Chronic Neuropathic Disorders Research Articles

Study of monomelic amyotrophy of the lower limbs in the territory of the Western Balkans: Case series.

Monomelic amyotrophy is a rare form of motor neuron disease in which the neurogenic atrophy is restricted to 1 limb, mostly the distal part of the arm. The disease most often occurs in Asia, especially in Japan and India, while in European countries, this disease is rarely recognized. Registration and publication of new cases of this disease aims to increase the awareness of clinicians about the existence of this disease in European countries, and with the aim of easier recognition and faster diagnosis of this essentially benign disorder. Five patients with signs of atrophy of the muscles of 1 leg were examined at our Institution. The criteria for selecting patients were as follows: clinical evidence of wasting and weakness confined to the 1 lower limb; progressive course, or initial progression followed by stationary course; absence of any definite sensory loss or central nervous system involved; no evidence of compression lesion of the spinal cord. The clinical characteristics of our patients were similar to those previously described in the literature. The characteristic clinical features were sporadic occurrence, predominance in males with an initially progressive course for 2 to 5 years followed by a stationary state. There was no family history of neuromuscular disease. The electromyographic finding was consistent with a chronic neuropathic disorder. Magnetic resonance imaging of the lumbosacral spine excluded intraspinal pathologies and root compression in all cases. Monomelic amyotrophy of the lower limb is a rare disease that should be considered in cases of slow progressive unilateral amyotrophy of a single leg, especially in younger and middle-aged men, not only in Asia but also in the Western Balkans and Europe.

A Study on Assessment of Attitude and its Impact on Practice in Patients with Diabetes Mellitus

<p style="text-align: justify;"><strong>Background:</strong> Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycaemia and is associated with abnormalities in carbohydrate, fat, and protein metabolism, which results in chronic complications, comprising microvascular, macro vascular, and neuropathic disorders. Key complications of diabetes are avoidable by proper control on their blood glucose levels and this needs training of the person with diabetes in handling their condition. The aim of the study was to analyse the Attitude and its influence on Practice of patients with Diabetes. <strong>Methods:</strong>Patients of either sex with &ge;1-year history of diabetes and who were willing to give the consent were involved in the study. Patients of either sex with &lt;1year history of Diabetes Mellitus, Pregnant/lactating women and patients who are not ready to give the consent were excluded from the study. Attitude and practice was assessed by means of questionnaire which was closed ended consisting of 8 Attitude and 7 Practice questions. 200 patients were analysed in the study.<strong> Results:</strong> When Attitude and Practice scores were compared, results showed that despite having good attitude on Diabetes, many patients did not have good practice towards Diabetes in many terms which indicates that there is an increased need for creating awareness on the importance of Attitude and Practice with regards to the disease, that helps in appropriate management and prevention of its complications. <strong>Conclusion: </strong>The study directs the significant evidence on the role of pharmacists in providing Diabetes care, however the provision of such services remains inconsistent. <p style="text-align: justify;"><strong>Key words:</strong> Diabetes Mellitus, Attitude, Practice, Complications, Pharmacist,

Effectiveness of Duloxetine for Postsurgical Chronic Neuropathic Disorders after Spine and Spinal Cord Surgery.

Study DesignThis is a retrospective observational study with an outpatient setting.PurposeThis study aimed to describe the effects of duloxetine (DLX) administration for postsurgical chronic neuropathic disorders (both pain and numbness) following spinal surgery in patients without depression.Overview of LiteratureAlthough several reports indicated the potential of DLX to effectively treat postoperative symptoms as a perioperative intervention, there have been no reports of its positive effect on postsurgical chronic neuropathic disorders.MethodsA total of 24 patients with postsurgical chronic pain and/or numbness Numeric Rating Scale (NRS) scores of ≥4 were enrolled. All patients underwent spine or spinal cord surgery at Keio University Hospital and received daily administration of DLX for more than 3 months. The mean postoperative period before the first administration of DLX was 35.5±57.0 months. DLX was administered for more than 3 months at a dose of 20, 40, or 60 mg/day, and the degree of pain and numbness was evaluated using the NRS before administration and 3 months after administration. Effectiveness was defined as more than a 2-point decrease in the NRS score following administration.ResultsIn terms of the type of symptoms, 15 patients experienced only numbness, eight experienced both pain and numbness, and one experienced only pain. Of the 24 patients, 19 achieved effective relief with DLX. DLX was effective for all patients with postsurgical chronic pain (n=9), and it reduced postsurgical chronic numbness in 18 of 23 patients. No significant difference was observed in background spinal disorders. DLX was not effective for five patients who complained only of postsurgical chronic numbness.ConclusionsThis study reports the effectiveness of DLX for postsurgical chronic neuropathic disorders. Although DLX reduced postsurgical chronic pain (efficacy rate=100%) and numbness (78.3%) in certain patients, further investigation is needed to determine its optimal use.

A Descriptive Study to Assess the Quality of Life of Patient with Type 2 Diabetes Mellitus in a Selected Rural Community at Kancheepuram District Tamil Nadu, India

Diabetic 2 mellitus is also known as non-insulin dependent diabetic mellitus. It is associated withabnormalities in carbohydrate, fat and protein metabolism and may result in the chronic complicationincluding micro vascular, macro vascular and neuropathic disorders. The reality is that diabetes influencespatients’ lives. The mere presence of diabetes deteriorates a person’s quality of life. When diabetes coexistswith other chronic illnesses the effect is even worse. The objectives of the study is to assess the quality oflife of type 2 diabetes mellitus patient in a selected rural area and association between the quality of lifeand the demographic variables. A purposive sampling technique is used to collect drug from the samples.The sample size was 93 type 2 diabetes patients at selected rural community area. The quality of life wasassessed by final quolid questionnaires. The result shows that 6(6%) of sample had low level of quality oflife, 79(85%) of the sample had average level of quality of life, 8(9%) of sample had high level of qualityof life.

Neuropathic Pain and Itch Mechanisms Underlying Allergic Conjunctivitis.

Among the constellation of symptoms that characterizes allergic conjunctivitis, many (eg, burning and stinging) can be attributed to chronic neuropathic pain. Cumulative data support that these hallmark symptoms might be linked to the effects of allergen-induced neuromodulation. This review investigates the key characteristics of neuropathic itch and pain in allergic conjunctivitis and their underlying pathogenic mechanisms. A literature review was conducted using a PubMed search focusing on allergic conjunctivitis, neurogenic inflammation, neuropathic itch, and neuropathic pain. Articles were reviewed, and those discussing clinical course, pathophysiology, and neuronal regulation of chronic neuropathic symptoms as related to allergic disease were summarized. Recent evidence suggests that some symptoms of allergic conjunctivitis may be better represented as a chronic neuropathic disorder. We found that neurogenic mechanisms may have a significant role in chronic ocular surface inflammation from allergic inflammation. Manifestations may be associated with repeated ocular sensory nerve injury leading to an acute-to-chronic transition, which is in turn associated with neuropathologic changes (peripheral and central sensitization), neuronal dysfunction, and spontaneous ocular pain. Current goals in the management of allergic conjunctivitis aim to minimize the inflammatory cascade associated with the allergic response in the initial stages of the pathogenic mechanism. Based on the mechanistic data reviewed herein, the recognition that neuronal inflammation explains many of the symptoms in allergic conjunctivitis opens new frontiers for drug discovery.

Validity of the Budapest Criteria For Poststroke Complex Regional Pain Syndrome.

Complex regional pain syndrome-1 is a chronic neuropathic disorder, and poststroke complex regional pain syndrome (PS-CRPS) is not a rare complication. There is a lack of study implementing the Budapest criteria for PS-CRPS diagnosis. Thus, the present study investigated the validity of the Budapest criteria for PS-CRPS diagnosis and assessed the PS-CRPS-related factors in stroke patients with an affected upper extremity. The study included 72 patients with first-ever stroke resulting in hemiplegia. The prevalence of PS-CRPS and diagnostic validity were compared among the Budapest clinical criteria, Budapest research criteria, modified Budapest criteria (removal of the motor factor from the motor/trophic category), and International Association for the Study of Pain (IASP) criteria in patients diagnosed with PS-CRPS according to the Budapest clinical criteria. PS-CRPS was diagnosed in 6 (8.3%), 1 (1.4%), 6 (8.3%), and 11 patients (15.3%) according to the Budapest clinical criteria, Budapest research criteria, modified Budapest criteria, and IASP criteria, respectively. The Budapest criteria and IASP criteria had sensitivities of 0.99 and 1.00, respectively, and specificities of 0.68 and 0.41, respectively, for PS-CRPS diagnosis. There were no differences in risk factors between PS-CRPS patients and non-PS-CRPS patients when the diagnosis was based on the Budapest clinical criteria. However, there were differences in muscle strength and Brunnstrom stage between PS-CRPS patients and non-PS-CRPS patients when the diagnosis was based on the IASP criteria. Our findings indicate that the diagnostic validity of the current Budapest clinical criteria for PS-CRPS is low. Thus, the current Budapest criteria might not be appropriate for PS-CRPS diagnosis.

The analgesic potential of cytokine neutralization with biologicals

Many acute and chronic inflammatory diseases, cancer and neuropathic disorders are accompanied by severe pain states reducing drastically the life quality of the patients. Biologicals which preferentially target cytokines often reduce the disease processes by influencing immune cells, tissue healing, inflammatory aspects and other typical processes of the diseases. Remarkably the effect of biologicals in pain and nociception is often neglected or insufficiently explored. However, because of the dense interaction of the nociceptive system with the surrounding peripheral or central tissue, targeting cytokines has the potential to treat pain at the same time as the other symptoms of the disease. The following review shows mainly results from animal experiments (with some parallels to human studies). It depicts where and how cytokines are involved in nociceptive processing and pain and also indicates possible target strategies. It concentrates on the excitatory cytokines IL-6, TNF-α, IL-1ß, IFN-γ and IL-17.

Earlier treatment improves the chances of complete relief from postherpetic neuralgia.

BackgroundAs herpes zoster progresses via postherpetic neuralgia (PHN) to well-established PHN, it presents its recalcitrant nature to the treatment. At this point, the well-established PHN is fixed as a non-treatable, but manageable chronic painful neuropathic disorder. This study evaluated the incidence of complete relief from PHN according to PHN duration at their first visit, and the other factors influencing it.MethodsA retrospective chart review was performed on patients with PHN at a university-based pain clinic over 7 years. The responders were defined as patients who had complete relief from pain after 1 year of active treatment. Age, sex, PHN duration at their first visit, dermatomal distribution, and underlying disorders were compared in the responder and non-responder groups. Responders were also compared according to these factors.ResultsAmong 117 PHN patients (M/F = 48/69), 35 patients (29.9%) had complete relief from PHN. Mean ages were 64.3 ± 10.6 and 66.9 ± 10.7 years, numbers of male to female patients were 11/24 and 37/45, and mean durations of PHN at their first visit were 8.5 ± 6.3 and 15.3 ± 10.7 months in the responder and non- responder groups, respectively. In addition, PHN patients who visited the clinic before 9 months showed a better result. Dermatomal distribution and underlying disorders did not show significant differences.ConclusionsAlmost 30% of PHN patients received complete relief. Those who sought treatment in a pain clinic before 9 months received a better result.

Management of Central Poststroke Pain: Systematic Review of Randomized Controlled Trials.

Central poststroke pain is a chronic neuropathic disorder that follows a stroke. Current research on its management is limited, and no review has evaluated all therapies for central poststroke pain. We conducted a systematic review of randomized controlled trials to evaluate therapies for central poststroke pain. We identified eligible trials, in any language, by systematic searches of AMED, CENTRAL, CINAHL, DARE, EMBASE, HealthSTAR, MEDLINE, and PsychINFO. Eligible trials (1) enrolled ≥10 patients with central poststroke pain; (2) randomly assigned them to an active therapy or a control arm; and (3) collected outcome data≥14 days after treatment. Pairs of reviewers, independently and in duplicate, screened titles and abstracts of identified citations, reviewed full texts of potentially eligible trials, and extracted information from eligible studies. We used a modified Cochrane tool to evaluate risk of bias of eligible studies, and collected patient-important outcomes according to recommendations by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. We conducted, when possible, random effects meta-analyses, and evaluated our certainty in treatment effects using the Grading of Recommendations Assessment, Development, and Evaluation System. Eight eligible English language randomized controlled trials (459 patients) tested anticonvulsants, an antidepressant, an opioid antagonist, repetitive transcranial magnetic stimulation, and acupuncture. Results suggested that all therapies had little to no effect on pain and other patient-important outcomes. Our certainty in the treatment estimates ranged from very low to low. Our findings are inconsistent with major clinical practice guidelines; the available evidence suggests no beneficial effects of any therapies that researchers have evaluated in randomized controlled trials.

P160. Transcranial magnetic stimulation in chronic neuropathic pain – A prospective study of 45 patients

Introduction Chronic neuropathic disorders remain difficult to treat. Analgesic medication often achieve only an insufficient effect, therefore other non-pharmacological treatment has to be considered. One option for management of intractable pain is stimulation of the motor cortex by implantation of an epidural electrode. This effect of invasive stimulation could be replaced by transcranial magnetic stimulation. Objectives The objective of the study was to observe the pain reducing effect of non-invasive transcranial magnetic stimulation (rTMS) in patients suffering from different types of chronic neuropathic pain. Materials and methods The study was prospective. We included patients suffering from chronic pain syndroms, such chronic facial pain, poststroke pain, phantom pain and FBSS. The corresponding primary motor cortex has been stimulated with high-frequent, repetitive transcranial magnetic stimulation (rTMS). Stimulation was daily repeated. The individual pain level was assessed by the visual analogue scale (VAS) and documented daily for three weeks. The first follow up was done after 6 weeks. Results We included 45 patients (24 female/21 male) between 31 and 78 years of age. The follow up was done at least after six weeks, further intervals were determined individually with a maximum follow up time of 4 years. A pain reduction in terms of a decrease in the VAS scale was obtained in 58% of patients over all groups, ranging from 2 to 8 points on VAS with a mean value of 3,6. Regarding the etiology of pain we observe a responding rate of 72% in the facial pain group, 40% in the poststroke pain group, 25% in the FBSS group and no responding in the phantom pain group. The pain reduction occurred with a delay between 4 days and 3 weeks, and showed a long term effect up to 10 months. Conclusion Non-invasive transcranial magnetic stimulation seems to be applicable for neuropathic pain syndromes. In chronic facial pain we could observe a higher responding rate than in any other chronic pain syndrome. Pain reduction has a long term effect, which outlast the stimulation period.

Comment on “The Combined Extract ofZingiber officinaleandZea mays(Purple Color) Improves Neuropathy, Oxidative Stress, and Axon Density in Streptozotocin Induced Diabetic Rats”

In a recent study, Wattanathorn et al. identified that the combined extract of purple waxy corn and ginger was effective in improving functional and structural changes in STZ-diabetic rats submitted to chronic constriction of the sciatic nerve, an effect that is potentially mediated by the antioxidant properties of these combined extracts. Although the results have been quite interesting, we would like to present a complementary conceptual perspective to improve the interpretation of the findings considering the disease model investigated. In the natural course of nontreated diabetes mellitus, diabetic neuropathy represents a chronic metabolic neuropathic disorder secondary to accumulated molecular and microvascular damage that impairs nerve structure and function [1, 2]. Fundamentally, diabetic neuropathy consists of a nontraumatic condition with prolonged time-course in which functional impairment overcomes the nerve structural damage, especially in the early stages of neuropathy [1–3]. Thus, even when applied to diabetic animals, the model of nerve constriction represents a traditional model of traumatic neuropathy and neuropathic pain [4, 5], which manifests a completely different pathophysiologic mechanism compared to diabetic neuropathy. In this trauma model, nerve ligation causes variable degrees of injury, which is difficult to measure directly and can range from neuropraxia (less severe functional nerve lesion) to neurotmesis (extensive and complex morphofunctional nerve lesion) [4, 5]. Furthermore, the injured nerve fibers cause chromatolysis and distal Wallerian degeneration, processes that are associated with intense focal inflammation and fibrosis, which limits axonal reparation [4, 5]. All of these structural changes are typical of traumatic lesions, but less frequent in diabetic neuropathy [1–3]. From this conceptual basis, the current interpretation of the findings reflects a construct bias since the results described cannot be used as an empirical basis to explain the improvements in diabetic neuropathy. Thus, a proper interpretation of the findings should consider the effect of treatments on healing/repair of traumatic nerve injury in diabetic animals, which recognizably presents an impaired healing process [1, 3]. When reviewing animal models of diabetic neuropathy, Klusakova and Dubový [5] indicated that rats with partial sciatic nerve ligation present minor pathogenesis of diabetic neuropathy, which is hardly representative of the human condition. This argument is reinforced by the short time course for neuropathy evolution, which showed a significant impairment of sciatic function index 24 hours after nerve ligation. This finding indicates a typical acute effect of mechanical nerve injuries [4, 5], which is not consistent with the chronic and progressive clinical course of diabetic neuropathy [1–3]. Although the relevance of the results is evident in traumatic nerve injury, it is wise to discuss the limitations of the model used and the interpretation of the findings. Whereas diabetic neuropathy is a condition of difficult clinical management that demands high cost to health care, we are looking forward to further studies by Wattanathorn et al. investigating whether the extracts tested can also bring similar benefits in specific and robust models, such as genetic or genetically modified models [3, 5, 6] of diabetic neuropathy.

Complex Regional Pain Syndrome in an Adult Following Tetanus–Diphteria Toxoid Vaccine: Case Report and Review of the Literature

AbstractBackground: Complex regional pain syndrome [CRPS] is a painful and disabling chronic neuropathic disorder, and unfortunately, due to its wide spectrum of clinical manifestations, the diagnosis may often be missed by primary-care physicians. To the authors’ knowledge, there are no reported cases of CRPS following immunization with tetanus–diphteria toxoid booster vaccine in an adult.Findings: We present a 26-year-old woman with severe pain, swelling, and limited range of motion of the left forearm following a booster dose of the tetanus–diphteria toxoid vaccine.Conclusion: Disease awareness among practitioners, early recognition, and appropriate treatment is essential to minimize the risk of adverse outcome.

Methodologic Quality of Studies on Prognostic Factors for Primary Open-angle Glaucoma Progression Measured by Visual Field Deterioration

Glaucoma is a chronic, slowly progressing, and asymptomatic optic neuropathic disorder with a great variety of causes that involve gradual retinal ganglion cell axon loss. The disease is the second most common cause of blindness in the industrialized world. Once vision loss develops it is irreversible-although in many cases further loss can be slowed if adequate treatment is provided. If not treated, glaucoma can lead to complete vision loss in the affected eye. Primary open-angle glaucoma (POAG) is the most prevalent form of the disease in the industrialized countries, representing 94% of all glaucomas. In a Spanish study of 569 individuals, the prevalence of POAG was 2.1% (99% confidence interval 1.9%-2.3%) in the age range between 40 and 79 years. Assessing glaucomatous damage progression remains one of the most important and challenging aspects in glaucoma management. In addition, a better understanding of clinical risk factors for glaucoma worsening may help us to develop new strategies to improve glaucoma care. Over the past 2 decades, many studies have addressed the issue of risk factors associated with or predicting for glaucoma progression. Although many studies have attempted to identify the prognostic factors capable of predicting the course of POAG, the results have been varied and in some cases contradictory, and are thus of scant practical utility. This study was designed to evaluate the methodologic quality of the studies published in the literature on the prognostic factors for POAG progression measured by visual field deterioration.

Dietary fat and protein interact in suppressing neuropathic pain-related disorders following a partial sciatic ligation injury in rats

Chronic neuropathic sensory disorders (CNSD) of rats receiving a partial sciatic nerve ligation injury (the PSL model) are suppressed by dietary soy protein. Although previously shown to modify nociceptive behavior in acute pain models, dietary fat has never been tested for its putative analgesic properties in chronic pain states. Here we tested the role of dietary fat, protein and fat/protein interactions in the development of tactile allodynia and heat hyperalgesia in PSL-injured rats. Male Wistar rats were fed nine different diets, comprising of three proteins (soy, casein and albumin) and three fats (corn, soy and canola) for a week preceding PSL injury and for 2 weeks thereafter. Rats' responses to tactile and noxious heat stimuli were tested before surgery and 3, 7 and 14 days afterwards. Tactile and heat sensory abnormalities following PSL injury were significantly different among the nine dietary groups. Consumption of corn and soy fats suppressed the levels of tactile and heat allodynia and hyperalgesia, whereas consumption of soy and casein proteins was associated with lower levels of heat hyperalgesia but not tactile allodynia. A significant fat/protein interaction was found for the heat but not tactile stimuli. We conclude that dietary fat is a significant independent predictor of levels of neuropathic sensory disorders in rats and that this effect is accentuated by dietary protein. The mechanisms by which fat suppresses neuropathic disorders have yet to be determined.

Animal pain models: The effect of diet on the development of chronic neuropathic sensory disorders in three models of partial sciatic nerve injury

Diet is a significant predictor for levels of chronic neuropathic sensory disorders (CNSD) in rats undergoing a partial sciatic nerve ligation injury (the PSL model). We have shown that this dietary effect depends on both the protein and fat content of the diet (see our adjacent abstract). Although similar chronic behavioral signs of both spontaneous and evoked pain are seen with different models of surgically-induced neuropathic pain, it has been suggested that these models might differ in their pathophysiological basis. For example, the local inflammatory component of the chronic constriction injury (CCI model) could play a more central role in the development of CNSD (Maves TJ, et al, Pain 54;57-69:1993), compared with the spinal nerve ligation (SNL) and the PSL models. The aim was to compare the effect of diet on CNSD in different models of surgically-induced neuropathic pain. Two different diets were tested in three models of partial nerve injury (PSL, CCI, SNL). These diets differed in their protein and their fat source (soy protein/corn oil vs. albumin protein/canola oil). These diets have been chosen since they were associated with significantly different levels of CNSD in the PSL model. Rats were fed the two experimental diets a week before surgery and 2 weeks thereafter, and tactile and heat pain thresholds were tested on days 3, 7 and 14 postoperative. All rats developed significant tactile allodynia and heat hyperalgesia following the different surgeries. Feeding rats with the soy/corn diet was significantly associated, however, with suppressed CNSD levels in PSL, but not CCI and SNL-injured rats. CCI and SNL-injured rats might share some similar pathophysiological characteristics, making them less susceptible to the effect of diet.

Animal pain models: Dietary oil suppresses chronic neuropathic sensory disorders in nerve-injured rats

Animal pain models: Dietary oil suppresses chronic neuropathic sensory disorders in nerve-injured rats

Soy-containing diet suppresses chronic neuropathic sensory disorders in rats.

Partial sciatic nerve ligation (PSL) in rodents produces chronic neuropathic sensory disorders resembling neuropathic pain in humans. We previously reported that levels of allodynia and hyperalgesia after PSL injury were markedly attenuated by consumption of soy-containing diets. Here we aimed to show that dietary effect on pain behavior is not specific to a certain laboratory. For this purpose, experiments were conducted in a different laboratory (Baltimore rather than Jerusalem) and a different rat strain (Wistar rather than Sabra), with additional and different testing methods (radiant heat from a lamp rather than a CO(2) laser). Rats were fed two soy-free diets and a soy-containing one for 28 days. The sensitivity of rats to nonnoxious and noxious stimuli was determined before PSL injury, and levels of neuropathic sensory disorders were determined after it. We found that consuming the soy-containing diet prevented development of tactile and heat allodynia, but not mechanical hyperalgesia. This dietary effect was not correlated with calorie intake and weight gain or dietary concentration of fat and carbohydrates. We conclude that, regardless of experimental site, diet markedly affects chronic neuropathic sensory disorders in rats and should be standardized in animal models of pain. Levels of chronic sensory disorders in a rat model of allodynia and hyperalgesia after partial sciatic nerve ligation depend on the consumption of a soy-containing diet. Further studies are needed to determine the role of diet in humans with chronic pain.

Heat hyperalgesia following partial sciatic ligation in rats: interacting nature and nurture

As in humans, levels of neuropathic pain produced by nerve injury are highly variable among animals. This variability was attributed to genetic and environmental factors. For example, we reported that chronic neuropathic sensory disorders developing following total (autotomy) or partial nerve injury (allodynia and hyperalgesia) depended on the diet rats consumed. Here we investigated the interaction between genetic and dietary factors in the development of heat hyperalgesia in rats following partial sciatic ligation (the PSL model). We show that heat sensitivity of intact rats and levels of heat hyperalgesia of PSL-injured rats were highly variable across eight different rat strains and seven different diets. Thus, genetic and environmental variables interact in determination of levels of chronic neuropathic sensory disorders in rats.