Neuropathic Patients Research Articles

Electrophysiological characterization of ectopic spontaneous discharge in axotomized and intact fibers upon nerve transection: a role in spontaneous pain?

Many patients experience positive symptoms after traumatic nerve injury. Despite the increasing number of experimental studies in models of peripheral neuropathy and the knowledge acquired, most of these patients lack an effective treatment for their chronic pain. One possible explanation might be that most of the preclinical studies focused on the development of mechanical or thermal allodynia/hyperalgesia, neglecting that most of the patients with peripheral neuropathies complain mostly about spontaneous forms of pains. Here, we summarize the aberrant electrophysiological behavior of peripheral nerve fibers recorded in experimental models, the underlying pathophysiological mechanisms, and their relationship with the symptoms reported by patients. Upon nerve section, axotomized but also intact fibers develop ectopic spontaneous activity. Most interestingly, a proportion of axotomized fibers might present receptive fields in the skin far beyond the site of damage, indicative of a functional cross talk between neuromatose and intact fibers. All these features can be linked with some of the symptoms that neuropathic patients experience. Furthermore, we spotlight the consequence of primary afferents with different patterns of spontaneous discharge on the neural code and its relationship with chronic pain states. With this article, readers will be able to understand the pathophysiological mechanisms that might underlie some of the symptoms that experience neuropathic patients, with a special focus on spontaneous pain.

The Effect of Ankle Pumping on the Changes of ABI Value in Diabetic Neuropathic Patients

Introduction: Diabetes mellitus is a serious disease and is commonly known as the “mother of disease” because this disease can be a risk factor for various other diseases of the body organs. Some of the consequences of diabetes are an increased risk of hypertension, heart disease, stroke, retinopathy, including diabetic neuropathy. Diabetic neuropathy is a type of nerve damage that occurs due to diabetes. One of the non-pharmacological interventions is ankle pumping. Objectives: This study aimed to analyze the effect of ankle pumping on changes in ABI values ​​in diabetic neuropathy patients. Methods: This research comprised a Quasi-experimental research design with one group pretest-posttest—a total of 69 respondents were taken using the total sampling technique. Ankle pumping intervention is given to diabetic neuropathy patients at Massenrampulu Hospital in June-August 2020, two times a day for three consecutive days (@ 15 minutes). Results: From this study, the majority of respondents were seniors (n=31, 44.9%), female (n=42, 60.9%). Before the intervention, most respondents (68.1%) showed an abnormal ABI value at <0.90 for 47. Furthermore, after the intervention, more than half of respondents (69.6%) were on Borderline 0.91-0.99 for 48. The Wilcoxon test results significantly affect the ABI value before and after the intervention with a sig value of p = 0.003. Conclusions: There is a significant effect of ankle pumping therapy on changes/increases in ABI values ​​in type-2 DM patients with neuropathy at Massenrempulu General Hospital, Enrekang District.

Maladaptive motor cortical excitability and connectivity in polyneuropathy with neuropathic pain.

Sensory symptoms, especially neuropathic pain, are common in polyneuropathy. Conventional diagnostic tools can evaluate structural or functional impairment of nerves but cannot reveal mechanisms of neuropathic pain. Changes in the brain after polyneuropathy may play roles in the genesis of neuropathic pain. This cross-sectional study investigated changes of cortical excitability within left primary motor cortex (M1) by measuring resting motor thresholds, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and afferent inhibition between polyneuropathy patients and controls, and investigated the correlates of these parameters with neuropathic pain and M1 structural and functional connectivity assessed by diffusion tractography imaging and functional magnetic resonance imaging. Thirty-three painful and 15 nonpainful neuropathic patients and 21 controls were enrolled. There were no differences in intraepidermal nerve fiber density, nerve conduction studies, thermal thresholds, or autonomic functional tests between patients with and without neuropathic pain. Compared to controls, neuropathic patients exhibited similar resting motor thresholds or afferent inhibition, but attenuated SICI and augmented ICF, especially in painful patients. Changes of intracortical excitability in neuropathic patients were correlated with intensities of neuropathic pain, and different presentations of SICI and ICF were noted between patients with and without thermal paresthesia. Additionally, short-latency afferent inhibition at an interstimulus interval of 20ms was associated with structural connectivity of left M1 with brain areas associated with pain perception. Maladaptive cortical excitability with altered structural connectivity in left M1 developed after peripheral nerve degeneration and was associated with neuropathic pain and sensory symptoms in polyneuropathy.

Coronal Hindfoot Alignment in Midfoot Charcot Neuroarthropathy

Coronal plane hindfoot malalignment produces abnormal compensatory forces within the midfoot and forefoot. The primary aim of this study is to compare radiographic hindfoot alignment in patients with a midfoot Charcot event, and identify patterns associated with breakdown. A retrospective review of 43 patients (48 limbs) with midfoot Charcot neuroarthropathy were compared between the coronal hindfoot alignments and Charcot joint involvement. Coronal hindfoot alignment was classified as neutral (n = 15), valgus (n = 16), and varus (n = 17) utilizing the Saltzman hindfoot alignment radiograph. Charcot joint breakdown was classified as isolated tarsometatarsal joint (n = 8), combination of tarsometatarsal and naviculocuneiform joints (n = 22), and midtarsal joints including talonavicular and calcaneocuboid joints (n = 18). Patients exhibiting varus hindfoot alignment had 5.8 times greater risk of breakdown at the tarsometatarsal and naviculocuneiform joints (odds ratio 5.8, 95% confidence interval 1.7-22.9, p < .01). Hindfoot varus induces external rotation of the talus, resulting in compensation through the naviculocuneiform and tarsometatarsal joint, which correlates with our findings of a 6-fold increase in naviculocuneiform and tarsometatarsal joint collapse. Patients exhibiting valgus hindfoot alignment had 27 times greater risk of breakdown at the midtarsal joint (odds ratio 27.0; 95% confidence interval 5.6-207.0, p < .01). Hindfoot valgus induces internal rotation of the talonavicular joint, which correlates with our findings of a 27-fold increase in midtarsal joint breakdown. Varus and valgus hindfoot alignment are associated with different midfoot injury patterns, which may have implications in surgical management and allow for focused surveillance in neuropathic patients presenting with early-stage clinical findings consistent with Charcot neuroarthropathy.

In-Depth Characterization of Somatic and Orofacial Sensitive Dysfunctions and Interfering-Symptoms in a Relapsing-Remitting Experimental Autoimmune Encephalomyelitis Mouse Model.

Among the many symptoms (motor, sensory, and cognitive) associated with multiple sclerosis (MS), chronic pain is a common disabling condition. In particular, neuropathic pain symptoms are very prevalent and debilitating, even in early stages of the disease. Unfortunately, chronic pain still lacks efficient therapeutic agents. Progress is needed (i) clinically by better characterizing pain symptoms in MS and understanding the underlying mechanisms, and (ii) preclinically by developing a more closely dedicated model to identify new therapeutic targets and evaluate new drugs. In this setting, new variants of experimental autoimmune encephalomyelitis (EAE) are currently developed in mice to exhibit less severe motor impairments, thereby avoiding confounding factors in assessing pain behaviors over the disease course. Among these, the optimized relapsing-remitting EAE (QuilA-EAE) mouse model, induced using myelin oligodendrocyte glycoprotein peptide fragment (35–55), pertussis toxin, and quillaja bark saponin, seems very promising. Our study sought (i) to better define sensitive dysfunctions and (ii) to extend behavioral characterization to interfering symptoms often associated with pain during MS, such as mood disturbances, fatigue, and cognitive impairment, in this optimized QuilA-EAE model. We made an in-depth characterization of this optimized QuilA-EAE model, describing for the first time somatic thermal hyperalgesia associated with mechanical and cold allodynia. Evaluation of orofacial pain sensitivity showed no mechanical or thermal allodynia. Detailed evaluation of motor behaviors highlighted slight defects in fine motor coordination in the QuilA-EAE mice but without impact on pain evaluation. Finally, no anxiety-related or cognitive impairment was observed during the peak of sensitive symptoms. Pharmacologically, as previously described, we found that pregabalin, a treatment commonly used in neuropathic pain patients, induced an analgesic effect on mechanical allodynia. In addition, we showed an anti-hyperalgesic thermal effect on this model. Our results demonstrate that this QuilA-EAE model is clearly of interest for studying pain symptom development and so could be used to identify and evaluate new therapeutic targets. The presence of interfering symptoms still needs to be further characterized.

Exploring the Use of the Current Perception Threshold in Pharyngeal Paresthesia Patients.

To explore pharyngeal sensory function by current perception threshold (CPT) measurement in paresthetic pharynx. In total, 58 healthy participants and 66 patients with pharyngeal paresthetic symptoms underwent CPT evaluation. Pharyngeal paresthesia (n = 66) was classified into three categories based on aetiologies: six cases with pain in pharynx; 34 neuropathic patients with glossopharyngeal nerve and/or vagus nerve or recurrent laryngeal nerve injury; and 26 patients with globus pharyngeus. CPT measurements were obtained from bilateral palatoglossal arch and tongue base at 2000, 250 and 5Hz stimulation frequencies. Ranked from high to low, the CPT values for the bilateral palatoglossal arches and tongue bases were: lower cranial neuropathic patients, globus pharyngeus, healthy participants and patients with pain. The CPT values for neuropathic patients on the injured side were significantly higher than those on the healthy side (P < 0.05). The CPT values for patients with pain in pharynx were significantly lower than those of healthy participants (P < 0.05) when the bilateral tongue bases were stimulated. The CPT measurement is a reliable method for quantitatively assessing pharyngeal sensory function and able to differentiate pharyngeal paresthesia between lower cranial neuropathic and subjective discomfort. Pharyngeal sensory function is more sensitive in patients with pain in pharynx. Pharyngeal sensory function is significantly reduced in lower cranialneuropathic patients, especially on the injured side. Patients with globus pharyngeus have pharyngeal hyposensitivity.

Subgrouping of Peripheral Neuropathic Pain Patients According to Sensory Symptom Profile Using the Korean Version of the PainDETECT Questionnaire

BackgroundA culturally validated Korean version of the PainDETECT Questionnaire (PD-Q) was used to identify neuropathic pain components (NeP) in patients suffering from chronic pain. The purpose of this study was to determine if the Korean PD-Q can be used to subgroup patients with peripheral NeP according to sensory symptom profiles.MethodsThis study included 400 Korean patients with peripheral neuropathic pain diagnosed as probable or definite NeP. The total scores and subscores for each item in PD-Q were transformed into a Z-score for standardization. Hierarchical cluster analysis was performed to identify clusters of subjects by PD-Q scores.ResultsThe mean total PD-Q score of the study participants was 14.57 ± 6.46. A hierarchical cluster analysis identified 5 clusters with distinct pain characteristic profiles. Cluster 1 had relatively severe burning and tingling sensations. The mean total PD-Q score for cluster 2 was the lowest of the 5 clusters. Cluster 3 tended to be vulnerable to pain in response to cold/heat stimulation. Cluster 4 showed relatively severe pain induced by physical stimuli, such as light touch or slight pressure. Cluster 5 had high scores for all NeP symptoms.ConclusionThis study demonstrates the ability of patients to cluster by symptoms using the Korean PD-Q. Subgrouping of peripheral neuropathic pain by sensory symptom profile may be useful in making effective drug treatment decisions.

POSC376 Speak up Your Pain: Patient Care Course in Chronic Pain

In France 11% of the population suffers from chronic pain translating to 72 million consultations a year. Furthermore, up to 7% of the population suffers from neuropathies. The aim of the study was to apprehend the daily life of patients suffering from chronic pain in France. A questionnaire was created with the inputs of patients’ associations. The questions were about social characteristics, disease history, relationship with healthcare professionals, pain description – both quantitative and qualitative (French Version of Short McGill Pain Questionnaire (SMGPQ ). From June to September 2020, patients answered online the 113 questions of the survey. 643 patients answered the questionnaire among them 121 were considered as suffering from neuropathies. The mean age was 52,21 +/- 17,23. 90% of the respondent were women. 80% of the respondents were satisfied with the attention they received from their GPs, with no significant difference in this respect between patients with nociceptive and neuropathic pain. The values of the visual analogue scales for patients with neuropathic and nociceptive pain were significantly different 7.20±1.46 vs 6.31±2.03. (p<0,001) A significant difference (p<0.001) was found using the SMGPQ on the intensity of clinical signs characteristic of neuropathic pain compared to nociceptive pain: hot/burning (2.07±1.31 vs. 1.47±1.30), tingling (1.98±1.17 vs. 1.47±1.22), electric discharges (1.98±1.16 vs. 1.38±1.17) Discontinuation of treatment was more frequent in the neuropathic pain population than in the nociceptive pain population. Neuropathic patients preferred and found more effective the use of hypnosis (26% vs. 10%), psychiatry (31% vs. 17%), neurostimulation (36% vs. 18%) than patients with nociceptive pain. There was no significant difference in the breakdown of non-reimbursed expenses between the two cohorts. Overall both spend 352€ a year in out-of-pocket expense. While having different type of pain, French patient suffering from neuropathy have the same care course.

Comparison of Kinesio Taping and Nerve Flossing Technique on Balance, Gait and Ankle Flexibility in Diabetic Neuropathy

Introduction: Diabetic Neuropathy (DN) is the most frequent neuropathy in developed countries, with a wide spectrum of clinical symptoms. Kinesiology Tape (KT) is a thin, stretchy, elastic cotton strip with an acrylic adhesive almost identical to human skin in both thickness and elasticity. Nerve Flossing Technique (NFT) is an alternation of combined movements of atleast two joints. Aim: To assess and compare the effects of KT and NFT on diabetic neuropathy patients’ balance, gait and ankle flexibility. Materials and Methods: This experimental study was conducted in Outpatient Department of Physiotherapy at SGT University, Gurugram, Haryana, India, from March 2021 to May 2021. Total 20 diabetic neuropathy patients were conveniently included from the hospital environment and were divided into two treatment groups. Group A (KT) included 10 patients, kinesio taping along with conventional physiotherapy and group B (NFT) included 10 patients, nerve flossing technique along with conventional physiotherapy. In both the groups, treatment was provided for three days a week for two weeks to improve their balance, gait and ankle flexibility. Performance Oriented Mobility Assessment (POMA) scores were utilised to assess balance and gait, and a universal goniometer was used to assess ankle Range Of Motion (ROM). Data was analysed by using Independent and Paired t-test. Results: The mean age in group A was 55.3±5.056 years and in group B was 55±4.714 years and there was no significant difference (t=0.137, p-value=0.892). There was a significant difference in POMA score in both the groups (t=-5.344, p-value&lt;0.001) after two weeks of treatment. Ankle joint ROM was improved in group B than group A. Conclusion: The study concludes that KT improves balance and gait more than NFT, whereas NFT improves ankle range of motion more than KT in diabetic neuropathic patients.

Exercise and Neuropathy: Systematic Review with Meta-Analysis.

Peripheral neuropathies are a prevalent, heterogeneous group of diseases of the peripheral nervous system. Symptoms are often debilitating, difficult to treat, and usually become chronic. Not only do they diminish patients' quality of life, but they can also affect medical therapy and lead to complications. To date, for most conditions there are no evidence-based causal treatment options available. Research has increased considerably since the last review in 2014 regarding the therapeutic potential of exercise interventions for patients with polyneuropathy. Our objective in this systematic review with meta-analysis was to analyze exercise interventions for neuropathic patients in order to update a systematic review from 2014 and to evaluate the potential benefits of exercise on neuropathies of different origin that can then be translated into practice. Two independent reviewers performed a systematic review with meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Inclusion criteria according to the PICOS approach were: neuropathic patients, exercise interventions only, an inactive or non-exercising control group, and solely randomized controlled trials with the following outcome parameters: neuropathic symptoms, balance parameters, functional mobility, gait, health-related quality of life, and HbA1c (glycated hemoglobin). A total of 41 randomized, controlled trials met all inclusion criteria, 20 of which could be included in the quantitative analysis. Study quality varied from moderate to high. Current data further support the hypothesis that exercise is beneficial for neuropathic patients. This is best documented for patients with diabetic peripheral neuropathy (DPN) (27 studies) as well as for chemotherapy-induced peripheral neuropathy (CIPN) (nine studies), while there are only few studies (five) on all other causes of neuropathy. We found standardized mean differences in favor of the exercise group of 0.27-2.00 for static balance, Berg Balance Scale, Timed-up-and-go-test, nerve conduction velocity of peroneal and sural nerve as well as for HbA1c in patients with DPN, and standardized mean differences of 0.43-0.75 for static balance, quality of life, and neuropathy-induced symptoms in patients with CIPN. For DPN, evidence-based recommendations can now be made, suggesting a combination of endurance and sensorimotor training to be most beneficial. For patients with CIPN, sensorimotor training remains the most crucial component. For all other neuropathies, more high-quality research is needed to derive evidence-based recommendations. Overall, it seems that sensorimotor training has great potential to target most neuropathies and combined with endurance training is therefore currently the best treatment option for neuropathies. (PROSPERO 2019 CRD42019124583)/16.04.2019.

Potamogeton perfoliatus L. Extract Attenuates Neuroinflammation and Neuropathic Pain in Sciatic Nerve Chronic Constriction Injury-Induced Peripheral Neuropathy in Rats.

Sciatic nerve injury is often associated with neuropathic pain and neuroinflammation in the central and peripheral nervous systems. In our previous work, Potamogeton perfoliatus L. displayed anti-inflammatory, antipyretic and analgesic properties, predominantly via the inhibition of COX-2 enzyme and attenuation of oxidative stress. Herein, we extended our investigations to study the effects of the plant’s extract on pain-related behaviors, oxidative stress, apoptosis markers, GFAP, CD68 and neuro-inflammation in sciatic nerve chronic constriction injury (CCI) rat model. The levels of the pro-inflammatory marker proteins in sciatic nerve and brainstem were measured with ELISA 14 days after CCI induction. Pretreatment with the extract significantly attenuated mechanical and cold allodynia and heat hyperalgesia with better potential than the reference drug, pregabalin. In addition, CCI lead to the overexpression of prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), tumor necrosis alpha (TNFα), nuclear factor κB (NF-κB), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and NADPH oxidase-1 (NOX-1) and decreased the catalase level in sciatic nerve and brainstem. The observed neuro-inflammatory changes were accompanied with glial cells activation (increased GFAP and CD68 positive cells), apoptosis (increased Bax) and structural changes in both brainstem and sciatic nerve. The studied extract attenuated the CCI-induced neuro-inflammatory changes, oxidative stress, and apoptosis while it induced the expression of Bcl-2 and catalase in a dose dependent manner. It also decreased the brainstem expression of CD68 and GFAP indicating a possible neuroprotection effect. Taking together, P. perfoliatus may be considered as a novel therapy for neuropathic pain patients after performing the required clinical trials.

Laser-evoked potentials recover gradually when using dorsal root ganglion stimulation, and this influences nociceptive pathways in neuropathic pain patients.

Dorsal root ganglion stimulation (DRGS) is able to relieve chronic neuropathic pain. There seems evidence that DRGS might achieve this by gradually influencing pain pathways. We used laser-evoked potentials (LEP) to verify our hypothesis that the recovery of the LEP may reflect DRGS-induced changes within the nociceptive system. Nine patients (mean age 56.8years, range 36-77years, two females) diagnosed with chronic neuropathic pain in the knee or groin were enrolled in the study. We measured each patient's LEP at the painful limb and contralateral control limb on the first, fourth, and seventh day after implantation of the DRGS system. We used the numeric rating scale (NRS) for the simultaneous pain assessment. The LEP amplitude of the N2-P2 complex showed a significant increase on day 7 when compared to day 1 (Z=-2.666, p=0.008) and to day 4 (Z=-2.547, p=0.011), respectively. There was no significant difference in the N2-P2 complex amplitude between ON and OFF states during DRGS. The patients' NRS significantly decreased after 1day (p=0.007), 4days (p=0.007), and 7days (p=0.007) when compared to the baseline. The results show that with DRGS, the LEP recovered gradually within 7days in neuropathic pain patients. Therefore, reduction of the NRS in patients with chronic neuropathic pain might be due to DRGS-induced processes within the nociceptive system. These processes might indicate neuroplasticity mediated recovery of the LEP.

Influence in the outcome of neuropathic pediatric patients after early treatment

BackgroundClean intermittent catheterization (CIC) and anticholinergic drugs are the mainstay treatment for neuropathic bladder (NB). However, there is not consensus about the time therapy should be started in pediatric patients. AimTo analyze the impact of early start (first year of life) of CIC and anticholinergic treatment on long-term renal and bladder function. Our hypothesis is that those children who start conservative treatment in the first year of life have better outcome in terms of bladder and renal function and less need of surgical procedures, compared to those who started treatment later in life. Patients and methodRetrospective study of pediatric patients with NB treated in our hospital (1995–2005) dividing them for comparison in two groups: group 1 started treatment in the first year of life and group 2 between 1 and 5 years old. Collected data included: date of CIC and anticholinergic initiation, presence of VUR or UHN, renal function, UTIs, renal scars, bladder behavior, surgery and urinary continence. ResultsSixty-one patients were included, 25 in group 1 and 36 in group 2. Initially vesico-ureteral reflux (VUR) and overactive bladders were more frequent in group 2. In group 1 one overactive bladder changed to low compliant and in group 2, one normal bladder and 4 overactive bladders changed. At the end of follow-up there were 11 low compliant bladders in group 1 and 17 in group 2. However, in group 1, only 2 patients required bladder augmentation (BA) while in group 2, 12 patients needed it. At the end of the study only 2 patients in group 2 had slight renal insufficiency. ConclusionsPatients who started conservative treatment in the first year of life have better long-term outcome in terms of UTI, renal scars and surgical procedures. Even if they initially had low compliant bladders, these patients require less BA.

Amelioration of Neuropathic Pain and Attenuation of Neuroinflammation Responses by Tetrahydropalmatine Through the p38MAPK/NF-\u03baB/iNOS Signaling Pathways in Animal and Cellular Models

—Neuropathic pain (NP) treatment remains a challenge because the pathomechanism is not yet fully understood. Because of low treatment efficacy, there is an important unmet need in neuropathic pain patients, and the development of a more effective pharmacotherapy is urgently required. Neuroinflammation induced by oxidative stress-mediated activation of nuclear factor-kappa B (NF-κB) plays an important role in NP. In this study, we aimed to investigate the protective properties of tetrahydropalmatine (THP) on a spared nerve injury (SNI) model of neuropathic pain in mice in in vivo and also in in vitro experiments. THP decreased mechanical hyperalgesia and cold allodynia compared with the SNI group. A microarray was applied to analyze differentially expressed of mRNA among different groups, and THP noticeably changed the expression of MAPK-related proteins compared with the SNI groups. H&E staining showed that the THP changed the inflammation after the spared nerve injury, with decreased NO expression in the THP group as compared to the SNI group. In addition, SNI-induced pain was reversed by intraperitoneal administration of THP, and further results indicated that THP suppressed inducible nitric oxide synthase (iNOS, pro-nociceptive mediators), phosphorylated MAPKs, and p65 in the dorsal root ganglions and sciatic nerve, while the serum levels of the pro-inflammatory cytokines IL-1β were significantly higher in the SNI group as compared to the THP group. To identify the molecular mechanism of the antineuropathic activity of THP, sodium nitroprusside (SNP)-induced neuro-2a (N2a) cells, LPS-induced BV2 cells, and LTA-induced astrocytes were further investigated in signaling pathways. In vitro experiments indicated that THP suppressed the expression of IL-1β, iNOS, phosphorylated MAPKs, and p65, which were assayed using western blotting, and immunofluorescence.

Paired Acute Invasive/Non-invasive Stimulation (PAINS) study: A phase I/II randomized, sham-controlled crossover trial in chronic neuropathic pain

BackgroundDorsal root ganglion (DRG) stimulation, an invasive method of neuromodulation, and transcranial direct current stimulation (tDCS), a non-invasive method of altering cortical excitability, have both proven effective in relieving chronic pain. ObjectiveWe employed a randomized, sham-controlled crossover study design to investigate whether single-session tDCS would have an additive therapeutic effect alongside DRG stimulation (DRGS) in the treatment of chronic pain. MethodsSixteen neuropathic pain patients who were previously implanted with DRG stimulators were recruited. Baseline pain scores were established with DRGS-OFF. Pain scores were then recorded with DRGS-ON, after paired sham tDCS stimulation, and after paired active anodal tDCS (a-tDCS) stimulation. For active tDCS, patients were randomized to ‘MEG (magnetoencephalography) localized’ tDCS or contralateral motor cortex (M1) tDCS for 30 min. EEG recordings and evaluations of tDCS adverse effects were also collected. ResultsAll participants reported the interventions to be tolerable with no significant adverse effects during the session. Paired DRGS/active tDCS resulted in a significant reduction in pain scores compared to paired DRGS-ON/sham tDCS or DRGS alone. There was no difference in the additive effect of M1 vs. MEG-localized tDCS. Significant augmentation of beta activity was observed between DRGS-OFF and DRGS-ON conditions, as well as between paired DRGS-ON/sham tDCS and paired DRGS-ON/active tDCS. ConclusionOur results indicate that a single session of tDCS alongside DRGS is safe and can significantly reduce pain acutely in neuropathic pain patients. Paired invasive/non-invasive neuromodulation is a promising new treatment strategy for pain management and should be evaluated further to assess long-term benefits.

Gallic Acid Improved Amytryptiline Effect in Neuropathic Pain Induced by Partial Sciatic Nerve Ligation (PSNL) in Rats

Aim and Backround: Amytriptiline (AMY), an antidepressant, is used in the treatment of neuropathic pain. However, with limited therapeutic benefits and side effects of AMY, it is not helpful to the majority of the neuropathic pain patients. Gallic acid (GA) is a polyphenolic product with potential antioxidant effects, useful in neuropathic pain. Objective: The purpose of the study was to investigate the improved neuropathic pain relief with GA in combination with AMY in rats. Methods: Partial sciatic nerve ligation (PSNL) method is used for neuropathic pain induction in rats. The rats were randomly divided into 6 groups (n = 8), and treated with drugs or vehicle once daily for 15 days after the pain induction. The first group served as Normal control and received normal saline (p.o), the second group served as Sham Control and received Normal Saline (p.o), the third group served as Surgery Control and received normal saline (p.o), the fourth group received AMY (25mg/kg, p.o), while the fifth group received GA (100mg/kg,p.o), and the sixth group received both AMY and GA. Further behavioural studies for pain were carried out on days 1,4,7,10,13,16,19 and 22. Histological studies of sciatic nerves were carried out on days 1, 15 and 22, and on the 22nd day, all the remaining animals were sacrificed for the biochemical estimations of the sciatic nerve tissues. Results: GA attenuates neuropathic pain better in combination with AMY by ameliorating the behavioral, biochemical and histopathological signs and symptoms. This resultant effect is due to its antioxidant, antinociceptive and anti-inflammatory actions. It also potentiates AMY antinociceptive and antioxidant effects when given in combination in a continuous treatment. Conclusion: The results suggest that GA in combination with AMYattenuated the neuropathic pain. Hence, the use of GA as an adjunctive with AMY in the neuropathic pain will be more therapeutically beneficial; further studies on patients to confirm the results are warranted.

EFFECT OF NEURODYNAMIC TECHNIQUES IN DIABETIC NEUROPATHY PATIENTS ON WEIGHT BEARING ASYMMETRY OF LOWER EXTRIMITY

Diabetes is a long-term (chronic) disease in which the body cannot regulate the amount of sugar in the blood. Diabetic peripheral neuropathy (DPN), a microvascular complication of diabetes, is associated with considerable mortality, morbidity and diminished quality of life. The aim of this study is to measure effect of Neurodynamic techniques on weight bearing asymmetry of lower extremity in diabetic neuropathic patients. Method: - We have screened 35 patients and out of that 28 were fullled the inclusion criteria that deemed t as a sample. However, 20 patients were randomly selected as subjects using simple random sampling technique (Lottery method). In the subject experimental (A=10) patients were treated by sciatic nerve mobilization with conventional physical therapy. In the control (B=10), only conventional physical therapy was applied to diabetic neuropathy patients and both group assess weight bearing by foot print and ROM (exion and extension). Group A and B were treated 5 days a week for 4weeks. The m RESULT: ean differences in Clarke's Angel, ChippauxSmirak and Staheli indexes at left and right sides of diabetic neuropathy patient of experimental group between pre and post administration of modality were statistically highly signicant (p&lt;0.001). Conclusion: Sciatic nerve mobilization with conventional physical therapy was more effective for lower limb function than conventional physical therapy alone in patient with diabetic neuropathy patients

Cardiovascular Autonomic Neuropathy in Patients with Diabetes in Cotonou, Benin: A Cross-Sectional Study

Background Diabetes mellitus is well known as a major risk factor for cardiovascular diseases. Cardiovascular autonomic neuropathy is one of the diabetes complications that has a major impact on cardiovascular morbidity and mortality in patients with diabetes. Aim : To determine the prevalence of cardiovascular autonomic neuropathy in patients with diabetes attending the diabetic center in Cotonou and to identify its risk factors. Materials and Methods : It was a cross-sectional study. Cardiovascular autonomic neuropathy was identified using deep breathing test, standind test and the blood pressure response to standing test (orthostatic hypotension). Chi square test was used for statistical analysis and différence was considered significant when p&lt;0.05. Results : A total of 405 subjects were included in the study. Their mean age was 53.67±11,68 years and the mean diabetes duration was 6.66 years. The prevalence of cardiovascular autonomic neuropathy was 65.9%. Regarding the severity of the complication in neuropathic patients, 51.7% of them had an early neuropathy, 41.2% have presented a moderate neuropathy and 7.1% have presented a severe neuropathy. Factors associated with cardiovascular autonomic neuropathy were age of patients (p = 0.0002), diabetes duration (p = 0.0012), hypertension (p =0.0015), dyslipidemia (p = 0.027) and high pulsed blood pressure (p = 0.032) Conclusion : Cardiovascular autonomic neuropathy is a very frequent complication of diabetes mellitus. Unfortunately this complication of diabetes is not often explored in the patient's follow-up examination. As this complication is recognised to be associated with high cardiovascular morbidity and mortality, systematic screening can be recommanded in patients with long duration of diabetes or presenting an other cardiovascular risk factor.

Psychometric and accuracy comparison of three commonly used questionnaires for the diagnosis of neuropathic pain.

Objectives:Diagnosis of neuropathic pain is challenging. Recently, scientists developed multiple questionnaires to expedite this diagnosis including the Self-completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), Douleur Neuropathique 4 questionnaire (DN4), and Neuropathic Pain Questionnaire–Short Form (NPQ-SF).Materials and Methods:We conducted a prospective cohort study to compare the psychometric characteristics and accuracy of the three questionnaires. We assessed reliability with the Cronbach's α reliability coefficient and inter-item correlations, and validity with receiver operating characteristic (ROC) and correlation analyses. We assessed agreement between the diagnosis of the questionnaires and the reference clinical diagnosis using Cohen's kappa coefficient.Results:188 patients were analyzed: 141 (75%) had “definite neuropathic” and 47 (25%) had “nonneuropathic” pain. The NPQ-SF and S-LANSS questionnaires demonstrated acceptable reliability with Cronbach's α coefficient values of 0.54 (95% CI: 0.41–0.64) and 0.65, (95%CI: 0.57–0.72), respectively. The DN4 questionnaire demonstrated high reliability with Cronbach's α coefficient of 0.74 (95%CI: 0.68–0.79). The NPQ-SF, DN4, and S-LANSS questionnaires demonstrated “excellent” diagnostic ability with an area under the ROC curve of 0.82 (95% CI: 0.75–0.89), 0.89 (95% CI: 0.83–0.95), and 0.83 (95% CI: 0.75–0.90), respectively. Based on their optimal cutoff values, the DN4 had the highest sensitivity and lowest specificity in discriminating between neuropathic and nonneuropathic patients, while the S-LANSS had the lowest sensitivity and highest specificity.Conclusion:Both NPQ-SF and S-LANSS demonstrated acceptable reliability, while DN4 demonstrated high reliability. All three demonstrated excellent diagnostic validities; however, it is important to consider the sensitivity and specificity of each.

Na+-dependent inactivation of vascular Na+/Ca2+ exchanger responsible for reduced peripheral blood flow in neuropathic pain model

Reduced skin blood flow has been reported in neuropathic pain patients as well as various peripheral neuropathic pain model animals. We have previously shown that vasodilators, which improves reduced skin blood flow, correlatively alleviate neuropathic pain in chronic constriction injury (CCI) mice, a model of neuropathic pain from peripheral nerve injury. Here, we sought to elucidate the mechanism underlying the reduced skin blood flow in CCI rats. The skin blood flow of the ipsilateral plantar arteries was significantly reduced compared to that of the contralateral ones 4 weeks after loose ligation of the sciatic nerve. The contraction induced by noradrenaline, serotonin, and U46619, a thromboxane receptor agonist, in the isolated ipsilateral plantar arteries was significantly enhanced compared to that in the contralateral ones. KB-R7943, a Na+/Ca2+ exchanger (NCX) inhibitor, shifted the concentration-response curves of noradrenaline to the left in the contralateral arteries but had no effect on the ipsilateral side. There was no significant difference in concentration-response curves of noradrenaline between the ipsilateral and contralateral arteries in the presence of KB-R7943. Amiloride, a non-specific inhibitor of Na+ channels and transporters, comparably shifted concentration-response curves of noradrenaline to the left in both the contralateral and ipsilateral arteries. One hundred nM of noradrenaline induced intracellular Ca2+ elevation in the ipsilateral arteries, which was significantly larger than that induced by 300-nM noradrenaline in the contralateral arteries. These results suggest that reduced peripheral blood flow after nerve injury is due to Na+-dependent inactivation of NCX in the ipsilateral plantar arteries.