scholarly journals Pentoxifylline Ameliorates Mechanical Hyperalgesia in a Rat Model of ChemotherapyInduced Neuropathic Pain

2016 ◽  
Vol 4;19 (4;5) ◽  
pp. E589-E600
Author(s):  
Salahadin Abdi
Keyword(s):  
Neuropathic Pain ◽  
Continuous Infusion ◽  
Inflammatory Cytokines ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Pain Treatment ◽  
Phosphodiesterase Inhibitor ◽  
Pain Behavior ◽  
Sprague Dawley ◽  
Tnf Α

Background: Chemotherapy-induced neuropathic pain is difficult to treat. Pentoxifylline inhibits the production of inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Objective: The aims of our study were to investigate the analgesic and preventive effects of pentoxifylline on paclitaxel-induced neuropathic pain in rats and to identify its mechanisms of action. Study Design: Controlled animal study. Methods: Neuropathic pain was induced with intraperitoneally injected paclitaxel on 4 alternate days in male Sprague-Dawley rats. Pentoxifylline was administered systemically as a single injection and a continuous infusion before or after the injection of paclitaxel. The mechanical threshold for allodynia was measured by using von Frey filaments. Protein levels and localization of inflammatory cytokines were performed by using Western blotting and immunohistochemistry, respectively. Results: After the rats developed neuropathic pain behavior, a single intraperitoneal injection and continuous infusion of pentoxifylline ameliorated paclitaxel-induced mechanical allodynia. In addition, systemic infusion of pentoxifylline in the early phase of the development of pain behavior delayed the onset of paclitaxel-induced pain behavior. Paclitaxel increased the levels of the catalytic subunit α of protein kinase A, phosphorylated nuclear factor κB, TNF-α, and IL-1β in the lumbar dorsal root ganglia. Pentoxifylline decreased the paclitaxel-induced TNF-α and IL1β levels. In addition, IL-1β was expressed in neurons and satellite cells in the lumbar dorsal root ganglia after paclitaxel. Limitations: Although this study was performed in the animal model by well-designed manner, clinical study will be needed to confirm the analgesic effect of pentoxifylline. Conclusion: Pentoxifylline alleviated chemotherapy-induced neuropathic pain in rats by reducing the levels of inflammatory cytokines in dorsal root ganglia and may be effective chemotherapyinduced neuropathic pain in patients. Key words: Chemotherapy, chronic pain, inflammatory cytokines, neuropathic pain, paclitaxel, pain behavior, pain treatment, pentoxifylline, phosphodiesterase inhibitor

scholarly journals Metamizole relieves pain by influencing cytokine levels in dorsal root ganglia in a rat model of neuropathic pain

2020 ◽  
Vol 72 (5) ◽  
pp. 1310-1322
Author(s):  
Renata Zajaczkowska ◽  
Klaudia Kwiatkowski ◽  
Katarzyna Pawlik ◽  
Anna Piotrowska ◽  
Ewelina Rojewska ◽  
...  
Keyword(s):  
Nervous System ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Pain Treatment ◽  
Opioid Analgesic ◽  
Intraperitoneal Administration ◽  
Pain Symptoms

Abstract Background Treatment of neuropathic pain is still challenging. Recent studies have suggested that dorsal root ganglia (DRG), which carry sensory neural signals from the peripheral nervous system to the central nervous system, are important for pathological nociception. A proper understanding of the significance and function of DRG and their role in pharmacotherapy can help to improve the treatment of neuropathic pain. Metamizole, also known as sulpyrine or dipyrone, is a non-opioid analgesic commonly used in clinical practice, but it is not used for neuropathic pain treatment. Methods Chronic constriction injury (CCI) of the sciatic nerve was induced in Wistar rats. Metamizole was administered intraperitoneally (ip) preemptively at 16 and 1 h before CCI and then twice a day for 7 days. To evaluate tactile and thermal hypersensitivity, von Frey and cold plate tests were conducted, respectively. Results Our behavioral results provide evidence that repeated intraperitoneal administration of metamizole diminishes the development of neuropathic pain symptoms in rats. Simultaneously, our findings provide evidence that metamizole diminishes the expression of pronociceptive interleukins (IL-1beta, IL-6, and IL-18) and chemokines (CCL2, CCL4, and CCL7) in DRG measured 7 days after sciatic nerve injury. These assays indicate, for the first time, that metamizole exerts antinociceptive effects on nerve injury-induced neuropathic pain at the DRG level. Conclusions Finally, we indicate that metamizole-induced analgesia in neuropathy is associated with silencing of a broad spectrum of cytokines in DRG. Our results also suggest that metamizole is likely to be an effective medication for neuropathic pain. Graphic abstract

scholarly journals Astragalin Alleviates Neuropathic Pain by Suppressing P2X4-Mediated Signaling in the Dorsal Root Ganglia of Rats

2021 ◽  
Vol 14 ◽  
Author(s):  
Mengke Wang ◽  
Xia Cai ◽  
Yueying Wang ◽  
Shizhen Li ◽  
Na Wang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Therapeutic Potential ◽  
Purinergic Receptor ◽  
Pain Behavior ◽  
Hek293 Cells ◽  
Protective Effects ◽  
Satellite Glial Cell ◽  
Clinical Pain

Neurologic damage often leads to neuropathic pain, for which there are no effective treatments owing to its complex pathogenesis. The purinergic receptor P2X4 is closely associated with neuropathic pain. Astragalin (AST), a compound that is used in traditional Chinese medicine, has protective effects against allergic dermatitis and neuronal injury, but its mechanism of action is not well understood. The present study investigated whether AST can alleviate neuropathic pain in a rat model established by chronic constriction injury (CCI) to the sciatic nerve. The model rats exhibited pain behavior and showed increased expression of P2X4 and the activated satellite glial cell (SGC) marker glial fibrillary acidic protein in dorsal root ganglia (DRG). AST treatment partly abrogated the upregulation of P2X4, inhibited SGC activation, and alleviated pain behavior in CCI rats; it also suppressed ATP-activated currents in HEK293 cells overexpressing P2X4. These data demonstrate that AST relieves neuropathic pain by inhibiting P2X4 and SGC activation in DRG, highlighting its therapeutic potential for clinical pain management.

Pulsed radiofrequency to the dorsal root ganglion or the sciatic nerve reduces neuropathic pain behavior, decreases peripheral pro-inflammatory cytokines and spinal β-catenin in chronic constriction injury rats

2019 ◽  
Vol 44 (7) ◽  
pp. 742-746 ◽  
Author(s):  
Ren Jiang ◽  
Ping Li ◽  
Yong-Xing Yao ◽  
Hong Li ◽  
Rongjun Liu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Dorsal Root Ganglion ◽  
Inflammatory Cytokines ◽  
Dorsal Root ◽  
Chronic Constriction Injury ◽  
Pain Behavior ◽  
Pulsed Radiofrequency ◽  
Behavioral Tests ◽  
Pro Inflammatory Cytokines

Background and objectivesPulsed radiofrequency (PRF) is a minimal neurodestructive interventional pain therapy. However, its analgesic mechanism remains largely unclear. We aimed to investigate the peripheral and spinal mechanisms of PRF applied either adjacent to the ipsilateral L5 dorsal root ganglion (PRF-DRG) or PRF to the sciatic nerve (PRF-SN) in the neuropathic pain behavior induced by chronic constriction injury (CCI) in rats.MethodsOn day 0, CCI or sham surgeries were performed. Rats then received either PRF-DRG, PRF-SN, or sham PRF treatment on day 4. Pain behavioral tests were conducted before surgeries and on days 1, 3, 5, 7, 9, 11, 13, and 14. After the behavioral tests, the rats were sacrificed. The venous blood or sciatic nerve samples were collected for ELISAs and the dorsal horns of the L4–L6 spinal cord were collected for western blot examination.ResultsThe mechanical allodynia and the thermal hyperalgesia has been relieved by a single PRF-DRG or PRF-SN application. In addition, the analgesic effect of PRF-DRG was superior to PRF-SN on CCI-induced neuropathic pain. Either PRF-DRG or PRF-SN reversed the enhancement of interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels in the blood of CCI rats. PRF-DRG or PRF-SN also downregulated spinal β-catenin expression.ConclusionsPRF treatment either to DRG or to sciatic nerve reduced neuropathic pain behavior, and reduced peripheral levels of pro-inflammatory cytokines and spinal β-catenin expression in CCI rats. PRF to DRG has a better analgesic effect than PRF to the nerve.

scholarly journals Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Runan Yang ◽  
Zijing Li ◽  
Yuting Zou ◽  
Jingjian Yang ◽  
Lin Li ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Gallic Acid ◽  
Signaling Pathway ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
P2x7 Receptor ◽  
Pain Behaviors ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tnf Α

Neuropathic pain is a complex disease with high incidence. Adenosine triphosphate (ATP) and its activated P2X7 receptor are involved in the signal transmission of neuropathic pain. Gallic acid (3,4,5-trihydroxybenzoic acid) is a traditional Chinese medicine obtained from natural plants that exhibit anti-inflammatory, analgesic, and antitumor effects. However, the underlying mechanism for gallic acid in analgesia remains unknown. This study aims to reveal how gallic acid alleviates neuropathic pain behaviors in a rat model with chronic constriction injury (CCI). Real-time PCR, western blotting, double-label immunofluorescence, molecular docking, and whole-cell patch clamp technology were used to explore the therapeutic action of gallic acid on neuropathic pain. The results showed that after CCI rats were treated with gallic acid for 1 week, the mechanical withdrawal threshold and thermal withdrawal latency were increased, accompanied by inhibition of the upregulated expression of P2X7 and TNF-α at both mRNA and protein levels, and reduced NF-κB and phosphorylated-STAT3 in the dorsal root ganglia. At the same time, gallic acid significantly decreased the coexpression of P2X7 and glial fibrillary acidic protein in the dorsal root ganglia. In addition, gallic acid could suppress ATP-activated current in human embryonic kidney 293 (HEK293) cells transfected with the plasmid expressing P2X7 but had no effect on ATP activation current of P2X7-mutant plasmid (with the point mutation sequence of the key site where gallic acid binds to the P2X7 receptor). Therefore, our work suggests that gallic acid may alleviate neuropathic pain in CCI rats by inhibiting the P2X7 receptor and subsequent activation of the TNF-α/STAT3 signaling pathway.

scholarly journals Relationship between Pain Behavior and Changes in KCNA2 Expression in the Dorsal Root Ganglia of Rats with Osteoarthritis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Qihong Zhao ◽  
Lei Fan ◽  
Jiafeng Wang ◽  
Xiaoming Deng
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Saline Group ◽  
Pain Behavior ◽  
Control Group ◽  
Sprague Dawley ◽  
Blank Control Group ◽  
Cartilage Surface ◽  
Gated Channel ◽  
Surface Destruction

Objective. To investigate the relationship between pain behavior and potassium voltage-gated channel subfamily A member 2 (KCNA2) expression in dorsal root ganglia (DRGs) of rats with osteoarthritis (OA). Methods. Male Sprague-Dawley rats were randomly divided into three groups: blank control group (group C), normal saline group (group S), and group OA. Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured one day before injection and one, two, four, and six weeks after injection. At one, two, four, and six weeks after injection, pathological knee joint changes and activated transcription factor-3 (ATF-3) and KCNA2 expressions in DRGs were analyzed. Results. Compared with preinjection, PWMT and PWTL at two, four, and six weeks after injection were significantly decreased in the group OA (P<0.05 or 0.01). Compared with group C, PWMT and PWTL at two, four, and six weeks after injection were significantly decreased in the group OA (P<0.05 or 0.01). In the group OA, slight local articular cartilage surface destruction was found at week one. The cartilage surface destruction gradually developed, and the exacerbation of cartilage matrix reduction and bone hyperplasia were increasingly aggravated and eventually evolved into advanced OA in the second to sixth weeks. Compared with group C, ATF-3 expression was significantly increased, and KCNA2 expression was significantly decreased in the group OA at two, four, and six weeks after injection (P<0.05 or 0.01). Compared to baseline, ATF-3 expression was significantly increased, and KCNA2 expression was significantly decreased in the group OA (P<0.05 or 0.01). Conclusion. Pain behavior in OA rats was associated with decreased KCNA2 expression in DRGs.

scholarly journals POS1290 CYTOKINE BIOMARKERS IN COMMON LOW BACK PAIN

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 926.3-926
Author(s):  
R. Dhahri ◽  
A. Dghaies ◽  
M. Slouma ◽  
L. Metoui ◽  
I. Gharsallah ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Low Back Pain ◽  
Back Pain ◽  
Inflammatory Cytokines ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Low Back ◽  
Tnf Α ◽  
Functional Scores ◽  
The Mean

Background:Common low back pain (LBP) is a common health problem affecting 50 to 80% of working age adults. It is one of the common and costly health problems in Tunisia. Actually, the role of the immune response and inflammatory cytokines in the pathogenesis of chronic pain has been of growing interest.Objectives:The aim of this study was to assess whether pro and anti-inflammatory cytokines could be detected in serum in patients with LBP compared with healthy subjects and whether they could be related to pain severity and to clinical findings.Methods:It was a an analytical cross-sectional study including 50 patients with at least three months of LBP, in the department of rheumatology, orthopedics and immunology at the Military Hospital of Tunis between January 1st and March 31, 2020. All patients had a standardized clinical assessment.Levels of serum cytokines IL-6, IL-8, IL-1β and TNF- α, were measured using the chimiluminescence technique. Serum concentration of IL-10 was assayed by the enzyme-linked immunosorbent assay technique (ELISA). The normal levels of cytokines were determined in 50 healthy controls.Results:The mean age of the patients was 41.9 ± 8.4 years and the sex ratio was 4.5. LBP duration was 66.4 months. The mean lumbar visual analog scale (VAS) was 4.5 ± 1.9, and the root VAS was 2.6 ± 2.5. Neuropathic pain was found in 26% of patients. The average BMI was 27 ± 3.7 kg/m2. Only serum level of IL-8 was significantly higher in subjects with LBP compared to healthy controls (p <10-3). IL-1β was indetectable in both patients and controls. Positive correlations were found between IL-8 levels and anxiety/functional scores (r = 0.3; p = 0.02/ r = 0.3; p = 0.04). IL-6 was positively correlated with BMI, and negatively correlated with the Schober test. No correlations were found between serum levels of IL-6, IL-8, IL-10, TNF-α and pain intensity (VAS), neuropathic pain (DN4), fibromyalgia (FIRST), depression (HAD) and various radiological data.Conclusion:Interleukin-8 is a biomarker of common low back pain and correlate with anxiety and functional disability. These results suggest that IL-8 may be a therapeutic target to reduce chronic back pain and reduce the social and profession impact.Disclosure of Interests:None declared

Transient early expression of TNF-α in sciatic nerve and dorsal root ganglia in a mouse model of painful peripheral neuropathy

2008 ◽  
Vol 436 (2) ◽  
pp. 210-213 ◽  
Author(s):  
Paola Sacerdote ◽  
Silvia Franchi ◽  
Anna Elisa Trovato ◽  
Anna Elisa Valsecchi ◽  
Alberto E. Panerai ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Mouse Model ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Tnf Α ◽  
Early Expression
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