz/120 Hz and 80% of the bearable intensity) at 12 standard acupuncture points (bilateral ST36, GB39, SP9, SP6, LR3 and GB41) twice per week for eight weeks (a total of 16 sessions) as well as the usual care. The participants in the sham group will receive sham electroacupuncture (no electrical current will be passed to the needle, but the light will be seen, and the sound of the pulse generator will be heard by the participants) at non-acupuncture points as well as the usual care. The participants in the usual care group will not receive electroacupuncture treatment during the study period and will receive only the usual care. The follow-up will be in the 5th, 9th and 17th weeks after random allocation. The PI-NRS score assessed at the ninth week will be the primary outcome measurement used in this study. The Short-Form McGill Pain Questionnaire (SF-MPQ), a sleep disturbance score (11-point Likert scale), the Short-Form 36v2 Health Survey (SF-36), the Beck Depression Inventory (BDI) and the Patient Global Impression of Change (PGIC) will be used as outcome variables to evaluate the effectiveness of the acupuncture. Safety will be assessed at every visit. The result

[Regional anaesthesia for labor adn delivery in a parturient with neuropathy with liability to pressure palsy (tomaculous neuropathy)].

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Berdai, S; Benhamou, D

2004-10-01

Tomaculous neuropathy (or hereditary neuropathy with liability to pressure palsy [HNLPP]) is a rare and hereditary disease which incidence has probably been underestimated. It is characterised by demyelination resulting in numbness and weakness after nerve pressure, injury or stretch. Despite a well-documented genetic pathophysiologic mechanism, implications for anaesthesia in patients with HNLPP are only speculative and the use of regional anaesthesia is debatable. We report here the case of a patient with HNLPP who was followed during two consecutive pregnancies in the same hospital and for whom an expert of the SOS-RA hotline service was consulted before each delivery. For the first delivery, epidural analgesia was performed for labour pain control but a caesarean section was necessary because of failure to progress (0.0625% bupivacaine with 0.2 microg/ml sufentanil for labour then 2% lidocaine with adrenaline for surgery). Two years later, the patient was again seen for a preanaesthetic visit because elective Caesarean section was planned. Spinal anaesthesia using hyperbaric bupivacaine and sufentanil was used. Both deliveries were uneventful and there were no neurologic complaints in the postpartum periods.

Dose Titration of Pregabalin in Patients with Painful Diabetic Peripheral Neuropathy: Simulation Based on Observational Study Patients Enriched with Data from Randomized Studies.

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Alexander, Joe; Edwards, Roger A; Manca, Luigi; Grugni, Roberto; Bonfanti, Gianluca; Emir, Birol; Whalen, Edward; Watt, Stephen; Parsons, Bruce

2018-03-01

Achieving a therapeutic response to pregabalin in patients with painful diabetic peripheral neuropathy (pDPN) requires adequate upward dose titration. Our goal was to identify relationships between titration and response to pregabalin in patients with pDPN. Data were integrated from nine randomized, placebo-controlled clinical trials as well as one 6-week open-label observational study conducted by 5808 physicians (2642 patients with pDPN) in standard outpatient settings in Germany. These studies evaluated pregabalin for treatment of pDPN. Using these data, we examined "what if" scenarios using a microsimulation platform that integrates data from randomized and observational sources as well as autoregressive-moving-average with exogenous inputs models that predict pain outcomes, taking into account weekly changes in pain, sleep interference, dose, and other patient characteristics that were unchanging. Final pain levels were significantly different depending on dose changes (P titration regardless of baseline pain severity. Altogether, 78.5% of patients with pDPN had 0-1 dose change, and 15.2% had ≥ 2 dose changes. Simulation demonstrated that the 4.8% of inadequately titrated patients who did not improve/very much improve their pain levels would have benefited from ≥ 2 dose changes. Patient satisfaction with tolerability (range 90.3-96.2%) was similar, regardless of baseline pain severity, number of titrations, or extent of improvement, suggesting that tolerability did not influence treatment response patterns. Upward dose titration reduced pain in patients with pDPN who actually received it. Simulation also predicted pain reduction in an inadequately titrated nonresponder subgroup of patients had they actually received adequate titration. The decision not to uptitrate must have been driven by factors other than tolerability. Pfizer, Inc.

Trichloropropane and dichlorohydrin associated with painful peripheral neurotoxicity.

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Shi, Xiaobing; Yu, Shengyuan

2013-10-01

Trichloropropane (TCP) and dichlorohydrin are widely used in industrial production; however, TCP and dichlorohydrin poisoning are rarely encountered in clinical practice. There have been no cases of peripheral neurotoxicity previously reported. A cluster of 23 patients who had been exposed to high levels of TCP and dichlorohydrin presented with painful peripheral neuropathy, and the pain was assessed using a visual analogue scale (VAS). Nerve conduction studies (NCS) were performed in all patients. All patients demonstrated symmetrical pin-prick pain in a stocking distribution in the lower limbs, with VAS scores between 3 and 10, with an average score of 6.8. NCS showed a mild mixture of axonal and demyelinating sensorimotor polyneuropathy in 14 of the 23 patients. After administration of standard neuropathic pain medication, pain was relieved in most patients. Painful peripheral neuropathy was the primary symptom observed in our patients, which differs from clinical and animal model reports of TCP or dichlorohydrin poisoning. However, the pathogenesis remains unidentified. TCP may be added to the list of industrial products that are toxic to the peripheral sensory nerves. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fibromyalgia as a neuropathic pain syndrome

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Manuel Martinez-Lavin

2003-06-01

Full Text Available This article discusses scientific evidence supporting the notion that all fibromyalgia (FM features can be explained on the basis of autonomic (sympathetic nervous system dysfunction. Also suggests that FM main features (widespread pain and tenderness at palpation on specific anatomic points are manifestations of painful neuropathy. On these bases, a holistic approach for FM treatment is proposed.

Neuropathic orofacial pain: Facts and fiction.

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Baad-Hansen, Lene; Benoliel, Rafael

2017-06-01

Definition and taxonomy This review deals with neuropathic pain of traumatic origin affecting the trigeminal nerve, i.e. painful post-traumatic trigeminal neuropathy (PTTN). Symptomatology The clinical characteristics of PTTN vary considerably, partly due to the type and extent of injury. Symptoms involve combinations of spontaneous and evoked pain and of positive and negative somatosensory signs. These patients are at risk of going through unnecessary dental/surgical procedures in the attempt to eradicate the cause of the pain, due to the fact that most dentists only rarely encounter PTTN. Epidemiology Overall, approximately 3% of patients with trigeminal nerve injuries develop PTTN. Patients are most often female above the age of 45 years, and both physical and psychological comorbidities are common. Pathophysiology PTTN shares many pathophysiological mechanisms with other peripheral neuropathic pain conditions. Diagnostic considerations PTTN may be confused with one of the regional neuralgias or other orofacial pain conditions. For intraoral PTTN, early stages are often misdiagnosed as odontogenic pain. Pain management Management of PTTN generally follows recommendations for peripheral neuropathic pain. Expert opinion International consensus on classification and taxonomy is urgently needed in order to advance the field related to this condition.

Profound and persistent painful paclitaxel peripheral neuropathy in a premenopausal patient

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Quintyne, K I; Mainstone, P; McNamara, B; Boers, P; Wallis, F; Gupta, R K

2011-01-01

The authors herein report the case of a 35-year-old woman undergoing adjuvant therapy for node positive breast cancer, who presented with short and rapidly progressive history of bilateral lower limb symptoms of peripheral neuropathy following therapy with paclitaxel. MRI of her neural axis revealed no leptomeningeal enhancement or focal metastatic lesions. Neurophysiological tests favoured toxic sensory axonal polyneuropathy. She remains symptomatic following discontinuation of therapy 20 mo...

Herpes Zoster Optic Neuropathy.

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Kaufman, Aaron R; Myers, Eileen M; Moster, Mark L; Stanley, Jordan; Kline, Lanning B; Golnik, Karl C

2018-06-01

Herpes zoster optic neuropathy (HZON) is a rare manifestation of herpes zoster ophthalmicus (HZO). The aim of our study was to better characterize the clinical features, therapeutic choices, and visual outcomes in HZON. A retrospective chart review was performed at multiple academic eye centers with the inclusion criteria of all eyes presenting with optic neuropathy within 1 month of cutaneous zoster of the ipsilateral trigeminal dermatome. Data were collected regarding presenting features, treatment regimen, and visual acuity outcomes. Six patients meeting the HZON inclusion criteria were identified. Mean follow-up was 2.75 months (range 0.5-4 months). Herpes zoster optic neuropathy developed at a mean of 14.1 days after initial rash (range 6-30 days). Optic neuropathy was anterior in 2 eyes and retrobulbar in 4 eyes. Other manifestations of HZO included keratoconjunctivitis (3 eyes) and iritis (4 eyes). All patients were treated with systemic antiviral therapy in addition to topical and/or systemic corticosteroids. At the last follow-up, visual acuity in 3 eyes had improved relative to presentation, 2 eyes had worsened, and 1 eye remained the same. The 2 eyes that did not receive systemic corticosteroids had the best observed final visual acuity. Herpes zoster optic neuropathy is an unusual but distinctive complication of HZO. Visual recovery after HZON is variable. Identification of an optimal treatment regiment for HZON could not be identified from our patient cohort. Systemic antiviral agents are a component of HZON treatment regimens. Efficacy of systemic corticosteroids for HZON remains unclear and should be considered on a case-by-case basis.

Dissection of internal carotid artery presenting as isolated ischaemic optic neuropathy

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Serdar Oruc

2016-08-01

Full Text Available Carotid artery dissections are one of the important reasons of cerebrovascular events that are observed before the age of 45. Besides the local findings such as head, neck and face pains, Horner syndrome findings, pulsatile tinnitus and cranial nerve involvements, some other symptoms such as ischemic stroke, transient ischemic attacks and amaurosis fugax can also be observed in the approximately three quarters of patients. Ischemic optic neuropathy may be seen as %4 in the carotid artery dissections and it mostly accompanies other ischemic local symptoms. It is rare to observe the ischemic optic neuropathy as the first and unique finding in the carotid artery dissections. In this study, a 55 year old male patient with carotid artery dissection was represented. He did not have any other complaint, except the sudden unilateral visual loss and he was sent to our clinics from the opthalmology clinics in order to search for the etiology of ischemic optic neuropathy. It should be kept in mind that there can be a possibility to have carotid artery dissections in patients with unilateral visual loss.

Possible involvement of the Sigma-1 receptor chaperone in chemotherapeutic-induced neuropathic pain.

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Tomohisa, Mori; Junpei, Ohya; Aki, Masumoto; Masato, Harumiya; Mika, Fukase; Kazumi, Yoshizawa; Teruo, Hayashi; Tsutomu, Suzuki

2015-11-01

Previous studies have shown that ligands of the sigma-1 receptor chaperone (Sig-1R) regulate pain-related behaviors. Clinical use of chemotherapeutics is often compromised due to their adverse side effects, particularly those related to neuropathy. Previous studies have shown that repeated administration of oxaliplatin and paclitaxel produces neuropathy in rodents. Therefore, the aim of the present study was to clarify the involvement of the Sig-1R in chemotherapeutic-induced neuropathy by examining the effects of oxaliplatin and paclitaxel on the Sig-1R levels in the spinal cord, and by examining the effects of Sig-1R agonist and antagonist on oxaliplatin- and paclitaxel-induced neuropathy in rats. Chemotherapeutic-induced neuropathic pain was accompanied by a significant reduction of the Sig-1R level in the spinal cord. Furthermore, the administration of paclitaxel to CHO cells that stably overexpressed Sig-1Rs induced the clustering of Sig-1Rs. We also found that the Sig-1R agonist SA4503 potently inhibited the neuropathy induced by oxaliplatin- and paclitaxel, whereas this action was abolished by the Sig-1R antagonist NE-100. These results suggest that the reduction of Sig-1R activity is involved in chemotherapeutic-induced neuropathy, and the Sig-1R agonist SA4503 could serve as a potential candidate for the treatment of chemotherapeutic-induced neuropathy. © 2015 Wiley Periodicals, Inc.

Burden of illness associated with painful diabetic peripheral neuropathy among adults seeking treatment in the US: results from a retrospective chart review and cross-sectional survey

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Sadosky A

2013-02-01

Full Text Available Alesia Sadosky,1 Caroline Schaefer,2 Rachael Mann,3 Felicia Bergstrom,2 Rebecca Baik,2 Bruce Parsons,1 Srinivas Nalamachu,4 Edward Nieshoff,5 Brett R Stacey,6 Alan Anschel,7 Michael Tuchman81Pfizer Inc, New York, NY, 2Covance Market Access Services Inc, Gaithersburg, MD, 3Covance Market Access Services Inc, San Diego, CA, 4International Clinical Research Institute, Overland Park, KS, 5Rehabilitation Institute of Michigan/Wayne State University, Detroit, MI, 6Oregon Health and Science University, Portland, OR, 7Rehabilitation Institute of Chicago, Chicago, IL, 8Palm Beach Neurological Center, Palm Beach Gardens, FL, USABackground: The purpose of this study was to characterize the burden of illness among adult subjects with painful diabetic peripheral neuropathy (pDPN seeking treatment in the US.Methods: This observational study recruited 112 subjects with pDPN during routine visits from general practitioner and specialist sites. Subjects completed a one-time questionnaire, which included demographics, symptom duration, health care resource use, out-of-pocket costs, employment status, and validated measures that assessed pain, functioning, sleep, anxiety and depression, health status, and productivity. Investigators completed a case report form based on a 6-month retrospective chart review to capture clinical information, pDPN-related treatments, and other pDPN-related health care resource use over the past 6 months. Annualized costs were extrapolated based on reported 6-month health care resource use.Results: The mean age of the subjects was 61.1 years, 52.7% were female, and 17.9% were in paid employment. The most common comorbid conditions were sleep disturbance/insomnia (43.8%, depressive symptoms (41.1%, and anxiety (35.7%. The mean pain severity score was 5.2 (0–10 scale, and 79.5% reported moderate or severe pain. The mean pain interference with function score was 5.0 (0–10 scale overall, with 2.0 among mild, 5.1 among moderate, and 7

Peripheral neuropathy in a diabetic child treated with linezolid for multidrug-resistant tuberculosis: a case report and review of the literature.

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Swaminathan, Aravind; du Cros, Philipp; Seddon, James A; Mirgayosieva, Shamsiya; Asladdin, Rajabov; Dusmatova, Zulfiya

2017-06-12

Extensively drug-resistant (XDR) tuberculosis (TB) and multidrug resistant (MDR)-TB with additional resistance to injectable agents or fluoroquinolones are challenging to treat due to lack of available, effective drugs. Linezolid is one of the few drugs that has shown promise in treating these conditions. Long-term linezolid use is associated with toxicities such as peripheral and optic neuropathies. Diabetes mellitus (DM), especially when uncontrolled, can also result in peripheral neuropathy. The global burden of DM is increasing, and DM has been associated with a three-fold increased risk of developing TB disease. TB and DM can be a challenging combination to treat. DM can inhibit the host immune response to tuberculosis infection; and TB and some anti-TB drugs can worsen glycaemic control. A child experiencing neuropathy that is a possible complication of both DM and linezolid used to treat TB has not been reported previously. We report peripheral neuropathy in a 15-year-old boy with type 1 DM, diagnosed with MDR-TB and additional resistance to injectable TB medications. The boy was treated with a linezolid-based regimen, but after 8 months developed peripheral neuropathy. It was unclear whether the neuropathy was caused by the DM or the linezolid therapy. He had clinical improvement following cessation of linezolid and was declared cured following 21 months of treatment. Following completion of treatment, nerve conduction studies demonstrated significant improvement in neuropathy. To the best of our knowledge, this is the first case of peripheral neuropathy reported in a diabetic child on long-term linezolid therapy for tuberculosis. This case study underlines the importance of stringent follow-up for side effects of linezolid, especially when associated with co-morbidity such as DM that increases the chances of adverse effects. The presence of both DM and TB should alert a physician to strive for optimal glycaemic control to minimize the risk of

HIV-related neuropathy: current perspectives

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Schütz SG

2013-09-01

Full Text Available Sonja G Schütz, Jessica Robinson-Papp Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA Abstract: Distal symmetric polyneuropathy (DSP related to human immunodeficiency virus (HIV is one of the most common neurologic complications of HIV, possibly affecting as many as 50% of all individuals infected with HIV. Two potentially neurotoxic mechanisms have been proposed to play a crucial role in the pathogenesis of HIV DSP: neurotoxicity resulting from the virus and its products; as well as adverse neurotoxic effects of medications used in the treatment of HIV. Clinically, HIV DSP is characterized by a combination of signs and symptoms that include decreased deep tendon reflexes at the ankles and decreased sensation in the distal extremities as well as paresthesias, dysesthesias, and pain in a symmetric stocking–glove distribution. These symptoms are generally static or slowly progressive over time, and depending on the severity, may interfere significantly with the patient's daily activities. In addition to the clinical picture, nerve conduction studies and skin biopsies are often pursued to support the diagnosis of HIV DSP. Anticonvulsants, antidepressants, topical agents, and nonspecific analgesics may help relieve neuropathic pain. Specifically, gabapentin, lamotrigine, pregabalin, amitriptyline, duloxetine, and high-dose topical capsaicin patches have been used in research and clinical practice. Further research is needed to elucidate the pathogenesis of HIV DSP, thus facilitating the development of novel treatment strategies. This review discusses the epidemiology, pathophysiology, clinical findings, diagnosis, and management of DSP in the setting of HIV. Keywords: neuropathy, human immunodeficiency virus, acquired immunodeficiency syndrome, AIDS, distal symmetric polyneuropathy, DSP, pain

Carcinomatous versus radiation-induced brachial plexus neuropathy in breast cancer

International Nuclear Information System (INIS)

Bagley, F.H.; Walsh, J.W.; Cady, B.; Salzman, F.A.; Oberfield, R.A.; Pazianos, A.G.

1978-01-01

A retrospective study was performed of 18 women in whom ipsilateral brachial plexus neuropathy developed after treatment for carcinoma of the breast. In the absence of metastatic tumor elsewhere, the only distinguishing feature between carcinomatous neuropathy and radiation-induced neuropathy was the symptom-free interval after mastectomy and radiation therapy. Women with an interval of less than a year have radiation-induced neuropathy. Brachial plexus exploration in difficult diagnostic situations will permit early treatment and avoid debilitating loss of function. Brachial plexus exploration for biopsy is safe and free of complications if performed carefully. Treatment of carcinomatous neuropathy is most likely to succeed if the tumor is hormonally sensitive, but radiotherapy may also be effective. Treatment of radiation-induced neuropathy remains largely ineffective

Chemotherapy-induced peripheral neuropathy: an update on the current understanding.

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Addington, James; Freimer, Miriam

2016-01-01

Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

Drug-induced peripheral neuropathy

DEFF Research Database (Denmark)

Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed

2014-01-01

Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...

Hereditary neuropathy with liability to pressure palsies presenting with sciatic neuropathy.

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Topakian, Raffi; Wimmer, Sibylle; Pischinger, Barbara; Pichler, Robert

2014-10-17

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant disorder associated with recurrent mononeuropathies following compression or trivial trauma. Reports on sciatic neuropathy as the presenting manifestation of HNPP are very scarce. We report on a 21-year-old previously healthy man who was admitted with sensorimotor deficits in his left leg. He had no history of preceding transient episodes of weakness or sensory loss. Clinical and electrophysiological examinations were consistent with sciatic neuropathy. Cerebrospinal fluid investigation and MRI of the nerve roots, plexus, and sciatic nerve did not indicate the underlying aetiology. When extended electrophysiological tests revealed multiple subclinical compression neuropathies in the upper limbs, HNPP was contemplated and eventually confirmed by genetic testing. 2014 BMJ Publishing Group Ltd.

Oral manifestations, dental management, and a rare homozygous mutation of the PRDM12 gene in a boy with hereditary sensory and autonomic neuropathy type VIII: a case report and review of the literature.

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Elhennawy, Karim; Reda, Seif; Finke, Christian; Graul-Neumann, Luitgard; Jost-Brinkmann, Paul-Georg; Bartzela, Theodosia

2017-08-15

Hereditary sensory and autonomic neuropathy type VIII is a rare autosomal recessive inherited disorder. Chen et al. recently identified the causative gene and characterized biallelic mutations in the PR domain-containing protein 12 gene, which plays a role in the development of pain-sensing nerve cells. Our patient's family was included in Chen and colleagues' study. We performed a literature review of the PubMed library (January 1985 to December 2016) on hereditary sensory and autonomic neuropathy type I to VIII genetic disorders and their orofacial manifestations. This case report is the first to describe the oral manifestations, and their treatment, of the recently discovered hereditary sensory and autonomic neuropathy type VIII in the medical and dental literature. We report on the oral manifestations and dental management of an 8-month-old white boy with hereditary sensory and autonomic neuropathy-VIII over a period of 16 years. Our patient was homozygous for a mutation of PR domain-containing protein 12 gene and was characterized by insensitivity to pain and thermal stimuli, self-mutilation behavior, reduced sweat and tear production, absence of corneal reflexes, and multiple skin and bone infections. Oral manifestations included premature loss of teeth, associated with dental traumata and self-mutilation, severe soft tissue injuries, dental caries and submucosal abscesses, hypomineralization of primary teeth, and mandibular osteomyelitis. The lack of scientific knowledge on hereditary sensory and autonomic neuropathy due to the rarity of the disease often results in a delay in diagnosis, which is of substantial importance for the prevention of many complications and symptoms. Interdisciplinary work of specialized medical and dental teams and development of a standardized treatment protocols are essential for the management of the disease. There are many knowledge gaps concerning the management of patients with hereditary sensory and autonomic neuropathy

[Acrodystrophic neuropathy in an alcoholic].

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Yamamura, Y; Hironaka, M; Shimoyama, M; Toyota, Y; Kurokawa, M; Kohriyama, T; Nakamura, S

1993-01-01

The patient was a 48-year-old alcoholic man with no contributory family history. At age 36 he had developed sensory dominant polyneuropathy with highly impaired temperature sensation and deep sensation in the lower extremities, recurrent ulcers of the toes, and sexual impotence. A sural nerve biopsy at this time revealed marked loss of myelinated fibers with relative preservation of the population of unmyelinated fibers. Subsequently, he developed muscle atrophy of the lower thighs, urinary incontinence, and Wernicke's encephalopathy, and became non-ambulatory at age 44. The peripheral nerve conduction findings suggested predominantly axonal degeneration. The entire course was characterized by alternative progression and partial recovery influenced by his alcohol intake and nutritional state. Alcoholic neuropathy is a major cause of solitary acrodystrophic neuropathy (ADN). Manifestations of autonomic and motor neuropathy are more marked in alcoholic ADN than in HSAN-I, and central nervous system involvement is the hallmark of alcoholic ADN. In the treatment of patients with alcoholic ADN, attention should be paid to diabetes mellitus, malnutritional state, and vitamin deficiency, which frequently complicate alcoholism.

Adalimumab and Non-Arteritic Anterior Ischaemic Optic Neuropathy: A Case Report.

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Kinard, Krista; Walsh, Jessica A; Penmetsa, Gopi K; Warner, Judith E A

2014-01-01

Sequential anterior ischaemic optic neuropathy was observed in a patient treated with a tumour necrosis factor α (TNF) inhibitor, adalimumab, for ankylosing spondylitis. He developed decreased visual acuity in the right eye after 17 months of treatment. Findings showed right optic disc oedema with haemorrhages and visual field defect. Adalimumab was discontinued and vision stabilised. After restarting adalimumab, he developed optic neuropathy in the left eye. Findings showed optic disc oedema, with haemorrhages and visual field changes in the left eye. Adalimumab may be associated with optic neuropathy; providers prescribing TNF inhibitors should be aware of optic neuropathy as a potential complication.

Acute optic neuropathy associated with a novel MFN2 mutation.

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Leonardi, Luca; Marcotulli, Christian; Storti, Eugenia; Tessa, Alessandra; Serrao, Mariano; Parisi, Vincenzo; Santorelli, F M; Pierelli, Francesco; Casali, Carlo

2015-07-01

Mutations in the mitofusin 2 (MFN2) gene cause CMT2A the most common form of autosomal dominant axonal Charcot-Marie-Tooth (CMT). In addition, mutations in MFN2 have been shown to be responsible for Hereditary Motor Sensory Neuropathy type VI (HSMN VI), a rare early-onset axonal CMT associated with optic neuropathy. Most reports of HMSN VI presented with a sub-acute form of optic neuropathy. Herein, we report a CMT2A patient, who developed very rapidly progressing severe optic neuropathy. A 40-year-old Caucasian man was evaluated for gait disturbance and lower limbs weakness, slowly progressed over the last 2 years. Due to clinical data and family history, a diagnosis of CMT2 was made. The novel heterozygous c.775C > T (p.Arg259Cys) mutation in MFN2 was detected in the patient and his clinical affected mother. Interestingly, the patient developed a severe sudden bilateral visual deterioration few years early, with clinical and instrumental picture suggestive of acute bilateral optic neuropathy. Our report expands the spectrum of MFN2-related manifestation because it indicates that visual symptoms of HMSN VI may enter in the differential with acquired or hereditary acute optic neuropathies, and that severe optic neuropathy is not invariably an early manifestation of the disease but may occur as disease progressed. This report could have an impact on clinicians who evaluate patients with otherwise unexplainable bilateral acute-onset optic neuropathy, especially if associated with a motor and sensory axonal neuropathy.

Painful Na-channelopathies: an expanding universe.

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Waxman, Stephen G

2013-07-01

The universe of painful Na-channelopathies--human disorders caused by mutations in voltage-gated sodium channels--has recently expanded in three dimensions. We now know that mutations of sodium channels cause not only rare genetic 'model disorders' such as inherited erythromelalgia and channelopathy-associated insensitivity to pain but also common painful neuropathies. We have learned that mutations of NaV1.8, as well as mutations of NaV1.7, can cause painful Na-channelopathies. Moreover, recent studies combining atomic level structural models and pharmacogenomics suggest that the goal of genomically guided pain therapy may not be unrealistic. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genetic heterogeneity of motor neuropathies.

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Bansagi, Boglarka; Griffin, Helen; Whittaker, Roger G; Antoniadi, Thalia; Evangelista, Teresinha; Miller, James; Greenslade, Mark; Forester, Natalie; Duff, Jennifer; Bradshaw, Anna; Kleinle, Stephanie; Boczonadi, Veronika; Steele, Hannah; Ramesh, Venkateswaran; Franko, Edit; Pyle, Angela; Lochmüller, Hanns; Chinnery, Patrick F; Horvath, Rita

2017-03-28

To study the prevalence, molecular cause, and clinical presentation of hereditary motor neuropathies in a large cohort of patients from the North of England. Detailed neurologic and electrophysiologic assessments and next-generation panel testing or whole exome sequencing were performed in 105 patients with clinical symptoms of distal hereditary motor neuropathy (dHMN, 64 patients), axonal motor neuropathy (motor Charcot-Marie-Tooth disease [CMT2], 16 patients), or complex neurologic disease predominantly affecting the motor nerves (hereditary motor neuropathy plus, 25 patients). The prevalence of dHMN is 2.14 affected individuals per 100,000 inhabitants (95% confidence interval 1.62-2.66) in the North of England. Causative mutations were identified in 26 out of 73 index patients (35.6%). The diagnostic rate in the dHMN subgroup was 32.5%, which is higher than previously reported (20%). We detected a significant defect of neuromuscular transmission in 7 cases and identified potentially causative mutations in 4 patients with multifocal demyelinating motor neuropathy. Many of the genes were shared between dHMN and motor CMT2, indicating identical disease mechanisms; therefore, we suggest changing the classification and including dHMN also as a subcategory of Charcot-Marie-Tooth disease. Abnormal neuromuscular transmission in some genetic forms provides a treatable target to develop therapies. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Pressure pain perception in the diabetic Charcot foot: facts and hypotheses

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Ernst A. Chantelau

2013-05-01

Full Text Available Background:Reduced traumatic and posttraumatic (nociceptive pain is a key feature of diabetic neuropathy. Underlying condition is a gradual degeneration of endings of pain nerves (A-delta fibers and C-fibers, which operate as receivers of noxious stimuli (nociceptors. Hence, the absence of A-delta fiber mediated sharp pain (“first” pain, and of C-fiber mediated dull pain (“second” pain. However, patients with diabetic neuropathy and acute Charcot foot often experience deep dull aching in the Charcot foot while walking on it. Aim: To create a unifying hypothesis on the kind of pain in an acute Charcot foot. Result: Absence of punctuate (pinprick pain perception at the sole of a Charcot foot, as was shown recently, likely corresponds to vanished intraepidermal A-delta fiber endings. C-fiber nociceptors are reduced, according to histopathology studies. Both types of fibers contribute to posttraumatic hyperalgesia at the skin level, as studies show. Their deficiencies likely impact on posttraumatic hyperalgesia at the skin level and, probably, also at the skeletal level. Conclusion: It is hypothesised that deep dull aching in an acute diabetic Charcot foot may represent faulty posttraumatic hyperalgesia involving cutaneous and skeletal tissues.

Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.

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Philpott, Holly T; OʼBrien, Melissa; McDougall, Jason J

2017-12-01

Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a noneuphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine whether CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. Osteoarthritis was induced in male Wistar rats (150-175 g) by intra-articular injection of sodium monoiodoacetate (MIA; 3 mg). On day 14 (end-stage OA), joint afferent mechanosensitivity was assessed using in vivo electrophysiology, whereas pain behaviour was measured by von Frey hair algesiometry and dynamic incapacitance. To investigate acute joint inflammation, blood flow and leukocyte trafficking were measured on day 1 after MIA. Joint nerve myelination was calculated by G-ratio analysis. The therapeutic and prophylactic effects of peripheral CBD (100-300 μg) were assessed. In end-stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (P < 0.0001; n = 8). Acute, transient joint inflammation was reduced by local CBD treatment (P < 0.0001; n = 6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (P < 0.0001; n = 8), and was also found to be neuroprotective (P < 0.05; n = 6-8). The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.

Evaluation and Prevention of Diabetic Neuropathy

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Pajouhi M

2007-07-01

Full Text Available Background: Diabetic neuropathy is an incapacitating disease that afflicts almost 50 percent of patients with diabetes. A late finding in type 1 diabetes, diabetic neuropathy can be an early finding in non insulin-dependent diabetes. Diabetic neuropathies are divided primarily into two groups, sensorimotor and autonomic. Patients may acquire only one type of diabetic neuropathy or may present with combinations of neuropathies, such as autonomic neuropathy or distal symmetric polyneuropathy, the latter of which the most common form. Motor deficits, orthostatic hypotension, silent cardiac ischemia, hyperhidrosis, vasomotor instability, gastroparesis, bladder dysfunction, and sexual dysfunction can also result from diabetic neuropathy. Strict control of blood sugar, combined with proper daily foot care, is essential to avoid the complications of this disorder. With the potential to afflict any part of the nervous system, diabetic neuropathy should be suspected in all patients with type 2 diabetes as well as patients who have had type 1 diabetes for over five years. Although some patients with diabetic neuropathy notice few symptoms, upon physical examination mild to moderately severe sensory loss may be noted by the physician. Idiopathic neuropathy has been known to precede the onset of type 2 diabetes.

Chronic pain in Gaucher disease: skeletal or neuropathic origin?

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Devigili, Grazia; De Filippo, Michele; Ciana, Giovanni; Dardis, Andrea; Lettieri, Christian; Rinaldo, Sara; Macor, Daniela; Moro, Alessandro; Eleopra, Roberto; Bembi, Bruno

2017-08-31

Pain is one of the most disabling symptoms of Gaucher disease. It is referred by the majority of Gaucher patients and often persists despite long-term enzyme replacement treatment. It has been mainly considered as nociceptive pain secondary to skeletal involvement but it is described even in the absence of bone disease without a clear explanation. In the last years an increasing number of reports have described the presence of neurological manifestation in Gaucher type 1 patients, including subclinical large fibre neuropathy. In our Gaucher clinic we have observed the recurrence of painful symptoms in a group of type 1 Gaucher patients even after a long-term enzyme replacement therapy. A cross-sectional study was designed to investigate the pathophysiology of pain in a cohort of 25 Gaucher patients (13 females, 12 males). Twenty-two patients received enzyme replacement therapy for a period of time ranging from 10 to >20 years, while three were new diagnosis. Pain was classified as bone or neurologic related on the basis of anamnestic data, clinical and electrophysilogical examinations. Intensity and quality of pain were recorded by Douleur Neuropathique en 4 questionnaire and Neuropathic Pain Symptom Inventory. Neuroalgological evaluation, quantitative sensory testing, nerve conduction studies and evaluation of epidermal nerve fibres density were performed. Comorbidities for peripheral neuropathy were excluded. Thirteen patients complained of pain suggestive of neuropathic origin with proximal patchy distribution, six manifested severe pain paroxysmal, nine pinprick hypoesthesia and 17 thermal hypoesthesia. At quantitative sensory testing, all of them showed high cold thresholds with errata sensation (burning instead of cold), paradoxical heat sensation and mechanic hypoesthesia; three patients showed pressure pain hyperalgesia. Epidermal denervation was present in 19 patients, 12 of them with non-length dependent pattern. These results confirm the role of

Peripheral Neuropathy and Agent Orange

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... Enter ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... 10 percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

The evidence for pharmacological treatment of neuropathic pain.

Science.gov (United States)

Finnerup, Nanna Brix; Sindrup, Søren Hein; Jensen, Troels Staehelin

2010-09-01

Randomized, double-blind, placebo-controlled trials on neuropathic pain treatment are accumulating, so an updated review of the available evidence is needed. Studies were identified using MEDLINE and EMBASE searches. Numbers needed to treat (NNT) and numbers needed to harm (NNH) values were used to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions. One hundred and seventy-four studies were included, representing a 66% increase in published randomized, placebo-controlled trials in the last 5 years. Painful poly-neuropathy (most often due to diabetes) was examined in 69 studies, postherpetic neuralgia in 23, while peripheral nerve injury, central pain, HIV neuropathy, and trigeminal neuralgia were less often studied. Tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, the anticonvulsants gabapentin and pregabalin, and opioids are the drug classes for which there is the best evidence for a clinical relevant effect. Despite a 66% increase in published trials only a limited improvement of neuropathic pain treatment has been obtained. A large proportion of neuropathic pain patients are left with insufficient pain relief. This fact calls for other treatment options to target chronic neuropathic pain. Large-scale drug trials that aim to identify possible subgroups of patients who are likely to respond to specific drugs are needed to test the hypothesis that a mechanism-based classification may help improve treatment of the individual patients. Copyright (c) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Peripheral Neuropathy: Symptoms and Signs

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... Utah Research News Make a Difference Symptoms of Peripheral Neuropathy Print This Page Peripheral Neuropathy symptoms usually start ... more slowly over many years. The symptoms of peripheral neuropathy often include: A sensation of wearing an invisible “ ...

Duloxetine Contributing to a Successful Multimodal Treatment Program for Peripheral Femoral Neuropathy and Comorbid ‘Reactive Depression’ in an Adolescent

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Ludmyla Kachko

2011-01-01

Full Text Available In the United States, duloxetine has been approved for the treatment of major depressive disorder, diabetic peripheral neuropathic pain and fibromyalgia in the adult population. Data regarding the use of duloxetine in the pediatric population, however, are very limited. Femoral nerve injury is a rare complication of cardiac catheterization. In the case described, duloxetine contributed to a successful multimodal treatment program for peripheral neuropathic pain due to femoral neuropathy in an adolescent with ‘reactive depression’ and conversion symptoms. To the best of the authors’ knowledge, the present article is only the third such report on this dual use of duloxetine in children and adolescents, and the first report of such treatment following femoral neuropathy induced by cardiac catheterization.

Peripheral neuropathy in thalassemia

International Nuclear Information System (INIS)

Sawaya, Raja A.; Tahir, A.; Zahad, L.

2006-01-01

Patients with thalassemia may complain of numbness and weakness of lower extremities. The aim of the study was to determine whether these patients suffer from a polyneuropathy and to determine any contributing factors for the development of neuropathy. We examined 30 patients with thalasemia major and intermedia, clinically and electrophysiologically. We correlated these findings with demographics, blood status and treatment and compared electrophysiologic data with 30 age and sex matched normal subjects or historical controls. We found that 78% of thalassemia patients suffer from a mild sensory polyneuropathy. The neuropathy seemed to be worse in the intermedia type. Thalassemia patients who received blood transfusions and deferoaximine had better nerve faction than those who did not, irrespective of the dose of the deferoxamine. The neuropathy was worse for the older patients, irrespective of the sex. The hemoglobin level, and the fact that some patients underwent spleenctomy, did not affect the status of the patient's nerves. Patients with thalassemia may suffer from a sensor polyneuropathy especially as they grow older and they are not optimally treated. (author)

Catecholamines and diabetic autonomic neuropathy

DEFF Research Database (Denmark)

Hilsted, J

1995-01-01

In diabetic patients with autonomic neuropathy plasma noradrenaline concentration, used as an index of sympathetic nervous activity, is low. This decrease is, however, only found in patients with a long duration of diabetes with clinically severe autonomic neuropathy. This apparent insensitivity...... of plasma catecholamine measurements is not due to changes in the clearance of catecholamines in diabetic autonomic neuropathy. The physiological responses to infused adrenaline and to noradrenaline are enhanced, for noradrenaline mainly cardiovascular responses. Adrenoceptors (alpha and beta adrenoceptors......) are not altered in circulating blood cells in diabetic autonomic neuropathy. Thus, a generalized up-regulation of adrenoceptors does not occur in diabetic autonomic neuropathy....

Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy

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Victoria L. Newton

2017-01-01

Full Text Available Spinal glial cell activation and cytokine secretion have been implicated in the etiology of neuropathic pain in a number of experimental models, including diabetic neuropathy. In this study, streptozotocin- (STZ- induced diabetic rats were either untreated or treated with gabapentin (50 mg/kg/day by gavage for 2 weeks, from 6 weeks after STZ. At 8 weeks after STZ, hypersensitivity was confirmed in the untreated diabetic rats as a reduced response threshold to touch, whilst mechanical thresholds in gabapentin-treated diabetic rats were no different from controls. Diabetes-associated thermal hypersensitivity was also ameliorated by gabapentin. We performed a cytokine profiling array in lumbar spinal cord samples from control and diabetic rats. This revealed an increase in L-selectin, an adhesion molecule important for neutrophil transmigration, in the spinal cord of diabetic rats but not diabetic rats treated with gabapentin. Furthermore, we found an increase in the number of neutrophils present in the parenchyma of the spinal cord, which was again ameliorated in gabapentin-treated diabetic rats. Therefore, we suggest that dysregulated spinal L-selectin and neutrophil infiltration into the spinal cord could contribute to the pathogenesis of painful diabetic neuropathy.

Poly(ADP-ribose polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain

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Prashanth Komirishetty

2016-01-01

Full Text Available Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose polymerase (PARP upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neuronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the involvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.

Poly(ADP-ribose) polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain.

Science.gov (United States)

Komirishetty, Prashanth; Areti, Aparna; Gogoi, Ranadeep; Sistla, Ramakrishna; Kumar, Ashutosh

2016-10-01

Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose) polymerase (PARP) upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neuronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the involvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.

Glia and pain: is chronic pain a gliopathy?

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Ji, Ru-Rong; Berta, Temugin; Nedergaard, Maiken

2013-12-01

Activation of glial cells and neuro-glial interactions are emerging as key mechanisms underlying chronic pain. Accumulating evidence has implicated 3 types of glial cells in the development and maintenance of chronic pain: microglia and astrocytes of the central nervous system (CNS), and satellite glial cells of the dorsal root and trigeminal ganglia. Painful syndromes are associated with different glial activation states: (1) glial reaction (ie, upregulation of glial markers such as IBA1 and glial fibrillary acidic protein (GFAP) and/or morphological changes, including hypertrophy, proliferation, and modifications of glial networks); (2) phosphorylation of mitogen-activated protein kinase signaling pathways; (3) upregulation of adenosine triphosphate and chemokine receptors and hemichannels and downregulation of glutamate transporters; and (4) synthesis and release of glial mediators (eg, cytokines, chemokines, growth factors, and proteases) to the extracellular space. Although widely detected in chronic pain resulting from nerve trauma, inflammation, cancer, and chemotherapy in rodents, and more recently, human immunodeficiency virus-associated neuropathy in human beings, glial reaction (activation state 1) is not thought to mediate pain sensitivity directly. Instead, activation states 2 to 4 have been demonstrated to enhance pain sensitivity via a number of synergistic neuro-glial interactions. Glial mediators have been shown to powerfully modulate excitatory and inhibitory synaptic transmission at presynaptic, postsynaptic, and extrasynaptic sites. Glial activation also occurs in acute pain conditions, and acute opioid treatment activates peripheral glia to mask opioid analgesia. Thus, chronic pain could be a result of "gliopathy," that is, dysregulation of glial functions in the central and peripheral nervous system. In this review, we provide an update on recent advances and discuss remaining questions. Copyright © 2013 International Association for the

Analgesic Microneedle Patch for Neuropathic Pain Therapy.

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Xie, Xi; Pascual, Conrado; Lieu, Christopher; Oh, Seajin; Wang, Ji; Zou, Bende; Xie, Julian; Li, Zhaohui; Xie, James; Yeomans, David C; Wu, Mei X; Xie, Xinmin Simon

2017-01-24

Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.

Pilot evaluation of Scrambler therapy for the treatment of chemotherapy-induced peripheral neuropathy.

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Pachman, Deirdre R; Weisbrod, Breanna L; Seisler, Drew K; Barton, Debra L; Fee-Schroeder, Kelliann C; Smith, Thomas J; Lachance, Daniel H; Liu, Heshan; Shelerud, Randy A; Cheville, Andrea L; Loprinzi, Charles L

2015-04-01

Chemotherapy-induced peripheral neuropathy (CIPN), a common side effect of chemotherapy, needs better effective treatments. Preliminary data support the use of Scrambler therapy, a device which treats pain via noninvasive cutaneous electrostimulation, for the treatment of CIPN. The current manuscript reports data from a pilot trial, performed to investigate the effect of Scrambler therapy for the treatment of established CIPN. Eligible patients had CIPN symptoms of ≥1 month duration with tingling and/or pain ≥4/10 during the prior week. Patients were treated with Scrambler therapy to the affected area(s) for up to ten daily 30-min sessions. Symptoms were monitored using a neuropathy questionnaire consisting of numerical analog scales ranging from 0 to 10, daily before therapy as well as weekly for 10 weeks after therapy. Descriptive summary statistics formed the basis of data analysis. Thirty-seven patients were enrolled. Twenty-five patients were treated primarily on their lower extremities while 12 were treated primarily on their upper extremities. There was a 53 % reduction in pain score from baseline to day 10; a 44 % reduction in tingling; and a 37 % reduction in numbness. Benefit appeared to last throughout 10 weeks of follow-up. There were no substantial adverse events. Preliminary data support that Scrambler therapy may be effective for the treatment of CIPN: a prospective placebo-controlled clinical trial should be performed.

Impaired Hedgehog signalling-induced endothelial dysfunction is sufficient to induce neuropathy: implication in diabetes.

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Chapouly, Candice; Yao, Qinyu; Vandierdonck, Soizic; Larrieu-Lahargue, Frederic; Mariani, John N; Gadeau, Alain-Pierre; Renault, Marie-Ange

2016-02-01

Microangiopathy, i.e. endothelial dysfunction, has long been suggested to contribute to the development of diabetic neuropathy, although this has never been fully verified. In the present paper, we have identified the role of Hedgehog (Hh) signalling in endoneurial microvessel integrity and evaluated the impact of impaired Hh signalling in endothelial cells (ECs) on nerve function. By using Desert Hedgehog (Dhh)-deficient mice, we have revealed, that in the absence of Dhh, endoneurial capillaries are abnormally dense and permeable. Furthermore, Smoothened (Smo) conditional KO mice clarified that this increased vessel permeability is specifically due to impaired Hh signalling in ECs and is associated with a down-regulation of Claudin5 (Cldn5). Moreover, impairment of Hh signalling in ECs was sufficient to induce hypoalgesia and neuropathic pain. Finally in Lepr(db/db) type 2 diabetic mice, the loss of Dhh expression observed in the nerve was shown to be associated with increased endoneurial capillary permeability and decreased Cldn5 expression. Conversely, systemic administration of the Smo agonist SAG increased Cldn5 expression, decreased endoneurial capillary permeability, and restored thermal algesia to diabetic mice, demonstrating that loss of Dhh expression is crucial in the development of diabetic neuropathy. The present work demonstrates the critical role of Dhh in maintaining blood nerve barrier integrity and demonstrates for the first time that endothelial dysfunction is sufficient to induce neuropathy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Neuropathic pain-like alterations in muscle nociceptor function associated with vibration-induced muscle pain.

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Chen, Xiaojie; Green, Paul G; Levine, Jon D

2010-11-01

We recently developed a rodent model of the painful muscle disorders induced by occupational exposure to vibration. In the present study we used this model to evaluate the function of sensory neurons innervating the vibration-exposed gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were recorded. In vibration-exposed rats ∼15% of nociceptors demonstrated an intense and long-lasting barrage of action potentials in response to sustained suprathreshold mechanical stimulation (average of 2635 action potentials with frequency of ∼44Hz during a 1min suprathreshold stimulus) much greater than that has been reported to be produced even by potent inflammatory mediators. While these high-firing nociceptors had lower mechanical thresholds than the remaining nociceptors, exposure to vibration had no effect on conduction velocity and did not induce spontaneous activity. Hyperactivity was not observed in any of 19 neurons from vibration-exposed rats pretreated with intrathecal antisense for the IL-6 receptor subunit gp130. Since vibration can injure peripheral nerves and IL-6 has been implicated in painful peripheral neuropathies, we suggest that the dramatic change in sensory neuron function and development of muscles pain, induced by exposure to vibration, reflects a neuropathic muscle pain syndrome. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Scrambler therapy efficacy and safety for neuropathic pain correlated with chemotherapy-induced peripheral neuropathy in adolescents: A preliminary study.

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Tomasello, Caterina; Pinto, Rita Maria; Mennini, Chiara; Conicella, Elena; Stoppa, Francesca; Raucci, Umberto

2018-04-06

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy, in need of effective treatment. Preliminary data support the efficacy of scrambler therapy (ST), a noninvasive cutaneous electrostimulation device, in adults with CIPN. We test the efficacy, safety, and durability of ST for neuropathic pain in adolescents with CIPN. We studied nine pediatric patients with cancer and CIPN who received ST for pain control. Each patient received 45-min daily sessions for 10 consecutive days as a first step, but some of them required additional treatment. Pain significantly improved comparing Numeric Rate Scale after 10 days of ST (9.22 ± 0.83 vs. 2.33 ± 2.34; P < 0.001) and at the end of the optimized cycle (EOC) (9.22 ± 0.83 vs. 0.11 ± 0.33, P < 0.001). The improvement in quality of life was significantly reached on pain interference with general activity (8.67 ± 1.66 vs. 3.33 ± 2.12, P < 0.0001), mood (8.33 ± 3.32 vs. 2.78 ± 2.82, P < 0.0005), walking ability (10.00 vs. 2.78 ± 1.22, P < 0.0001), sleep (7.56 ± 2.24 vs. 2.67 ± 1.41, P < 0.001), and relations with people (7.89 ± 2.03 vs. 2.11 ± 2.03, P < 0.0002; Lansky score 26.7 ± 13.2 vs. 10 days of ST 57.8 ± 13.9, P < 0.001; 26.7 ± 13.2 vs. EOC 71.1 ± 16.2, P < 0.001). Based on these preliminary data, ST could be a good choice for adolescents with CIPN for whom pain control is difficult. ST caused total relief or dramatic reduction in CIPN pain and an improvement in quality of life, durable in follow-up. It caused no detected side effects, and can be retrained successfully. Further larger studies should be performed to confirm our promising preliminary data in pediatric patients with cancer. © 2018 Wiley Periodicals, Inc.

Leber's hereditary optic neuropathy and vitamin B12 deficiency

NARCIS (Netherlands)

Pott, Jan Willem R.; Wong, Kwok H.

2006-01-01

Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three

Sympathetic neuropathy in diabetes mellitus patients does not elicit Charcot osteoarthropathy

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Christensen, Tomas M; Simonsen, Lene; Holstein, Per E

2011-01-01

AIM: The aim of the study was to determine the degree of neuropathy (autonomic and somatic) in patients with diabetes mellitus with or without Charcot osteoarthropathy (CA). METHODS: Forty-nine patients with diabetes mellitus type 1 or 2 were investigated. The patient population of interest...... with first toe amputation (n=5), a high-risk group for development of CA, and two control groups consisting of diabetes patients with (n=9) or without somatic neuropathy (n=11) were investigated. Regional blood flow in the feet was measured by venous occlusion plethysmography. Quantitation of somatic...... neuropathy was done by the Neuropathy Disability Score and modified Neuropathy Symptom Score. Quantitation of autonomic neuropathy was done by measurements of local venoarteriolar sympathetic axon reflex in the feet and of heart rate variability during deep breathing and orthostatic challenge. RESULTS...

Evaluation and diagnosis of wrist pain: a case-based approach.

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Shehab, Ramsey; Mirabelli, Mark H

2013-04-15

Patients with wrist pain commonly present with an acute injury or spontaneous onset of pain without a definite traumatic event. A fall onto an outstretched hand can lead to a scaphoid fracture, which is the most commonly fractured carpal bone. Conventional radiography alone can miss up to 30 percent of scaphoid fractures. Specialized views (e.g., posteroanterior in ulnar deviation, pronated oblique) and repeat radiography in 10 to 14 days can improve sensitivity for scaphoid fractures. If a suspected scaphoid fracture cannot be confirmed with plain radiography, a bone scan or magnetic resonance imaging can be used. Subacute or chronic wrist pain usually develops gradually with or without a prior traumatic event. In these cases, the differential diagnosis is wide and includes tendinopathy and nerve entrapment. Overuse of the muscles of the forearm and wrist may lead to tendinopathy. Radial pain involving mostly the first extensor compartment is commonly de Quervain tenosynovitis. The diagnosis is based on history and examination findings of a positive Finkelstein test and a negative grind test. Nerve entrapment at the wrist presents with pain and also with sensory and sometimes motor symptoms. In ulnar neuropathies of the wrist, the typical presentation is wrist discomfort with sensory changes in the fourth and fifth digits. Activities that involve repetitive or prolonged wrist extension, such as cycling, karate, and baseball (specifically catchers), may increase the risk of ulnar neuropathy. Electrodiagnostic tests identify the area of nerve entrapment and the extent of the pathology. Copyright © 2013 American Academy of Family Physicians.

Clinical Trial Assessing the Efficacy of Gabapentin Plus B Complex (B1/B12 versus Pregabalin for Treating Painful Diabetic Neuropathy

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Alberto Mimenza Alvarado

2016-01-01

Full Text Available Introduction. Painful diabetic neuropathy (PDN is a prevalent and impairing disorder. The objective of this study was to show the efficacy and safety of gabapentin (GBP plus complex B vitamins: thiamine (B1 and cyanocobalamine (B12 compared to pregabalin in patients with moderate to severe intensity PDN. Method. Multicenter, randomized, blind study. Two hundred and seventy patients were evaluated, 147 with GBP/B1/B12 and 123 with PGB, with a 7/10 pain intensity on the Visual Analog Scale (VAS. Five visits (12 weeks were scheduled. The GBP/B1 (100 mg/B12 (20 mg group started with 300 mg at visit 1 to 3600 mg at visit 5. The PGB group started with 75 mg/d at visit 1 to 600 mg/d at visit 5. Different safety and efficacy scales were applied, as well as adverse event assessment. Results. Both drugs showed reduction of pain intensity, without significant statistical difference (P=0.900. In the GBP/B1/B12 group, an improvement of at least 30% on VAS correlated to a 900 mg/d dose, compared with PGB 300 mg/d. Likewise, occurrence of vertigo was lower in the GBP/B1-B12 group, with a significant statistical difference, P=0.014. Conclusions. Our study shows that GPB/B1-B12 combination is as effective as PGB. Nonetheless, pain intensity reduction is achieved with 50% of the minimum required gabapentin dose alone (800 to 1600 mg/d in classic NDD trials. Less vertigo and dizziness occurrence was also observed in the GBP/B1/B12 group. This trial is registered with ClinicalTrials.gov NCT01364298.

Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors

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Alireza Abed

2017-11-01

Full Text Available Objective(s: Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception. Materials and Methods: Paclitaxel (2 mg/kg IP was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia. Results: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist. Conclusion: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine.

Taking pain out of NGF: a "painless" NGF mutant, linked to hereditary sensory autonomic neuropathy type V, with full neurotrophic activity.

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Simona Capsoni

2011-02-01

Full Text Available During adulthood, the neurotrophin Nerve Growth Factor (NGF sensitizes nociceptors, thereby increasing the response to noxious stimuli. The relationship between NGF and pain is supported by genetic evidence: mutations in the NGF TrkA receptor in patients affected by an hereditary rare disease (Hereditary Sensory and Autonomic Neuropathy type IV, HSAN IV determine a congenital form of severe pain insensitivity, with mental retardation, while a mutation in NGFB gene, leading to the aminoacid substitution R100W in mature NGF, determines a similar loss of pain perception, without overt cognitive neurological defects (HSAN V. The R100W mutation provokes a reduced processing of proNGF to mature NGF in cultured cells and a higher percentage of neurotrophin secreted is in the proNGF form. Moreover, using Surface Plasmon Resonance we showed that the R100W mutation does not affect NGF binding to TrkA, while it abolishes NGF binding to p75NTR receptors. However, it remains to be clarified whether the major impact of the mutation is on the biological function of proNGF or of mature NGF and to what extent the effects of the R100W mutation on the HSAN V clinical phenotype are developmental, or whether they reflect an impaired effectiveness of NGF to regulate and mediate nociceptive transmission in adult sensory neurons. Here we show that the R100 mutation selectively alters some of the signaling pathways activated downstream of TrkA NGF receptors. NGFR100 mutants maintain identical neurotrophic and neuroprotective properties in a variety of cell assays, while displaying a significantly reduced pain-inducing activity in vivo (n = 8-10 mice/group. We also show that proNGF has a significantly reduced nociceptive activity, with respect to NGF. Both sets of results jointly contribute to elucidating the mechanisms underlying the clinical HSAN V manifestations, and to clarifying which receptors and intracellular signaling cascades participate in the pain

Multiple cranial neuropathies without limb involvements: guillain-barre syndrome variant?

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Yu, Ju Young; Jung, Han Young; Kim, Chang Hwan; Kim, Hyo Sang; Kim, Myeong Ok

2013-10-01

Acute multiple cranial neuropathies are considered as variant of Guillain-Barre syndrome, which are immune-mediated diseases triggered by various cases. It is a rare disease which is related to infectious, inflammatory or systemic diseases. According to previous case reports, those affected can exhibit almost bilateral facial nerve palsy, then followed by bulbar dysfunctions (cranial nerves IX and X) accompanied by limb weakness and walking difficulties due to motor and/or sensory dysfunctions. Furthermore, reported cases of the acute multiple cranial neuropathies show electrophysiological abnormalities compatible with the typical Guillain-Barre syndromes (GBS). We recently experienced a patient with a benign infectious disease who subsequently developed symptoms of variant GBS. Here, we describe the case of a 48-year-old male patient who developed multiple symptoms of cranial neuropathy without limb weakness. His laboratory findings showed a positive result for anti-GQ1b IgG antibody. As compared with previously described variants of GBS, the patient exhibited widespread cranial neuropathy, which included neuropathies of cranial nerves III-XII, without limb involvement or ataxia.

A Cross-Sectional Clinic-Based Study in Patients With Side-Locked Unilateral Headache and Facial Pain.

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Prakash, Sanjay; Rathore, Chaturbhuj; Makwana, Prayag; Dave, Ankit

2016-07-01

To undertake the epidemiological evaluation of the patients presenting with side-locked headache and facial pain in a tertiary neurology outpatient clinic. Side-locked unilateral headache and facial pain include a large number of primary and secondary headaches and cranial neuropathies. A diagnostic approach for the patients presenting with strictly unilateral headaches is important as many of these headache disorders respond to a highly selective drug. Epidemiological data may guide us to formulate a proper approach for such patients. However, the literature is sparse on strictly unilateral headache and facial pain. We prospectively recruited 307 consecutive adult patients (>18 years) with side-locked headache and facial pain presenting to a neurology outpatient clinic between July 2014 and December 2015. All patients were subjected to MRI brain and other investigations to find out the different secondary causes. The diagnosis was carried out by at least two headache specialists together. All patients were classified according to the International Classification of Headache Disorder-third edition (ICHD-3β). The mean age at the time of examination was 42.4 ± 13.6 years (range 18-80 years). Forty-eight percent of patients were male. Strictly unilateral headaches accounted for 19.2% of the total headaches seen in the clinic. Headaches were classified as primary in 58%, secondary in 18%, and cranial neuropathies and other facial pain in 16% patients. Five percent of patients could not be classified. Three percent of patients were classified as per the Appendix section of ICHD-3β. The prevalence of secondary headaches and painful cranial neuropathies increased with age. A total of 36 different diagnoses were made. Only two diseases (migraine and cluster headache) had a prevalence of more than 10%. The prevalence of 13 diseases varied between 6 and 9%. The prevalence of other 14 groups was ≤1%. Migraine was the most common diagnosis (15%). Cervicogenic headache

Effects of fenofibrate in patients with type 2 diabetes mellitus complicated by diabetic neuropathy

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Olga Nikolaevna Tkacheva

2010-03-01

Full Text Available Diabetic neuropathy is a severe complication of diabetes mellitus (DM that considerably worsens the patients quality of life and reduces life expectancy.The FIELD study for the first time demonstrated the ability of fenofibrate to prevent macro- and microvacular complications in patientswith DM2 regardless of glycated hemoglobin level and dyslipidemia at the early stage of the disease. Neuropathy being a manifestation of microangiopathy,it suggests the possibility to treat this disorder with fenofibrate.Aim. To study effects of fenofibrate in patients with type 2 diabetes mellitus complicated by diabetic neuropathy. Materials and methods. The present study included 73 patients with DM2 randomized into 2 groups to receive standard therapy (antihypertensiveand glucose control, statins or fenofibrate (Tricor 145 mg, Solvay Pharma in addition to the standard treatment. Results. Positive effect of fenofibrate on autonomous and peripheral neuropathy was apparent within 6 months after the onset of therapy when thesought parameters of AP, glycemia, and lipid spectrum were achieved. Fenofibrate improved cardiovascular function, reduced cardiac rhythm variability;QT length and dispersion, pain and paresthesia thereby enhancing quality of life and preventing cardiovascular catastrophes including death. Conclusion. It is concluded that supplementation of standard therapy of DM with fenofibrate is both safe and pathogenetically sound.

HIV Associated Sensory Neuropathy.

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G, Amruth; S, Praveen-Kumar; B, Nataraju; Bs, Nagaraja

2014-07-01

In the era of highly active antiretroviral therapy, sensory neuropathies have increased in prevalence. We have documented the frequency and profile of the two most common forms of sensory neuropathies associated with Human Immunodeficiency Virus (HIV) infection and looked into clinicoelectrophysiological correlates to differentiate the two entities. The study population comprised of all consecutive patients detected to be HIV positive and attending the Neurology outpatient department (from March 2011 to March 2012) who were aged ≥ 18 years and were able to give informed consent. The data were collected from the patient records (including CD4 counts and treatment details) and questionnaire based interview with each patient. All patients underwent detailed clinical examination and nerve conduction studies (NCSs). Among the total study population of 50 patients, there were 31 men and 19 women. Thirty two patients were in age range of 21 - 40 years and rest were above 40 years. 25 were on antiretroviral therapy (18 on regimen containing zidovudine; seven on regimen containing stavudine). The mean duration of antiretroviral therapy was 16.6±8.4 months. Low CD4 counts ( 40 years. Subclinical neuropathy was common in those on antiretroviral therapy. Axonal neuropathy was the commonest pattern noted in patients who were receiving antiretroviral therapy and demyelinating neuropathy in patients not on antiretroviral therapy. Surprisingly no significant correlation was found between low CD4 counts and symptomatic neuropathy.

Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy [v2; ref status: indexed, http://f1000r.es/3am

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Lori Sames

2014-04-01

Full Text Available Approximately 1 in 2500 Americans suffer from Charcot-Marie-Tooth (CMT disease. The underlying disease mechanisms are unique in most forms of CMT, with many point mutations on various genes causing a toxic accumulation of misfolded proteins. Symptoms of the disease often present within the first two decades of life, with CMT1A patients having reduced compound muscle and sensory action potentials, slow nerve conduction velocities, sensory loss, progressive distal weakness, foot and hand deformities, decreased reflexes, bilateral foot drop and about 5% become wheelchair bound. In contrast, the ultra-rare disease Giant Axonal Neuropathy (GAN is frequently described as a recessively inherited condition that results in progressive nerve death. GAN usually appears in early childhood and progresses slowly as neuronal injury becomes more severe and leads to death in the second or third decade. There are currently no treatments for any of the forms of CMTs or GAN. We suggest that further clinical studies should analyse electrical impedance myography as an outcome measure for CMT. Further, additional quality of life (QoL assessments for these CMTs are required, and we need to identify GAN biomarkers as well as develop new genetic testing panels for both diseases. We propose that using the Global Registry of Inherited Neuropathy (GRIN could be useful for many of these studies. Patient advocacy groups and professional organizations (such as the Hereditary Neuropathy Foundation (HNF, Hannah's Hope Fund (HHF, The Neuropathy Association (TNA and the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM can play a central role in educating clinicians and patients. Undertaking these studies will assist in the correct diagnosis of disease recruiting patients for clinical studies, and will ultimately improve the endpoints for clinical trials. By addressing obstacles that prevent industry investment in various forms of inherited neuropathies

Interventional management of neuropathic pain: NeuPSIG recommendations

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Dworkin, Robert H.; O’Connor, Alec B.; Kent, Joel; Mackey, Sean C.; Raja, Srinivasa N.; Stacey, Brett R.; Levy, Robert M.; Backonja, Miroslav; Baron, Ralf; Harke, Henning; Loeser, John D.; Treede, Rolf-Detlef; Turk, Dennis C.; Wells, Christopher D.

2015-01-01

Neuropathic pain (NP) is often refractory to pharmacologic and non-interventional treatment. On behalf of the International Association for the Study of Pain Neuropathic Pain Special Interest Group (NeuPSIG), the authors evaluated systematic reviews, clinical trials, and existing guidelines for the interventional management of NP. Evidence is summarized and presented for neural blockade, spinal cord stimulation (SCS), intrathecal medication, and neurosurgical interventions in patients with the following peripheral and central NP conditions: herpes zoster and postherpetic neuralgia (PHN); painful diabetic and other peripheral neuropathies; spinal cord injury NP; central post-stroke pain; radiculopathy and failed back surgery syndrome (FBSS); complex regional pain syndrome (CRPS); and trigeminal neuralgia and neuropathy. Due to the paucity of high-quality clinical trials, no strong recommendations can be made. Four weak recommendations based on the amount and consistency of evidence, including degree of efficacy and safety, are: (1) epidural injections for herpes zoster; (2) steroid injections for radiculopathy; (3) SCS for FBSS; and (4) SCS for CRPS type 1. Based on the available data, we recommend not to use sympathetic blocks for PHN nor RF lesions for radiculopathy. No other conclusive recommendations can be made due to the poor quality of available of data. Whenever possible, these interventions should either be part of randomized clinical trials or documented in pain registries. Priorities for future research include randomized clinical trials; long-term studies; and head-to-head comparisons among different interventional and non-interventional treatments. PMID:23748119

Immunoglobulin deposits in peripheral nerve endings detected by skin biopsy in patients with IgM M proteins and neuropathy

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Jønsson, V; Jensen, T S; Friis, M L

1987-01-01

biopsies provide a simple effective method of detecting immunoglobulin binding to peripheral nerves in patients suspected of having an autoimmune neuropathy. In contrast to sural nerve biopsy, skin biopsy does not cause sensory loss or pain in a denervated area and can easily be repeated.......Immunofluorescence studies of sural nerve and skin biopsies from three patients with IgM M proteins and clinical neuropathy showed that IgM M protein was bound to the nerve myelin in two patients and by the peri- and endoneurium in one. It is suggested that immunohistochemical studies of skin...

Burn-related peripheral neuropathy: A systematic review.

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Tu, Yiji; Lineaweaver, William C; Zheng, Xianyou; Chen, Zenggan; Mullins, Fred; Zhang, Feng

2017-06-01

Peripheral neuropathy is the most frequent disabling neuromuscular complication of burns. However, the insidious and progressive onset of burn neuropathy makes it often undiagnosed or overlooked. In our study, we reviewed the current studies on the burn-related peripheral neuropathy to summarize the morbidity, mechanism, detecting method and management of peripheral neuropathy in burn patients. Of the 1533 burn patients included in our study, 98 cases (6.39%) were presented with peripheral neuropathy. Thermal and electrical burns were the most common etiologies. Surgical procedures, especially nerve decompression, showed good effect on functional recovery of both acute and delayed peripheral neuropathy in burn patients. It is noteworthy that, for early detection and prevention of peripheral neuropathy, electrodiagnostic examinations should be performed on burn patients independent of symptoms. Still, the underlying mechanisms of burn-related peripheral neuropathy remain to be clarified. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Hereditary motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough.

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Miura, Shiroh; Shibata, Hiroki; Kida, Hiroshi; Noda, Kazuhito; Tomiyasu, Katsuro; Yamamoto, Ken; Iwaki, Akiko; Ayabe, Mitsuyoshi; Aizawa, Hisamichi; Taniwaki, Takayuki; Fukumaki, Yasuyuki

2008-10-15

We studied a four-generation pedigree of a Japanese family with hereditary neuropathy to elucidate the genetic basis of this disease. Twelve members of the family were enrolled in this study. The clinical features were neurogenic muscle weakness with proximal dominancy in the lower extremities, sensory involvement, areflexia, fine postural tremors, painful muscle cramps, elevated creatine kinase levels, recurrent paroxysmal dry cough, and neurogenic bladder. We performed a genome-wide search using genetic loci spaced at about 13 Mb intervals. Although nine chromosomes (1, 3, 4, 5, 6, 10, 17, 19, and 22) had at least one region in which the logarithm of odds (LOD) score was over 1.0, no loci fulfilled the criteria for significant evidence of linkage. Moreover, we analyzed an extra 14 markers on 3p12-q13 (the locus of hereditary motor and sensory neuropathy, proximal dominant form) and an extra five markers on 3p22-p24 (the locus of hereditary sensory neuropathy with chronic cough) and observed LOD scores of hereditary motor and sensory neuropathy with autosomal dominant inheritance.

Mechanisms and Management of Diabetic Painful Distal Symmetrical Polyneuropathy

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Tesfaye, Solomon; Boulton, Andrew J.M.; Dickenson, Anthony H.

2013-01-01

Although a number of the diabetic neuropathies may result in painful symptomatology, this review focuses on the most common: chronic sensorimotor distal symmetrical polyneuropathy (DSPN). It is estimated that 15–20% of diabetic patients may have painful DSPN, but not all of these will require therapy. In practice, the diagnosis of DSPN is a clinical one, whereas for longitudinal studies and clinical trials, quantitative sensory testing and electrophysiological assessment are usually necessary. A number of simple numeric rating scales are available to assess the frequency and severity of neuropathic pain. Although the exact pathophysiological processes that result in diabetic neuropathic pain remain enigmatic, both peripheral and central mechanisms have been implicated, and extend from altered channel function in peripheral nerve through enhanced spinal processing and changes in many higher centers. A number of pharmacological agents have proven efficacy in painful DSPN, but all are prone to side effects, and none impact the underlying pathophysiological abnormalities because they are only symptomatic therapy. The two first-line therapies approved by regulatory authorities for painful neuropathy are duloxetine and pregabalin. α-Lipoic acid, an antioxidant and pathogenic therapy, has evidence of efficacy but is not licensed in the U.S. and several European countries. All patients with DSPN are at increased risk of foot ulceration and require foot care, education, and if possible, regular podiatry assessment. PMID:23970715

Peripheral neuropathy associated with mitochondrial disease in children.

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Menezes, Manoj P; Ouvrier, Robert A

2012-05-01

Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

Osteomalacia induced peripheral neuropathy after obesity reduction surgery

Directory of Open Access Journals (Sweden)

Samhita Panda

2013-01-01

Full Text Available Osteomalacia and rickets are important reversible causes of debilitating muscular weakness and bony pains in India among all socio-economic strata and at all ages. Osteomalacia after bariatric surgery is documented in literature. Most reports on osteomalacic weakness note myopathic pattern on electromyography. We present the case of a young obese girl from a good socio-economic status who developed severe muscular weakness after sleeve gastrectomy surgery. The patient was found to have osteomalacia with normal vitamin B12 and folate levels. Electrodiagnostic studies demonstrated neuropathic pattern while radiological tests confirmed osteopenia and Looser′s zones. Specific vitamin D supplementation was associated with improvement though contribution of other micronutrients in diet cannot be ruled out. Relevance of vitamin D deficiency and urgent need for its correction in the population all over the world and especially in Asia is an emerging health issue. Peripheral motor neuropathy is a rare, seldom reported presentation of osteomalacia.

Duloxetine Contributing to a Successful Multimodal Treatment Program for Peripheral Femoral Neuropathy and Comorbid ‘Reactive Depression’ in an Adolescent

OpenAIRE

Kachko, Ludmyla; Ben Ami, Shiri; Liberman, Alon; Birk, Einat; Kronenberg, Sefi

2011-01-01

In the United States, duloxetine has been approved for the treatment of major depressive disorder, diabetic peripheral neuropathic pain and fibromyalgia in the adult population. Data regarding the use of duloxetine in the pediatric population, however, are very limited. Femoral nerve injury is a rare complication of cardiac catheterization. In the case described, duloxetine contributed to a successful multimodal treatment program for peripheral neuropathic pain due to femoral neuropathy in an...

Metabolic Correction in the Management of Diabetic Peripheral Neuropathy: Improving Clinical Results Beyond Symptom Control

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Miranda-Massari, Jorge R.; Gonzalez, Michael J.; Jimenez, Francisco J.; Allende-Vigo, Myriam Z.; Duconge, Jorge

2013-01-01

Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications. In USA alone, it has been estimated that there are more than 5,000,000 patients suffering from DPN and the total annual cost of treating the disease and its complications is over $10,000 million dollars. In order to be able to reduce complications of DPN, it is crucial to improve or correct the metabolic conditions that lead to the pathology present in this condition. Pathophysiologic mechanisms implicated in diabetic neuropathy include: increased polyol pathway with accumulation of sorbitol and reduced Na+/K+-ATPase activity, microvascular damage and hypoxia due to nitric oxide deficit and increased oxygen free radical activity. Moreover, there is a decrease in glutathione and increase in homocysteine. Clinical trials in the last two decades have demonstrated that the use of specific nutrients can correct some of these metabolic derangements, improving symptom control and providing further benefits such as improved sensorium, blood flow and nerve regeneration. We will discuss the evidence on lipoic acid, acetyi-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metforrnin, an important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk

Hereditary sensory and autonomic neuropathy type IV and orthopaedic complications.

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Kim, W; Guinot, A; Marleix, S; Chapuis, M; Fraisse, B; Violas, P

2013-11-01

Hereditary sensory and autonomic neuropathy type IV (HSAN-IV) is a very rare autosomal recessive disorder characterized by recurrent episodes of unexplained fever, extensive anhidrosis, total insensitivity to pain, hypotonia, and mental retardation. The most frequent complications of this disease are corneal scarring, multiple fractures, joint deformities, osteomyelitis, and disabling self-mutilations. We reported the case of a 12-year-old boy. The goal was to discuss our decision-making and compare this case with cases described in the literature. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Hyperacute peripheral neuropathy is a predictor of oxaliplatin-induced persistent peripheral neuropathy.

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Tanishima, Hiroyuki; Tominaga, Toshiji; Kimura, Masamichi; Maeda, Tsunehiro; Shirai, Yasutsugu; Horiuchi, Tetsuya

2017-05-01

Chronic peripheral neuropathy is a major adverse response to oxaliplatin-containing chemotherapy regimens, but there are no established risk factors pertaining to it. We investigated the efficacy of hyperacute peripheral neuropathy (HAPN) as a predictor of oxaliplatin-induced persistent peripheral neuropathy (PPN). Forty-seven cases of stage III colorectal cancer who received adjuvant chemotherapy with oxaliplatin after curative surgery between January 2010 and August 2014 were retrospectively reviewed. HAPN was defined as acute peripheral neuropathy (APN) occurring on day 1 (≤24 h after oxaliplatin infusion) of the first cycle. PPN was defined as neuropathy lasting >1 year after oxaliplatin discontinuation. The average total dose of oxaliplatin was 625.8 mg/m 2 , and the average relative dose intensity was 66.7%. Twenty-two of the 47 patients (46.8%) had PPN and 13 (27.7%) had HAPN. Male sex, treatment for neuropathy, HAPN, and APN were significantly more frequent in patients with PPN (p = 0.013, 0.02, <0.001, and 0.023, respectively). There was no significant difference in the total oxaliplatin dose between patients with and without PPN (p = 0.061). Multivariate analyses revealed total dose of oxaliplatin and HAPN as independent predictors of PPN [p = 0.015; odds ratio (OR) = 1.005, 95% confidence interval (CI), 1.001-1.009 and p = 0.001; OR = 75.307, 5.3-1070.123, respectively]. The total dose of oxaliplatin was relatively lower in patients with HAPN than that in those without HAPN in the PPN-positive group (not significant, p = 0.068). HAPN was found to be a predictor of oxaliplatin-induced PPN.

Continuous neurophatic orofacial pain: A retrospective study of 23 cases.

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Sotorra-Figuerola, Dídac; Sánchez-Torres, Alba; Valmaseda-Castellón, Eduard; Gay-Escoda, Cosme

2016-04-01

To determine the clinical characteristics of Continuous Neuropathic Orofacial Pain in patients that suffer Persistent Idiopathic Facial Pain (PIFP), Painful Post-Traumatic Trigeminal Neuropathy (PPTTN) or Burning Mouth Syndrome (BMS) and to describe their treatment. A retrospective observational study was made, reviewing the clinical history of the patients diagnosed with Continuous Neuropathic Orofacial Pain between 2004 and 2011 at the Orofacial Pain Unit of the Master of Oral Surgery and Implantology of the University of Barcelona and at the Orofacial Pain Unit of the Teknon Medical Center of Barcelona. The average age of the patients with Continuous Neuropathic Orofacial Pain was 54.5, with a clear female predominance (86.9%, n=20). Of all patients, 60.9% (n=14) were suffering a PIFP, 21.7% (n=5) had a BMS and 17.4% (n=4) were presenting a PPTTN. The pain quality described by the patients with Continuous Neuropathic Orofacial Pain was oppressive (43.47%, n=10), widely represented by patients with PIFP, and burning (39.13%, n=9) being the only quality that described patients with BMS. The treatment carried out with the patients was only pharmacologic. The most used drugs for the treatment of PIFP and PPTTN were clonazepam (50%, n=9) and amitriptyline (44.44%, n=8). However, a 55.5% (n=10) of the patients with PIFP or PPTTN required the association of two or more drugs for a correct pain control. All the patients with BMS responded satisfactorily to clonazepam. Continuous Neuropathic Orofacial Pain is a little known condition among the general population, physicians and dentists. This favors a late diagnosis and inaccurate treatments which entail unnecessary suffering. It is important to inform both the general population and health professionals concerning this painful condition. Continuous neuropathic orofacial pain, persistent idiopathic facial pain, painful post-traumatic trigeminal neuropathy, burning mouth syndrome, atypical odontalgia.

Diabetic peripheral neuropathy, is it an autoimmune disease?

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Janahi, Noor M; Santos, Derek; Blyth, Christine; Bakhiet, Moiz; Ellis, Mairghread

2015-11-01

Autoimmunity has been identified in a significant number of neuropathies, such as, proximal neuropathies, and autonomic neuropathies associated with diabetes mellitus. However, possible correlations between diabetic peripheral neuropathy and autoimmunity have not yet been fully investigated. This study was conducted to investigate whether autoimmunity is associated with the pathogenesis of human diabetic peripheral neuropathy. A case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 diabetic control patients without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the percentages of positive antinuclear antibodies (ANA) between the three groups. Secondary analysis investigated the correlations between the presence of autoimmune antibodies and sample demographics and neurological manifestations. This research was considered as a pilot study encouraging further investigations to take place in the near future. Antinuclear antibodies were significantly present in the blood serum of patients with diabetic peripheral neuropathy in comparison to the control groups (pneuropathy group were 50 times higher when compared to control groups. Secondary analysis showed a significant correlation between the presence of ANA and the neurological manifestation of neuropathy (Neuropathy symptom score, Neuropathy disability score and Vibration Perception Threshold). The study demonstrated for the first time that human peripheral diabetic neuropathy may have an autoimmune aetiology. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers. Copyright © 2015 Elsevier B.V. All rights reserved.

Oral manifestations and prosthetic rehabilitation in hereditary sensory and autonomic neuropathy (HSAN)type IV: a case report.

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Ofluoglu, Duygu; Altin, Nazli; Yaman, Elif; Tuna İnce, Elif Bahar; Aytepe, Zeynep; Tanyeri, Hakki

2016-01-01

Hereditary sensory and autonomic neuropathies (HSAN) are rare genetic syndromes of unknown etiology. They are seen in early childhood and are categorized into six different types by their symptoms. HSAN type 4 demonstrates autosomal recessive transmission pattern, with such major characteristics as loss of sense of pain, self-mutilation, anhydrosis and mental retardation. Sympathetic innervations are deficient despite the existence of sweat glands. Sufferers are hypotonic without any tendon reflexes, and neuro-motor development is retarded. In some cases tactile sensation and vibration may be intact. Biting injuries due to lack of pain sensation cause laceration, ulceration and scarring of the tongue, lips and other parts of oral mucosa. Tooth luxation and severe dental attrition have been observed. This case report presents oral and dental findings, surgical treatments and prosthetic rehabilitation of an 11- year-old boy with HSAN type 4.

Pharmacologic management of neuropathic pain.

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Gordon, Debra B; Love, Georgette

2004-12-01

The mechanisms underlying the pathogenesis of neuropathic pain are complex but are gradually coming to light. Agents that have been found effective in a variety of neuropathic pain conditions include drugs that act to modulate (a) sodium or calcium channels, (b) N-methyl-D-aspartate receptors, (c) norepinephrine or serotonin reuptake, (d) opioid receptors, and (e) other cellular processes. Clinical trials have primarily evaluated these treatments for postherpetic neuralgia and painful diabetic neuropathy, the two most common types of neuropathic pain. Nonetheless, the identification of effective treatment regimens remains challenging, often because multiple mechanisms may be operating in a given patient giving rise to the same symptom. Alternatively, a single mechanism may be responsible for multiple symptoms. Currently available diagnostic tools are inadequate to determine the best treatment using a mechanism-based model. Clinically, drug treatment of neuropathic pain is often a matter of treatment trials. This article presents a summary of available clinical information on first-line and lesser-known treatments for neuropathic pain.

Interactions of Notch1 and TLR4 signaling pathways in DRG neurons of in vivo and in vitro models of diabetic neuropathy.

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Chen, Tianhua; Li, Hao; Yin, Yiting; Zhang, Yuanpin; Liu, Zhen; Liu, Huaxiang

2017-11-02

Understanding the interactions between Notch1 and toll-like receptor 4 (TLR4) signaling pathways in the development of diabetic peripheral neuropathy may lead to interpretation of the mechanisms and novel approaches for preventing diabetic neuropathic pain. In the present study, the interactions between Notch1 and TLR4 signaling pathways were investigated by using dorsal root ganglion (DRG) from diabetic neuropathic pain rats and cultured DRG neurons under high glucose challenge. The results showed that high glucose induced not only Notch1 mRNA, HES1 mRNA, and TLR4 mRNA expression, but also Notch1 intracellular domain (NICD1) and TLR4 protein expression in DRG neurons. The proportion of NICD1-immunoreactive (IR) and TLR4-IR neurons in DRG cultures was also increased after high glucose challenge. The above alterations could be partially reversed by inhibition of either Notch1 or TLR4 signaling pathway. Inhibition of either Notch1 or TLR4 signaling pathway could improve mechanical allodynia and thermal hyperalgesia thresholds. Inhibition of Notch1 or TLR4 signaling also decreased tumor necrosis factor-α (TNF-α) levels in DRG from diabetic neuropathic rats. These data imply that the interaction between Notch1 and TLR4 signaling pathways is one of the important mechanisms in the development or progression of diabetic neuropathy.

Pain severity and the economic burden of neuropathic pain in the United States: BEAT Neuropathic Pain Observational Study

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Schaefer C

2014-10-01

Full Text Available Caroline Schaefer,1 Alesia Sadosky,2 Rachael Mann,3 Shoshana Daniel,4 Bruce Parsons,2 Michael Tuchman,5 Alan Anschel,6 Brett R Stacey,7 Srinivas Nalamachu,8 Edward Nieshoff9 1Covance Market Access Services Inc., Gaithersburg, MD, 2Pfizer, Inc., New York, NY, 3Covance Market Access Services Inc., San Diego, CA, 4Covance Market Access Services Inc., Conshohocken, PA, 5Palm Beach Neurological Center, Palm Beach Gardens, FL, 6Rehabilitation Institute of Chicago, Chicago, IL, 7Oregon Health and Science University, Portland, OR, 8International Clinical Research Institute, Overland Park, KS, 9Rehabilitation Institute of Michigan/Wayne State University, Detroit, MI, USABackground: As with many chronic conditions, patients with neuropathic pain (NeP are high consumers of health care resources. However, limited literature exists on the economic burden of NeP, including its impact on productivity. The aim of this study was to characterize health care resource utilization, productivity, and costs associated with NeP by pain severity level in US adults.Methods: Subjects (n=624 with painful diabetic peripheral neuropathy, human immunodeficiency virus-related peripheral NeP, post-trauma/post-surgical NeP, spinal cord injury with NeP, chronic low back pain with NeP, and small fiber neuropathy were recruited during routine office visits to US community-based general practitioners and specialists. Clinicians captured clinical characteristics, NeP-related medications, and health care resource utilization based on 6-month retrospective medical chart review. Subjects completed questionnaires on demographics, pain/symptoms, costs, and productivity. Brief Pain Inventory pain severity scores were used to classify subjects by mild, moderate, or severe pain. Annualized NeP-related costs (adjusted for covariates were estimated, and differences across pain severity groups were evaluated.Results: In total, 624 subjects were recruited (mean age 55.5±13.7 years; 55.4% male

Mechanisms of Distal Axonal Degeneration in Peripheral Neuropathies

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Cashman, Christopher R.; Höke, Ahmet

2015-01-01

Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wlds) and Sarmknockout animal models. These studies have shown axonal degeneration to occur througha programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration. PMID:25617478

Electrochemical skin conductance to detect sudomotor dysfunction, peripheral neuropathy and the risk of foot ulceration among Saudi patients with diabetes mellitus.

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Sheshah, Eman; Madanat, Amal; Al-Greesheh, Fahad; Al-Qaisi, Dalal; Al-Harbi, Mohammad; Aman, Reem; Al-Ghamdi, Abdul Aziz; Al-Madani, Khaled

2015-01-01

Sudomotor dysfunction is manifested clinically as abnormal sweating leading to dryness of feet skin and increased risk of foot ulceration. The aim of this study was to test the performance of foot electrochemical skin conductance (ESC) to detect diabetic peripheral neuropathy and the risk of foot ulceration against traditional methods in Saudi patients with diabetes mellitus. This cross-sectional study was conducted on 296 Saudi patients with diabetes mellitus. Painful neuropathic symptoms were evaluated using the neuropathy symptom score (NSS). The risk of foot ulceration and diabetic peripheral neuropathy were determined using the neuropathy disability score (NDS). Vibration perception threshold (VPT) was assessed using neurothesiometer. Neurophysiological assessment of the right and left sural, peroneal and tibial nerves was performed in 222 participants. Diabetic peripheral neuropathy was defined according to the definition of the American Academy of Neurology. ESC was measured with Sudoscan. Feet-ESC decreased as the scores of sensory and motor function tests increased. Feet-ESC decreased as the NSS, NDS and severity of diabetic peripheral neuropathy increased. Sensitivity of feet-ESC peripheral neuropathy assessed by VPT ≥ 25 V, NDS ≥ 3, NDS ≥ 6 was 90.1, 61 and 63.8 % respectively and specificity 77, 85 and 81.9 % respectively. Sensitivity of feet-ESC peripheral neuropathy assessed by VPT ≥ 25 V, NDS ≥ 3, NDS ≥ 6 was 100, 80.6 and 80.9 % respectively. Sensitivity and specificity of feet-ESC peripheral neuropathy were 67.5 and 58.9 % respectively. Sudoscan a simple and objective tool can be used to detect diabetic peripheral neuropathy and the risk of foot ulceration among patients with diabetes mellitus. Prospective studies to confirm our results are warranted.

Genetically determined optic neuropathies

DEFF Research Database (Denmark)

Milea, Dan; Amati-Bonneau, Patrizia; Reynier, Pascal

2010-01-01

The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions.......The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions....

One-stop microvascular screening service: an effective model for the early detection of diabetic peripheral neuropathy and the high-risk foot.

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Binns-Hall, O; Selvarajah, D; Sanger, D; Walker, J; Scott, A; Tesfaye, S

2018-04-02

To evaluate the feasibility of a one-stop microvascular screening service for the early diagnosis of diabetic distal symmetrical polyneuropathy, painful distal symmetrical polyneuropathy and the at-risk diabetic foot. People with diabetes attending retinal screening in hospital and community settings had their feet examined by a podiatrist. Assessment included: Toronto Clinical Neuropathy Score evaluation; a 10-g monofilament test; and two validated, objective and quick measures of neuropathy obtained using the point-of-care devices 'DPN-Check', a hand-held device that measures sural nerve conduction velocity and amplitude, and 'Sudoscan', a device that measures sudomotor function. The diagnostic utility of these devices was assessed against the Toronto Clinical Neuropathy Score as the 'gold standard'. A total of 236 consecutive people attending the retinal screening service, 18.9% of whom had never previously had their feet examined, were evaluated. The prevalence of distal symmetrical polyneuropathy, assessed using the Toronto Clinical Neuropathy Score, was 30.9%, and was underestimated by 10-g monofilament test (14.4%). The prevalence of distal symmetrical polyneuropathy using DPN-check was 51.5% (84.3% sensitivity, 68.3% specificity), 38.2% using Sudoscan foot electrochemical skin conductance (77.4% sensitivity, 68.3% specificity), and 61.9% using abnormality in either of the results (93.2% sensitivity, 52.8% specificity). The results of both devices correlated with Toronto Clinical Neuropathy Score (Peye, foot and renal screening is feasible, has a high uptake, reduces clinic visits, and identifies painful distal symmetrical polyneuropathy and the at-risk foot. Combined large- and small-nerve-fibre assessment using non-invasive, quantitative and quick point-of-care devices may be an effective model for the early diagnosis of distal symmetrical polyneuropathy. © 2018 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Incidence and impact of pain conditions and comorbid illnesses

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Davis JA

2011-10-01

Full Text Available Jessica A Davis, Rebecca L Robinson, Trong Kim Le, Jin XieLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USABackground: Individuals with pain often present with more than one painful condition. The purpose of this study was to characterize the rates of comorbidity, pain medication use, and health care costs for 23 selected pain conditions in a large health plan using administrative claims data from 2005 to 2007.Methods: Eligible patients included 1,211,483 adults with at least one pain condition during the one-year study period. Pain condition cohorts were classified based on the first diagnosis present in the claims during the study period.Results: Musculoskeletal pain conditions were among the most prevalent cohorts including low back pain, osteoarthritis, and fibromyalgia. Cancer pain was the least prevalent cohort. Conditions with the lowest illness severity included migraine and painful bladder syndrome cohorts, while cohorts with diabetic neuropathy, human immunodeficiency virus (HIV-associated pain, and cancer pain were the most severe. Across cohorts, the mean number of comorbid pain conditions ranged from 1.39 (for cancer pain and migraine to 2.65 (for multiple sclerosis pain. High rates of mental health conditions were found in cohorts with HIV-associated pain and multiple sclerosis pain (42.59% and 34.78% and were lowest among cohorts with rheumatoid arthritis and psoriatic arthropathy (12.73% and 13.31%, respectively. Rates of sleep disorders ranged from 5.47% (for painful bladder syndrome to 11.59% (for multiple sclerosis pain. Overall, patients averaged 3.53 unique pain medications during the study period. Considerable annual total health care costs were observed in the cancer pain cohort and the lowest costs were observed in the postherpetic neuropathy, surgically-induced pain, migraine, and irritable bowel syndrome cohorts. Costs attributed to pain were highest among the multiple sclerosis, HIV, and cancer

Modulation of spinal cord synaptic activity by tumor necrosis factor α in a model of peripheral neuropathy

Czech Academy of Sciences Publication Activity Database

Špicarová, Diana; Nerandžič, Vladimír; Paleček, Jiří

2011-01-01

Roč. 8, - (2011), e177 E-ISSN 1742-2094 R&D Projects: GA ČR(CZ) GA305/09/1228; GA MŠk(CZ) LC554 Grant - others:Univerzita Karlova(CZ) 309211 Institutional research plan: CEZ:AV0Z50110509 Keywords : TNF * neuropathy * pain Subject RIV: FH - Neurology Impact factor: 3.827, year: 2011

ORAL MANIFESTATIONS AND PROSTHETIC REHABILITATION IN HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY (HSANTYPE IV:A CASE REPORT*

Directory of Open Access Journals (Sweden)

Duygu OFLUOĞLU

2016-04-01

Full Text Available Hereditary sensory and autonomic neuropathies (HSAN are rare genetic syndromes of unknown etiology. They are seen in early childhood and are categorized into six different types by their symptoms. HSAN type 4 demonstrates autosomal recessive transmission pattern, with such major characteristics as loss of sense of pain, self-mutilation, anhydrosis and mental retardation. Sympathetic innervations are deficient despite the existence of sweat glands. Sufferers are hypotonic without any tendon reflexes, and neuro-motor development is retarded. In some cases tactile sensation and vibration may be intact. Biting injuries due to lack of pain sensation cause laceration, ulceration and scarring of the tongue, lips and other parts of oral mucosa. Tooth luxation and severe dental attrition have been observed. This case report presents oral and dental findings, surgical treatments and prosthetic rehabilitation of an 11- year-old boy with HSAN type 4.

Comparison of peripheral nerve blockade characteristics between non-diabetic patients and patients suffering from diabetic neuropathy: a prospective cohort study.

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Baeriswyl, M; Taffé, P; Kirkham, K R; Bathory, I; Rancati, V; Crevoisier, X; Cherix, S; Albrecht, E

2018-06-02

Animal data have demonstrated increased block duration after local anaesthetic injections in diabetic rat models. Whether the same is true in humans is currently undefined. We, therefore, undertook this prospective cohort study to test the hypothesis that type-2 diabetic patients suffering from diabetic peripheral neuropathy would have increased block duration after ultrasound-guided popliteal sciatic nerve block when compared with patients without neuropathy. Thirty-three type-2 diabetic patients with neuropathy and 23 non-diabetic control patients, scheduled for fore-foot surgery, were included prospectively. All patients received an ultrasound-guided popliteal sciatic nerve block with a 30 ml 1:1 mixture of lidocaine 1% and bupivacaine 0.5%. The primary outcome was time to first opioid request after block procedure. Secondary outcomes included the time to onset of sensory blockade, and pain score at rest on postoperative day 1 (numeric rating scale 0-10). These outcomes were analysed using an accelerated failure time regression model. Patients in the diabetic peripheral neuropathy group had significantly prolonged median (IQR [range]) time to first opioid request (diabetic peripheral neuropathy group 1440 (IQR 1140-1440 [180-1440]) min vs. control group 710 (IQR 420-1200 [150-1440] min, p = 0.0004). Diabetic peripheral neuropathy patients had a time ratio of 1.57 (95%CI 1.10-2.23, p peripheral neuropathy group 0 (IQR 0-1 [0-5]) vs. control group 3 (IQR 0-5 [0-9]), p = 0.001). In conclusion, after an ultrasound-guided popliteal sciatic nerve block, patients with diabetic peripheral neuropathy demonstrated reduced time to onset of sensory blockade, with increased time to first opioid request when compared with patients without neuropathy. © 2018 The Association of Anaesthetists.

Influence of Age and Neurotoxic HAART Use on Frequency of HIV Sensory Neuropathy

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Olajumoke Oshinaike

2012-01-01

Full Text Available Background. Sensory neuropathy (SN is one of the most common AIDS-associated neurologic disorders especially in the era of highly active antiretroviral therapy (HAART. The aim of this study was to determine the prevalence of SN among highly-active-antiretroviral-therapy- (HAART- experienced and HAART-naïve HIV-positive individuals and to investigate the relationship to demographic, clinical, and laboratory factors. Methods. 323 patients with HIV infection (142 on HAART and 181 HAART naïve were enrolled in a cross-sectional neuropathy screening program. Data was collected using structured questionnaires which contained the brief peripheral neuropathy screening tool of AIDS Clinical Trial Group protocol. Neuropathy was defined by the presence of at least 1 clinical sign in a distal, symmetrical pattern. Patients were classified as symptomatic if they described aching, stabbing, or burning pain, paresthesia, or numbness in a similar distribution. Demographic, clinical, and laboratory details were documented as risk factors. Result. The prevalence of sensory neuropathy was 39.0% (126/323, (of which 29/126 (23% were symptomatic. Amongst those on HAART, 60/142 (42.3% had SN compared to 66/181 (36.5% HAART-naïve individuals (P=0.29. On multivariate analyses, the independent associations with SN were increasing age (P=0.03 and current exposure to stavudine (P=0.00. Gender (P=0.99 height (P=0.07 use of HAART (P=0.50, duration of HAART treatment (P=0.10, and lower CD4 count (P=0.12 were not associated with an increased SN risk. Conclusion. HIV SN remains common despite improved immunologic function associated with HAART and decreased neurotoxic HAART use. In this cross-sectional analysis, age and stavudine-based therapies were the independent risk factors.

[Joint diagnostic value of four temperature sensation tests in elderly patients with type 2 diabetic peripheral neuropathy].

Science.gov (United States)

Guo, Wei; Li, Yun-Ming; Ai, Zhi-Hua; You, Zhi-Qing; Wan, Yong; Cheng, Ying; Lang, Hong-Mei

2013-07-01

To explore the joint diagnostic value of four temperature sensation tests in elderly patients with type 2 diabetic peripheral neuropathy. Thermal sensory analyzer-II were applied to measure cool sensation (CS), warm sensation (WS), cold pain sensation (CP)and heat pain sensation (HP) of 308 elderly patients with type 2 diabetes. Logistic regression model was adopted to create the new variable Temp4 from four temperature sensation tests to diagnose type 2 diabetic peripheral neuropathy. The ROC curve analysis was used to determine the best cut-off points of the four temperature sensation and Temp4, and the diagnostic value of it was evaluated. The means of temperature sensation tests of the diabetic peripheral neuropathy (DPN) group were significantly different from those of the non-DPN group (P sensation tests to diagnose the DPN, the sensitivity of WS test was the highest, and the value was 0.710; but the specificity, positive predictive value, negative predictive value, Youden index, diagnostic accuracy and Kappa value of cold sensation test were the highest, and the values were 0.842, 0.746, 0.799, 0.528, 77.92% and 0.535, respectively; the Kappa values of the other three temperature sensation tests were all greater than 0.4 (P sensation tests (P sensation quantitative tests were in good agreementand could be applied to diagnose DPN; the new variable Temp4 could be used for diagnosis of DPN with a higher diagnostic accuracy.

Giant iliopectineal bursitis presenting as neuropathy and severe edema of the lower limb: case illustration and review of the literature.

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Iwata, Takahiro; Nozawa, Satoshi; Ohashi, Minoru; Sakai, Hiroshi; Shimizu, Katsuji

2013-05-01

We report a 61-year-old woman with rheumatoid arthritis (RA: Steinblocker stage III, class 3) who developed severe swelling and neuropathy of the right lower limb caused by an iliopectineal bursa associated with destruction of the hip joint. Physical examination revealed an inguinal mass and groin pain. X-ray examination indicated destruction of the hip joint. Contrast-enhanced computed tomography showed the bursa connected with the hip joint and a markedly compressed external iliac vein among the inguinal ligament, pubis, and bursa. The patient underwent partial synovial resection and total hip arthroplasty for recovery of hip function, and this led to successful resolution of the symptoms and bursa. We present the characteristic images from this case and review all previously reported cases of RA iliopsoas bursitis causing leg swelling or neuropathy, and summarize the background. Since this lesion may cause various symptoms, clinical awareness that iliopsoas bursitis may present with unique clinical symptoms may aid correct diagnosis.

New Insights into Potential Prevention and Management Options for Chemotherapy-Induced Peripheral Neuropathy

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Janet Schloss

2016-01-01

Full Text Available Objective: Neurological complications such as chemotherapy-induced peripheral neuropathy (CIPN and neuropathic pain are frequent side effects of neurotoxic chemotherapy agents. An increasing survival rate and frequent administration of adjuvant chemotherapy treatments involving neurotoxic agents makes it imperative that accurate diagnosis, prevention, and treatment of these neurological complications be implemented. Methods: A consideration was undertaken of the current options regarding protective and treatment interventions for patients undergoing chemotherapy with neurotoxic chemotherapy agent or experience with CIPN. Current knowledge on the mechanism of action has also been identified. The following databases PubMed, the Cochrane Library, Science Direct, Scopus, EMBASE, MEDLINE, CINAHL, CNKI, and Google Scholar were searched for relevant article retrieval. Results: A range of pharmaceutical, nutraceutical, and herbal medicine treatments were identified that either showed efficacy or had some evidence of efficacy. Duloxetine was the most effective pharmaceutical agent for the treatment of CIPN. Vitamin E demonstrated potential for the prevention of cisplatin-IPN. Intravenous glutathione for oxaliplatin, Vitamin B6 for both oxaliplatin and cisplatin, and omega 3 fatty acids for paclitaxel have shown protection for CIPN. Acetyl-L-carnitine may provide some relief as a treatment option. Acupuncture may be of benefit for some patients and Gosha-jinki-gan may be of benefit for protection from adverse effects of oxaliplatin induced peripheral neuropathy. Conclusions: Clinicians and researchers acknowledge that there are numerous challenges involved in understanding, preventing, and treating peripheral neuropathy caused by chemotherapeutic agents. New insights into mechanisms of action from chemotherapy agents may facilitate the development of novel preventative and treatment options, thereby enabling medical staff to better support patients by

Cisplatin neuropathy. Risk factors, prognosis, and protection by WR-2721

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Mollman, J.E.; Glover, D.J.; Hogan, W.M.; Furman, R.E.

1988-01-01

A prospective study of patients receiving cis-diaminedichloroplatin II (DDP) was carried out to determine if risk factors could be identified related to the patient's living habits or past medical history that would predict in which patients DDP neuropathy might develop. Sixty-nine patients receiving six different combinations of chemotherapeutic agents, including DDP were examined. Twenty-eight of these patients received DDP in combination with the radioprotective agent S-2-(3-aminopropylamino)-ethylphosporothioic acid (WR 2721). No risk factors were identified relating to personal habits or past medical history of the patients. However, patients receiving DDP (40 mg/m2) on 5 consecutive days had a significantly higher incidence of neuropathy. Patients receiving DDP in combination with WR 2721 had a significantly lower incidence of neuropathy, and the mean dose at onset was significantly higher than the mean dose at onset of neuropathy for all other groups. In addition, five of six patients who were available for long-term follow-up demonstrated nearly complete reversal of the signs and symptoms of neuropathy

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

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Gewandter, Jennifer S; Dworkin, Robert H; Turk, Dennis C; Farrar, John T; Fillingim, Roger B; Gilron, Ian; Markman, John D; Oaklander, Anne Louise; Polydefkis, Michael J; Raja, Srinivasa N; Robinson, James P; Woolf, Clifford J; Ziegler, Dan; Ashburn, Michael A; Burke, Laurie B; Cowan, Penney; George, Steven Z; Goli, Veeraindar; Graff, Ole X; Iyengar, Smriti; Jay, Gary W; Katz, Joel; Kehlet, Henrik; Kitt, Rachel A; Kopecky, Ernest A; Malamut, Richard; McDermott, Michael P; Palmer, Pamela; Rappaport, Bob A; Rauschkolb, Christine; Steigerwald, Ilona; Tobias, Jeffrey; Walco, Gary A

2015-07-01

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

Gastrodin Inhibits Allodynia and Hyperalgesia in Painful Diabetic Neuropathy Rats by Decreasing Excitability of Nociceptive Primary Sensory Neurons

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Ye, Xin; Han, Wen-Juan; Wang, Wen-Ting; Luo, Ceng; Hu, San-Jue

2012-01-01

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients’ quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (I NaT) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I NaT and a decrease of potassium currents, especially slowly inactivating potassium currents (I AS); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I NaT and total potassium current as well as I AS currents induced by STZ were normalized by GAS. This study provides a

ANTIOXIDANT STATUS IN DIABETIC NEUROPATHY

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Giriraja Vrushabaiah Kanakapura

2017-09-01

Full Text Available BACKGROUND Diabetic neuropathy, retinopathy and nephropathy are the chronic complications of diabetes mellitus. Neuropathy, retinopathy and nephropathy are microvascular complication of diabetes mellitus. Antioxidant status is reduced in DM-induced retinopathy and nephropathy. Present study is undertaken to evaluate the degree of oxidative stress in diabetic neuropathy patients. The aim of the study is to study on oxidative stress as measured by lipid peroxidation marker, malondialdehyde and antienzyme status in type II DM patients with neuropathy and compared them with a controlled nondiabetic group. MATERIALS AND METHODS The study included 100 subjects from Sapthagiri Medical College, Bangalore, from January 1, 2015, to December 31, 2015, of age group 50 to 70 yrs. out of which 50 patients were non-insulin-dependent DM with neuropathy and rest 50 age and sex matched apparently healthy individuals (control group. Antioxidant status was assessed by measuring superoxide dismutase (SOD, glutathione peroxidase (GPx, glutathione reductase (GR, Catalase and Reduced Glutathione (GSH. RESULTS It showed a significant increase p<0.001 in FBS, PPBS, TC, TG, LDL, VLDL, CAT, MDA, while HDL, GSH, GPX, GR and SOD were found to be decreased significantly (p 0.001. CONCLUSION MDA was significantly elevated in diabetic group, whereas antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase and reduced glutathione were significantly decreased, which might be helpful in risk assessment of various complications of DM. The data suggests that alteration in antioxidant status and MDA may help to predict the risk of diabetic neuropathy.

Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

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Liu Xian-Guo

2011-03-01

Full Text Available Abstract Long-term potentiation (LTP in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.

Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

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Kannan, Anusha; Srinivasan, Sivasubramanian

2012-01-01

We read with great interest, the case report on ischemic optic neuropathy (1). We would like to add a few points concerning the blood supply of the optic nerve and the correlation with the development of post-operative ischemic neuropathy. Actually, the perioperative or post-operative vision loss (postoperative ischemic neuropathy) is most likely due to ischemic optic neuropathy. Ischemic optic neuropathy (2) is classified as an anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). This classification is based on the fact that blood supply (2) to the anterior segment of the optic nerve (part of the optic nerve in the scleral canal and the optic disc) is supplied by short posterior ciliary vessels or anastamotic ring branches around the optic nerve. The posterior part of the optic canal is relatively less perfused, and is supplied by ophthalmic artery and central fibres are perfused by a central retinal artery. So, in the post-operative period, the posterior part of the optic nerve is more vulnerable for ischemia, especially, after major surgeries (3), one of the theories being hypotension or anaemia (2) and resultant decreased perfusion. The onset of PION is slower than the anterior ischemic optic neuropathy. AION on the other hand, is usually spontaneous (idiopathic) or due to arteritis, and is usually sudden in its onset. The reported case is most likely a case of PION. The role of imaging, especially the diffusion weighted magnetic resonance imaging, is very important because the ophthalmoscopic findings in early stages of PION is normal, and it may delay the diagnosis. On the other hand, edema of the disc is usually seen in the early stages of AION.

Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

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Kannan, Anusha; Srinivasan, Sivasubramanian [Khoo Teck Puat Hospital, Singapore (Singapore)

2012-09-15

We read with great interest, the case report on ischemic optic neuropathy (1). We would like to add a few points concerning the blood supply of the optic nerve and the correlation with the development of post-operative ischemic neuropathy. Actually, the perioperative or post-operative vision loss (postoperative ischemic neuropathy) is most likely due to ischemic optic neuropathy. Ischemic optic neuropathy (2) is classified as an anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). This classification is based on the fact that blood supply (2) to the anterior segment of the optic nerve (part of the optic nerve in the scleral canal and the optic disc) is supplied by short posterior ciliary vessels or anastamotic ring branches around the optic nerve. The posterior part of the optic canal is relatively less perfused, and is supplied by ophthalmic artery and central fibres are perfused by a central retinal artery. So, in the post-operative period, the posterior part of the optic nerve is more vulnerable for ischemia, especially, after major surgeries (3), one of the theories being hypotension or anaemia (2) and resultant decreased perfusion. The onset of PION is slower than the anterior ischemic optic neuropathy. AION on the other hand, is usually spontaneous (idiopathic) or due to arteritis, and is usually sudden in its onset. The reported case is most likely a case of PION. The role of imaging, especially the diffusion weighted magnetic resonance imaging, is very important because the ophthalmoscopic findings in early stages of PION is normal, and it may delay the diagnosis. On the other hand, edema of the disc is usually seen in the early stages of AION.

Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3'-dideoxycytidine (ddC).

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Dalakas, M C; Semino-Mora, C; Leon-Monzon, M

2001-11-01

The 2'3'-dideoxycytidine (ddC), a nonazylated dideoxynucleoside analog used for the treatment of AIDS, causes a dose-dependent, painful, sensorimotor axonal peripheral neuropathy in up to 30% of the patients. To investigate the cause of the neuropathy, we performed morphological and molecular studies on nerve biopsy specimens from well-selected patients with ddC-neuropathy and from control subjects with disease, including patients with AIDS-related neuropathy never treated with ddC. Because ddC, in vitro, inhibits the replication of mitochondrial DNA (mtDNA), we counted the number of normal and abnormal mitochondria in a 0.04 mm(2) cross-sectional area of the nerves and quantified the copy numbers of mtDNA by competitive PCR in all specimens. A varying degree of axonal degeneration was present in all nerves. Abnormal mitochondria with enlarged size, excessive vacuolization, electron-dense concentric inclusions and degenerative myelin structures were prominent in the ddC-neuropathy and accounted for 55% +/- 2.5% of all counted mitochondria in the axon and Schwann cells, compared with 9% +/- 0.7% of the controls (p ddC-treated patients compared with the controls. We conclude that ddC induces a mitochondrial neuropathy with depletion of the nerve's mtDNA. The findings are consistent with the ability of ddC to selectively inhibit the gamma-DNA polymerase in neuronal cell lines. Toxicity to mitochondria of the peripheral nerve is a new cause of acquired neuropathy induced by exogenous toxins and may be the cause of neuropathy associated with the other neurotoxic antiretroviral drugs or toxic-metabolic conditions.

Peripheral neuropathy in HIV: prevalence and risk factors

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Evans, Scott R.; Ellis, Ronald J.; Chen, Huichao; Yeh, Tzu-min; Lee, Anthony J.; Schifitto, Giovanni; Wu, Kunling; Bosch, Ronald J.; McArthur, Justin C.; Simpson, David M.; Clifford, David B.

2011-01-01

Objectives To estimate neuropathic sign/symptom rates with initiation of combination antiretroviral therapy (cART) in HIV-infected ART-naive patients, and to investigate risk factors for: peripheral neuropathy and symptomatic peripheral neuropathy (SPN), recovery from peripheral neuropathy/SPN after neurotoxic ART (nART) discontinuation, and the absence of peripheral neuropathy/SPN while on nART. Design AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trial participants who initiated cART in randomized trials for ART-naive patients were annually screened for symptoms/signs of peripheral neuropathy. ART use and disease characteristics were collected longitudinally. Methods Peripheral neuropathy was defined as at least mild loss of vibration sensation in both great toes or absent/hypoactive ankle reflexes bilaterally. SPN was defined as peripheral neuropathy and bilateral symptoms. Generalized estimating equation logistic regression was used to estimate associations. Results Two thousand, one hundred and forty-one participants were followed from January 2000 to June 2007. Rates of peripheral neuropathy/SPN at 3 years were 32.1/8.6% despite 87.1% with HIV-1RNA 400 copies/ml or less and 70.3% with CD4 greater than 350 cells/µl. Associations with higher odds of peripheral neuropathy included older patient age and current nART use. Associations with higher odds of SPN included older patient age, nART use, and history of diabetes mellitus. Associations with lower odds of recovery after nART discontinuation included older patient age. Associations with higher odds of peripheral neuropathy while on nART included older patient age and current protease inhibitor use. Associations with higher odds of SPN while on nART included older patient age, history of diabetes, taller height, and protease inhibitor use. Conclusion Signs of peripheral neuropathy remain despite virologic/immunologic control but frequently occurs without symptoms. Aging is a risk factor for

[Perception of pain by patients receiving antiretroviral treatment in North Kivu, DR Congo].

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Escoffier, Claire; Kambale, Alain; Paluku, Faustin; Kabuayi, Jean-Pierre; Boillot, François

2010-01-01

This operational research conducted among TB patients co-infected with HIV in North Kivu had three objectives: (i) to clarify the local perception of a certain type of pain (michi in the local language) in patients on antiretroviral treatment (ART); (ii) to identify the attitudes of health care personnel regarding the management of ART side effects; and (iii) to explore ways to improve the quality of life of patients on ART and provide them with pain relief. Twenty in-depth interviews were conducted with patients on ART and their medical care providers in district health centers of North-Kivu and at patients' homes. A semantic analysis of the term michi revealed a nosologic folk entity based on a naturalistic view of the body; the term michi is used to name: (i) the "roots" of plants or trees; (ii) channels (veins, arteries, but also nerves and tendons) in the body through which fluids (blood, water) and energy are conveyed; (iii) different types of acute pain, possibly located along these channels. The description (location, duration, and intensity) of the functional signs and the context of their occurrence (while taking Stavudine) confirmed the medical diagnosis of acute sensory neuropathies. Although a classic ART side effect, neuropathies are underdiagnosed by health workers who find it difficult to recognize signs of treatment toxicity in apparently trivial symptoms. Different reasons account for this: (i) healthcare staff have little time to spend with TB/HIV patients and thus provide inadequate management of functional symptoms; (ii) insufficient attention is paid to patients' acute pain, which is often perceived as "normal"; (iii) insufficient knowledge of ART side effects due to staff turnover higher than the frequency of training that programmes. The study was conducted as part of the DR Congo national programmes for TB and AIDS and led to the formulation of recommendations about improving, especially through training, the assessment of functional

Deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy.

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Turkiew, Elliot; Falconer, Debbie; Reed, Nicole; Höke, Ahmet

2017-09-01

Distal axon degeneration seen in many peripheral neuropathies is likely to share common molecular mechanisms with Wallerian degeneration. Although several studies in mouse models of peripheral neuropathy showed prevention of axon degeneration in the slow Wallerian degeneration (Wlds) mouse, the role of a recently identified player in Wallerian degeneration, Sarm1, has not been explored extensively. In this study, we show that mice lacking the Sarm1 gene are resistant to distal axonal degeneration in a model of chemotherapy induced peripheral neuropathy caused by paclitaxel and a model of high fat diet induced putative metabolic neuropathy. This study extends the role of Sarm1 to axon degeneration seen in peripheral neuropathies and identifies it as a likely target for therapeutic development. © 2017 Peripheral Nerve Society.

Tapentadol extended-release for treatment of chronic pain: a review

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Vadivelu N

2011-08-01

Full Text Available Nalini Vadivelu1, Alexander Timchenko1, Yili Huang2, Raymond Sinatra11Department of Anesthesiology, Yale University School of Medicine, New Haven, CT; 2Internal Medicine, North Shore-LIJ Plainview Hospital, Plainview, NY, USAAbstract: Tapentadol is a centrally acting analgesic with a dual mechanism of action of mu receptor agonism and norepinephrine reuptake inhibition. Tapentadol immediate-release is approved by the US Food and Drug Administration for the management of moderate-to-severe acute pain. It was developed to decrease the intolerability issue associated with opioids. Tapentadol extended-release has a 12-hour duration of effect, and has recently been evaluated for pain in patients with chronic osteoarthritis, low back pain, and pain associated with diabetic peripheral neuropathy. Tapentadol extended-release was found to provide safe and highly effective analgesia for the treatment of chronic pain conditions, including moderate-to-severe chronic osteoarthritis pain and low back pain. Initial trials demonstrating efficacy in neuropathic pain suggest that tapentadol has comparable analgesic effectiveness and better gastrointestinal tolerability than opioid comparators, and demonstrates effectiveness in settings of inflammatory, somatic, and neuropathic pain. Gastrointestinal intolerance and central nervous system effects were the major adverse events noted. Tapentadol will need to be rigorously tested in chronic neuropathic pain, cancer-related pain, and cancer-related neuropathic pain.Keywords: osteoarthritis, neuropathic pain, analgesic, opioids, norepinephrine

Cutaneous nociceptors lack sensitisation, but reveal μ-opioid receptor-mediated reduction in excitability to mechanical stimulation in neuropathy

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Schmidt Yvonne

2012-11-01

Full Text Available Abstract Background Peripheral nerve injuries often trigger a hypersensitivity to tactile stimulation. Behavioural studies demonstrated efficient and side effect-free analgesia mediated by opioid receptors on peripheral sensory neurons. However, mechanistic approaches addressing such opioid properties in painful neuropathies are lacking. Here we investigated whether opioids can directly inhibit primary afferent neuron transmission of mechanical stimuli in neuropathy. We analysed the mechanical thresholds, the firing rates and response latencies of sensory fibres to mechanical stimulation of their cutaneous receptive fields. Results Two weeks following a chronic constriction injury of the saphenous nerve, mice developed a profound mechanical hypersensitivity in the paw innervated by the damaged nerve. Using an in vitro skin-nerve preparation we found no changes in the mechanical thresholds and latencies of sensory fibres from injured nerves. The firing rates to mechanical stimulation were unchanged or reduced following injury. Importantly, μ-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly5]-ol-enkephalin (DAMGO significantly elevated the mechanical thresholds of nociceptive Aδ and C fibres. Furthermore, DAMGO substantially diminished the mechanically evoked discharges of C nociceptors in injured nerves. These effects were blocked by DAMGO washout and pre-treatment with the selective μ-opioid receptor antagonist Cys2-Tyr3-Orn5-Pen7-amide. DAMGO did not alter the responses of sensory fibres in uninjured nerves. Conclusions Our findings suggest that behaviourally manifested neuropathy-induced mechanosensitivity does not require a sensitised state of cutaneous nociceptors in damaged nerves. Yet, nerve injury renders nociceptors sensitive to opioids. Prevention of action potential generation or propagation in nociceptors might represent a cellular mechanism underlying peripheral opioid-mediated alleviation of mechanical hypersensitivity in neuropathy.

Clinical diagnosis of diabetic polyneuropathy with the diabetic neuropathy symptom and diabetic neuropathy examination scores

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Meijer, J.W.; Lefrandt, J.D.; Links, T.P.; Smit, J.A.; Stewart, R.E.; van der Hoeven, J.H.; Hoogenberg, K.

OBJECTIVE - To evaluate the discriminative power of the Diabetic Neuropathy Symptom (DNS) and Diabetic Neuropathy Examination (DNE) scores for diagnosing diabetic polyneuropathy (PNP), as well as their relation with cardiovascular autonomic function testing (cAFT) and electro-diagnostic studies

Involvement of TRPM2 in a wide range of inflammatory and neuropathic pain mouse models

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Kanako So

2015-03-01

Full Text Available Recent evidence suggests a role of transient receptor potential melastatin 2 (TRPM2 in immune and inflammatory responses. We previously reported that TRPM2 deficiency attenuated inflammatory and neuropathic pain in some pain mouse models, including formalin- or carrageenan-induced inflammatory pain, and peripheral nerve injury-induced neuropathic pain models, while it had no effect on the basal mechanical and thermal nociceptive sensitivities. In this study, we further explored the involvement of TRPM2 in various pain models using TRPM2-knockout mice. There were no differences in the chemonociceptive behaviors evoked by intraplantar injection of capsaicin or hydrogen peroxide between wildtype and TRPM2-knockout mice, while acetic acid-induced writhing behavior was significantly attenuated in TRPM2-knockout mice. In the postoperative incisional pain model, no difference in mechanical allodynia was observed between the two genotypes. By contrast, mechanical allodynia in the monosodium iodoacetate-induced osteoarthritis pain model and the experimental autoimmune encephalomyelitis model were significantly attenuated in TRPM2-knockout mice. Furthermore, mechanical allodynia in paclitaxel-induced peripheral neuropathy and streptozotocin-induced painful diabetic neuropathy models were significantly attenuated in TRPM2-knockout mice. Taken together, these results suggest that TRPM2 plays roles in a wide range of pathological pain models based on peripheral and central neuroinflammation, rather than physiological nociceptive pain.

Dose–Volume Modeling of Brachial Plexus-Associated Neuropathy After Radiation Therapy for Head-and-Neck Cancer: Findings From a Prospective Screening Protocol

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Chen, Allen M.; Wang, Pin-Chieh; Daly, Megan E.; Cui, Jing; Hall, William H.; Vijayakumar, Srinivasan; Phillips, Theodore L.; Farwell, D. Gregory; Purdy, James A.

2014-01-01

Purpose: Data from a prospective screening protocol administered for patients previously irradiated for head-and-neck cancer was analyzed to identify dosimetric predictors of brachial plexus-associated neuropathy. Methods and Materials: Three hundred fifty-two patients who had previously completed radiation therapy for squamous cell carcinoma of the head and neck were prospectively screened from August 2007 to April 2013 using a standardized self-administered instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from radiation therapy was 40 months (range, 6-111 months). A total of 177 patients (50%) underwent neck dissection. Two hundred twenty-one patients (63%) received concurrent chemotherapy. Results: Fifty-one patients (14%) reported brachial plexus-related neuropathic symptoms with the most common being ipsilateral pain (50%), numbness/tingling (40%), and motor weakness and/or muscle atrophy (25%). The 3- and 5-year estimates of freedom from brachial plexus-associated neuropathy were 86% and 81%, respectively. Clinical/pathological N3 disease (P<.001) and maximum radiation dose to the ipsilateral brachial plexus (P=.01) were significantly associated with neuropathic symptoms. Cox regression analysis revealed significant dose–volume effects for brachial plexus-associated neuropathy. The volume of the ipsilateral brachial plexus receiving >70 Gy (V70) predicted for symptoms, with the incidence increasing with V70 >10% (P<.001). A correlation was also observed for the volume receiving >74 Gy (V74) among patients treated without neck dissection, with a cutoff of 4% predictive of symptoms (P=.038). Conclusions: Dose–volume guidelines were developed for radiation planning that may limit brachial plexus-related neuropathies

Dose–Volume Modeling of Brachial Plexus-Associated Neuropathy After Radiation Therapy for Head-and-Neck Cancer: Findings From a Prospective Screening Protocol

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Chen, Allen M., E-mail: amchen@mednet.ucla.edu [Department of Radiation Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California (United States); Wang, Pin-Chieh [Department of Radiation Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California (United States); Daly, Megan E.; Cui, Jing; Hall, William H. [Department of Radiation Oncology, University of California, Davis, Comprehensive Cancer Center, Sacramento, California (United States); Vijayakumar, Srinivasan [Department of Radiation Oncology, University of Mississippi School of Medicine, Jackson, Mississippi (United States); Phillips, Theodore L. [Department of Radiation Oncology, University of California, Davis, Comprehensive Cancer Center, Sacramento, California (United States); Farwell, D. Gregory [Department of Otolaryngology–Head and Neck Surgery, University of California, Davis, Comprehensive Cancer Center, Sacramento, California (United States); Purdy, James A. [Department of Radiation Oncology, University of California, Davis, Comprehensive Cancer Center, Sacramento, California (United States)

2014-03-15

Purpose: Data from a prospective screening protocol administered for patients previously irradiated for head-and-neck cancer was analyzed to identify dosimetric predictors of brachial plexus-associated neuropathy. Methods and Materials: Three hundred fifty-two patients who had previously completed radiation therapy for squamous cell carcinoma of the head and neck were prospectively screened from August 2007 to April 2013 using a standardized self-administered instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from radiation therapy was 40 months (range, 6-111 months). A total of 177 patients (50%) underwent neck dissection. Two hundred twenty-one patients (63%) received concurrent chemotherapy. Results: Fifty-one patients (14%) reported brachial plexus-related neuropathic symptoms with the most common being ipsilateral pain (50%), numbness/tingling (40%), and motor weakness and/or muscle atrophy (25%). The 3- and 5-year estimates of freedom from brachial plexus-associated neuropathy were 86% and 81%, respectively. Clinical/pathological N3 disease (P<.001) and maximum radiation dose to the ipsilateral brachial plexus (P=.01) were significantly associated with neuropathic symptoms. Cox regression analysis revealed significant dose–volume effects for brachial plexus-associated neuropathy. The volume of the ipsilateral brachial plexus receiving >70 Gy (V70) predicted for symptoms, with the incidence increasing with V70 >10% (P<.001). A correlation was also observed for the volume receiving >74 Gy (V74) among patients treated without neck dissection, with a cutoff of 4% predictive of symptoms (P=.038). Conclusions: Dose–volume guidelines were developed for radiation planning that may limit brachial plexus-related neuropathies.

Peripheral neuropathy in children with type 1 diabetes.

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Louraki, M; Karayianni, C; Kanaka-Gantenbein, C; Katsalouli, M; Karavanaki, K

2012-10-01

Diabetic neuropathy (DN) is a major complication of type 1 diabetes mellitus (T1DM) with significant morbidity and mortality in adulthood. Clinical neuropathy is rarely seen in paediatric populations, whereas subclinical neuropathy is commonly seen, especially in adolescents. Peripheral DN involves impairment of the large and/or small nerve fibres, and can be diagnosed by various methods. Nerve conduction studies (NCS) are the gold-standard method for the detection of subclinical DN; however, it is invasive, difficult to perform and selectively detects large-fibre abnormalities. Vibration sensation thresholds (VSTs) and thermal discrimination thresholds (TDTs) are quicker and easier and, therefore, more suitable as screening tools. Poor glycaemic control is the most important risk factor for the development of DN. Maintaining near-normoglycaemia is the only way to prevent or reverse neural impairment, as the currently available treatments can only relieve the symptoms of DN. Early detection of children and adolescents with nervous system abnormalities is crucial to allow all appropriate measures to be taken to prevent the development of DN. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment

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Mo, Michelle; Erdelyi, Ildiko; Szigeti-Buck, Klara; Benbow, Jennifer H.; Ehrlich, Barbara E.

2012-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect that occurs in many patients undergoing chemotherapy. It is often irreversible and frequently leads to early termination of treatment. In this study, we have identified two compounds, lithium and ibudilast, that when administered as a single prophylactic injection prior to paclitaxel treatment, prevent the development of CIPN in mice at the sensory-motor and cellular level. The prevention of neuropathy was not obs...

The rat intervertebral disk degeneration pain model: relationships between biological and structural alterations and pain.

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Kim, Jae-Sung; Kroin, Jeffrey S; Li, Xin; An, Howard S; Buvanendran, Asokumar; Yan, Dongyao; Tuman, Kenneth J; van Wijnen, Andre J; Chen, Di; Im, Hee-Jeong

2011-01-01

Degeneration of the interverterbral disk is as a cause of low-back pain is increasing. To gain insight into relationships between biological processes, structural alterations and behavioral pain, we created an animal model in rats. Disk degeneration was induced by removal of the nucleus pulposus (NP) from the lumbar disks (L4/L5 and L5/L6) of Sprague Dawley rats using a 0.5-mm-diameter microsurgical drill. The degree of primary hyperalgesia was assessed by using an algometer to measure pain upon external pressure on injured lumbar disks. Biochemical and histological assessments and radiographs of injured disks were used for evaluation. We investigated therapeutic modulation of chronic pain by administering pharmaceutical drugs in this animal model. After removal of the NP, pressure hyperalgesia developed over the lower back. Nine weeks after surgery we observed damaged or degenerated disks with proteoglycan loss and narrowing of disk height. These biological and structural changes in disks were closely related to the sustained pain hyperalgesia. A high dose of morphine (6.7 mg/kg) resulted in effective pain relief. However, high doses of pregabalin (20 mg/kg), a drug that has been used for treatment of chronic neuropathic pain, as well as the anti-inflammatory drugs celecoxib (50 mg/kg; a selective inhibitor of cyclooxygenase 2 (COX-2)) and ketorolac (20 mg/kg; an inhibitor of COX-1 and COX-2), did not have significant antihyperalgesic effects in our disk injury animal model. Although similarities in gene expression profiles suggest potential overlap in chronic pain pathways linked to disk injury or neuropathy, drug-testing results suggest that pain pathways linked to these two chronic pain conditions are mechanistically distinct. Our findings provide a foundation for future research on new therapeutic interventions that can lead to improvements in the treatment of patients with back pain due to disk degeneration.

Dyslipidemia as a contributory factor in etiopathogenesis of diabetic neuropathy

Directory of Open Access Journals (Sweden)

Fakhir S Al-Ani

2011-01-01

Full Text Available Objectives: The pathogenesis of neuropathy in type 2 diabetes mellitus is multifactorial.Dyslipidemia may contribute to the development of diabetic neuropathy. This study aimed to assess the atherogenic lipid indices in type 2 diabetic patients with neuropathy.Material and Methods: Fifty-one patients with type 2 diabetes mellitus and 31 healthy subjects were studied in the Unit of Neurophysiology at the University Hospital of Medical College, Al-Nahrin University in Baghdad, Iraq, from January 2002 to January 2003. Neuropathy total symptom score (NTSS, neuropathy impairment score in the lower leg (NIS-LL, and electrophysiological study of sensory (ulnar and sural and motor (ulnar and common peroneal nerves were used to assess nerve function. Fasting venous blood was obtained from each participant for determination of lipid profile and atherogenic lipid ratios. Results: The frequency of high blood pressure was significantly higher in neuropathic patients. The electrophysiology study revealed significant decrease in conduction velocity of ulnar (sensory and motor components, sural, and common peroneal nerves. The minimum F-wave latency of motor nerve was significantly prolonged. Among the lipid fractions, only high-density lipoprotein-cholesterol was significantly reduced by 14% of healthy participant′s value. Atherogenic lipid ratios were significantly higher in diabetic patients than corresponding healthy ratios. Conclusion: Metabolic lipid disturbances in terms of atherogenicity co-existwith neuropathy in type 2 diabetes mellitus, irrespective of duration of disease.

Chinese herbal medicine for diabetic peripheral neuropathy.

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Chen, Wei; Zhang, Yin; Li, Xinxue; Yang, Guoyan; Liu, Jian Ping

2013-10-06

Chinese herbal medicine is frequently used for treating diabetic peripheral neuropathy in China. Many controlled trials have been undertaken to investigate its efficacy.This is an update of a Cochrane review that was first published in the year 2011. To assess the beneficial effects and harms of Chinese herbal medicine for people with diabetic peripheral neuropathy. On 14 May 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register CENTRAL (2012, Issue 4 in The Cochrane Library), MEDLINE (January 1966 to May 2012), EMBASE (January 1980 to May 2012), AMED (January 1985 to May 2012) and in October 2012, the Chinese Biomedical Database (CBM) (1979 to October 2012), Chinese National Knowledge Infrastructure Database (CNKI) (1979 to October 2012), and VIP Chinese Science and Technique Journals Database (1989 to October 2012). We searched for unpublished literature in the Chinese Conference Papers Database, and Chinese Dissertation Database (from inception to October 2012). There were no language or publication restrictions. We included randomised controlled trials of Chinese herbal medicine (with a minimum of four weeks treatment duration) for people with diabetic peripheral neuropathy compared with placebo, no intervention, or conventional interventions. Trials of herbal medicine plus a conventional drug versus the drug alone were also included. Two authors independently extracted data and evaluated trial quality. We contacted study authors for additional information. Forty-nine randomised trials involving 3639 participants were included. All trials were conducted and published in China. Thirty-eight different herbal medicines were tested in these trials, including four single herbs (extracts from a single herb), eight traditional Chinese patent medicines, and 26 self concocted Chinese herbal compound prescriptions. The trials reported on global symptom improvement (including improvement in numbness or pain) and changes in nerve conduction

Diagnosis and therapeutic options for peripheral vasculitic neuropathy

Science.gov (United States)

2015-01-01

Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955

Genetics Home Reference: hereditary sensory neuropathy type IA

Science.gov (United States)

... sensory neuropathy type IA Hereditary sensory neuropathy type IA Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary sensory neuropathy type IA is a condition characterized by nerve abnormalities in ...

Multifocal visual evoked potential in optic neuritis, ischemic optic neuropathy and compressive optic neuropathy

Science.gov (United States)

Jayaraman, Manju; Gandhi, Rashmin Anilkumar; Ravi, Priya; Sen, Parveen

2014-01-01

Purpose: To investigate the effect of optic neuritis (ON), ischemic optic neuropathy (ION) and compressive optic neuropathy (CON) on multifocal visual evoked potential (mfVEP) amplitudes and latencies, and to compare the parameters among three optic nerve disorders. Materials and Methods: mfVEP was recorded for 71 eyes of controls and 48 eyes of optic nerve disorders with subgroups of optic neuritis (ON, n = 21 eyes), ischemic optic neuropathy (ION, n = 14 eyes), and compressive optic neuropathy (CON, n = 13 eyes). The size of defect in mfVEP amplitude probability plots and relative latency plots were analyzed. The pattern of the defect in amplitude probability plot was classified according to the visual field profile of optic neuritis treatment trail (ONTT). Results: Median of mfVEP amplitude (log SNR) averaged across 60 sectors were reduced in ON (0.17 (0.13-0.33)), ION (0.14 (0.12-0.21)) and CON (0.21 (0.14-0.30)) when compared to controls. The median mfVEP relative latencies compared to controls were significantly prolonged in ON and CON group of 10.53 (2.62-15.50) ms and 5.73 (2.67-14.14) ms respectively compared to ION group (2.06 (-4.09-13.02)). The common mfVEP amplitude defects observed in probability plots were diffuse pattern in ON, inferior altitudinal defect in ION and temporal hemianopia in CON eyes. Conclusions: Optic nerve disorders cause reduction in mfVEP amplitudes. The extent of delayed latency noted in ischemic optic neuropathy was significantly lesser compared to subjects with optic neuritis and compressive optic neuropathy. mfVEP amplitudes can be used to objectively assess the topography of the visual field defect. PMID:24088641

Idiopathic facial pain related with dental implantation

Directory of Open Access Journals (Sweden)

Tae-Geon Kwon

2016-06-01

Full Text Available Chronic pain after dental implantation is rare but difficult issue for the implant practitioner. Patients with chronic pain who had been performed previous implant surgery or related surgical intervention sometimes accompany with psychological problem and difficult to adequately manage. According to the International Classification of Headache Disorders (ICHD 3rd eds, Cepalagia 2013, painful neuropathies and other facial pains are subdivided into the 12 subcategories; 13.1. Trigeminal neuralgia; 13.2 Glossopharyngeal neuralgia; 13.3 Nervus intermedius (facial nerve neuralgia; 13.4 Occipital neuralgia; 13.5 Optic neuritis; 13.6 Headache attributed to ischaemic ocular motor nerve palsy; 13.7 Tolosa-Hunt syndrome; 13.8 Paratrigeminal oculo-sympathetic (Raeder’s syndrome; 13.9 Recurrent painful ophthalmoplegic neuropathy; 13.10 Burning Mouth Syndrome (BMS; 13.11 Persistent Idiopathic Facial Pain (PIFP; 13.12 Central neuropathic pain. Chronic orofacial pain after dental implant surgery can be largely into the two main categories that can be frequently encountered in clinical basis ; 1 Neuropathic pain, 2 Idiopathic pain. If there is no direct evidence of the nerve injury related with the implant surgery, the clinician need to consider the central cause of pain instead of the peripheral cause of the pain. There might be several possibilities; 1 Anaesthesia dolorosa, 2 Central post-stroke pain, 3 Facial pain attributed to multiple sclerosis, 4 Persistent idiopathic facial pain (PIFP, 5 Burning mouth syndrome. In this presentation, Persistent idiopathic facial pain (PIFP, the disease entity that can be frequently encountered in the clinic would be discussed. Persistent idiopathic facial pain (PIFP can be defined as “persistent facial and/or oral pain, with varying presentations but recurring daily for more than 2 hours per day over more than 3 months, in the absence of clinical neurological deficit”. ‘Atypical’ pain is a diagnosis of

Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

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Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

2016-03-01

Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

HIV Distal Neuropathic Pain Is Associated with Smaller Ventral Posterior Cingulate Cortex.

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Keltner, John R; Connolly, Colm G; Vaida, Florin; Jenkinson, Mark; Fennema-Notestine, Christine; Archibald, Sarah; Akkari, Cherine; Schlein, Alexandra; Lee, Jisu; Wang, Dongzhe; Kim, Sung; Li, Han; Rennels, Austin; Miller, David J; Kesidis, George; Franklin, Donald R; Sanders, Chelsea; Corkran, Stephanie; Grant, Igor; Brown, Gregory G; Atkinson, J Hampton; Ellis, Ronald J

2017-03-01

. Despite modern antiretroviral therapy, HIV-associated neuropathy is one of the most prevalent, disabling and treatment-resistant complications of HIV disease. The presence and intensity of distal neuropathic pain is not fully explained by the degree of peripheral nerve damage. A better understanding of brain structure in HIV distal neuropathic pain may help explain why some patients with HIV neuropathy report pain while the majority does not. Previously, we reported that more intense distal neuropathic pain was associated with smaller total cerebral cortical gray matter volumes. The objective of this study was to determine which parts of the cortex are smaller. . HIV positive individuals with and without distal neuropathic pain enrolled in the multisite (N = 233) CNS HIV Antiretroviral Treatment Effects (CHARTER) study underwent structural brain magnetic resonance imaging. Voxel-based morphometry was used to investigate regional brain volumes in these structural brain images. . Left ventral posterior cingulate cortex was smaller for HIV positive individuals with versus without distal neuropathic pain (peak P  = 0.017; peak t = 5.15; MNI coordinates x = -6, y = -54, z = 20). Regional brain volumes within cortical gray matter structures typically associated with pain processing were also smaller for HIV positive individuals having higher intensity ratings of distal neuropathic pain. . The posterior cingulate is thought to be involved in inhibiting the perception of painful stimuli. Mechanistically a smaller posterior cingulate cortex structure may be related to reduced anti-nociception contributing to increased distal neuropathic pain. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Excitability of Aβ sensory neurons is altered in an animal model of peripheral neuropathy

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Zhu Yong

2012-01-01

Full Text Available Abstract Background Causes of neuropathic pain following nerve injury remain unclear, limiting the development of mechanism-based therapeutic approaches. Animal models have provided some directions, but little is known about the specific sensory neurons that undergo changes in such a way as to induce and maintain activation of sensory pain pathways. Our previous studies implicated changes in the Aβ, normally non-nociceptive neurons in activating spinal nociceptive neurons in a cuff-induced animal model of neuropathic pain and the present study was directed specifically at determining any change in excitability of these neurons. Thus, the present study aimed at recording intracellularly from Aβ-fiber dorsal root ganglion (DRG neurons and determining excitability of the peripheral receptive field, of the cell body and of the dorsal roots. Methods A peripheral neuropathy was induced in Sprague Dawley rats by inserting two thin polyethylene cuffs around the right sciatic nerve. All animals were confirmed to exhibit tactile hypersensitivity to von Frey filaments three weeks later, before the acute electrophysiological experiments. Under stable intracellular recording conditions neurons were classified functionally on the basis of their response to natural activation of their peripheral receptive field. In addition, conduction velocity of the dorsal roots, configuration of the action potential and rate of adaptation to stimulation were also criteria for classification. Excitability was measured as the threshold to activation of the peripheral receptive field, the response to intracellular injection of depolarizing current into the soma and the response to electrical stimulation of the dorsal roots. Results In control animals mechanical thresholds of all neurons were within normal ranges. Aβ DRG neurons in neuropathic rats demonstrated a mean mechanical threshold to receptive field stimulation that were significantly lower than in control rats, a

Towards a neurobiological understanding of pain in chronic pancreatitis

DEFF Research Database (Denmark)

Olesen, Søren S; Krauss, Theresa; Demir, Ihsan Ekin

2017-01-01

a chronic pain syndrome. Objectives: We aimed to characterize the neurobiological signature of pain associated with CP and to discuss its implications for treatment strategies. Methods: Relevant basic and clinical articles were selected for review following an extensive search of the literature. Results......: Pathophysiological changes in the peripheral (pancreatic gland) and central nervous system characterize the pain syndrome associated with CP; involved mechanisms can be broken down to 3 main branches: (1) peripheral sensitization, (2) pancreatic neuropathy, and (3) neuroplastic changes in the central pain pathways...... with those observed in neuropathic pain disorders and have important implications for treatment; adjuvant analgesics are effective in a subset of patients, and neuromodulation and neuropsychological interventions may prove useful in the future. Conclusion: Chronic pancreatitis is associated with abnormal...

Hypothyroidism: Can It Cause Peripheral Neuropathy?

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Hypothyroidism: Can it cause peripheral neuropathy? Can hypothyroidism cause peripheral neuropathy and, if so, how is it treated? Answers from Todd B. Nippoldt, M.D. Hypothyroidism — a condition in which your ...

Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy

Science.gov (United States)

2014-12-29

Fatigue; Malignant Ovarian Mixed Epithelial Tumor; Neuropathy; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Pain; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Diabetic cachectic neuropathy: An uncommon neurological ...

African Journals Online (AJOL)

Diabetic cachectic neuropathy, also called diabetic neuropathic cachexia, is a very rare ... type 1 and type 2 diabetics and occurs irrespective of the duration of diabetes. .... distal symmetrical peripheral neuropathy in pregnancy. However,.

Facial Pain Followed by Unilateral Facial Nerve Palsy: A Case Report with Literature Review

OpenAIRE

GV, Sowmya; BS, Manjunatha; Goel, Saurabh; Singh, Mohit Pal; Astekar, Madhusudan

2014-01-01

Peripheral facial nerve palsy is the commonest cranial nerve motor neuropathy. The causes range from cerebrovascular accident to iatrogenic damage, but there are few reports of facial nerve paralysis attributable to odontogenic infections. In majority of the cases, recovery of facial muscle function begins within first three weeks after onset. This article reports a unique case of 32-year-old male patient who developed facial pain followed by unilateral facial nerve paralysis due to odontogen...

Oxcarbazepine for neuropathic pain.

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Zhou, Muke; Chen, Ning; He, Li; Yang, Mi; Zhu, Cairong; Wu, Fengbo

2017-12-02

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. To assess the benefits and harms of oxcarbazepine for different types of neuropathic pain. On 21 November 2016, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase. We searched the Chinese Biomedical Retrieval System (January 1978 to November 2016). We searched the US National Institutes of Health (NIH) databases and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials in January 2017, and we wrote to the companies who make oxcarbazepine and to pain experts requesting additional information. All RCTs and randomised cross-over studies of oxcarbazepine for the treatment of people of any age or sex with any neuropathic pain were eligible. We planned to include trials of oxcarbazepine compared with placebo or any other intervention with a treatment duration of at least six weeks, regardless of administration route and dose. We used standard methodological procedures expected by Cochrane. Five multicentre, randomised, placebo-controlled, double-blind trials with a total of 862 participants were eligible for inclusion in this updated review. Three trials involved participants with painful diabetic peripheral neuropathy (DPN) (n = 634), one included people with neuropathic pain due to radiculopathy (n = 145), and one, which was newly identified at this update, involved participants with peripheral neuropathic pain of mixed origin (polyneuropathy, peripheral nerve injury or postherpetic neuralgia) (n = 83). Some studies did not report all outcomes of interest. For

Pain in Fabry Disease: Practical Recommendations for Diagnosis and Treatment.

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Politei, Juan M; Bouhassira, Didier; Germain, Dominique P; Goizet, Cyril; Guerrero-Sola, Antonio; Hilz, Max J; Hutton, Elspeth J; Karaa, Amel; Liguori, Rocco; Üçeyler, Nurcan; Zeltzer, Lonnie K; Burlina, Alessandro

2016-07-01

Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed. In 2014, experts met to discuss recent advances on this topic and update clinical guidance. Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Würzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs. To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications. © 2016 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

New Treatments for Nonarteritic Anterior Ischemic Optic Neuropathy.

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Foroozan, Rod

2017-02-01

Despite increasing knowledge about the risk factors and clinical findings of nonarteritic anterior ischemic optic neuropathy (NAION), the treatment of this optic neuropathy has remained limited and without clear evidence-based benefit. Historical treatments of NAION are reviewed, beginning with the Ischemic Optic Neuropathy Decompression Trial. More recent treatments are placed within the historical context and illustrate the need for evidence-based therapy for ischemic optic neuropathy. Copyright © 2016 Elsevier Inc. All rights reserved.

Does a Rehabilitation Program of Aerobic and Progressive Resisted Exercises Influence HIV-Induced Distal Neuropathic Pain?

Science.gov (United States)

Maharaj, Sonill S; Yakasai, Abdulsalam M

2018-05-01

Distal symmetrical polyneuropathy is a common neurological sequela after HIV, which leads to neuropathic pain and functional limitations. Rehabilitation programs with exercises are used to augment pharmacological therapy to relieve pain but appropriate and effective exercises are unknown. This study explored the safety and effect of moderate-intensity aerobic exercises and progressive resisted exercises for HIV-induced distal symmetrical polyneuropathy neuropathic pain. A randomized pretest, posttest of 12 wks of aerobic exercise or progressive resisted exercise compared with a control. Outcome measures were assessed using the subjective periphery neuropathy, brief peripheral neuropathy screening, and numeric pain rating scale. Pain was assessed at baseline, 6 and 12 wks. Data between groups were compared using Kruskal-Wallis, Mann-Whitney U test, and within-groups Friedman and Wilcoxon signed rank tests. There were 136 participants (mean [SD] age = 36.79 [8.23] yrs) and the exercise groups completed the protocols without any adverse effects. Pain scores within and between aerobic exercise and progressive resisted exercise groups showed significant improvement (P 0.05). This study supports a rehabilitation program of moderate-intensity aerobic exercise and progressive resisted exercise being safe and effective for reducing neuropathic pain and is beneficial with analgesics for HIV-induced distal symmetrical polyneuropathy.

Effect of Urtica dioica on memory dysfunction and hypoalgesia in an experimental model of diabetic neuropathy.

Science.gov (United States)

Patel, Sita Sharan; Udayabanu, M

2013-09-27

Diabetic neuropathy is considered as a disease of the peripheral nervous system, but recent evidences suggest the involvement of central nervous system as well. In this study we evaluated the effect of Urtica dioica (UD) extract against memory dysfunction and hypoalgesia on a mouse model of streptozotocin (STZ) induced diabetic neuropathy. STZ (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes, followed by treatment with the UD extract (50 mg/kg, oral) and rosiglitazone (5 mg/kg, oral) for 8 weeks. Cognitive functions were evaluated using Morris water maze and passive avoidance step through task. Pain thresholds were measured using thermal, mechanical and chemical induced hyperalgesia. We observed that chronic diabetes resulted in a decline in circulating insulin level, elevated blood glucose, reduced body weight, increased water intake, cognitive impairment and hypoalgesia. UD significantly reduced the blood glucose and polydypsia, as well as improved the body weight, insulin level, cognition and insensate neuropathy. In conclusion, UD showed results comparable to rosiglitazone in reversing the long standing diabetes induced complications such as central and peripheral neuronal dysfunction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Docetaxel-induced neuropathy

DEFF Research Database (Denmark)

Eckhoff, Lise; Feddersen, Søren; Knoop, Ann

2015-01-01

Background. Docetaxel is a highly effective treatment of a wide range of malignancies but is often associated with peripheral neuropathy. The genetic variability of genes involved in the transportation or metabolism of docetaxel may be responsible for the variation in docetaxel-induced peripheral...... neuropathy (DIPN). The main purpose of this study was to investigate the impact of genetic variants in GSTP1 and ABCB1 on DIPN. Material and methods. DNA was extracted from whole blood from 150 patients with early-stage breast cancer who had received adjuvant docetaxel from February 2011 to May 2012. Two...

The neuropathic oesophagus. A radiographic and manometric study on the evolution of megaoesophagus in dogs with developing axonal neuropathy

International Nuclear Information System (INIS)

Satchell, P.M.

1990-01-01

Dogs given the neurotoxin acrylamide develop peripheral neuropathy and megaoesophagus. Sequential radiographic and manometric studies on the oesophagus demonstrated that the initial abnormalities consisted of a progressive decrease in the proportion of swallows that initiated peristalsis and a gradual increase in oesophageal calibre. Regurgitation, peristaltic failure and oesophageal dilatation all appeared within three days. The eating behaviour and gait abnormalities quickly resolved on stopping the neurotoxin, but the oesophagus remained dilated for longer. Previous studies have suggested that the abnormalities present in dogs which are developing a distal axonal neuropathy or in some dogs with idiopathic megaoesophagus may be limited to the proprioceptive elements of the oesophageal innervation. The present study suggests that the progressive inefficiency in the transmission of swallows and changes in oesophageal calibre in dogs with evolving megaoesophagus may be a consequence of damage to these proprioceptive elements

Ambulatory screening of diabetic neuropathy and predictors of its severity in outpatient settings.

Science.gov (United States)

Qureshi, M S; Iqbal, M; Zahoor, S; Ali, J; Javed, M U

2017-04-01

Diabetic neuropathy is one of the most common causes of chronic neuropathic symptomatology and the most disabling and difficult-to-treat diabetic microangiopathic complication. The neuropathies associated with diabetes are typically classified into generalized, focal and multifocal varieties. There exists a scarcity of literature studying the correlation of different patient- and disease-related variables with severity of neuropathy. This study aims to delineate the prevalence of diabetic neuropathy in type 2 diabetes, describe its characteristics and find out predictors of its severity. Eight hundred consecutive diabetic patients presenting to outpatient department (OPD) of Khan Research Labs (KRL) General Hospital and Centre for Diabetes and Liver diseases, Islamabad, during March-June, 2015 were made to complete a self-administered questionnaire (Michigan Neuropathy Screening Instrument-MNSI) and underwent a thorough physical examination according to MNSI protocols. A score of >2 was considered to be diagnostic for DPN. Patient and disease variables were noted. MNSI score was used as an index of severity of diabetic peripheral neuropathy (DPN). Correlation of several patient- and disease-related variables with the severity of DPN was determined using multivariate regression. Out of a total 800 patients screened, 90 (11.25%) were found to have diabetic neuropathy. Of these 90, 45.5% were males, the median age was 54.47 ± 10.87 years and the median duration of diabetes was 11.12 ± 9.8 years. The most common symptom was found to be numbness (63.6%) followed by generalized body weakness (61.5%). The common findings on physical examination were dry skin/callus (38.7%) and deformities (14.7%). Duration of diabetes was found to be the strongest predictor for development and severity of diabetic neuropathy followed by glycemic controls (HbA1c values) and age. Duration of diabetes rather than diabetic controls predicts better the development and severity of

Amelioration of Diabetes and Painful Diabetic Neuropathy by Punica granatum L. Extract and Its Spray Dried Biopolymeric Dispersions

Directory of Open Access Journals (Sweden)

K. Raafat

2014-01-01

Full Text Available Aims. To evaluate the effect of Punica granatum (Pg rind extract and its spray dried biopolymeric dispersions with casein (F1 or chitosan (F2 against Diabetes mellitus (DM and diabetic neuropathy (DN. Methods. We measured the acute (6 h and subacute (8 days effect of various doses of Pg, F1, and F2 and the active compounds on alloxan-induced DM mouse model. We evaluated DN utilizing latency tests for longer period of time (8 weeks. In addition, the in vivo antioxidant activity was assessed utilizing serum catalase level. Results. The results proved that the highest dose levels of Pg extract, F1, F2 exerted remarkable hypoglycemic activity with 48, 52, and 40% drop in the mice glucose levels after 6 hours, respectively. The tested compounds also improved peripheral nerve function as observed from the latency tests. Bioguided fractionation suggested that gallic acid (GA was Pg main active ingredient responsible for its actions. Conclusion. Pg extract, F1, F2, and GA could be considered as a new therapeutic potential for the amelioration of diabetic neuropathic pain and the observed in vivo antioxidant potential may be involved in its antinociceptive effect. It is highly significant to pay attention to Pg and GA for amelioration and control of DM and its complications.

Amelioration of Diabetes and Painful Diabetic Neuropathy by Punica granatum L. Extract and Its Spray Dried Biopolymeric Dispersions

Science.gov (United States)

Raafat, K.; Samy, W.

2014-01-01

Aims. To evaluate the effect of Punica granatum (Pg) rind extract and its spray dried biopolymeric dispersions with casein (F1) or chitosan (F2) against Diabetes mellitus (DM) and diabetic neuropathy (DN). Methods. We measured the acute (6 h) and subacute (8 days) effect of various doses of Pg, F1, and F2 and the active compounds on alloxan-induced DM mouse model. We evaluated DN utilizing latency tests for longer period of time (8 weeks). In addition, the in vivo antioxidant activity was assessed utilizing serum catalase level. Results. The results proved that the highest dose levels of Pg extract, F1, F2 exerted remarkable hypoglycemic activity with 48, 52, and 40% drop in the mice glucose levels after 6 hours, respectively. The tested compounds also improved peripheral nerve function as observed from the latency tests. Bioguided fractionation suggested that gallic acid (GA) was Pg main active ingredient responsible for its actions. Conclusion. Pg extract, F1, F2, and GA could be considered as a new therapeutic potential for the amelioration of diabetic neuropathic pain and the observed in vivo antioxidant potential may be involved in its antinociceptive effect. It is highly significant to pay attention to Pg and GA for amelioration and control of DM and its complications. PMID:24982685

Puerarin Alleviates Neuropathic Pain by Inhibiting Neuroinflammation in Spinal Cord

OpenAIRE

Ming Liu; Kaijun Liao; Changxi Yu; Xuejun Li; Suhuan Liu; Shuyu Yang

2014-01-01

Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI) and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4–100 nM) ...

DNA testing in hereditary neuropathies.

LENUS (Irish Health Repository)

Murphy, Sinéad M

2013-01-01

The inherited neuropathies are a clinically and genetically heterogeneous group of disorders in which there have been rapid advances in the last two decades. Molecular genetic testing is now an integral part of the evaluation of patients with inherited neuropathies. In this chapter we describe the genes responsible for the primary inherited neuropathies. We briefly discuss the clinical phenotype of each of the known inherited neuropathy subgroups, describe algorithms for molecular genetic testing of affected patients and discuss genetic counseling. The basic principles of careful phenotyping, documenting an accurate family history, and testing the available genes in an appropriate manner should identify the vast majority of individuals with CMT1 and many of those with CMT2. In this chapter we also describe the current methods of genetic testing. As advances are made in molecular genetic technologies and improvements are made in bioinformatics, it is likely that the current time-consuming methods of DNA sequencing will give way to quicker and more efficient high-throughput methods, which are briefly discussed here.

Corneal markers of diabetic neuropathy.

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Pritchard, Nicola; Edwards, Katie; Shahidi, Ayda M; Sampson, Geoff P; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2011-01-01

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies. This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new noninvasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and noncontact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Regulatable Transgene Expression for Prevention of Chemotherapy-Induced Peripheral Neuropathy

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Daisuke Kawata

2017-09-01

Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3 or interleukin-10 (IL-10 from replication-defective herpes simplex virus (HSV-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet-on-based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2, and expression of the transgene was controlled by doxycycline (DOX. We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy.

Regulatable Transgene Expression for Prevention of Chemotherapy-Induced Peripheral Neuropathy.

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Kawata, Daisuke; Wu, Zetang

2017-09-15

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3) or interleukin-10 (IL-10) from replication-defective herpes simplex virus (HSV)-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG) on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet)-on-based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2), and expression of the transgene was controlled by doxycycline (DOX). We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg) once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy.

Peripheral Neuropathy

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... wasting. Various dietary strategies can improve gastrointestinal symptoms. Timely treatment of injuries can help prevent permanent damage. ... diabetic neuropathy is more limited. Transcutaneous electrical nerve stimulation (TENS) is a non-invasive intervention used for ...

Auditory Neuropathy

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... children and adults with auditory neuropathy. Cochlear implants (electronic devices that compensate for damaged or nonworking parts ... and Drug Administration: Information on Cochlear Implants Telecommunications Relay Services Your Baby's Hearing Screening News Deaf health ...

Mitochondrial dysfunction in an animal model of diabetic neuropathy is associated with a reduction of neurosteroid synthesis. [version 2; referees: 2 approved

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Stephen R. Humble

2018-03-01

Full Text Available Background: Recent work in a model of diabetic neuropathy revealed that layer 2/3 cortical pyramidal neurones of the pain pathway exhibited reduced endogenous neurosteroid modulation of the GABAAR and exogenously applied neurosteroids had an exaggerated impact. It is postulated that this is related to reduced precursor synthesis, due to mitochondrial dysfunction in diabetic neuropathy. Benzodiazepines are also known to activate neurosteroidogenesis by binding to mitochondrial translocator protein (TSPO. This study explored the differential effect of diazepam on GABAAR modulation via neurosteroidogenesis in diabetic and wild type (WT mice. Methods: Whole-cell patch-clamp technique was used on slices of neural tissue. Electrophysiological recordings were obtained from layer 2/3 cortical pyramidal neurons of the pain pathway from mice with type-II diabetic neuropathy (ob/ob and WT controls aged 60-80 days. Results: There was a key difference in the response of the WT and ob/ob cortical neurons to simultaneous incubation with diazepam and flumazenil. In contrast, diazepam and the 5a-reductase inhibitor finasteride, individually or in combination, produced the same response in both strains. Conclusions: The exaggerated effect of diazepam on GABAergic inhibitory tone in the ob/ob, despite the presence of the GABAAR benzodiazepine antagonist flumazenil is likely observed due to physiological upregulation of key neurosteroidogenic enzymes in response to the reduced pregnenolone synthesis by the mitochondria. By increasing pregnenolone via TSPO activation, it is possible to promote enhanced neurosteroidogenesis and increase GABAergic inhibitory tone via an alternate route. In diabetic neuropathy, mitochondrial dysfunction may play an important role. Enhancing the GABAergic neurosteroid tone could be of potential therapeutic benefit.

Activated microglia in the spinal cord underlies diabetic neuropathic pain.

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Wang, Dongmei; Couture, Réjean; Hong, Yanguo

2014-04-05

Diabetes mellitus is an increasingly common chronic medical condition. Approximately 30% of diabetic patients develop neuropathic pain, manifested as spontaneous pain, hyperalgesia and allodynia. Hyperglycemia induces metabolic changes in peripheral tissues and enhances oxidative stress in nerve fibers. The damages and subsequent reactive inflammation affect structural properties of Schwann cells and axons leading to the release of neuropoietic mediators, such as pro-inflammatory cytokines and pro-nociceptive mediators. Therefore, diabetic neuropathic pain (DNP) shares some histological features and underlying mechanisms with traumatic neuropathy. DNP displays, however, other distinct features; for instance, sensory input to the spinal cord decreases rather than increasing in diabetic patients. Consequently, development of central sensitization in DNP involves mechanisms that are distinct from traumatic neuropathic pain. In DNP, the contribution of spinal cord microglia activation to central sensitization and pain processes is emerging as a new concept. Besides inflammation in the periphery, hyperglycemia and the resulting production of reactive oxygen species affect the local microenvironment in the spinal cord. All these alterations could trigger resting and sessile microglia to the activated phenotype. In turn, microglia synthesize and release pro-inflammatory cytokines and neuroactive molecules capable of inducing hyperactivity of spinal nociceptive neurons. Hence, it is imperative to elucidate glial mechanisms underlying DNP for the development of effective therapeutic agents. The present review highlights the recent developments regarding the contribution of spinal microglia as compelling target for the treatment of DNP. Copyright © 2014 Elsevier B.V. All rights reserved.

Penicillamin-induced neuropathy in rheumatoid arthritis

DEFF Research Database (Denmark)

Pedersen, P B; Hogenhaven, H

1990-01-01

A case of penicillamin-induced severe polyradiculopathy in rheumatoid arthritis is presented. The neuropathy was of demyelinating type, purely motor, proximal and clinically fully reversible when the drug ceased. In case of a progressive neuropathy, during penicillamin treatment, this adverse...

Image analysis software for following progression of peripheral neuropathy

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Epplin-Zapf, Thomas; Miller, Clayton; Larkin, Sean; Hermesmeyer, Eduardo; Macy, Jenny; Pellegrini, Marco; Luccarelli, Saverio; Staurenghi, Giovanni; Holmes, Timothy

2009-02-01

A relationship has been reported by several research groups [1 - 4] between the density and shapes of nerve fibers in the cornea and the existence and severity of peripheral neuropathy. Peripheral neuropathy is a complication of several prevalent diseases or conditions, which include diabetes, HIV, prolonged alcohol overconsumption and aging. A common clinical technique for confirming the condition is intramuscular electromyography (EMG), which is invasive, so a noninvasive technique like the one proposed here carries important potential advantages for the physician and patient. A software program that automatically detects the nerve fibers, counts them and measures their shapes is being developed and tested. Tests were carried out with a database of subjects with levels of severity of diabetic neuropathy as determined by EMG testing. Results from this testing, that include a linear regression analysis are shown.

Diagnostic imaging of compression neuropathy; Bildgebende Diagnostik von Nervenkompressionssyndromen

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Weishaupt, D.; Andreisek, G. [Universitaetsspital, Institut fuer Diagnostische Radiologie, Zuerich (Switzerland)

2007-03-15

Compression-induced neuropathy of peripheral nerves can cause severe pain of the foot and ankle. Early diagnosis is important to institute prompt treatment and to minimize potential injury. Although clinical examination combined with electrophysiological studies remain the cornerstone of the diagnostic work-up, in certain cases, imaging may provide key information with regard to the exact anatomic location of the lesion or aid in narrowing the differential diagnosis. In other patients with peripheral neuropathies of the foot and ankle, imaging may establish the etiology of the condition and provide information crucial for management and/or surgical planning. MR imaging and ultrasound provide direct visualization of the nerve and surrounding abnormalities. Bony abnormalities contributing to nerve compression are best assessed by radiographs and CT. Knowledge of the anatomy, the etiology, typical clinical findings, and imaging features of peripheral neuropathies affecting the peripheral nerves of the foot and ankle will allow for a more confident diagnosis. (orig.) [German] Kompressionsbedingte Schaedigungen peripherer Nerven koennen die Ursache hartnaeckiger Schmerzen im Bereich des Sprunggelenks und Fusses sein. Eine fruehzeitige Diagnose ist entscheidend, um den Patienten der richtigen Therapie zuzufuehren und potenzielle Schaedigungen zu vermeiden oder zu verringern. Obschon die klinische Untersuchung und die elektrophysiologische Abklaerungen die wichtigsten Elemente der Diagnostik peripherer Nervenkompressionssyndrome sind, kann die Bildgebung entscheidend sein, wenn es darum geht, die Hoehe des Nervenschadens festzulegen oder die Differenzialdiagnose einzugrenzen. In gewissen Faellen kann durch Bildgebung sogar die Ursache der Nervenkompression gefunden werden. In anderen Faellen ist die Bildgebung wichtig bei der Therapieplanung, insbesondere dann, wenn die Laesion chirurgisch angegangen wird. Magnetresonanztomographie (MRT) und Sonographie ermoeglichen eine

A pilot study of minocycline for the prevention of paclitaxel-associated neuropathy: ACCRU study RU221408I.

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Pachman, Deirdre R; Dockter, Travis; Zekan, Patricia J; Fruth, Briant; Ruddy, Kathryn J; Ta, Lauren E; Lafky, Jacqueline M; Dentchev, Todor; Le-Lindqwister, Nguyet Anh; Sikov, William M; Staff, Nathan; Beutler, Andreas S; Loprinzi, Charles L

2017-11-01

Paclitaxel is associated with both an acute pain syndrome (P-APS) and chronic chemotherapy-induced peripheral neuropathy (CIPN). Given that extensive animal data suggest that minocycline may prevent chemotherapy-induced neurotoxicity, the purpose of this pilot study was to investigate the efficacy of minocycline for the prevention of CIPN and the P-APS. Patients with breast cancer were enrolled prior to initiating neoadjuvant or adjuvant weekly paclitaxel for 12 weeks and were randomized to receive minocycline 200 mg on day 1 followed by 100 mg twice daily or a matching placebo. Patients completed (1) an acute pain syndrome questionnaire daily during chemotherapy to measure P-APS and (2) the EORTC QLQ-CIPN20 questionnaire at baseline, prior to each dose of paclitaxel, and monthly for 6 months post treatment, to measure CIPN. Forty-seven patients were randomized. There were no remarkable differences noted between the minocycline and placebo groups for the overall sensory neuropathy score of the EORTC QLQ-CIPN20 or its individual components, which evaluate tingling, numbness and shooting/burning pain in hands and feet. However, patients taking minocycline had a significant reduction in the daily average pain score attributed to P-APS (p = 0.02). Not only were no increased toxicities reported with minocycline, but there was a significant reduction in fatigue (p = 0.02). Results of this pilot study do not support the use of minocycline to prevent CIPN, but suggest that it may reduce P-APS and decrease fatigue; further study of the impact of this agent on those endpoints may be warranted.

Role of sigma 1 receptor in high fat diet-induced peripheral neuropathy.

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Song, Tieying; Zhao, Jianhui; Ma, Xiaojing; Zhang, Zaiwang; Jiang, Bo; Yang, Yunliang

2017-09-26

The neurobiological mechanisms of obesity-induced peripheral neuropathy are poorly understood. We evaluated the role of Sigma-1 receptor (Sig-1R) and NMDA receptor (NMDARs) in the spinal cord in peripheral neuropathy using an animal model of high fat diet-induced diabetes. We examined the expression of Sig-1R and NMDAR subunits GluN2A and GluN2B along with postsynaptic density protein 95 (PSD-95) in the spinal cord after 24-week HFD treatment in both wild-type and Sig-1R-/- mice. Finally, we examined the effects of repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice on peripheral neuropathy. Wild-type mice developed tactile allodynia and thermal hypoalgesia after 24-week HFD treatment. HFD-induced peripheral neuropathy correlated with increased expression of GluN2A and GluN2B subunits of NMDARs, PDS-95, and Sig-1R, as well as increased Sig-1R-NMDAR interaction in the spinal cord. In contrast, Sig-1R-/- mice did not develop thermal hypoalgesia or tactile allodynia after 24-week HFD treatment, and the levels of GluN2A, GluN2B, and PSD-95 were not altered in the spinal cord of HFD-fed Sig-1R-/- mice. Finally, repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice attenuated peripheral neuropathy. Our results suggest that obesity-associated peripheral neuropathy may involve Sig-1R-mediated enhancement of NMDAR expression in the spinal cord.

The effect of Neuragen PN® on Neuropathic pain: A randomized, double blind, placebo controlled clinical trial

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Li Li

2010-05-01

Full Text Available Abstract Background A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain. Methods Sixty participants with plantar cutaneous (foot sole pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale. Results There was an overall pain reduction for both treatments from pre to post application. As compared to the placebo, Neuragen PN® led to significantly (p ® reported pain reduction within 30 minutes. This reduction within 30 minutes occurred in only twenty one of sixty (35.0% subjects receiving the placebo. In a break out analysis of the diabetic only subgroup, 94% of subjects in the Neuragen PN® group achieved pain reduction within 30 minutes vs 11.0% of the placebo group. No adverse events were observed. Conclusions This randomized, placebo controlled, clinical trial with crossover design revealed that the naturally derived oil, Neuragen PN®, provided significant relief from neuropathic pain in an all cause neuropathy group. Participants with diabetes within this group experienced similar pain relief. Trial registration ISRCTN registered: ISRCTN13226601

Infantile Pain Episodes Associated with Novel Nav1.9 Mutations in Familial Episodic Pain Syndrome in Japanese Families.

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Okuda, Hiroko; Noguchi, Atsuko; Kobayashi, Hatasu; Kondo, Daiki; Harada, Kouji H; Youssefian, Shohab; Shioi, Hirotomo; Kabata, Risako; Domon, Yuki; Kubota, Kazufumi; Kitano, Yutaka; Takayama, Yasunori; Hitomi, Toshiaki; Ohno, Kousaku; Saito, Yoshiaki; Asano, Takeshi; Tominaga, Makoto; Takahashi, Tsutomu; Koizumi, Akio

2016-01-01

Painful peripheral neuropathy has been correlated with various voltage-gated sodium channel mutations in sensory neurons. Recently Nav1.9, a voltage-gated sodium channel subtype, has been established as a genetic influence for certain peripheral pain syndromes. In this study, we performed a genetic study in six unrelated multigenerational Japanese families with episodic pain syndrome. Affected participants (n = 23) were characterized by infantile recurrent pain episodes with spontaneous mitigation around adolescence. This unique phenotype was inherited in an autosomal-dominant mode. Linkage analysis was performed for two families with 12 affected and nine unaffected members, and a single locus was identified on 3p22 (LOD score 4.32). Exome analysis (n = 14) was performed for affected and unaffected members in these two families and an additional family. Two missense variants were identified: R222H and R222S in SCN11A. Next, we generated a knock-in mouse model harboring one of the mutations (R222S). Behavioral tests (Hargreaves test and cold plate test) using R222S and wild-type C57BL/6 (WT) mice, young (8-9 weeks old; n = 10-12 for each group) and mature (36-38 weeks old; n = 5-6 for each group), showed that R222S mice were significantly (p pain. The mouse model developed here will be useful for drug screening for familial episodic pain syndrome associated with SCN11A mutations.

IL-10 mediated by herpes simplex virus vector reduces neuropathic pain induced by HIV gp120 combined with ddC in rats.

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Zheng, Wenwen; Huang, Wan; Liu, Shue; Levitt, Roy C; Candiotti, Keith A; Lubarsky, David A; Hao, Shuanglin

2014-07-30

HIV-associated sensory neuropathy affects over 50% of HIV patients and is a common peripheral nerve complication of HIV infection and highly active antiretroviral therapy (HAART). Evidence shows that painful HIV sensory neuropathy is influenced by neuroinflammatory events that include the proinflammatory molecules, MAP Kinase, tumor necrosis factor-α (TNFα), stromal cell-derived factor 1-α (SDF1α), and C-X-C chemokine receptor type 4 (CXCR4). However, the exact mechanisms of painful HIV sensory neuropathy are not known, which hinders our ability to develop effective treatments. In this study, we investigated whether inhibition of proinflammatory factors reduces the HIV-associated neuropathic pain state. Neuropathic pain was induced by peripheral HIV coat protein gp120 combined with 2',3'-dideoxycytidine (ddC, one of the nucleoside reverse transcriptase inhibitors (NRTIs)). Mechanical threshold was tested using von Frey filament fibers. Non-replicating herpes simplex virus (HSV) vectors expressing interleukin 10 (IL10) were inoculated into the hindpaws of rats. The expression of TNFα, SDF1α, and CXCR4 in the lumbar spinal cord and L4/5 dorsal root ganglia (DRG) was examined using western blots. IL-10 expression mediated by the HSV vectors resulted in a significant elevation of mechanical threshold. The anti-allodynic effect of IL-10 expression mediated by the HSV vectors lasted more than 3 weeks. The area under the effect-time curves (AUC) in mechanical threshold in rats inoculated with the HSV vectors expressing IL-10, was increased compared with the control vectors, indicating antinociceptive effect of the IL-10 vectors. The HSV vectors expressing IL-10 also concomitantly reversed the upregulation of p-p38, TNFα, SDF1α, and CXCR4 induced by gp120 in the lumbar spinal dorsal horn and/or the DRG at 2 and/or 4 weeks. The blocking of the signaling of these proinflammatory molecules is able to reduce HIV-related neuropathic pain, which provide a novel

Aromatherapy Massage for Neuropathic Pain and Quality of Life in Diabetic Patients.

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Gok Metin, Zehra; Arikan Donmez, Ayse; Izgu, Nur; Ozdemir, Leyla; Arslan, Ismail Emre

2017-07-01

This study aimed to examine the effects of aromatherapy massage on neuropathic pain severity and quality of life (QoL) in patients suffering from painful diabetic neuropathy. This open-label randomized controlled clinical study was conducted in a university hospital endocrine outpatient clinic in Turkey. The study sample consisted of 46 patients, randomly allocated to an intervention group (n = 21) and a control group (n = 25). The intervention group received aromatherapy massage three times per week for a period of 4 weeks. The control group received only routine care. Data were collected from patients using the Douleur Neuropathique questionnaire, the visual analog scale, and the Neuropathic Pain Impact on Quality of Life questionnaire. Neuropathic pain scores significantly decreased in the intervention group compared with the control group in the fourth week of the study. Similarly, QoL scores significantly improved in the intervention group in the fourth week of the study. Aromatherapy massage is a simple and effective nonpharmacological nursing intervention that can be used to manage neuropathic pain and improve QoL in patients with painful neuropathy. Aromatherapy massage is a well-tolerated, feasible, and safe nonpharmacological method that can be readily integrated into clinical settings by nursing staff. The essential oils rosemary, geranium, lavender, eucalyptus, and chamomile can be safely used by nurses in the clinical setting, if applicable. However, training and experience of nurses in aromatherapy massage is critical to achieving positive results. © 2017 Sigma Theta Tau International.

Radiographic Abnormalities in the Feet of Diabetic Patients with Neuropathy and Foot Ulceration.

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Viswanathan, Vijay; Kumpatla, Satyavani; Rao, V Narayan

2014-11-01

People with diabetic neuropathy are frequently prone to several bone and joint abnormalities. Simple radiographic findings have been proven to be quite useful in the detection of such abnormalities, which might be helpful not only for early diagnosis but also in following the course of diabetes through stages of reconstruction of the ulcerated foot.The present study was designed to identify the common foot abnormalities in south Indian diabetic subjects with and without neuropathy using radiographic imaging. About 150 (M:F 94:56) subjects with type 2 diabetes were categorised into three groups: Group I (50 diabetic patients), Group II (50 patients with neuropathy), and Group III (50 diabetic patients with both neuropathy and foot ulceration). Demographic details, duration of diabetes and HbA1c values were recorded. Vibration perception threshold was measured for assessment of neuropathy. Bone and joint abnormalities in the feet and legs of the study subjects were identified using standardised dorsi-plantar and lateral weight-bearing radiographs. Radiographic findings of the study subjects revealed that those with both neuropathy and foot ulceration and a longer duration of diabetes had more number of bone and joint abnormalities. Subjects with neuropathy alone also showed presence of several abnormalities, including periosteal reaction, osteopenia, and Charcot changes. The present findings highlight the impact of neuropathy and duration of diabetes on the development of foot abnormalities in subjects with diabetes. Using radiographic imaging can help in early identification of abnormalities and better management of the diabetic foot.

Suboccipital neuropathy after bone conduction device placement

NARCIS (Netherlands)

Faber, H.T.; Ru, J.A. de

2013-01-01

OBJECTIVE: To describe the clinical characteristics of a 70-year-old female with occipital neuropathy following bone conduction device surgery. DESCRIPTION: A 65-year-old woman underwent bone conduction device placement surgery on the left temporal bone. Postoperatively she progressively developed

Viral vector mediated continuous expression of interleukin-10 in DRG alleviates pain in type 1 diabetic animals.

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Thakur, Vikram; Gonzalez, Mayra; Pennington, Kristen; Chattopadhyay, Munmun

2016-04-01

Painful diabetic neuropathy is a common and difficult to treat complication of diabetes. A growing body of evidence implicates the role of inflammatory mediators in the damage to the peripheral axons and in the pathogenesis of neuropathic pain. Increased expression of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the peripheral nervous system suggests the possibility of change in pain perception in diabetes. In this study we investigated that continuous delivery of IL10 in the nerve fibers achieved by HSV vector mediated transduction of dorsal root ganglion (DRG) in animals with Type 1 diabetes, blocks the nociceptive and stress responses in the DRG neurons by reducing IL1β expression along with inhibition of phosphorylation of p38 MAPK (mitogen-activated protein kinase) and protein kinase C (PKC). The continuous expression of IL10 also alters Toll like receptor (TLR)-4 expression in the DRG with increased expression of heat shock protein (HSP)-70 in conjunction with the reduction of pain. Taken together, this study suggests that macrophage activation in the peripheral nervous system may be involved in the pathogenesis of pain in Type 1 diabetes and therapeutic benefits of HSV mediated local expression of IL10 in the DRG with the reduction of a number of proinflammatory cytokines, subsequently inhibits the development of painful neuropathy along with a decrease in stress associated markers in the DRG. This basic and preclinical study provides an important evidence for a novel treatment strategy that could lead to a clinical trial for what is currently a treatment resistant complication of diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Herbal Medicine AC591 Prevents Oxaliplatin-Induced Peripheral Neuropathy in Animal Model and Cancer Patients

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Xiaolan Cheng

2017-06-01

Full Text Available Oxaliplatin is clinically compelling because of severe peripheral neuropathy. The side effect can result in dosage reductions or even cessation of chemotherapy, and no effective treatments are available. AC591 is a standardized extract of Huangqi Guizhi Wuwu decoction, an herbal formula recorded in “Synopsis of the Golden Chamber” for improving limb numbness and pain. In this study, we investigated whether AC591 could protect against oxaliplatin-induced peripheral neuropathy. To clarify it, a rat model of oxaliplatin-induced peripheral neuropathy was established, and neuroprotective effect of AC591 was studied. Our results showed that pretreatment with AC591 reduced oxaliplatin-induced cold hyperalgesia, mechanical allodynia as well as morphological damage of dorsal root ganglion. Microarray analysis indicated the neuroprotective action of AC591 depended on the modulation of multiple molecular targets and pathways involved in the downregulation of inflammation and immune response. Moreover, AC591 enhanced the antitumor activity of oxaliplatin to some extent in Balb/c mice bearing CT-26 carcinoma cells. The efficacy of AC591 is also investigated in 72 colorectal cancer patients. After four cycles of treatment, the percentage of grades 1–2 neurotoxicity in AC591-treated group (n = 36 was 25%, whereas in the control group the incidence was 55.55% (P < 0.01 (n = 36. No significant differences in the tumor response rate between the two groups were found. These evidences suggested that AC591 can prevent oxaliplatin-induced neuropathy without reducing its antitumor activity, and may be a promising adjuvant to alleviate sensory symptoms in clinical practice.

Chronic obstructive pulmonary disease and peripheral neuropathy

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Gupta Prem

2006-01-01

Full Text Available Chronic obstructive pulmonary disease (COPD is the fourth leading cause of death world-wide and a further increase in the prevalence as well as mortality of the disease is predicted for coming decades. There is now an increased appreciation for the need to build awareness regarding COPD and to help the thousands of people who suffer from this disease and die prematurely from COPD or its associated complication(s. Peripheral neuropathy in COPD has received scanty attention despite the fact that very often clinicians come across COPD patients having clinical features suggestive of peripheral neuropathy. Electrophysiological tests like nerve conduction studies are required to distinguish between axonal and demyelinating type of disorder that cannot be analyzed by clinical examination alone. However, various studies addressing peripheral neuropathy in COPD carried out so far have included patients with COPD having markedly varying baseline characteristics like severe hypoxemia, elderly patients, those with long duration of illness, etc. that are not uniform across the studies and make it difficult to interpret the results to a consistent conclusion. Almost one-third of COPD patients have clinical evidence of peripheral neuropathy and two-thirds have electrophysiological abnormalities. Some patients with no clinical indication of peripheral neuropathy do have electrophysiological deficit suggestive of peripheral neuropathy. The more frequent presentation consists of a polyneuropathy that is subclinical or with predominantly sensory signs, and the neurophysiological and pathological features of predominantly axonal neuropathy. The presumed etiopathogenic factors are multiple: chronic hypoxia, tobacco smoke, alcoholism, malnutrition and adverse effects of certain drugs.

Chemotherapy-Induced Neuropathy in Cancer Survivors.

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Miaskowski, Christine; Mastick, Judy; Paul, Steven M; Topp, Kimberly; Smoot, Betty; Abrams, Gary; Chen, Lee-May; Kober, Kord M; Conley, Yvette P; Chesney, Margaret; Bolla, Kay; Mausisa, Grace; Mazor, Melissa; Wong, Melisa; Schumacher, Mark; Levine, Jon D

2017-08-01

Evidence suggests that chemotherapy-induced neuropathy (CIN) is a significant problem for cancer survivors. However, a detailed phenotypic characterization of CIN in cancer survivors is not available. To evaluate between-group differences in demographic and clinical characteristics, as well as in measures of sensation, function, and postural control, in a sample of cancer survivors who received a platinum and/or a taxane-based CTX regimen and did (n = 426) and did not (n = 197) develop CIN. Survivors completed self-report questionnaires and underwent objective testing (i.e., light touch, pain sensation, cold sensation, vibration, muscle strength, grip strength, Purdue Pegboard test, Timed Get Up and Go test, Fullerton Advanced Balance test). Parametric and nonparametric statistics were used to compare between-group differences in study outcomes. Of the 426 survivors with CIN, 4.9% had CIN only in their upper extremities, 27.0% only in their lower extremities, and 68.1% in both their upper and lower extremities. Demographic and clinical characteristics associated with CIN included the following: older age, lower annual income, higher body mass index, a higher level of comorbidity, being born prematurely, receipt of a higher cumulative dose of chemotherapy, and a poorer functional status. Survivors with CIN had worse outcomes for all of the following objective measures: light touch, pain, temperature, vibration, upper and lower extremity function, and balance. This study is the first to provide a detailed phenotypic characterization of CIN in cancer survivors who received a platinum and/or a taxane compound. These data can serve as a benchmark for future studies of CIN in cancer survivors. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Pain leads the way: the development of evidence-based medicine for pain relief.

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Wiffen, Phil; Moore, Andrew

2016-07-01

This paper describes the development of evidence based methods in pain medicine since the 1980s at the Pain Research Department of the Nuffield Department of Clinical Neurosciences, Oxford University. Pain medicine can be said to have led the way in terms of developing registers of randomized controlled trials (RCTs) and in developing appropriate methodology for assessing clinical trials and developing metanalytical techniques. This paper tells the story of that development which occurred in conjunction with the development of the Cochrane Collaboration. Pain has a larger body of evidence than many medical specialties with more than 30,000 RCTs and over 2,500 published systematic reviews. Our work continues to raise methodological challenges and a number of key ones are described: Size: We have added to the existing literature to show that small studies overestimate treatment effects. We consider studies with less than 50 participants per treatment group to be at high risk of bias. Mean pain scores: We have shown these to be unhelpful and misleading. We illustrate that response to analgesics is a U-shaped curve with a larger proportion of participants having either a poor response or a good response. Imputation: We discuss the problems of current methods. Tiers of evidence: We propose a way to assess evidence for pain studies. Duplicate publication of data can lead to inflated benefits in systematic reviews. In addition we touch on fraud, pharmaceutical company funding. The final sections cover developments in several areas of pain medicine, and suggest some developments going forward.

Capsaicin 8% Patch for Central and Peripheral Neuropathic Pain of Persons with Incomplete Spinal Cord Injury: Two Case Reports.

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Trbovich, Michelle; Yang, Huiqing

2015-08-01

Neuropathic pain after spinal cord injury is common and often refractory to standard treatments. The capsaicin 8% patch is a Food and Drug Administration-approved treatment of neuropathic pain in postherpetic neuralgia and has demonstrated significant efficacy in human immunodeficiency virus-autonomic neuropathy. The patch defunctionalizes transient receptor potential vanilloid 1 receptors, impairing cutaneous nociceptors for a prolonged period (i.e., 8-12 wks) with no systemic side effects. A retrospective review was conducted on the effects of the patch in two patients with spinal cord injury and neuropathic pain refractory to standard treatments. Two weeks after application, both patients reported complete pain relief. Average onset of relief of 4 days and average duration of relief of 197 days, requiring only one to four applications per year, paralleled findings reported in postherpetic neuralgia and human immunodeficiency virus-autonomic neuropathy trials. Upregulation of capsaicin-sensitive transient receptor potential vanilloid 1 receptors after spinal cord injury has been reported. The capsaicin 8% patch is a promising therapeutic agent for neuropathic pain in spinal cord injury.

Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy.

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Jia-Ying Sung

Full Text Available This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr. Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05, shortened strength-duration time constant (P<0.01, increased superexcitability (P<0.01, decreased subexcitability (P<0.05, decreased accommodation to depolarizing current (P<0.01, and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1-8 and G2+3 (TNSr 9-24 groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01 in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches.

Unipedal stance testing in the assessment of peripheral neuropathy.

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Hurvitz, E A; Richardson, J K; Werner, R A

2001-02-01

To define further the relation between unipedal stance testing and peripheral neuropathy. Prospective cohort. Electroneuromyography laboratory of a Veterans Affairs medical center and a university hospital. Ninety-two patients referred for lower extremity electrodiagnostic studies. A standardized history and physical examination designed to detect peripheral neuropathy, 3 trials of unipedal stance, and electrodiagnostic studies. Peripheral neuropathy was identified by electrodiagnostic testing in 32%. These subjects had a significantly shorter (p unipedal stance time (15.7s, longest of 3 trials) than the patients without peripheral neuropathy (37.1s). Abnormal unipedal stance time (unipedal stance time had a negative predictive value of 90%. Abnormal unipedal stance time was associated with an increased risk of having peripheral neuropathy on univariate analysis (odds ratio = 8.8, 95% confidence interval = 2.5--31), and was the only significant predictor of peripheral neuropathy in the regression model. Aspects of the neurologic examination did not add to the regression model compared with abnormal unipedal stance time. Unipedal stance testing is useful in the clinical setting both to identify and to exclude the presence of peripheral neuropathy.

Gabapentin for chronic neuropathic pain and fibromyalgia in adults.

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Moore, R Andrew; Wiffen, Philip J; Derry, Sheena; Toelle, Thomas; Rice, Andrew S C

2014-04-27

to treat to benefit (NNT), concentrating on at least 50% pain intensity reduction, and Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT) definitions of at least moderate and substantial benefit. For harm we calculated number needed to treat for harm (NNH) for adverse effects and withdrawal. Meta-analysis was undertaken using a fixed-effect model. We emphasised differences between conditions now defined as neuropathic pain, and other conditions like masticatory pain, complex regional painsyndrome type 1 (CRPS-1), and fibromyalgia. Seven new studies with 1919 participants were added. Another report (147 participants) provided results for a study already included, but which previously had no usable data. A further report (170 participants) used an experimental formulation of intrathecal gabapentin. Thirty-seven studies (5633 participants) studied oral gabapentin at daily doses of 1200 mg or more in 12 chronic pain conditions; 84% of participants were in studies of postherpetic neuralgia, painful diabetic neuropathy or mixed neuropathic pain. There was no first tier evidence.Second tier evidence for the outcome of at least 50% pain intensity reduction, considered valuable by patients with chronic pain, showed that gabapentin was significantly better than placebo in postherpetic neuralgia (34% gabapentin versus 21% placebo; NNT 8.0, 95% CI 6.0 to 12) and painful diabetic neuropathy (38% versus 21%, NNT 5.9, 95% CI 4.6 to 8.3). There was insufficient information in other pain conditions to reach any reliable conclusion. There was no obvious difference between standard gabapentin formulations and recently-introduced extended-release or gastro-retentive formulations, or between different doses of gabapentin.Adverse events occurred significantly more often with gabapentin. Persons taking gabapentin could expect to have at least one adverse event (62%), withdraw because of an adverse event (11%), suffer dizziness (19%), somnolence (14

Ethambutol/Linezolid Toxic Optic Neuropathy.

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Libershteyn, Yevgeniya

2016-02-01

To report a rare toxic optic neuropathy after long-term use of two medications: ethambutol and linezolid. A 65-year-old man presented to the Miami Veterans Affairs Medical Center in December 2014 for evaluation of progressive vision decrease in both eyes. The patient presented with best-corrected visual acuities of 20/400 in the right eye and counting fingers at 5 feet in the left eye. Color vision was significantly reduced in both eyes. Visual fields revealed a cecocentral defect in both eyes. His fundus and optic nerve examination was unremarkable. Because vision continued to decline after discontinuation of ethambutol, linezolid was also discontinued, after which vision, color vision, and visual fields improved. Because of these findings, the final diagnosis was toxic optic neuropathy. Final visual outcome was 20/30 in the right eye and 20/40 in the left eye. Drug-associated toxic optic neuropathy is a rare but vision-threatening condition. Diagnosis is made based on an extensive case history and careful clinical examination. The examination findings include varying decrease in vision, normal pupils and extraocular muscles, and unremarkable fundoscopy, with the possibility of swollen optic discs in the acute stage of the optic neuropathy. Other important findings descriptive of toxic optic neuropathy include decreased color vision and cecocentral visual field defects. This case illustrates the importance of knowledge of all medications and/or substances a patient consumes that may cause a toxic reaction and discontinuing them immediately if the visual functions are worsening or not improving.

Measuring Vincristine-Induced Peripheral Neuropathy in Children with Acute Lymphoblastic Leukemia

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Lavoie Smith, Ellen M.; Li, Lang; Hutchinson, Raymond J.; Ho, Richard; Burnette, W. Bryan; Wells, Elizabeth; Bridges, Celia; Renbarger, Jamie

2014-01-01

Background Vincristine-induced peripheral neuropathy (VIPN) is difficult to quantify in children. Objective The study objective was to examine the reliability, validity, and clinical feasibility of several VIPN measures for use in children with acute lymphoblastic leukemia. Interventions/Methods Children (N = 65) aged 1–18 years receiving vincristine at four academic centers participated in the study. Baseline and pre-vincristine VIPN assessments were obtained using the Total Neuropathy Score-Pediatric Vincristine (TNS-PV), the National Cancer Institute Common Terminology Criteria for Adverse Events, the Balis grading scale, and the FACES pain scale. TNS-PV scores (n = 806) were obtained over 15 weeks. Blood was obtained at several time-points to quantify pharmacokinetic parameters. Results Cronbach’s alpha for a reduced TNS-PV scale was 0.84. TNS-PV scores correlated with cumulative vincristine dosage (r = 0.53, p = 0.01), pharmacokinetic parameters (r = 0.41, p = 0.05), and grading scale scores (r = 0.46 – 0.52; p = 0.01). FACES scores correlated with the TNS-PV neuropathic pain item (r = 0.48; p = 0.01), and were attainable in all ages. A 2-item V-Rex score (vibration and reflex items) was the most responsive to change (es 0.65, p < 0.001). TNS-PV scores were attainable in 95% of children ≥ 6 years. Conclusions The TNS-PV is reliable and valid for measuring VIPN. It is sensitive to change over time (15 weeks) and feasible for use in children ≥ 6 years of age. Implications for Practice The TNS-PV may be a useful tool for assessing vincristine toxicity in children with acute lymphoblastic leukemia. PMID:23842524

Benfotiamine relieves inflammatory and neuropathic pain in rats.

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Sánchez-Ramírez, Gabriela M; Caram-Salas, Nadia L; Rocha-González, Héctor I; Vidal-Cantú, Guadalupe C; Medina-Santillán, Roberto; Reyes-García, Gerardo; Granados-Soto, Vinicio

2006-01-13

Benfotiamine has shown therapeutic efficacy in the treatment of painful diabetic neuropathy in human beings. However, so far there is no evidence about the efficacy of this drug in preclinical models of pain. The purpose of this study was to assess the possible antinociceptive and antiallodynic effect of benfotiamine in inflammatory and neuropathic pain models in the rat. Inflammatory pain was induced by injection of formalin in non-diabetic and diabetic (2 weeks) rats. Reduction of flinching behavior was considered as antinociception. Neuropathic pain was induced by either ligation of left L5/L6 spinal nerves or administration of streptozotocin (50 mg/kg, i.p.) in Wistar rats. Benfotiamine significantly reduced inflammatory (10-300 mg/kg) and neuropathic (75-300 mg/kg) nociception in non-diabetic and diabetic rats. Results indicate that oral administration of benfotiamine is able to reduce tactile allodynia from different origin in the rat and they suggest the use of this drug to reduce inflammatory and neuropathic pain in humans.

Improving pain assessment and managment in stroke patients.

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Nesbitt, Julian; Moxham, Sian; Ramadurai, Gopinath; Williams, Lucy

2015-01-01

Stroke patients can experience a variety of pain. Many stroke patients have co-morbidities such as osteoporosis, arthritis or diabetes causing diabetic neuropathy. As well as pain from other long term conditions, stroke patients can experience central post-stroke pain, headaches, and musculoskeletal issues such as hypertonia, contractures, spasticity, and subluxations. These stroke patients can also have communication difficulties in the form of expressive dysphasia and/or global aphasia. Communication difficulties can result in these patients not expressing their pain and therefore not having it assessed, leading to inadequate pain relief that could impact their rehabilitation and recovery. By implementing an observational measurement of pain such as the Abbey pain scale, patients with communication difficulties can have their pain assessed and recorded. Initially 30% of patients on the acute stroke ward did not have their pain assessed and adequately recorded and 15% of patients had inadequate pain relief. The patient was assessed if they were in pain and therefore not receiving adequate pain relief by measuring their pain on the Abbey pain scale. After introducing the Abbey pain scale and creating a nurse advocate, an improvement was shown such that only 5% of patients did not have their pain recorded and all had adequate pain relief.

Peripheral neuropathy in HIV-infected and uninfected patients in Rakai, Uganda.

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Saylor, Deanna; Nakigozi, Gertrude; Nakasujja, Noeline; Robertson, Kevin; Gray, Ronald H; Wawer, Maria J; Sacktor, Ned

2017-08-01

To determine the prevalence, risk factors, and functional impairment associated with peripheral neuropathy in a prospective cohort of adults in rural Uganda. Eight hundred participants (400 HIV- and 400 antiretroviral-naive HIV+) in the Rakai Community Cohort Study underwent detailed neurologic evaluations including assessment of neuropathy symptoms, functional measures (Patient Assessment of Own Functioning Inventory and Karnofsky Performance Status scores), and neurologic evaluation by a trained medical officer. Neuropathy was defined as ≥1 subjective symptom and ≥1 sign of neuropathy on examination. Neuropathy risk factors were assessed using log binomial regression. Fifty-three percent of participants were men, with a mean (SD) age of 35 (8) years. Neuropathy was present in 13% of the cohort and was more common in HIV+ vs HIV- participants (19% vs 7%, p neuropathy in the overall cohort. Only older age was associated with neuropathy risk in the HIV+ (RR 1.03, 95% CI 1.01-1.05) and HIV- (RR 1.06, 95% CI 1.02-1.10) cohorts. Neuropathy was associated with impaired functional status on multiple measures across all participant groups. Peripheral neuropathy is relatively common and associated with impaired functional status among adults in rural Uganda. Older age, female sex, and HIV infection significantly increase the risk of neuropathy. Neuropathy may be an underrecognized but important condition in rural Uganda and warrants further study. © 2017 American Academy of Neurology.

Diagnostic capability of retinal thickness measures in diabetic peripheral neuropathy

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Sangeetha Srinivasan

2017-10-01

Conclusions: The GCC FLV can differentiate individuals with diabetic neuropathy from healthy controls, while the inferior RNFL thickness is able to differentiate those with greater degrees of neuropathy from those with mild or no neuropathy, both with an acceptable level of accuracy. Optical coherence tomography represents a non-invasive technology that aids in detection of retinal structural changes in patients with established diabetic neuropathy. Further refinement of the technique and the analytical approaches may be required to identify patients with minimal neuropathy.

Four cases of radiation retinopathy and optic neuropathy

International Nuclear Information System (INIS)

Konari, Kenji; Suzuki, Jun-ichi; Nakagawa, Takashi

1996-01-01

We observed retinopathy and optic neuropathy in 4 patients after radiation for malignancies in the paranasal sinus or the brain. The dosis ranged from 56 Gy for 14 days to 64 Gy for 32 days. The interval between the termination of radiation and onset of fundus lesions ranged from 1 to 36 months, average 16.6 months. The retinopathy appeared as retinal hemorrhage, soft exudates and vitreous hemorrhage. Neovascular glaucoma developed in one eye. The optic neuropathy appeared as pallor of optic disc, disc edema or optic papillitis. Histological studies of one eye with retinopathy showed thickening of retinal capillary walls and rubeosis iridis with angle closure. (author)

Four cases of radiation retinopathy and optic neuropathy

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Konari, Kenji; Suzuki, Jun-ichi; Nakagawa, Takashi [Sapporo Medical Coll. (Japan)

1996-03-01

We observed retinopathy and optic neuropathy in 4 patients after radiation for malignancies in the paranasal sinus or the brain. The dosis ranged from 56 Gy for 14 days to 64 Gy for 32 days. The interval between the termination of radiation and onset of fundus lesions ranged from 1 to 36 months, average 16.6 months. The retinopathy appeared as retinal hemorrhage, soft exudates and vitreous hemorrhage. Neovascular glaucoma developed in one eye. The optic neuropathy appeared as pallor of optic disc, disc edema or optic papillitis. Histological studies of one eye with retinopathy showed thickening of retinal capillary walls and rubeosis iridis with angle closure. (author).

Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy

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Kramer, Rita; Bielawski, Jacek; Kistner-Griffin, Emily; Othman, Alaa; Alecu, Irina; Ernst, Daniela; Kornhauser, Drew; Hornemann, Thorsten; Spassieva, Stefka

2015-01-01

Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses l-alanine instead of l-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 µM) and cisplatin (250 nM, 1 µM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P neuropathy (P peripheral neuropathy.—Kramer, R., Bielawski, J., Kistner-Griffin, E., Othman, A., Alecu, I., Ernst, D., Kornhauser, D., Hornemann, T., Spassieva, S. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy. PMID:26198449

Effect of optically modified polyethylene terephthalate fiber socks on chronic foot pain

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Gordon Ian L

2009-04-01

Full Text Available Abstract Background Increasing experimental and clinical evidence suggests that illumination of the skin with relatively low intensity light may lead to therapeutic results such as reduced pain or improved wound healing. The goal of this study was to evaluate prospectively whether socks made from polyethylene terephthalate (PET incorporating optically active particles (Celliant™ ameliorates chronic foot pain resulting from diabetic neuropathy or other disorders. Such optically modified fiber is thought to modify the illumination of the skin in the visible and infrared portions of the spectrum, and consequently reduce pain. Methods A double-blind, randomized trial with 55 subjects (38 men, 17 women enrolled (average age 59.7 ± 11.9 years, 26 with diabetic neuropathy and 29 with other pain etiologies. Subjects twice completed the Visual Analogue Scale (VAS, Brief Pain Inventory (BPI, McGill Pain Questionnaire (MPQ, and SF-36 a week apart (W1+2 before receiving either control or Celliant™ socks. The same questionnaires were answered again one and two weeks (W3+4 later. The questionnaires provided nine scores for analyzing pain reduction: one VAS score, two BPI scores, five MPQ scores, and the bodily pain score on the SF-36. Mean W1+2 and W3+4 scores were compared to measure pain reduction. Results More pain reduction was reported by Celliant™ subjects for 8 of the 9 pain questions employed, with a significant (p = 0.043 difference between controls and Celliant™ for McGill question III. In neuropathic subjects, Celliant™ caused more pain reduction in 6 of the 9 questions, but not significantly. In non-neuropathic subjects 8 of 9 questions showed more pain reduction with the Celliant™ socks. Conclusion Socks with optically modified PET (Celliant™ appear to have a beneficial impact on chronic foot pain. The mechanism could be related to the effects seen with illumination of tissues with visible and infrared light. Trial Registration

MR Angiography for the Evaluation of Non-Systemic Vasculitic Neuropathy

International Nuclear Information System (INIS)

Sanada, M.; Terada, M.; Yasuda, H.; Suzuki, E.; Kashiwagi, A.

2003-01-01

Peripheral neuropathy due to vasculitis without any complications of vasculitis in other organs was first reported in 1987. This condition was termed non-systemic vasculitic neuropathy (NSVN). Although vasculitis is believed to develop in small arteries and arterioles in this disease, the level of vascular involvement has not been fully established. We present a case of NSVN followed up by MR angiography, which was thought to be useful to assess the level as well as the state of vascular lesions in this condition

MR Angiography for the Evaluation of Non-Systemic Vasculitic Neuropathy

Energy Technology Data Exchange (ETDEWEB)

Sanada, M.; Terada, M.; Yasuda, H. [Shiga Univ. of Medical Science (Japan). Div. of Neurology; Suzuki, E.; Kashiwagi, A. [Shiga Univ. of Medical Science (Japan). Div. of Endocrinology and Metabolism

2003-05-01

Peripheral neuropathy due to vasculitis without any complications of vasculitis in other organs was first reported in 1987. This condition was termed non-systemic vasculitic neuropathy (NSVN). Although vasculitis is believed to develop in small arteries and arterioles in this disease, the level of vascular involvement has not been fully established. We present a case of NSVN followed up by MR angiography, which was thought to be useful to assess the level as well as the state of vascular lesions in this condition.

Neuropathies optiques héréditaires

DEFF Research Database (Denmark)

Milea, D; Verny, C

2012-01-01

Hereditary optic neuropathies are a group of heterogeneous conditions affecting both optic nerves, with an autosomal dominant, autosomal recessive, X-related or mitochondrial transmission. The two most common non-syndromic hereditary optic neuropathies (Leber's hereditary optic neuropathy...... and autosomal dominant optic atrophy) are very different in their clinical presentation and their genetic transmission, leading however to a common, non-specific optic nerve atrophy. Beyond the optic atrophy-related visual loss, which is the clinical hallmark of this group of diseases, other associated...

Hereditary motor and sensory neuropathy with proximal predominance (HMSN-P).

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Campellone, Joseph V

2013-06-01

Hereditary motor and sensory neuropathy with proximal predominance (HMSN-P) is a rare disorder inherited in an autosomal dominant fashion. Patients present with slowly progressive proximal-predominant weakness, painful muscle cramps, fasciculations, large-fiber sensory loss, and areflexia. Electrodiagnostic (EDX) studies typically reveal abnormalities consistent with a sensorimotor neuronopathy. A patient with HMSN-P underwent EDX studies, revealing ongoing and chronic neurogenic denervation, motor unit instability, and neuromyotonic discharges, further defining the spectrum of EDX findings in HMSN-P. The clinical, pathological, and genetic features are also reviewed. The appearance of HMSN-P in the United States and elsewhere calls for clinicians in nonendemic regions to be familiar with this rare disorder, which has typically been geographically confined.

Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis

DEFF Research Database (Denmark)

Brock, Christina; Søfteland, Eirik; Gunterberg, Veronica

2013-01-01

electrostimulations, and brain activity was modeled by brain electrical source analysis. Self-reported gastrointestinal symptoms (per the Patient Assessment of Upper Gastrointestinal Disorder Severity Symptom Index) and quality of life (per short-form health survey with 36 questions) were collected...... symptoms.RESEARCH DESIGN AND METHODSFifteen healthy volunteers and 15 diabetic patients (12 with type 1 diabetes) with severe gastrointestinal symptoms and clinical suspicion of autonomic neuropathy were included. Psychophysics and evoked brain potentials were assessed after painful rectosigmoid...... component in evoked potentials (P = 0.01). There was a caudoanterior shift of the insular brain source (P = 0.01) and an anterior shift of the cingulate generator (P = 0.01). Insular source location was associated with HRV assessments (all P

Testing for autonomic neuropathy

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Hilsted, J

1984-01-01

Autonomic neuropathy is a common complication in long-term diabetes, about 30% of the patients showing measurable signs of autonomic dysfunction after 10 years duration of disease. The diagnosis is often difficult to establish because clinical symptoms generally occur late in the course of the di......Autonomic neuropathy is a common complication in long-term diabetes, about 30% of the patients showing measurable signs of autonomic dysfunction after 10 years duration of disease. The diagnosis is often difficult to establish because clinical symptoms generally occur late in the course...

Talectomy for Equinovarus Deformity in Family Members with Hereditary Motor and Sensory Neuropathy Type I

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Hristo Georgiev

2014-01-01

Full Text Available The treatment of severe rigid neurogenic clubfoot deformities still remains a challenging problem in modern paediatric orthopaedics. In those cases, in spite of being a palliative procedure, talectomy has been advocated for the correction of the deformity thus providing a stable plantigrade foot which allows pain-free walking with standard footwear. Herein, we present the results after talectomy in two patients (brother and sister affected by a hereditary motor and sensory neuropathy type I, with rigid severe pes equinovarus deformities.

Immune mediated neuropathy following checkpoint immunotherapy.

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Gu, Yufan; Menzies, Alexander M; Long, Georgina V; Fernando, S L; Herkes, G

2017-11-01

Checkpoint immunotherapy has revolutionised cancer therapy and is now standard treatment for many malignancies including metastatic melanoma. Acute inflammatory neuropathies, often labelled as Guillain-Barre syndrome, are an uncommon but potentially severe complication of checkpoint immunotherapy with individual cases described but never characterised as a group. We describe a case of acute sensorimotor and autonomic neuropathy following a single dose of combination ipilimumab and nivolumab for metastatic melanoma. A literature search was performed, identifying 14 other cases of acute neuropathy following checkpoint immunotherapy, with the clinical, electrophysiological and laboratory features summarised. Most cases described an acute sensorimotor neuropathy (92%) with hyporeflexia (92%) that could occur from induction up till many weeks after the final dose of therapy. In contrast to Guillain-Barre syndrome, the cerebrospinal fluid (CSF) analysis often shows a lymphocytic picture (50%) and the electrophysiology showed an axonal pattern (55%). Treatment was variable and often in combination. 11 cases received steroid therapy with only 1 death within this group, whereas of the 4 patients who did not receive steroid therapy there were 3 deaths. In conclusion checkpoint immunotherapy - induced acute neuropathies are distinct from and progress differently to Guillain-Barre syndrome. As with other immunotherapy related adverse events corticosteroid therapy should be initiated in addition to usual therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immune-mediated neuropathies our experience over 3 years

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Sadanandavalli Retnaswami Chandra

2018-01-01

Full Text Available Introduction: Immune-mediated peripheral neuropathy is the term applied to a spectrum of peripheral nerve disorders where immune dysregulation plays a role. Therefore, they are treatable. We analyzed the cases seen in the past 3 years by us and evaluated the clinical, laboratory, and outcome parameters in these patients. Patients and Methods: Consecutive patients seen by the authors and diagnosed as immune-mediated neuropathy were analyzed for etiology, pathology, and outcome assessed. Results: A total of sixty patients, 31 acute and 29 chronic neuropathies, were identified. Their subtypes treatment and outcome assessed. Males were significantly more in both acute and chronic cases. Miller Fisher 4, AMAN 1, paraplegic type 1, motor dominant type 19, Sensory-motor 1, MADSAM 3, Bifacial 2. Nonsystemic vasculitis was seen in 16 out of 29 chronic neuropathy and HIV, POEMS, and diabetes mellitus one each. Discussion: There is a spectrum of immune-mediated neuropathy which varies in clinical course, response to treatment, etc., Small percentage of uncommon cases are seen. In this group, mortality was nil and morbidity was minimal. Conclusion: Immune-mediated neuropathies are treatable and hence should be diagnosed early for good quality outcome.

Determination of Efficacy of Reflexology in Managing Patients with Diabetic Neuropathy: A Randomized Controlled Clinical Trial

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Krishna Dalal

2014-01-01

Full Text Available Background. The restricted usage of existing pharmacological methods which do not seem to provide the treatment of diabetic neuropathy may lead to exploring the efficacy of a complementary therapy. In this context, this paper was devoted to evaluate the efficacy of foot reflexology. This health science works on the hypothesis that the dysfunctional states of body parts could be identified by observing certain skin features and be rectified by stimulating certain specific areas mapped on feet. Method. Subjects (N=58 with diagnosed diabetic neuropathy were randomly distributed into reflexology and control groups in which both group patients were treated with ongoing pharmacological drugs. Reflexology group patients were additionally treated holistically with the hypothesis that this therapy would bring homeostasis among body organ functions. This was a caregiver-based study with a follow-up period of 6 months. The outcome measures were pain reduction, glycemic control, nerve conductivity, and thermal and vibration sensitivities. The skin features leading to the detection of the abnormal functional states of body parts were also recorded and analyzed. Results. Reflexology group showed more improvements in all outcome measures than those of control subjects with statistical significance. Conclusion. This study exhibited the efficient utility of reflexology therapy integrated with conventional medicines in managing diabetic neuropathy.

Determination of Efficacy of Reflexology in Managing Patients with Diabetic Neuropathy: A Randomized Controlled Clinical Trial

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Dalal, Krishna; Maran, V. Bharathi; Pandey, Ravindra M.; Tripathi, Manjari

2014-01-01

Background. The restricted usage of existing pharmacological methods which do not seem to provide the treatment of diabetic neuropathy may lead to exploring the efficacy of a complementary therapy. In this context, this paper was devoted to evaluate the efficacy of foot reflexology. This health science works on the hypothesis that the dysfunctional states of body parts could be identified by observing certain skin features and be rectified by stimulating certain specific areas mapped on feet. Method. Subjects (N = 58) with diagnosed diabetic neuropathy were randomly distributed into reflexology and control groups in which both group patients were treated with ongoing pharmacological drugs. Reflexology group patients were additionally treated holistically with the hypothesis that this therapy would bring homeostasis among body organ functions. This was a caregiver-based study with a follow-up period of 6 months. The outcome measures were pain reduction, glycemic control, nerve conductivity, and thermal and vibration sensitivities. The skin features leading to the detection of the abnormal functional states of body parts were also recorded and analyzed. Results. Reflexology group showed more improvements in all outcome measures than those of control subjects with statistical significance. Conclusion. This study exhibited the efficient utility of reflexology therapy integrated with conventional medicines in managing diabetic neuropathy. PMID:24527055

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy.

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Köşkderelioğlu, Aslı; Ortan, Pınar; Ari, Alpay; Gedizlioğlu, Muhteşem

2016-03-01

To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in

[Review of the recent literature on hereditary neuropathies].

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Birouk, N

2014-12-01

The recent literature included interesting reports on the pathogenic mechanisms of hereditary neuropathies. The axonal traffic and its abnormalities in some forms of Charcot-Marie-Tooth (CMT) disease were particularly reviewed by Bucci et al. Many genes related to CMT disease code for proteins that are involved directly or not in intracellular traffic. KIF1B controls vesicle motility on microtubules. MTMR2, MTMR13 and FIG4 regulate the metabolism of phosphoinositide at the level of endosomes. The HSPs are involved in the proteasomal degradation. GDAP1 and MFN2 regulate the mitochondrial fission and fusion respectively and the mitochondial transport within the axon. Pareyson et al. reported a review on peripheral neuropathies in mitochondrial disorders. They used the term of "mitochondrial CMT" for the forms of CMT with abnormal mitochondrial dynamic or structure. Among the new entities, we can draw the attention to a proximal form of hereditary motor and sensory neuropathy with autosomal dominant inheritance, which is characterized by motor deficit with cramps and fasciculations predominating in proximal muscles. Distal sensory deficit can be present. The gene TFG on chromosome 3 has been recently identified to be responsible for this form. Another rare form of axonal autosomal recessive neuropathy due to HNT1 gene mutation is characterized by the presence of hands myotonia that appears later than neuropathy but constitute an interesting clinical hallmark to orientate the diagnosis of this form. In terms of differential diagnosis, CMT4J due to FIG4 mutation can present with a rapidly progressive and asymmetric weakness that resembles CIDP. Bouhy et al. made an interesting review on the therapeutic trials, animal models and the future therapeutic strategies to be developed in CMT disease. Copyright © 2014. Published by Elsevier Masson SAS.

Penicillamin-induced neuropathy in rheumatoid arthritis

DEFF Research Database (Denmark)

Pedersen, P B; Hogenhaven, H

1990-01-01

A case of penicillamin-induced severe polyradiculopathy in rheumatoid arthritis is presented. The neuropathy was of demyelinating type, purely motor, proximal and clinically fully reversible when the drug ceased. In case of a progressive neuropathy, during penicillamin treatment, this adverse eff...... effect should be born in mind, and discontinuation of the drug considered....

Topical Drugs for Pain Relief

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Anjali Srinivasan

2015-03-01

Full Text Available Topical therapy helps patients with oral and perioral pain problems such as ulcers, burning mouth syndrome, temporomandibular disorders, neuromas, neuropathies and neuralgias. Topical drugs used in the field of dentistry are topical anaesthetics, topical analgesics, topical antibiotics and topical corticosteroids. It provides symptomatic/curative effect. Topical drugs are easy to apply, avoids hepatic first pass metabolism and more sites specific. But it can only be used for medications that require low plasma concentrations to achieve a therapeutic effect.

Hyperbaric oxygen in the treatment of radiation-induced optic neuropathy

International Nuclear Information System (INIS)

Guy, J.; Schatz, N.J.

1986-01-01

Four patients with radiation-induced optic neuropathies were treated with hyperbaric oxygen. They had received radiation therapy for treatment of pituitary tumors, reticulum cell sarcoma, and meningioma. Two presented with amaurosis fugax before the onset of unilateral visual loss and began hyperbaria within 72 hours after development of unilateral optic neuropathy. Both had return of visual function to baseline levels. The others initiated treatment two to six weeks after visual loss occurred in the second eye and had no significant improvement of vision. Treatment consisted of daily administration of 100% oxygen under 2.8 atmospheres of pressure for 14-28 days. There were no medical complications of hyperbaria. While hyperbaric oxygen is effective in the treatment of radiation-induced optic neuropathy, it must be instituted within several days of deterioration in vision for restoration of baseline function

Ultrasound assessment on selected peripheral nerve pathologies. Part I: Entrapment neuropathies of the upper limb – excluding carpal tunnel syndrome

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Berta Kowalska

2012-09-01

Full Text Available Ultrasound (US is one of the methods for imaging entrapment neuropathies, post-trau‑ matic changes to nerves, nerve tumors and postoperative complications to nerves. This type of examination is becoming more and more popular, not only for economic reasons, but also due to its value in making accurate diagnosis. It provides a very precise assess‑ ment of peripheral nerve trunk pathology – both in terms of morphology and localization. During examination there are several options available to the specialist: the making of a dynamic assessment, observation of pain radiation through the application of precise palpation and the comparison of resultant images with the contra lateral limb. Entrap‑ ment neuropathies of the upper limb are discussed in this study, with the omission of median nerve neuropathy at the level of the carpal canal, as extensive literature on this subject exists. The following pathologies are presented: pronator teres muscle syndrome, anterior interosseus nerve neuropathy, ulnar nerve groove syndrome and cubital tun‑ nel syndrome, Guyon’s canal syndrome, radial nerve neuropathy, posterior interosseous nerve neuropathy, Wartenberg’s disease, suprascapular nerve neuropathy and thoracic outlet syndrome. Peripheral nerve examination technique has been presented in previous articles presenting information about peripheral nerve anatomy [Journal of Ultrasonog‑ raphy 2012; 12 (49: 120–163 – Normal and sonographic anatomy of selected peripheral nerves. Part I: Sonohistology and general principles of examination, following the exam‑ ple of the median nerve; Part II: Peripheral nerves of the upper limb; Part III: Peripheral nerves of the lower limb]. In this article potential compression sites of particular nerves are discussed, taking into account pathomechanisms of damage, including predisposing anatomical variants (accessory muscles. The parameters of ultrasound assessment have been established – echogenicity and

Properties of pattern standard deviation in open-angle glaucoma patients with hemi-optic neuropathy and bi-optic neuropathy.

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Heo, Dong Won; Kim, Kyoung Nam; Lee, Min Woo; Lee, Sung Bok; Kim, Chang-Sik

2017-01-01

To evaluate the properties of pattern standard deviation (PSD) according to localization of the glaucomatous optic neuropathy. We enrolled 242 eyes of 242 patients with primary open-angle glaucoma, with a best-corrected visual acuity ≥ 20/25, and no media opacity. Patients were examined via dilated fundus photography, spectral-domain optical coherence tomography, and Humphrey visual field examination, and divided into those with hemi-optic neuropathy (superior or inferior) and bi-optic neuropathy (both superior and inferior). We assessed the relationship between mean deviation (MD) and PSD. Using broken stick regression analysis, the tipping point was identified, i.e., the point at which MD became significantly associated with a paradoxical reversal of PSD. In 91 patients with hemi-optic neuropathy, PSD showed a strong correlation with MD (r = -0.973, β = -0.965, p < 0.001). The difference between MD and PSD ("-MD-PSD") was constant (mean, -0.32 dB; 95% confidence interval, -2.48~1.84 dB) regardless of visual field defect severity. However, in 151 patients with bi-optic neuropathy, a negative correlation was evident between "-MD-PSD" and MD (r2 = 0.907, p < 0.001). Overall, the MD tipping point was -14.0 dB, which was close to approximately 50% damage of the entire visual field (p < 0.001). Although a false decrease of PSD usually begins at approximately 50% visual field damage, in patients with hemi-optic neuropathy, the PSD shows no paradoxical decrease and shows a linear correlation with MD.

Genes for hereditary sensory and autonomic neuropathies: a genotype–phenotype correlation

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Rotthier, Annelies; Baets, Jonathan; Vriendt, Els De; Jacobs, An; Auer-Grumbach, Michaela; Lévy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andrés; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter

2009-01-01

Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven genes: two genes for autosomal dominant (SPTLC1 and RAB7) and five genes for autosomal recessive forms of HSAN (WNK1/HSN2, NTRK1, NGFB, CCT5 and IKBKAP). We performed a systematic mutation screening of the coding sequences of six of these genes on a cohort of 100 familial and isolated patients diagnosed with HSAN. In addition, we screened the functional candidate gene NGFR (p75/NTR) encoding the nerve growth factor receptor. We identified disease-causing mutations in SPTLC1, RAB7, WNK1/HSN2 and NTRK1 in 19 patients, of which three mutations have not previously been reported. The phenotypes associated with mutations in NTRK1 and WNK1/HSN2 typically consisted of congenital insensitivity to pain and anhidrosis, and early-onset ulcero-mutilating sensory neuropathy, respectively. RAB7 mutations were only found in patients with a Charcot-Marie-Tooth type 2B (CMT2B) phenotype, an axonal sensory-motor neuropathy with pronounced ulcero-mutilations. In SPTLC1, we detected a novel mutation (S331F) corresponding to a previously unknown severe and early-onset HSAN phenotype. No mutations were found in NGFB, CCT5 and NGFR. Overall disease-associated mutations were found in 19% of the studied patient group, suggesting that additional genes are associated with HSAN. Our genotype–phenotype correlation study broadens the spectrum of HSAN and provides additional insights for molecular and clinical diagnosis. PMID:19651702

Pharmacological treatment of diabetic neuropathic pain.

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Smith, Howard S; Argoff, Charles E

2011-03-26

Neuropathic pain continues to be a difficult and challenging clinical issue to deal with effectively. Painful diabetic polyneuropathy is a complex pain condition that occurs with reasonable frequency in the population and it may be extremely difficult for clinicians to provide patients with effective analgesia. Chronic neuropathic pain may occur in approximately one of every four diabetic patients. The pain may be described as burning or a deep-seated ache with sporadic paroxysms of lancinating painful exacerbations. The pain is often constant, moderate to severe in intensity, usually primarily involves the feet and generally tends to worsen at night. Treatment may be multimodal but largely involves pharmacological approaches. Pharmacological therapeutic options include antidepressants (tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors), α2δ ligands and topical (5%) lidocaine patch. Other agents may be different antiepileptic drugs (carbamazepine, lamotrigine, topiramate), topical capsaicin, tramadol and other opioids. Progress continues with respect to understanding various mechanisms that may contribute to painful diabetic neuropathy. Agents that may hold some promise include neurotrophic factors, growth factors, immunomodulators, gene therapy and poly (adenosine diphosphate-ribose) polymerase inhibitors. It is hoped that in the future clinicians will be able to assess patient pathophysiology, which may help them to match optimal therapeutic agents to target individual patient aberrant mechanisms.

Autonomic Neuropathy in Diabetes Mellitus

OpenAIRE

Verrotti, Alberto; Prezioso, Giovanni; Scattoni, Raffaella; Chiarelli, Francesco

2014-01-01

Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent ...

Diagnostic ability of Barrett's index to detect dysthyroid optic neuropathy using multidetector computed tomography

International Nuclear Information System (INIS)

Monteiro, Mario L.R.; Goncalves, Allan C.P.; Silva, Carla T.M.; Moura, Janete P.; Ribeiro, Carolina S.; Gebrim, Eloisa M.M.S.; Universidade de Sao Paulo; Universidade de Sao Paulo

2008-01-01

Objectives: The objective of this study was to evaluate the ability of a muscular index (Barrett's Index), calculated with multidetector computed tomography, to detect dysthyroid optic neuropathy in patients with Graves' orbitopathy. Methods: Thirty-six patients with Graves' orbitopathy were prospectively studied and submitted to neuro-ophthalmic evaluation and multidetector computed tomography scans of the orbits. Orbits were divided into two groups: those with and without dysthyroid optic neuropathy. Barrett's index was calculated as the percentage of the orbit occupied by muscles. Sensitivity and specificity were determined for several index values. Results: Sixty-four orbits (19 with and 45 without dysthyroid optic neuropathy) met the inclusion criteria for the study. The mean Barrett's index values (±SD) were 64.47% ± 6.06% and 49.44% ± 10.94% in the groups with and without dysthyroid optic neuropathy, respectively (p 60% should be carefully examined and followed for the development of dysthyroid optic neuropathy. (author)

Diagnostic ability of barrett's index to detect dysthyroid optic neuropathy using multidetector computed tomography

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Mário L. R. Monteiro

2008-01-01

Full Text Available OBJECTIVES: The objective of this study was to evaluate the ability of a muscular index (Barrett's Index, calculated with multidetector computed tomography, to detect dysthyroid optic neuropathy in patients with Graves' orbitopathy. METHODS: Thirty-six patients with Graves' orbitopathy were prospectively studied and submitted to neuro-ophthalmic evaluation and multidetector computed tomography scans of the orbits. Orbits were divided into two groups: those with and without dysthyroid optic neuropathy. Barrett's index was calculated as the percentage of the orbit occupied by muscles. Sensitivity and specificity were determined for several index values. RESULTS: Sixty-four orbits (19 with and 45 without dysthyroid optic neuropathy met the inclusion criteria for the study. The mean Barrett's index values (± SD were 64.47% ± 6.06% and 49.44% ± 10.94%in the groups with and without dysthyroid optic neuropathy, respectively (p60% should be carefully examined and followed for the development of dysthyroid optic neuropathy.

Association between nasopharyngeal carcinoma and risk of optic neuropathy: A population-based cohort study.

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Fan, Chao-Yueh; Jen, Yee-Min; Su, Yuan-Chih; Chao, Hsing-Lung; Lin, Chun-Shu; Huang, Wen-Yen; Lin, Miao-Jung; Kao, Chia-Hung

2018-04-16

The purpose of this study was to assess the predictive factors of optic neuropathy among patients with nasopharyngeal carcinoma (NPC). The analysis included 16 297 patients with NPC and 65 187 controls. Each patient with NPC was randomly frequency-matched with 4 individuals without NPC by age, sex, and index year. Cox proportional hazard models were applied to measure the hazard ratios (HRs) and 95% confidence intervals (CIs) of optic neuropathy development associated with NPC. The risk of optic neuropathy was significantly higher in the NPC cohort (adjusted HR [aHR] 3.42; 95% CI 2.85-4.09; P optic neuropathy among patients with NPC included stroke (aHR 1.7; 95% CI 1.07-2.7; P = .03) and receipt of chemotherapy (aHR 1.55; 95% CI 1.17-2.06; P = .002). The risk of optic neuropathy was significantly higher in patients with NPC than in the general population. © 2018 Wiley Periodicals, Inc.

Nonlinear dimension reduction and clustering by Minimum Curvilinearity unfold neuropathic pain and tissue embryological classes

KAUST Repository

Cannistraci, Carlo; Ravasi, Timothy; Montevecchi, Franco Maria; Ideker, Trey; Alessio, Massimo

2010-01-01

algorithms, MCE and MCAP, whether individually or combined in H2P, overcome the limits of classical approaches. High performance was attained in the visualization and classification of: (i) pain patients (proteomic measurements) in peripheral neuropathy; (ii

Pain management in cancer cervix

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Palat Gayatri

2005-01-01

Full Text Available Cancer of the cervix uteri is a common cause of pain among women. On the physical realm, the cancer may cause somatic [soft tissue and bone], visceral and neuropathic pain [lumbosacral plexopathy]. Radiotherapy and chemotherapy may cause neuropathy too. Psychological, social and cultural factors modify the pain. Evaluation of the individual type of pain and a patient-centred approach are fundamental requirements for rational management. Disease modifying treatment like radiotherapy and chemotherapy must be considered when applicable. Pain control is usually achieved by the use of WHO three-step ladder, remembering that possible association of renal dysfunction would necessitate caution in the use of NSAIDs and opioids. Side effects must be anticipated, prevented when possible, and aggressively treated; nausea and vomiting may already be present, and constipation can worsen pain when there is a pelvic mass. Pain emergencies can be treated by quick titration with intravenous morphine bolus doses. Neuropathic pain may warrant the use of usual adjuvants, with particular reference to cortico-steroids and the NMDA antagonist, ketamine. In intractable pain, many neurolytic procedures are tried, but a solid evidence base to justify their use is lacking. Continuous epidural analgesia with local anaesthetic and opioid may be needed when drug therapy fails, and desperate situations may warrant interventions such as neurolysis. Such physical measures for pain relief must be combined with psychosocial support and adequate explanations to the patient and the family.

Infectious optic neuropathies: a clinical update

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Kahloun, Rim; Abroug, Nesrine; Ksiaa, Imen; Mahmoud, Anis; Zeghidi, Hatem; Zaouali, Sonia; Khairallah, Moncef

2015-01-01

Different forms of optic neuropathy causing visual impairment of varying severity have been reported in association with a wide variety of infectious agents. Proper clinical diagnosis of any of these infectious conditions is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular findings. Diagnosis is confirmed by serologic testing and polymerase chain reaction in selected cases. Treatment of infectious optic neuropathies involves the use of specific anti-infectious drugs and corticosteroids to suppress the associated inflammatory reaction. The visual prognosis is generally good, but persistent severe vision loss with optic atrophy can occur. This review presents optic neuropathies caused by specific viral, bacterial, parasitic, and fungal diseases. PMID:28539795

Vasculitic peripheral neuropathy

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Mona Amini

2014-02-01

Full Text Available Primary systemic vasculitis in pre-capillary arteries is associated with peripheral neuropathy. In some types of systematic vasculitis about 60 % of patients have peripheral nervous system (PNS involvement. In vasculitic peripheral neuropathies (VPN a necrotizing and inflammatory process leads to narrowing of vasa nervorum lumen and eventually the appearance of ischemic lesions in peripheral nerves. Some features might be suggestive of VPN, like: axonal nerve degeneration, wallerian-like degeneration, and diameter irregularity of nerve. Peripheral nervous system (PNS destruction during systemic vasculitides should be considered, due to its frequency and early occurrence in vasculitis progression. The first line treatment of non systematic VPNs is corticosteroid agents, but these drugs might worsen the VPNs or systemic vasculitis.

Comparison of Efficiencies of Michigan Neuropathy Screening Instrument, Neurothesiometer, and Electromyography for Diagnosis of Diabetic Neuropathy

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Turkan Mete

2013-01-01

Full Text Available Aim. This study compares the effectiveness of Michigan Neuropathy Screening Instrument (MNSI, neurothesiometer, and electromyography (EMG in detecting diabetic peripheral neuropathy in patients with diabetes type 2. Materials and Methods. 106 patients with diabetes type 2 treated at the outpatient clinic of Ankara Numune Education and Research Hospital Department of Endocrinology between September 2008 and May 2009 were included in this study. Patients were evaluated by glycemic regulation tests, MNSI (questionnaire and physical examination, EMG (for detecting sensorial and motor defects in right median, ulnar, posterior tibial, and bilateral sural nerves, and neurothesiometer (for detecting alterations in cold and warm sensations as well as vibratory sensations. Results. According to the MNSI score, there was diabetic peripheral neuropathy in 34 (32.1% patients (score ≥2.5. However, when the patients were evaluated by EMG and neurothesiometer, neurological impairments were detected in 49 (46.2% and 79 (74.5% patients, respectively. Conclusion. According to our findings, questionnaires and physical examination often present lower diabetic peripheral neuropathy prevalence. Hence, we recommend that in the evaluation of diabetic patients neurological tests should be used for more accurate results and thus early treatment options to prevent neuropathic complications.

Diagnosing ulnar neuropathy at the elbow using magnetic resonance neurography

International Nuclear Information System (INIS)

Keen, Nayela N.; Chin, Cynthia T.; Saloner, David; Steinbach, Lynne S.; Engstrom, John W.

2012-01-01

Early diagnosis of ulnar neuropathy at the elbow is important. Magnetic resonance neurography (MRN) images peripheral nerves. We evaluated the usefulness of elbow MRN in diagnosing ulnar neuropathy at the elbow. The MR neurograms of 21 patients with ulnar neuropathy were reviewed retrospectively. MRN was performed prospectively on 10 normal volunteers. The MR neurograms included axial T1 and axial T2 fat-saturated and/or axial STIR sequences. The sensitivity and specificity of MRN in detecting ulnar neuropathy were determined. The mean ulnar nerve size in the symptomatic and normal groups was 0.12 and 0.06 cm 2 (P 2 , sensitivity was 95% and specificity was 80%. Ulnar nerve size and signal intensity were greater in patients with ulnar neuropathy. MRN is a useful test in evaluating ulnar neuropathy at the elbow. (orig.)

Autosomal recessive type II hereditary motor and sensory neuropathy with acrodystrophy.

Science.gov (United States)

Thomas, P K; Claus, D; King, R H

1999-02-01

A family is described with presumed autosomal recessive inheritance in which three siblings developed a progressive neuropathy that combined limb weakness and severe distal sensory loss leading to prominent mutilating changes. Electrophysiological and nerve biopsy findings indicated an axonopathy. The disorder is therefore classifiable as type II hereditary motor and sensory neuropathy (HMSN II). The clinical features differ from those reported in previously described cases of autosomal recessive HMSN II. This disorder may therefore represent a new variant.

Diabetes and obesity are the main metabolic drivers of peripheral neuropathy.

Science.gov (United States)

Callaghan, Brian C; Gao, LeiLi; Li, Yufeng; Zhou, Xianghai; Reynolds, Evan; Banerjee, Mousumi; Pop-Busui, Rodica; Feldman, Eva L; Ji, Linong

2018-04-01

To determine the associations between individual metabolic syndrome (MetS) components and peripheral neuropathy in a large population-based cohort from Pinggu, China. A cross-sectional, randomly selected, population-based survey of participants from Pinggu, China was performed. Metabolic phenotyping and neuropathy outcomes were performed by trained personnel. Glycemic status was defined according to the American Diabetes Association criteria, and the MetS using modified consensus criteria (body mass index instead of waist circumference). The primary peripheral neuropathy outcome was the Michigan Neuropathy Screening Instrument (MNSI) examination. Secondary outcomes were the MNSI questionnaire and monofilament testing. Multivariable models were used to assess for associations between individual MetS components and peripheral neuropathy. Tree-based methods were used to construct a classifier for peripheral neuropathy using demographics and MetS components. The mean (SD) age of the 4002 participants was 51.6 (11.8) and 51.0% were male; 37.2% of the population had normoglycemia, 44.0% prediabetes, and 18.9% diabetes. The prevalence of peripheral neuropathy increased with worsening glycemic status (3.25% in normoglycemia, 6.29% in prediabetes, and 15.12% in diabetes, P peripheral neuropathy. Age, diabetes, and weight were the primary splitters in the classification tree for peripheral neuropathy. Similar to previous studies, diabetes and obesity are the main metabolic drivers of peripheral neuropathy. The consistency of these results reinforces the urgent need for effective interventions that target these metabolic factors to prevent and/or treat peripheral neuropathy.

Ketamine for cancer pain: what is the evidence?

Science.gov (United States)

Jonkman, Kelly; van de Donk, Tine; Dahan, Albert

2017-06-01

In this review, we assess the benefit of ketamine in the treatment of terminal cancer pain that is refractory to opioid treatment and/or complicated by neuropathy. While randomized controlled trials consistently show lack of clinical efficacy of ketamine in treating cancer pain, a large number of open-label studies and case series show benefit. Ketamine is an N-methyl-D-aspartate receptor antagonist that at low-dose has effective analgesic properties. In cancer pain, ketamine is usually prescribed as adjuvant to opioid therapy when pain becomes opioid resistant or when neuropathic pain symptoms dominate the clinical picture. A literature search revealed four randomized controlled trials that examined the benefit of oral, subcutaneous or intravenous ketamine in opioid refractory cancer pain. None showed clinically relevant benefit in relieving pain or reducing opioid consumption. This suggests absence of evidence of benefit for ketamine as adjuvant analgesic in cancer pain. These findings contrast the benefit from ketamine observed in a large number of open-label studies and (retrospective) case series. We relate the opposite outcomes to methodological issues. The complete picture is such that there is still insufficient evidence to state with certainty that ketamine is not effective in cancer pain.

The role of serum methylglyoxal on diabetic peripheral and cardiovascular autonomic neuropathy

DEFF Research Database (Denmark)

Hansen, C.S.; Jensen, T.M.; Jensen, J.S.

2015-01-01

AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy...... and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen......-detected Type 2 diabetes (duration ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy...

Intrathecal administration of rapamycin inhibits the phosphorylation of DRG Nav1.8 and attenuates STZ-induced painful diabetic neuropathy in rats.

Science.gov (United States)

He, Wan-You; Zhang, Bin; Xiong, Qing-Ming; Yang, Cheng-Xiang; Zhao, Wei-Cheng; He, Jian; Zhou, Jun; Wang, Han-Bing

2016-04-21

The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation and protein synthesis, and it is specifically inhibited by rapamycin. In chronic pain conditions, mTOR-mediated local protein synthesis is crucial for neuronal hyperexcitability and synaptic plasticity. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 plays a major role in action potential initiation and propagation and cellular excitability in DRG (dorsal root ganglion) neurons. In this study, we investigated if mTOR modulates the phosphorylation of Nav1.8 that is associated with neuronal hyperexcitability and behavioral hypersensitivity in STZ-induced diabetic rats. Painful diabetic neuropathy (PDN) was induced in Sprague-Dawley rats by intraperitoneal injection with streptozotocin (STZ) at 60mg/kg. After the onset of PDN, the rats received daily intrathecal administrations of rapamycin (1μg, 3μg, or 10μg/day) for 7 days; other diabetic rats received the same volumes of dimethyl sulfoxide (DMSO). Herein, we demonstrate a marked increase in protein expression of total mTOR and phospho-mTOR (p-mTOR) together with the up-regulation of phosphor-Nav1.8 (p-Nav1.8) prior to the mechanical withdrawal threshold reaching a significant reduction in dorsal root ganglions (DRGs). Furthermore, the intrathecal administration of rapamycin, inhibiting the activity of mTOR, suppressed the phosphorylation of DRG Nav1.8, reduced the TTX-R current density, heightened the voltage threshold for activation and lowered the voltage threshold for inactivation and relieved mechanical hypersensitivity in diabetic rats. An intrathecal injection (i.t.) of rapamycin inhibited the phosphorylation and enhanced the functional availability of DRG Nav1.8 attenuated STZ-induced hyperalgesia. These results suggest that rapamycin is a potential therapeutic intervention for clinical PDN. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Nonarteritic anterior ischemic optic neuropathy: cause, effect, and management

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Berry S

2017-09-01

Full Text Available Shauna Berry,1 Weijie V Lin,2 Ama Sadaka,1 Andrew G Lee1–7 1Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA; 2Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; 3Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch (UTMB, Galveston, TX, USA; 4Department of Ophthalmology, 5Department of Neurology, 6Department of Neurosurgery, Weill Cornell Medicine, Houston, TX, USA; 7Department of Ophthalmology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Nonarteritic anterior ischemic optic neuropathy (NAION is the most common form of ischemic optic neuropathy and the second most common optic neuropathy. Patients are generally over the age of 50 years with vasculopathic risk factors (eg, diabetes mellitus, hypertension, and obstructive sleep apnea. The exact mechanism of NAION is not fully understood. In addition, several treatment options have been proposed. This article summarizes the current literature on the diagnosis, treatment, and management of NAION. Keywords: anterior ischemic optic neuropathy, nonarteritic anterior ischemic optic neuropathy, ischemic optic neuropathy

Quality assessment of online patient education resources for peripheral neuropathy.

Science.gov (United States)

Hansberry, David R; Suresh, Ragha; Agarwal, Nitin; Heary, Robert F; Goldstein, Ira M

2013-03-01

Given its practicality, the internet is a primary resource for patients afflicted with diseases like peripheral neuropathy. Therefore, it is important that the readily available online resources on peripheral neuropathy are tailored to the general public, particularly concerning readability. Patient education resources were downloaded from the US National Library of Medicine, Mayo Clinic, National Institute of Neurological Disorders and Stroke, Neuropathy.org, GBS/CIDP Foundation International, Hereditary Neuropathy Foundation, Charcot-Marie-Tooth Association, Foundation for Peripheral Neuropathy, and Neuropathy Action Foundation websites. All patient education material related to peripheral neuropathy was evaluated for its level of readability using the Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level. The FRE scores averaged 43.4 with only the US National Library of Medicine scoring above 60 (76.5). The Flesch-Kincaid Grade Level scores averaged 11.0. All scores were above a seventh-grade level except the US National Library of Medicine, which had a score of a fifth-grade reading level. Most Americans may not fully benefit from patient education resources concerning peripheral neuropathy education on many of the websites. Only the US National Library of Medicine, which is written at a fifth-grade level, is likely to benefit the average American. © 2013 Peripheral Nerve Society.

Role of insulin signaling impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice

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Nicholas J. Anderson

2014-06-01

Full Text Available One of the tissues or organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high-fat diet (HFD can damage both the peripheral and central nervous systems. Groups of C57BL6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and streptozotocin (STZ-induced diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity and central nervous system function (learning ability, memory were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57BL6 mice showed statistically significant hyperglycemia. STZ-diabetic C57BL6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes, whereas neither C57BL6 nor Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57BL6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-induced diabetes or a HFD can damage both peripheral and central nervous systems, but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia might determine the neuropathy phenotype.

[Chemotherapy-induced peripheral neuropathies: an integrative review of the literature].

Science.gov (United States)

Costa, Talita Cassanta; Lopes, Miriam; Anjos, Anna Cláudia Yokoyama Dos; Zago, Marcia Maria Fontão

2015-04-01

To identify scientific studies and to deepen the knowledge of peripheral neuropathies induced by chemotherapy antineoplastic, seeking evidence for assistance to cancer patients. Integrative review of the literature conducted in the databases Latin American and Caribbean Health Sciences (LILACS), Scientific Electronic Library Online (SciELO), Medical Literature Analysis (PubMed/MEDLINE), the Cochrane Library and the Spanish Bibliographic Index Health Sciences (IBECS). The sample consisted of 15 studies published between 2005-2014 that met the inclusion criteria. Studies showed aspects related to advanced age, main symptoms of neuropathy and chemotherapy agents as important adverse effect of neuropathy. We identified a small number of studies that addressed the topic, as well as low production of evidence related to interventions with positive results. It is considered important to develop new studies proposed for the prevention and/or treatment, enabling adjustment of the patient's cancer chemotherapy and consequently better service.

Bi-modal radiofrequency treatment for coexisting neuralgia and neuropathy in adjacent divisions of the trigeminal nerve.

Science.gov (United States)

Bhatjiwale, M; Bhatjiwale, M; Naik, L D; Chopade, P

2018-05-29

Trigeminal neuralgia and deafferentation neuropathic pain, or trigeminal neuropathy, are different symptomatologies, rarely reported to present together. The case of a 65-year-old gentleman suffering from trigeminal neuralgia of the maxillary and mandibular division is reported. He first underwent an infraorbital neurectomy that was complicated by deafferentation neuropathic pain, whilst his mandibular neuralgia continued. He was treated successfully for both the neuropathic and neuralgic symptoms in the same session using ultra-extended euthermic pulsed radiofrequency treatment for the maxillary division (V2) and radiofrequency thermocoagulation for the mandibular division (V3). This report is novel in describing the use of dual modalities in the same session for two distinct coexisting clinical entities in two different divisions of the same cranial nerve. The use of ultra-extended pulsed radiofrequency treatment for neuropathic pain in this case is also unique. Nearly 2years after the procedure, the patient continues to have complete pain relief. Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Dose and diameter relationships for facial, trigeminal, and acoustic neuropathies following acoustic neuroma radiosurgery

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Flickinger, John C.; Kondziolka, Douglas; Lunsford, L. Dade

1996-01-01

Purpose and objective: To define the relationships between dose and tumor diameter for the risks of developing trigeminal, facial, and acoustic neuropathies after acoustic neuroma radiosurgery, a large single-institution experience was analyzed. Materials and methods: Two hundred and thirty-eight patients with unilateral acoustic neuromas who underwent Gamma knife radiosurgery between 1987-1994 with 6-91 months of follow-up (median 30 months) were studied. Minimum tumor doses were 12-20 Gy (median 15 Gy). Transverse tumor diameter varied from 0.3-5.5 cm (median 2.1 cm). The relationships of dose and diameter to the development of cranial neuropathies were delineated by multivariate logistic regression. Results: The development of post-radiosurgery neuropathies affecting cranial nerves V, VII, and VIII were correlated with minimum tumor dose and transverse tumor diameter (P min for VIII where P=0.10). A comparison of the dose-diameter response curves showed the acoustic nerve to be the most sensitive to doses of 12-16 Gy and the facial nerve to be the least sensitive. Conclusion: The risks of developing trigeminal, facial, and acoustic neuropathies following acoustic neuroma radiosurgery can be predicted from the transverse tumor diameter and the minimum tumor dose using models constructed from data presently available

Concurrent targeting of nitrosative stress-PARP pathway corrects functional, behavioral and biochemical deficits in experimental diabetic neuropathy

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Negi, Geeta; Kumar, Ashutosh [Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062 (India); Sharma, Shyam S., E-mail: sssharma@niper.ac.in [Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062 (India)

2010-01-01

Peroxynitrite mediated nitrosative stress, an indisputable initiator of DNA damage and overactivation of poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated after sensing DNA damage, are two crucial pathogenetic mechanisms in diabetic neuropathy. The intent of the present study was to investigate the effect of combination of a peroxynitrite decomposition catalyst (PDC), FeTMPyP and a PARP inhibitor, 4-ANI against diabetic peripheral neuropathy. The end points of evaluation of the study included motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) for evaluating nerve functions; thermal hyperalgesia and mechanical allodynia for assessing nociceptive alterations, malondialdehyde and peroxynitrite levels to detect oxidative stress-nitrosative stress; NAD concentration in sciatic nerve to assess overactivation of PARP. Additionally immunohistochemical studies for nitrotyrosine and Poly(ADP-ribose) (PAR) was also performed. Treatment with the combination of FeTMPyP and 4-ANI led to significant improvement in nerve functions and pain parameters and also attenuated the oxidative-nitrosative stress markers. Further, the combination also reduced the overactivation of PARP as evident from increased NAD levels and decreased PAR immunopositivity in sciatic nerve microsections. Thus, it can be concluded that treatment with the combination of a PDC and PARP inhibitor attenuates alteration in peripheral nerves in diabetic neuropathy (DN).

Use of Natural Compounds in the Management of Diabetic Peripheral Neuropathy

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Maria Galuppo

2014-03-01

Full Text Available Nephropathy, retinopathy cardiomyopathy and peripheral neuropathy are all recognized as important complications in about 50% of diabetes mellitus (DM patients, mostly related to a poor glycemic control or to an improper management of this pathology. In any case, amongst others, diabetic peripheral neuropathy (DPN seems the leading and most painful complication usually affecting many DM patients. For this reason, this work was conceived to review the large variety of strategies adopted for management of DPN, starting from the most conventional therapies to arrive at alternative approaches. From this perspective, both the most popular pharmacological treatments used to respond to the poorly effect of common analgesics—non-steroidal anti-inflammatory drugs (NSAIDS and opioids—understood as gabapentin vs. pregabalin clinical use, and the guidelines provided by Oriental Medicine as well as by a long list of natural compounds that many authors identify as possible therapeutic or alternative agents to replace or to combine with the existing therapies will be included. Moreover, in the effort to provide the widest panel of remedies, the most antique techniques of acupuncture and electrostimulation will be considered as alternative, which are useful approaches to take into account in any non-pharmacological strategy for DPN management.