scholarly journals Neuroprotective Propensity of 4-Allylpyrocatechol Derivatives against Oxaliplatin Induced Peripheral Neuropathy

2021 ◽  
pp. 92-100
Author(s):  
Tirupathi Rao Annavarapu ◽  
Sujana Kamepalli ◽  
Vijay Kotra ◽  
G. Venkata Rao
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Thermal Hyperalgesia ◽  
The Body ◽  
Protective Effects ◽  
Biochemical Alterations ◽  
Functional Deficits ◽  
Growing Cell ◽  
End Of Treatment ◽  
Number Of Patients

Chemotherapy is used for the treatment of rapidly growing cell diseases in the body. It is most used for the treatment of different kinds of tumors. It can develop neuropathic pain due to damage of peripheral nerve cells and it is called Chemotherapy-Induced Peripheral Neuropathy (CIPN). In this study, we have reported the protective effects of 4-allyl pyrocatechol (4-APC) and its derivatives from biochemical and functional deficits associated with oxaliplatin (OP) induced neuropathy. The animals were submitted to mechanical and thermal hyperalgesia tests, after treatment with OP three times weekly at 0.20 mg/kg and 4-APC and derivatives (10 mg/kg & 30 mg/kg). The pain parameters were evaluated during the treatment period and at the end of treatment. 4-APC significantly prevented the mice from behavioural and biochemical alterations associated with OP-induced neuropathy. Thus, we conclude from this study, the use of 4-APC and its derivatives with OP might reduce the number of patients who develop painful peripheral neuropathy.

scholarly journals Alpha lipoic acid attenuated neuropathic pain induced by chronic constriction Injury of sciatic nerve in rats

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Prasad Neerati ◽  
Harika Prathapagiri
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Lipoic Acid ◽  
Normal Saline ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Alpha Lipoic Acid ◽  
Chronic Neuropathic Pain ◽  
Neuropathic Pain Syndrome

Abstract Background Chronic neuropathic pain syndrome is associated with impaired quality of life and is poorly manageable. Alpha lipoic acid (ALA) is a powerful antioxidant and showed its effectiveness on diabetic neuropathy and other acute peripheral nerve injuries but it was not evaluated in the chronic neuropathic pain, chronic constriction injury (CCI) in rat model by using duloxetine (DLX) as standard. Methodology The main objective of the study was to expedite ALA effect on chronic peripheral neuropathy induced by CCI of sciatic nerve in rats. In this study, male Wister rats were randomly divided into six groups (n = 8) including, normal saline, sham operated, surgery control, DLX 30mg/kg treated, ALA treated 25mg/kg, and ALA+DLX. The CCI of sciatic nerve was conducted on all animals except normal saline group and studied for 21 days (i.e. 14 days treatment period & 7 days treatment free period) by using different behavioral, biochemical and, histopathology studies. Results ALA showed minor but significant decrease of thermal hyperalgesia, cold allodynia, malondialdehyde (MDA), total protein, lipid peroxidation, and nitric oxide levels and significant increase of motor coordination, glutathione level and decreased axonal degeneration significantly. These effects sustained even during treatment free period. ALA enhanced the effect of DLX when given in combination by showing sustained effect. In conclusion, ALA acted as potent antioxidant may be this activity is responsible for the potent neuroprotective effect. Conclusion Hence, ALA attenuated the nueroinflammation mediated by chronic peripheral neuropathy. Further studies are warranted with ALA to develop as a clinically relevant therapeutic agent for the treatment of neuropathic pain.

scholarly journals Nuclear PPAR-γ Activation Modulates Inflammation and Oxidative Stress in Attenuating Chemotherapy-Induced Neuropathic Pain in Vivo

2021 ◽  
pp. 167-179
Author(s):  
Haritha Pasupulati ◽  
Satyanarayana S. V. Padi ◽  
Sujatha Dodoala ◽  
Prasad V. S. R. G. Koganti
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Mechanical Allodynia ◽  
Antinociceptive Effect ◽  
Thermal Hyperalgesia ◽  
Ppar Γ ◽  
Markers Of Inflammation ◽  
And Oxidative Stress

Background: Paclitaxel-induced painful neuropathy is a major dose-limiting side effect and can persist for up to two years after completing treatment that greatly affects both the course of chemotherapy and quality of life in cancer patients. Peroxisome proliferator-activated receptor (PPAR)-γ belongs to a family of nuclear receptors known for their transcriptional and regulatory roles in metabolism, inflammation, and oxidative stress. However, the role of PPAR-γ activation on paclitaxel-induced neuropathic pain is not yet known. Objective: To investigate whether pioglitazone, a PPAR-γ agonist reduce paclitaxel-induced neuropathic pain and to elucidate underlying mechanisms. Methodology: Peripheral neuropathy was induced by administration of paclitaxel (2 mg/kg per injection) intraperitoneally on four alternate days (days 0, 2, 4, 6). Thermal hyperalgesia and mechanical allodynia were assessed and the markers of inflammation and nitroso-oxidative stress were estimated. Results: Pioglitazone did not induce hypoalgesia and had no effect on locomotor activity. Repeated oral administration of pioglitazone (10 and 20 mg/kg,) for 2 weeks started 14 days after paclitaxel injection markedly attenuated paw withdrawal responses to thermal (hyperalgesia) and mechanical (allodynia) stimuli. Further, pioglitazone administration significantly reduced elevated level of pro-inflammatory cytokine, TNF-α, in both the dorsal root ganglia and the spinal cord accompanied by marked decrease in oxidative stress parameters as well as increase in activity of antioxidant defense enzyme, superoxide dismutase, in the spinal cord after paclitaxel injection. Conclusion: The results of the present study demonstrate that pioglitazone, a PPAR-γ agonist exerted antinociceptive effect in paclitaxel-induced neuropathic pain through inhibiting neuroimmune inflammation in both the periphery and spinal cord and by reducing nitroso-oxidative stress in spinal cord. Our findings strongly suggest pharmacological activation of PPAR-g as a promising therapeutic target in paclitaxel-induced peripheral neuropathy and provide rationale for the clinical evaluation.

scholarly journals Pain Catastrophizing Predicts Poor Response to Topical Analgesics in Patients with Neuropathic Pain

2012 ◽  
Vol 17 (1) ◽  
pp. 10-14 ◽  
Author(s):  
Tsipora Mankovsky ◽  
Mary E Lynch ◽  
AJ Clark ◽  
J Sawynok ◽  
Michael JL Sullivan
Keyword(s):  
Neuropathic Pain ◽  
Clinical Relevance ◽  
Rating Scale ◽  
Pain Catastrophizing ◽  
The United States ◽  
Pharmacological Interventions ◽  
End Of Treatment ◽  
Number Of Patients ◽  
Pain Ratings ◽  
Topical Analgesics

The prevalence of neuropathic pain approaches 10% in Canada and the United States. Given the aging population and the increasing survival rates following interventions for neuropathic pain, the prevalence of neuropathic pain conditions is expected to rise significantly over the next 20 years. Although pharmacological interventions represent the dominant treatment approach for neuropathic pain, as many as 50% of patients are partially or completely refractory to the available treatments. Pain catastrophizing has been associated with heightened pain experiences in patients with neuropathic pain conditions; however, the clinical relevance of the relationship between catastrophizing and poor treatment outcomes is, to date, unclear. Accordingly, using a numerical rating scale, this study aimed to examine this relationship in patients with varied neuropathic pain conditions who completed a measure of catastrophizing before initiating a course of topical analgesic.BACKGROUND: Previous research suggests that high levels of pain catastrophizing might predict poorer response to pharmacological interventions for neuropathic pain.OBJECTIVE: The present study sought to examine the clinical relevance of the relation between catastrophizing and analgesic response in individuals with neuropathic pain. Clinically meaningful reductions were defined in terms of the magnitude of reductions in pain through the course of treatment, and in terms of the number of patients whose end-of-treatment pain ratings were below 4/10.METHODS: Patients (n=82) with neuropathic pain conditions completed a measure of pain catastrophizing at the beginning of a three-week trial examining the efficacy of topical analgesics for neuropathic pain.RESULTS: Consistent with previous research, high scores on the measure of pain catastrophizing prospectively predicted poorer response to treatment. Fewer catastrophizers than noncatastrophizers showed moderate (≥2 points) or substantial reductions in pain ratings through the course of treatment. Fewer catastrophizers than noncatastrophizers achieved end-of-treatment pain ratings below 4/10.CONCLUSIONS: The results of the present study suggest that the development of brief interventions specifically targeting catastrophic thinking might be useful for enhancing the effects of pharmacological interventions for neuropathic pain. Furthermore, failure to account for the level of catastrophizing might contribute to null findings in clinical trials of analgesic medication.

scholarly journals Quercetin Modulates Behavioural and Biochemical Alterations in Stressed Mice

2021 ◽  
Vol 18 (4) ◽  
pp. 681-689
Author(s):  
Anthony Taghogho Eduviere ◽  
Emuesiri Goodies Moke ◽  
Adrian Itivere Omogbiya ◽  
Lily Oghenevovwero Otomewo ◽  
Juliet Nnenda Olayinka ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Sleep Deprivation ◽  
Neuroprotective Effect ◽  
The Body ◽  
Sleep Disruption ◽  
Control Group ◽  
Protective Effects ◽  
Active Sleep ◽  
Metabolic System ◽  
Biochemical Alterations

Disruption of the active phase of sleep alters the physiological homeostasis of the body and results in oxidative breakdown which may trigger a wide array of defects. The central nervous system and the metabolic system are some of the most affected systems as described in several literatures. Some plant based compounds with antioxidant property have been previously described in the abrogation of the deleterious effects of active sleep disruption. One of such compounds is quercetin. This study was premeditated to expatiate on the probable neuroprotective effect of quercetin on mice exposed to 72hr active sleep disruption. Mice were allotted into five treatment groups (n = 6): group 1 served as control, group 2 received 10 mL/kg vehicle, groups 3 and 4 received 25 and 50 mg/kg quercetin respectively, and group 5 received 50 mg/kg astaxanthin. Treatment lasted for 7 days while groups 2-5 were exposed to the sleep deprivation protocol starting from day 4. Behavioural tests followed by biochemical assays and histopathological changes in the prefrontal cortex were evaluated. Data were analysed by ANOVA set at p<0.05 significance. The results revealed that quercetin, in both doses, significantly amplified memory performance, attenuated depression-like behaviour, replenished catalase and superoxide dismutase, attenuated nitric oxide levels in brain and liver of mice when compared to control group and protected against loss of prefrontal cortex neurons. In conclusion, quercetin possesses protective effects against sleep deprivation-induced brain damage.

scholarly journals Treatment of peripheral neuropathy: a multidisciplinary approach is necessary

2020 ◽  
Vol 63 (8) ◽  
pp. 432-434
Author(s):  
Ho Seong Lee
Keyword(s):  
Neuropathic Pain ◽  
Drug Therapy ◽  
Peripheral Neuropathy ◽  
Physical Therapy ◽  
Physical Exercise ◽  
Effective Treatment ◽  
Multidisciplinary Approach ◽  
Recommended Treatment ◽  
Appropriate Treatment ◽  
Number Of Patients

The number of patients with peripheral neuropathy or neuropathic pain is increasing. The recommended treatment for peripheral neuropathy and neuropathic pain is proper medications, exercise, physical therapy, and support. Overly invasive interventions can be harmful rather than beneficial to patients. Many doctors do not understand the characteristics of peripheral neuropathy and neuropathic pain. Peripheral neuropathy is not a problem that is confined to a particular department. The most appropriate treatment is a combination of drug therapy, physical exercise, and psychological support. Thus, a multidisciplinary approach is necessary for the effective treatment of peripheral neuropathy and neuropathic pain.

Curcumin Ameliorates Paclitaxel-Induced Pain Hypersensitivity via Alleviation of Inflammation and Oxidative Stress in Rats

2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Pasupulati Haritha ◽  
SV Padi Satyanarayana ◽  
Koganti Bharathi ◽  
Koganti Prasad VSRG
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Mechanical Allodynia ◽  
Nitrosative Stress ◽  
Therapeutic Potential ◽  
Thermal Hyperalgesia ◽  
Antioxidant Defenses ◽  
Markers Of Inflammation ◽  
Factor Α

Painful peripheral neuropathy is the main dose-limiting and long lasting side-effect of paclitaxel therapy. Despite enormous research, there is no effective treatment for paclitaxel-induced peripheral neuropathic pain owing to poor understanding of pathophysiological mechanisms. Growing evidence indicates oxidative-nitrosative stress is one of the leading factors causing chemotherapy induced peripheral neuropathy. Recently, involvement of neuroinflammation has been suggested in the development of paclitaxel-induced neuropathic pain. It is postulated that abrogating cytokine release and improving antioxidant defenses might be suitable targets in controlling neuroinflammation and oxidative-nitrosative stress mediated nociceptive hypersensitivities. Therefore, the study evaluated the effect of curcumin on paclitaxel-induced neuropathic pain in rats. Peripheral neuropathy was induced by administration of paclitaxel (2 mg/kg per injection) intraperitoneally on four alternate days (days 0, 2, 4, 6). Thermal hyperalgesia and mechanical allodynia were assessed and the markers of inflammation and oxidative-nitrosative stress were estimated. Administration of curcumin (50 and 100 mg/kg, p.o.) for 2 weeks started 14 days after paclitaxel injection significantly alleviated paclitaxel-induced nociceptive behavioural hypersensitivity observed as reduced thermal hyperalgesia and mechanical allodynia. These observed ameliorative effects of curcumin on paclitaxel-induced neuropathic pain are accompanied by reduction of tumour necrosis factor-α, a pro-inflammatory cytokine, in both spinal cord and dorsal root ganglia and oxidative-nitrosative stress in spinal cord. The results of the present study demonstrated antihyperalgesic and antiallodynic effects of curcumin. Additional clinical studies are warranted to evaluate therapeutic potential of curcumin as antinociceptive agent in the treatment of paclitaxel-induced neuropathic pain.

The antitoxic and protective effects of Curcuma longa and it`s active agent, Curcumin: оverview

2020 ◽  
pp. 66-72
Author(s):  
A. Khisamova ◽  
O. Gizinger
Keyword(s):  
Curcuma Longa ◽  
Physiological Activity ◽  
Active Agent ◽  
Modern Science ◽  
Physical Exertion ◽  
The Body ◽  
Modern World ◽  
Protective Effects ◽  
Daily Stress ◽  
Anti Cancer

In the modern world, where a person is exposed to daily stress, increased physical exertion, the toxic effect of various substances, including drugs. The task of modern science is to find antioxidants for the body. These can be additives obtained both synthetically and the active substances that we get daily from food. Such a striking example is turmeric, obtained from the plant Curcuma longa. Recently, it has been known that curcumin has an antioxidant, anti-inflammatory, anti-cancer effect and, thanks to these effects, plays an important role in the prevention and treatment of various diseases, in particular, from cancer to autoimmune, neurological, cardiovascular and diabetic diseases. In addition, much attention is paid to increasing the biological activity and physiological effects of curcumin on the body through the synthesis of curcumin analogues. This review discusses the chemical and physical characteristics, analogues, metabolites, the mechanisms of its physiological activity and the effect of curcumin on the body.

STEROID RECEPTOR PHENOTYPE, EXPRESSION OF HER-2/NEU, PD-1, PD-L1 AND LYMPHOCYTIC-MACROPHAGAL INFILTRATION OF ENDOMETRIAL CARCINOMAS: COMPARISON OF MODERN MOLECULAR BIOLOGICAL TYPES OF THE DISEASE (THE ROLE OF BODY MASS INDEX)

2020 ◽  
Vol 66 (1) ◽  
pp. 71-78
Author(s):  
Lev Bershteyn ◽  
Aleksandr Ivantsov ◽  
Aglaya Ievleva ◽  
A. Venina ◽  
I. Berlev
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Tumor Tissue ◽  
Immunohistochemical Analysis ◽  
The Body ◽  
Molecular Profile ◽  
Total N ◽  
Number Of Patients ◽  
Her 2

The aim of this study was to evaluate steroid receptors’ status of tumor tissue in different molecular biological types of endometrial cancer (EC), subdivided according to the current classification, and their colonization by lymphocytic and macrophage cells, taking into account body mass index of the patients. Materials and methods: Material from treatment-naive patients with EC (total n = 229) was included; the number of sick persons varied depending on the method used. The average age of patients was close to 60 years, and about 90% of them were postmenopausal. It was possible to divide the results of the work into two main subgroups: a) depending on the molecular biological type of the tumor (determined on the basis of genetic and immunohistochemical analysis), and b) depending on the value of the body mass index (BMI). The latter approach was used in patients with EC type demonstrating a defective mismatch repair of the incorrectly paired nucleotides (MMR-D) and with a type without characteristic molecular profile signs (WCMP), but was not applied (due to the smaller number of patients) in EC types with a POLE gene mutation or with expression of the oncoprotein p53. According to the data obtained, when comparing various types of EC, the lowest values of Allred ER and PR scores were revealed for POLE-mutant and p53 types, while the “triple-negative” variant of the tumor (ER-, PR-, HER2/neu-) was most common in POLE-mutant (45.5% of cases) and WCMP (19.4%) types of EC. The p53+ type of EC is characterized by inclination to the higher expression of the macrophage marker CD68 and lymphocytic Foxp3, as well as mRNA of PD-1 and SALL4. In addition to the said above, for WCMP type of EC is peculiar, on the contrary, a decrease in the expression of lymphocytic markers CD8 (protein) and PD-L1 (mRNA). When assessing the role of BMI, its value of >30.0 (characteristic for obesity) was combined with an inclination to the increase of HER-2/neu expression in the case of MMR-D EC type and to the decrease of HER-2 /neu, FOXp3 and ER expression in WCMP type. Conclusions: The accumulated information (mainly describing here hormonal sensitivity of the tumor tissue and its lymphocytic-macrophage infiltration) additionally confirms our earlier expressed opinion that the differences between women with EC are determined by both the affiliation of the neoplasm to one or another molecular biological type (subdivided according to the contemporary classification), as well as by body mass value and (very likely) the associated hormonal and metabolic attributes.

The Therapeutic Potential of Chemokines in the Treatment of Chemotherapy- Induced Peripheral Neuropathy

2020 ◽  
Vol 21 (3) ◽  
pp. 288-301 ◽  
Author(s):  
Lin Zhou ◽  
Luyao Ao ◽  
Yunyi Yan ◽  
Wanting Li ◽  
Anqi Ye ◽  
...  
Keyword(s):  
Nervous System ◽  
Neuropathic Pain ◽  
Immune System ◽  
Peripheral Neuropathy ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Chemotherapeutic Agents ◽  
Cell Trafficking ◽  
Mediated Communication ◽  
Novel Therapeutic Strategies

Background: Some of the current challenges and complications of cancer therapy are chemotherapy- induced peripheral neuropathy (CIPN) and the neuropathic pain that are associated with this condition. Many major chemotherapeutic agents can cause neurotoxicity, significantly modulate the immune system and are always accompanied by various adverse effects. Recent evidence suggests that cross-talk occurs between the nervous system and the immune system during treatment with chemotherapeutic agents; thus, an emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN, as demonstrated by the upregulation of chemokines. Chemokines were originally identified as regulators of peripheral immune cell trafficking, and chemokines are also expressed on neurons and glial cells in the central nervous system. Objective: In this review, we collected evidence demonstrating that chemokines are potential mediators and contributors to pain signalling in CIPN. The expression of chemokines and their receptors, such as CX3CL1/CX3CR1, CCL2/CCR2, CXCL1/CXCR2, CXCL12/CXCR4 and CCL3/CCR5, is altered in the pathological conditions of CIPN, and chemokine receptor antagonists attenuate neuropathic pain behaviour. Conclusion: By understanding the mechanisms of chemokine-mediated communication, we may reveal chemokine targets that can be used as novel therapeutic strategies for the treatment of CIPN.

Prevention and Healing of Calcium Signaling Mediated Neuronal Damage on successive Administration of Flavonoid Enriched Pterocarpus Marsupium Roxb in Peripheral Neuropathy Model

2020 ◽  
Vol 16 (9) ◽  
pp. 1346-1355
Author(s):  
Neethi Shaju ◽  
Mrinmoy Gautam ◽  
Abdul Khayum ◽  
Gunasekaran Venkatesh
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Motor Neurons ◽  
Neuronal Damage ◽  
Interleukin 10 ◽  
Central Mechanism ◽  
Behavioral Models ◽  
Cell Hyperplasia ◽  
Pterocarpus Marsupium

Background: Modern research on peripheral neuropathy circumstance utter that treatments with Vincristine (VCR) disturb the microtubular cells in sensory and motor neurons due to calcium over- load in sciatic nerve, unfortunately, VCR triggering the release of Tumor necrosis factor-α (TNFα) in central neurons causes excitotoxicity as well. Although ethnomedical information specifies that Pterocarpus marsupium Roxb (PM) is widely used for various nervous disorders, not yet justified on VCR induced peripheral neuropathy and in relation to central mechanism. Objective: This study is aimed to explore the possible central and peripheral mechanism of flavonoid enriched PM in VCR induced neuropathy model. Methods: Neuropathic pain was induced in female Wistar rats by VCR (75μg/ kg/day, i.p) for 10 days. Nociceptive thresholds were assessed by subjecting them to behavioral and biochemical estimation, proinflammatory cytokines along with morphological evaluation. Results: PM significantly increased the nociceptive threshold evident from various behavioral models in comparison to VCR group. More importantly, PM significantly reversed the VCR induced calcium elevation, glutamate and aspartate release in the brain. Discussion: It was also observed that the raised TNF-α, Interleukin-1β were controlled and interleukin- 10 was elevated in sciatic nerve after PM treatment. Evident from histology, PM markedly reversed the VCR induced axonal degeneration, Schwann cell hyperplasia, and myelin fibrosis. Conclusion: Flavonoid enriched PM both 100 & 200mg/kg post and co-administration exerted a preventive and curative effect in VCR induced neuropathic pain by controlling calcium-mediated excitotoxicity through peripheral and central mechanism.

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