scholarly journals The Protective Effect of Bergamot Polyphenolic Fraction (BPF) on Chemotherapy-Induced Neuropathic Pain

2021 ◽  
Vol 14 (10) ◽  
pp. 975
Author(s):  
Sara Ilari ◽  
Filomena Lauro ◽  
Luigino Antonio Giancotti ◽  
Valentina Malafoglia ◽  
Concetta Dagostino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Glutamate Transporter ◽  
Thermal Hyperalgesia ◽  
Chemotherapeutic Agents ◽  
Preventive Strategy ◽  
Polyphenolic Extract ◽  
Thermal Hypersensitivity

Paclitaxel is a chemotherapeutic drug used for cancer treatment. Chemotherapy-induced peripheral neuropathy (CIPN) is a common major dose-limiting side effect of many chemotherapeutic agents, including paclitaxel. CIPN is accompanied by mechanical and thermal hypersensitivity that resolves within weeks, months, or years after drug termination. To date, there is no available preventive strategy or effective treatment for CIPN due to the fact that its etiology has not been fully explained. It is clear that free radicals are implicated in many neurodegenerative diseases and recent studies have shown the important role of oxidative stress in development of CIPN. Here, we observed how, in rats, the administration of a natural antioxidant such as the bergamot polyphenolic extract (BPF), can play a crucial role in reducing CIPN. Paclitaxel administration induced mechanical allodynia and thermal hyperalgesia, which began to manifest on day seven, and reached its lowest levels on day fifteen. Paclitaxel-induced neuropathic pain was associated with nitration of proteins in the spinal cord including MnSOD, glutamine synthetase, and glutamate transporter GLT-1. This study showed that the use of BPF, probably by inhibiting the nitration of crucial proteins involved in oxidative stress, improved paclitaxel-induced pain behaviors relieving mechanical allodynia, thermal hyperalgesia, thus preventing the development of chemotherapy-induced neuropathic pain.

scholarly journals Role of Muscarinic Receptors in Hypoalgesia Induced by Crocin in Neuropathic Pain Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Hossein Ali Safakhah ◽  
Abbas Ali Vafaei ◽  
Azin Tavasoli ◽  
Simin Jafari ◽  
Ali Ghanbari
Keyword(s):  
Neuropathic Pain ◽  
Muscarinic Receptors ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Thermal Stimulus ◽  
Male Wistar Rats ◽  
Withdrawal Response ◽  
Plantar Test ◽  
Von Frey Filaments

Objective. Crocin as an important constituent of saffron has antineuropathic pain properties; however, the exact mechanism of this effect is not known. The aim of this study was whether the hypoalgesic effect of crocin can be exerted through muscarinic receptors. Materials and Methods. In the present project, 36 male Wistar rats (200 ± 20 g) were used. Animals randomly divided into six groups (sham, neuropathy, neuropathy + crocin, neuropathy + atropine 0.5 mg/kg, neuropathy + atropine 1 mg/kg, and neuropathy + atropine 1 mg/kg + crocin). Neuropathy was induced by the chronic constriction injury (CCI) method on the sciatic nerve. Crocin and atropine was administered intraperitoneally during 14 days following the 14th day after surgery. Pain response was detected every three days, two hours after each injection and 3 days following last injection. Mechanical allodynia and thermal hyperalgesia were detected using the Von Frey filaments and plantar test device, respectively. Results. CCI significantly reduced the paw withdrawal response to mechanical and thermal stimulus ( P < 0.01 and P < 0.05 , respectively). Crocin therapy significantly reduced mechanical allodynia and thermal hyperalgesia induced by CCI ( P < 0.05 ). Atropine pretreatment significantly blocked the hypoalgesic effect of crocin ( P < 0.05 in mechanical allodynia and P < 0.01 in thermal hyperalgesia). Fourteen days administration of atropine alone at a dose of 0.5 mg/kg but not 1 mg/kg significantly reduced CCI-induced mechanical allodynia at day 30 after surgery. Conclusion. Crocin significantly decreased CCI-induced neuropathic pain. The hypoalgesic effect of crocin was blocked by atropine pretreatment, which indicates an important role for muscarinic receptors in the effect of crocin.

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.

Dose and administration-period play a key role in the effect of ceftriaxone on neuropathic pain in CCI-operated rats

2012 ◽  
Vol 3 (3) ◽  
pp. 186-186 ◽  
Author(s):  
K.K. Frederiksen ◽  
P. Kristensen ◽  
P.H. Honoré ◽  
G. Gegelashvili ◽  
O.J. Bjerrum
Keyword(s):  
Neuropathic Pain ◽  
Glutamate Uptake ◽  
Glutamate Transporter ◽  
Thermal Hyperalgesia ◽  
Dynamic Effect ◽  
Withdrawal Threshold ◽  
Pain Transmission ◽  
Medical Need ◽  
Glutamate Transporter 1 ◽  
Thermal Hypersensitivity

Abstract Introduction An unmet medical need for more effective therapies of neuropathic pain exits. Here modulation of the glutaminergic system represents an unexplored possibility. Down-regulation ofglutamate transporters potentiates pain transmission by delaying the removal of glutamate from the synapse. In the spinal cord, glutamate transporter 1 (GLT–1) is responsible for more than 90% of the glutamate uptake. Ceftriaxone, a β-lactam, is believed to induce the expression of GLT–1 through the transcriptional factor (NF-ºB) pathway, which results in induced promoter activity and thereby increased synthesis of GLT-1 protein. Objectives To evaluate the analgesic effect of ceftriaxone in the Chronic Constriction Injury (CCI) rat model of neuropathic pain and to investigate the pharmacodynamics of ceftriaxone in a chronic dosing regime. Methods In CCI rats, mechanical and thermal hypersensitivity, were determined with von Frey filaments and Hargreaves test, respectively. Groups of rats received ceftriaxone (200, 300 or 400 mg/kg, i.p.) once daily in 7–19 days and the control groups received vehicle. Results From a total of 24 CCI operated rats, 16 rats developed both mechanical (withdrawal threshold ≤3g) and thermal hypersensitivity (latency threshold ≤13 s.). Ceftriaxone alleviated mechanical allodynia and thermal hyperalgesia in CCI operated. Daily dosing of ceftriaxone 200, 300 and 400 mg/kg reached the same withdrawal threshold levels as before the CCI surgery, after 18, 12 and 7 days, respectively. This indicates that the dynamic effect of ceftriaxone is not only dependent of the dose, but also the duration of administration. Thus, it seems that dose exposure above a certain threshold is necessary to induce protein synthesis. Conclusion The CCI model is a useful model to evaluate the anti-nociceptive effects of ceftriaxone. Increased dose do not only elevate effect magnitude but also the rate of with which the effect appears.

scholarly journals Sirt2 in the Spinal Cord Regulates Chronic Neuropathic Pain Through Nrf2-Mediated Oxidative Stress Pathway in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengnan Zhao ◽  
Xiaojiao Zhang ◽  
Xueshu Tao ◽  
Bohan Zhang ◽  
Cong Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Mechanical Allodynia ◽  
Intrathecal Injection ◽  
Thermal Hyperalgesia ◽  
Oxidative Stress Marker ◽  
Oxidative Stress Pathway ◽  
Stress Pathway

Reduction in Nrf2-mediated antioxidant response in the central nervous system plays an important role in the development and maintenance of neuropathic pain (NP). However, the mechanisms regulating Nrf2 activity in NP remain unclear. A recent in vitro study revealed that Sirt2, a member of the sirtuin family of proteins, affects antioxidant capacity by modulating Nrf2 activity. Here we examined whether central Sirt2 regulates NP through Nrf2-mediated oxidative stress pathway. In a rat model of spared nerve injury (SNI)-induced NP, mechanical allodynia and thermal hyperalgesia were observed on day 1 and up to day 14 post-SNI. The expression of Sirt2, Nrf2 and its target gene NQO1 in the spinal cord in SNI rats, compared with sham rats, was significantly decreased from day 7 and remained lower until the end of the experiment (day 14). The mechanical allodynia and thermal hyperalgesia in SNI rats were ameliorated by intrathecal injection of Nrf2 agonist tBHQ, which normalized expression of Nrf2 and NQO1 and reversed SNI-induced decrease in antioxidant enzyme superoxide dismutase (SOD) and increase in oxidative stress marker 8-hydroxy-2′-deoxyguanosine (8-OHdG) in the spinal cord. Moreover, intrathecal injection of a recombinant adenovirus expressing Sirt2 (Ad-Sirt2) that upregulated expression of Sirt2, restored expression of Nrf2 and NQO1 and attenuated oxidative stress in the spinal cord, leading to improvement of thermal hyperalgesia and mechanical allodynia in SNI rats. These findings suggest that peripheral nerve injury downregulates Sirt2 expression in the spinal cord, which inhibits Nrf2 activity, leading to increased oxidative stress and the development of chronic NP.

Lycopene and ketotifen potentiates the anti-hyperalgesic effect of gabapentin in PSNL-induced neuropathic pain in wistar rats

2018 ◽  
Vol 7 (1) ◽  
pp. 5568
Author(s):  
Nischal Tyagi
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Mast Cells ◽  
Sciatic Nerve ◽  
Reduced Glutathione ◽  
Thermal Hyperalgesia ◽  
Partial Sciatic Nerve Ligation ◽  
Antioxidant Mechanism ◽  
Cold Hyperalgesia

The present study is designed to investigate the involvement of antioxidant mechanism and role of mast cells in pathophysiology of neuropathic pain induced by partial sciatic nerve ligation. The effect was evaluated by assessing various behavioural parameters (thermal hyperalgesia, cold hyperalgesia), biochemical parameters (lipid peroxidation, reduced glutathione, superoxide dismutase and catalase). Partial Sciatic nerve ligation (PSNL) significantly caused thermal hyperalgesia, cold hyperalgesia and oxidative damage as compared to normal and sham and group. Upon daily administration of combination of lycopene (50 mg/kg), ketotifen (10mg/kg) and gabapentin (100 mg/kg) considerably reversed hyperalgesia, cold hyperalgesia and also attenuated oxidative stress when compared to PSNL group. The results indicated that combination lycopene, ketotifen and gabapentin exhibited a potentiating effect in neuropathic pain by inhibiting degranulation of mast cells and also by reducing oxidative stress.

scholarly journals Extracellular Signal-Regulated Kinase 5 in the Cerebrospinal Fluid-Contacting Nucleus Contributes to Neuropathic Pain in Rats

2015 ◽  
Vol 6;18 (6;11) ◽  
pp. E1073-E1082
Author(s):  
Li-Cai Zhang
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Element Binding Protein ◽  
Thermal Hypersensitivity

Background: The activation of mitogen-activated protein kinases (MAPKs) have been observed in synaptic plasticity processes of learning and memory in neuropathic pain. Cerebrospinal fluidcontacting nucleus (CSF-CN) has been identified with the onset and persistence of neuropathic pain. However, whether extracellular signal-regulated protein kinase 5 (ERK5), a member of MAPKs, in CSF-CN participates in neuropathic pain has not been studied yet. Objective: The aim of the present study was to identify the role of ERK5 in CSF-CN on the formation and development of neuropathic pain, and to investigate its possible mechanism. Study Design: Controlled animal study. Setting: University laboratory. Methods: After a chronic constriction injury (CCI) model was produced, BIX02188 was dissolved in 1% DMSO and injected into the lateral ventricles LV in a volume of 3 μl with different doses (0.1 μg, 1 μg, 10 μg). Mechanical allodynia and thermal hypersensitivity behavioral test, immunofluorescence, and western blot technique were used in this research. Result: Following CCI, mechanical allodynia and thermal hypersensitivity were developed within a day, peaked at 14 days, and persisted for 21 days. ERK5 was remarkably activated by CCI in CSFCN. Moreover, selective inhibiting of p-ERK5 expression in CSF-CN by BIX02188 could significantly relieve CCI-induced mechanical allodynia and thermal hypersensitivity, accompanying with the decreased phosphorylation of cAMP response-element binding protein (CREB) in CSF-CN. Limitations: More underlying mechanism(s) of the role of ERK5 in CSF-CN on the formation and development of neuropathic pain will be needed to explore in future research. Conclusion: These findings suggest activation of ERK5 in CSF-CN might contribute to the onset and development of neuropathic pain and its role might be partly accomplished by p-CREB. Key words: Neuropathic pain, extracellular signal-regulated kinase 5, distal cerebrospinal fluidcontacting neurons, cerebrospinal fluid-contacting nucleus, chronic constriction injury, cAMP response-element binding protein

scholarly journals Electroacupuncture Enhances Antioxidative Signal Pathway and Attenuates Neuropathic Pain Induced by Chemotherapeutic Paclitaxel

2019 ◽  
pp. 501-510 ◽  
Author(s):  
X. ZHAO ◽  
L. LIU ◽  
Y. WANG ◽  
G. WANG ◽  
Y. ZHAO ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Dorsal Root ◽  
Thermal Sensitivity ◽  
Antioxidant Response ◽  
Signal Pathway ◽  
Superoxide Dismutases ◽  
Behavioral Test ◽  
Thermal Hypersensitivity

One of the significant limiting complications of paclitaxel is painful peripheral neuropathy during its therapy for several types of cancers. Our recent study showed that impairment of Nrf2-antioxidant response element (Nrf2-ARE) and upregulation of oxidative signals in the dorsal root ganglion (DRG) of rats with treatment of paclitaxel result in neuropathic pain. The purpose of this study was to examine the beneficial role played by electroacupuncture (EA) in modifying neuropathic pain evoked by paclitaxel via Nrf2-ARE and oxidative mechanisms. Behavioral test was performed to determine mechanical and thermal sensitivity in rats. Western Blot analysis and ELISA were used to examine expression of Nrf2-ARE and superoxide dismutases (SOD); and the levels of products of oxidative stress in the DRG. Our data showed that paclitaxel increased mechanical and thermal sensitivity and this was accompanied with impaired Nrf2-ARE and SOD in the DRG and amplified products of oxidative stress (i.e. 8-isoprostaglandin F2α and 8-hydroxy-2’-deoxyguanosine). EA treatment largely restored the levels of Nrf2-ARE/SOD and inhibited products of oxidative stress and thereby attenuated mechanical and thermal hypersensitivity induced by paclitaxel. In conclusion, we revealed specific signaling pathways leading to paclitaxel-evoked neuropathic pain, including impairment of Nrf2-ARE and heightened oxidative signals. We further provided evidence for the role of EA in alleviating paclitaxel-neuropathic pain via these molecular mediators.

Age-dependent Responses to Thermal Hyperalgesia and Mechanical Allodynia in a Rat Model of Acute Postoperative Pain

2003 ◽  
Vol 99 (2) ◽  
pp. 443-448 ◽  
Author(s):  
Douglas G. Ririe ◽  
Teri L. Vernon ◽  
Joseph R. Tobin ◽  
James C. Eisenach
Keyword(s):  
Postoperative Pain ◽  
Mechanical Stimulation ◽  
Mechanical Allodynia ◽  
Time Course ◽  
Thermal Hyperalgesia ◽  
Developmental Differences ◽  
Thermal Stimulation ◽  
Age Difference ◽  
Normal Sensitivity ◽  
Thermal Hypersensitivity

Background Developmental differences in short- and long-term responses to pain, especially surgical pain, have received minimal attention. The purpose of the present study was to examine postoperative responses in rats of developmental ages paralleling the infant to young adult human. Methods The withdrawal threshold to von Frey filament testing and withdrawal latency to hind-paw radiant heating were determined before and for various times after hind-paw incision in rats 2, 4, and 16 weeks of age. Control rats of these ages were observed serially without surgery. Results In control animals, younger rats were more sensitive to mechanical stimulation and less sensitive to thermal stimulation. Paw incision resulted in similar changes to both types of stimulation in all age groups, peaking 4 h after surgery. However, the return to normal sensitivity to mechanical stimulation, as measured by return of threshold to 80% of normal, occurred more quickly in 2-week-old than in 4- and 16-week-old animals. In contrast, there was no age difference for time to return to normal sensitivity to thermal stimulation after surgery. Conclusions The more rapid recovery of the younger animals from the mechanical allodynia but not thermal hypersensitivity after surgery suggests the presence of developmental differences in modulation of A-fiber sensitization after surgery. However, the lack of age difference in recovery of thermal hypersensitivity after surgery suggests that sensitization of C-fiber input has a similar time course of resolution of pain over the ages studied in this model. The neural bases for these developmental differences are under study and may lead to a better understanding of pain during development and altered approaches to treatment of postoperative pain in neonates and infants.

scholarly journals Analgesic Effect of Moxibustion with Different Temperature on Inflammatory and Neuropathic Pain Mice: A Comparative Study

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Zhou ◽  
Ruxue Lei ◽  
Chuanyi Zuo ◽  
Yunqing Yue ◽  
Qin Luo ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Spared Nerve Injury ◽  
Chronic Neuropathic Pain ◽  
Chronic Inflammatory Pain ◽  
Significant Difference ◽  
Different Temperatures

The aim of this study was to determine whether variation of temperature during moxibustion would generate division of analgesic effect. The moxibustion with different temperatures (37°C, 42°C, 47°C, and 52°C) was applied to ST36 acupoint for 30 minutes in chronic inflammatory or neuropathic pain mice. The analgesic effect was evaluated by thermal hyperalgesia test in chronic inflammatory pain and by mechanical allodynia in neuropathic pain, respectively. The results indicated that interventions of moxibustion with different temperature caused different analgesic effect on either chronic inflammatory induced by injection of complete Freund’s adjuvant (CFA) or neuropathic pain induced by spared nerve injury (SNI). In chronic inflammatory pain, different moxibustion temperature generated different intensity of analgesic effect: the higher the better. In chronic neuropathic pain, stronger analgesic effect was found in moxibustion with temperature 47°C or 52°C other than 37°C and 42°C. However, there is no significant difference displayed between moxibustion temperatures 47°C and 52°C or 37°C and 42°C. It implies that the temperature should be taken into account for moxibustion treatment to chronic inflammatory or neuropathic pain.

Sign in / Sign up

Export Citation Format

Share Document