scholarly journals Pharmacological Modulation of Rate-Dependent Depression of the Spinal H-Reflex Predicts Therapeutic Efficacy against Painful Diabetic Neuropathy

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 283
Author(s):  
Corinne A. Lee-Kubli ◽  
XiaJun Zhou ◽  
Corinne G. Jolivalt ◽  
Nigel A. Calcutt
Keyword(s):  
Neuropathic Pain ◽  
Diabetic Neuropathy ◽  
Gabaa Receptor ◽  
Gabab Receptor ◽  
Diabetic Rats ◽  
H Reflex ◽  
Painful Diabetic Neuropathy ◽  
Painful Neuropathy ◽  
Inhibitory Function ◽  
Rate Dependent

Impaired rate-dependent depression (RDD) of the spinal H-reflex occurs in diabetic rodents and a sub-set of patients with painful diabetic neuropathy. RDD is unaffected in animal models of painful neuropathy associated with peripheral pain mechanisms and diabetic patients with painless neuropathy, suggesting RDD could serve as a biomarker for individuals in whom spinal disinhibition contributes to painful neuropathy and help identify therapies that target impaired spinal inhibitory function. The spinal pharmacology of RDD was investigated in normal rats and rats after 4 and 8 weeks of streptozotocin-induced diabetes. In normal rats, dependence of RDD on spinal GABAergic inhibitory function encompassed both GABAA and GABAB receptor sub-types. The time-dependent emergence of impaired RDD in diabetic rats was preceded by depletion of potassium-chloride co-transporter 2 (KCC2) protein in the dorsal, but not ventral, spinal cord and by dysfunction of GABAA receptor-mediated inhibition. GABAB receptor-mediated spinal inhibition remained functional and initially compensated for loss of GABAA receptor-mediated inhibition. Administration of the GABAB receptor agonist baclofen restored RDD and alleviated indices of neuropathic pain in diabetic rats, as did spinal delivery of the carbonic anhydrase inhibitor acetazolamide. Pharmacological manipulation of RDD can be used to identify potential therapies that act against neuropathic pain arising from spinal disinhibition.

Analgesic effects of mad honey (grayanotoxin) in mice models of acute pain and painful diabetic neuropathy

2013 ◽  
Vol 33 (2) ◽  
pp. 130-135 ◽  
Author(s):  
A Gunduz ◽  
I Eraydin ◽  
S Turkmen ◽  
O F Kalkan ◽  
S Turedi ◽  
...  
Keyword(s):  
Experimental Study ◽  
Neuropathic Pain ◽  
Diabetic Neuropathy ◽  
Acute Pain ◽  
Diabetic Mouse ◽  
Thermal Stimulus ◽  
Painful Diabetic Neuropathy ◽  
Mice Model ◽  
Painful Neuropathy ◽  
Mad Honey

Objectives: The aim of this experimental study was to investigate the effects of mad honey (grayanotoxin, GTX), used in complementary medicine for a variety of purposes besides being food, on pain thresholds in normal mice as model for acute pain and diabetic mouse as model for neuropathic pain. Methods: Hind paw withdrawal pain threshold to thermal stimulus was measured with a plantar analgesia meter in a mice model using healthy intact animals for acute pain and streptozotocin-induced diabetic animals for chronic neuropathic pain. Time and dose-dependent effects of intraperitoneally (i.p.) administered GTX were investigated in both acute and neuropathic pain. Results: In the acute pain model, administration of GTX caused a dose- and time-dependent marked increase in the pain latency values. In diabetic mice, which had markedly increased threshold to pain, GTX (0.1 mg/kg, i.p.) restored the mean pain latencies by decreasing from the pre-GTX treatment values of 3.2 ± 0.6 to 3.0 ± 0.9s at 10 min, 3.2 ± 0.6s at 20 min, 3.4 ± 0.6s at 30 min, 2.6 ± 0.5s at 60 min and 2.4 ± 0.6s ( p < 0.05) at 100 min. Conclusion: The results from this experimental study indicate that GTX exhibits significant analgesic activity and has potential benefits against painful diabetic neuropathy. This is compatible with the widespread use of GTX containing mad honey for alleviating pain. Further studies involving long-term applications are needed for a more decisive conclusion regarding the usefulness of GTX as an analgesic, especially in the treatment of painful neuropathy.

scholarly journals Optimal Utility of H-Reflex RDD as a Biomarker of Spinal Disinhibition in Painful and Painless Diabetic Neuropathy

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1247
Author(s):  
Anne Worthington ◽  
Alise Kalteniece ◽  
Maryam Ferdousi ◽  
Luca Donofrio ◽  
Shaishav Dhage ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Initial Response ◽  
Healthy Controls ◽  
Painful Diabetic Neuropathy ◽  
Stimulus Response ◽  
Rate Dependent ◽  
Potential Biomarker ◽  
Spinal Inhibition

Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2–4 and 2–5 at 1 Hz, AUC = 0.84 (95%CI 0.76–0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.

scholarly journals The H-Reflex as a Biomarker for Spinal Disinhibition in Painful Diabetic Neuropathy

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Corinne Lee-Kubli ◽  
Andrew G. Marshall ◽  
Rayaz A. Malik ◽  
Nigel A. Calcutt
Keyword(s):  
Diabetic Neuropathy ◽  
H Reflex ◽  
Painful Diabetic Neuropathy

Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy

Pain ◽  
2003 ◽  
Vol 105 (1) ◽  
pp. 71-78 ◽  
Author(s):  
Peter C.N. Watson ◽  
Dwight Moulin ◽  
Judith Watt-Watson ◽  
Allan Gordon ◽  
John Eisenhoffer
Keyword(s):  
Randomized Controlled Trial ◽  
Neuropathic Pain ◽  
Controlled Release ◽  
Diabetic Neuropathy ◽  
Controlled Trial ◽  
Painful Diabetic Neuropathy ◽  
Randomized Controlled

Effect of Pentoxifylline on Diabetic Neuropathic Pain in Rats

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Raghda A.M Salama ◽  
Amany H Hasanin ◽  
May Hamza ◽  
Lobna A Saleh ◽  
Eman K Habib
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Diabetic Neuropathy ◽  
Atpase Activity ◽  
Diabetic Rats ◽  
Developmental Phase ◽  
Epidermal Thickness ◽  
Diabetic Neuropathic Pain ◽  
Late Treatment ◽  
Antiallodynic Effect

Abstract Background and Aim Diabetic neuropathy (DN) is the most common diabetic complication, which has a lifetime prevalence of about 50%. About 20 to 30% of patients with DN suffer from neuropathic pain. This study was designed to investigate the role of early and late treatment of pentoxifylline (PTX) in management of diabetic neuropathic pain (DNP). Method Diabetic rats were administered PTX (50 and 200 mg/kg/day, in drinking water) either one week after STZ injection and for 7 weeks or 6 weeks after STZ injection and for 2 weeks. Mechanical allodynia were assessed weekly, Iba-1 and GFAP immunorectivity, spinal NFκB & spinal sciatic TNF-α were estimated at the end of the study. Epidermal thickness of the food pad and Na+/K+-ATPase activity in sciatic nerve were measured as an outcome measure for predegenerative markers of DN. Results The results of the present study suggest that activated microglia and not astrocytes are involved in the development of experimental diabetic neuropathy. PTX inhibit neuroimmune activation of microglia, reduce the levels of proinflammatory cytokines and improve epidermal thickness of the food pad and Na+/K+-ATPase activity in sciatic nerve. Only PTX 200 mg/kg/day when administered early and late treatment in diabetic rats produced antiallodynic effect. Conclusion PTX is a fundamental drug whose antiallodynic effect depends on the pathogenetic mechanisms and has the ability to halt or inhibit the progression of the disease. The earlier the use of PTX in the developmental phase of mechanical hyperalgesia the more the antiallodynic effect of the drug.

Tanshinone IIA Improves Painful Diabetic Neuropathy by Suppressing the Expression and Activity of Voltage-Gated Sodium Channel in Rat Dorsal Root Ganglia

2018 ◽  
Vol 126 (10) ◽  
pp. 632-639
Author(s):  
Ao Ri-Ge-le ◽  
Zhuang-Li Guo ◽  
Qi Wang ◽  
Bao-Jian Zhang ◽  
Da-Wei Kong ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Dorsal Root ◽  
Pain Perception ◽  
Salvia Miltiorrhiza ◽  
Thermal Hyperalgesia ◽  
Diabetic Rats ◽  
Tanshinone Iia ◽  
Painful Diabetic Neuropathy ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

AbstractPainful diabetic neuropathy (PDN) is one of the intractable complications of diabetes mellitus, which manifest as exaggerated pain perception. Previous studies showed that Tanshinone IIA (TIIA), one of the major bioactive extracts of Salvia miltiorrhiza Bunge, have obvious analgesic effect on different types of pain process, and the underlying analgesic mechanisms are not fully understood. The present study combined the behavioral, electrophysiological and biochemical methods to elucidate the analgesic mechanism of TIIA, using streptozotocin (STZ)-induced PDN rat models. Intraperitoneal injection (i.p.) of TIIA for 3 weeks in PDN rats significantly improved mechanical allodynia and thermal hyperalgesia. Patch clamp recordings showed that the excitability of dorsal root ganglion (DRG) nociceptive neuron was increased in diabetic state, and TIIA treatment effectively recovered the subnormality, which was achieved by preventing augments of both Tetrodotoxin-sensitive (TTX-resistant) and Tetrodotoxin-sensitive (TTX-S) sodium currents. Further, the protein expressions of voltage-gated sodium channels (VGSCs) α-subunits Nav1.3, Nav1.7 and Nav1.9 increased in DRG of diabetic rats and were normalized by TIIA application. In conclusion, this study provides evidence that the TIIA attenuated PDN by effecting VGSCs activities and expressions, indicating that the TIIA could be a promising agent for PDN treatment.

scholarly journals Impact of vitamin D level in diabetic people with peripheral neuropathy

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Mohammad H. Assy ◽  
Nashwa A. Draz ◽  
Sabah E. Fathy ◽  
Mohammad G. Hamed
Keyword(s):  
Vitamin D ◽  
Peripheral Neuropathy ◽  
Diabetic Neuropathy ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Painful Diabetic Neuropathy ◽  
Painful Neuropathy ◽  
Vitamin D Levels ◽  
Lower Vitamin

Abstract Background Diabetes mellitus (DM) is a metabolic disease which is complicated by occurrence of diabetic peripheral neuropathy (DPN). Vitamin D deficiency contributes to the etiology and progression of type 2 DM and development of micro-vascular complications so in this study we assessed vitamin D level in diabetic patients to evaluate the association between vitamin D level and occurrence of diabetic neuropathy and to assess if there is relationship with certain subtypes of diabetic neuropathy. This case–control study was conducted on 80 type 2 diabetic patients divided into four groups equally. (A): Diabetic patients with painful diabetic neuropathy. (B): Diabetic patients with painless diabetic neuropathy. (C): Diabetic patients with painless neuropathy, but have neuropathic ulcer. (D): Diabetic patients without neuropathy. All patients underwent clinical, neurological examination and nerve conduction study. Then CBC and vitamin D were estimated in the studied groups. Results Vitamin D level among the studied painful diabetic neuropathy group (A) ranged from 5.3 to 40.5 ng/dl with mean 17.4 ± 10.9. 70% of them had deficient vitamin D level. In the painless diabetic neuropathy group (B), vitamin D level ranged from 6.5 to 35.5 ng/dl with mean 18.9 ± 8.49. 60% of them had deficient vitamin D level, while only 5% of the diabetic patients without neuropathy had deficient vitamin D level. There is significant negative correlation between vitamin D level and score of neuropathy where the lower vitamin D level the higher neuropathy score. Conclusion Lower vitamin D levels were found in diabetic patients with neuropathy especially those with painful neuropathy.

scholarly journals Does the blood glucose control have an effect on the success of the painful diabetic neuropathy treatment?

2018 ◽  
Vol 75 (6) ◽  
pp. 552-557
Author(s):  
Olivera Jovanikic ◽  
Gordana Andjelic ◽  
Milan Lepic ◽  
Dusica Mirkovic ◽  
Bojan Jovanovic ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Blood Glucose ◽  
Diabetic Neuropathy ◽  
Glucose Control ◽  
Procaine Hydrochloride ◽  
Painful Diabetic Neuropathy ◽  
Pain Symptom ◽  
Excellent Outcome ◽  
Before And After ◽  
The Impact

Background/Aim. Diabetic neuropathy (DN) is the basic complication of diabetes, associated with impared glucoregulation, metabolic distrurbances, microvascular vessel damage and increased cardiovascular risk. We monitored the impact of glucoregulation on the efficacy of painful diabetic neuropathy (PDN) treatment, when all pharmaceutical treatment options were exhausted. Methods. Patients (n = 53, both gender, average age 68.3 ? 12.6) with PDN resistant to the pharmacotherapy were treated with the ultrasound- guided local anesthetic (0.5% procaine hydrochloride, 1% lidocaine, 0.25% levobupivacaine) blocks. Neuropathy was confirmed in accordance with the applicable European Federation of Neurological Societies (EFNS) criteria. Glycosylated hemoglobin (HbA1C) and blood glucose levels were monitored before and after therapy and one month after the treatment. Neuropathic pain was confirmed by Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) or Douleur neuropathique (DN4) or pain DETECT scales. The pain intensity was assessed by Visual analog scale, Neuropathic pain symptom and Neuropathic pain symptom inventory (VAS, NPS and NPSI, respectively) scales before and after therapy and one month after the treatment. The efficacy of the therapy was assessed as: excellent result (> 50% of pain loss), good result (30%?49% of pain loss and the therapy does not work (< 30% of pain loss). The correlation between glucoregulation and the outcome was examined. Results. Because the values of glycenia and HbA1c were not different among patients treated with different local anesthetics, they were presented together. All patients had elevated blood glucose and HbA1C levels before (8.23 ? 2.77 mmol/L and 8.53% ? 2.48% respectively), after (8.43 ? 2.461 mmol/L and 8.85% ? 2.87%, respectively) and one month after the treatment (8.49 ? 2.22 mmol/L and 8.51% ? 2.09%, respectively). The loss of the pain was not result of the decrease in blood glucose and HbA1C blood levels. VAS, NPS, NPSI values were the following before the therapy: 81.53 ? 11.62 mm; 62.00 ? 13.04; 53.40 ? 17.63, respectively; after the therapy: 29.00 ? 9.23 mm; 13.79 ? 6.65; 11.83 ? 7.93, respectively; and one month later: 26.15 ? 8.41 mm; 12.68 ? 6.03; 9.81 ? 7.64, respectively]. There was no correlation between glucoregulation and excellent outcome. Conclusion. Even though the disturbance of glucose control is the key factor for the progression of PDN, it is not significant for the outcome of the pain treatment. New investigations are required.

Synergistic Effects of Vitamin D and Mindfulness Training in Pain Severity, Pain-Related Disability and Neuropathy-Specific Quality of Life Dimensions in Painful Diabetic Neuropathy: A Randomized Clinical Trial with Placebo-controlled

2020 ◽  
Author(s):  
Roya taghadosi nia ◽  
mohammadreza davoudi ◽  
Seyyed Mojtaba Ahmadi ◽  
Amir Abbas Taheri
Keyword(s):  
Quality Of Life ◽  
Vitamin D ◽  
Neuropathic Pain ◽  
Diabetic Neuropathy ◽  
Mindfulness Training ◽  
Pain Severity ◽  
Oral Dosage ◽  
Life Questionnaire ◽  
Painful Diabetic Neuropathy

Abstract Background: This study aimed to examining Synergistic effect of Vitamin D (VD) Supplement and mindfulness on neuropathic pain severity, Pain-Related Disability and Neuropathy-Specific Quality of Life dimensions in painful diabetic neuropathy.Methods: In this randomized controlled trial, totally 225 patients with painful diabetic neuropathy were randomly allocated to five groups: (1) mindfulness and placebo, (2) placebo, (3) mindfulness, (4) VD, and (5) mindfulness and VD. Mindfulness training includes twelves sessions and VD patients received a daily four thousand IU oral dosage (four capsules) with 28,000 IU vitamin D weekly for 12 weeks. Laboratory analyses, Sun exposure time, Vitamin D intake, BMI and Physical activity measured in pre-test and posttest. Pain-Related Disability measured with The Pain Disability Index (PDI). For other outcome variables Neuropathy Specific Quality of Life questionnaire and Neuropathic pain severity scale was utilized.Results: In baseline, measures were not different among the groups. At the end-of-treatment, for outcome variables results showed improvement in all groups except the “placebo” group. About other groups, there was not any difference between VD and mindfulness groups (in and not combined with placebo). However, “VD + mindfulness” has a greater improvement rather than VD and mindfulness groups (P<0.05). Moreover, both protocols have no significant effects on, FBS, BMI and energy intakes (P>0.05).Conclusion: Combining VD and mindfulness can reduce pain severity and pain-related disability, so with these changes patients improve their quality of life.

scholarly journals Botulinum toxin type A for painful diabetic neuropathy: an open-label study

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Shahinaz Helmy ◽  
Tamer Emara ◽  
Amr Abdel Menem
Keyword(s):  
Neuropathic Pain ◽  
Botulinum Toxin ◽  
Diabetic Neuropathy ◽  
Botulinum Toxin Injection ◽  
Botulinum Toxin Type A ◽  
Type A ◽  
Botulinum Toxin Type ◽  
Intradermal Injection ◽  
Painful Diabetic Neuropathy ◽  
Significant Change

Abstract Background A large proportion of painful diabetic neuropathy cases either do not respond or are intolerant to the currently available oral and physical therapies. There is encouraging evidence from a small number of studies that those patients can improve using botulinum toxin injection. The aim of the study was to evaluate the effect of intradermal injection of botulinum toxin type A on painful diabetic neuropathy. Eight adult patients with diabetic peripheral neuropathy (DPN), confirmed by nerve conduction studies, were refractory to a minimum of two neuropathic pain treatments for 6 months or more were recruited. All cases received intradermal injection of 48 units of botulinum toxins—type A in each foot in 6×4 distribution. Follow-up was done after 8 weeks using the Neuropathic Pain Scale (NPS), Pittsburgh Sleep Quality Index (PSQI), and Overall Disability Sum Scale (ODSS). Results After 8 weeks, there was a significant change in NPS from 55.8 (7.8) to 38.5 (8.1) (p value 0.007), also there was significant improvement in ODDS from 4 (IQR, 2.25-4.75) to 2.5 (IQR, 0.5-3) (p value 0.01). However, there was no significant change in PSQI. Conclusion Botulinum toxin type A injection is a promising treatment option in Egyptian DPN adults in this study.

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