scholarly journals Pulsed Radiofrequency Reduced Neuropathic Pain Behavior in Rats Associated with Upregulation of GDNF Expression

2016 ◽  
Vol 19 (2;2) ◽  
pp. 49-58 ◽  
Author(s):  
Luo Fang

Background: Pulsed radiofrequency (PRF) is a novel nondestructive interventional technique for the treatment of neuropathic pain (NP). However, this intervention is still lack of relevant regulation and the mechanism of action is insofar not clear. Historically, most studies have reported that PRF can relieve reduce hyperalgesia in multiple NP animal models by acting on the dorsal root ganglion. However, a few recent studies have shown that PRF can effectively treat hyperalgesia in pain models by a direct application on injured peripheral nerves. Objectives: To observe changes in pain behavior and the pathology of the sciatic nerve (SN) after applying PRF at the ligation site in a chronic constriction injury (CCI) rat model and to investigate the effect of PRF on the expression of glia cell line-derived neurotrophic factor (GDNF) in nervous tissue. Study Design: A randomized, experimental trial. Setting: Experimental Animal Center, Beijing Tiantan Hospital, Capital Medical University. Methods: Thirty-six adult Sprague-Dawley rats were randomly divided into 3 groups: Sham-Sham (SS), CCI-Sham (CS), and CCI-PRF (CP). The right SNs of the rats in the CS and CP groups were ligated to create a CCI model. For the SS group, the right SN was separated without ligation. On the 14th fourteenth day after surgery, PRF treatment was applied at the ligation site of the SN for the rats in the CP group using a 45 V output voltage at 42°C for 3 minutes. The electrode was placed in rats in the SS and CS groups without electricity applied. The hindpaw withdrawal threshold (HWT) and thermal withdrawal latency (TWL) were measured at various time points before and after the treatments in each group. Optical microscopic scores and electron microscopic observation were given to the right SN ligation sites of the rats in each group 14 days after the treatment . Meanwhile, the GDNF expression levels in the ligation site of the SN and in the L4-L6 spinal cord segments were determined for each group by enzyme-linked immunosorbent assay (ELISA). Results: Fourteen days after PRF treatment, the HWT and TWL values in the CP group were significantly increased compared to those of the CS group (P < 0.01). Under the optical microscope, the axonal number, axonal diameter, and myelin sheath thickness in the CP group were significantly increased compared to those of the CS group 14 days after PRF treatment (P < 0.01). Under the electron microscope, the degeneration at the SN ligation site was significantly improved in the CP group compared to the CS group. The GDNF expression levels at the ligation site of the SN and the L4-L6 spinal segments in the CP and CS groups were increased compared to those of the SS group (P < 0.01). In addition, the GDNF expression in the CP group was significantly higher than that in the CS group (P < 0.01). Limitations: GDNF expression was only measured at day 14 after the treatment rather than at various time points during the experiment. Conclusions: The findings suggest that the application of PRF at the impaired SN relieved reduced the CCI-induced NP by through regulating the upregulation of the GDNF expression in the nervous tissues. Key words: Pulsed radiofrequency, chronic constriction injury, sciatic nerve, spinal cord, hind paw withdrawal threshold, thermal withdrawal latency, optical microscopic, electron microscope, glia cell line-derived neurotrophic factor, enzyme-linked immunosorbent assay

Author(s):  
Jiaqi Yuan ◽  
Yue Fei

Abstract Lidocaine is a commonly used drug to alleviate neuropathic pain (NP). This work aims to investigate the mechanism of lidocaine in alleviating NP. Chronic constriction injury (CCI) rats were established by surgery to induce NP. We observed the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats. Immunofluorescence staining was performed to determine the LC3/glial fibrillary acidic protein (GFAP)-positive cells. Rat astrocytes were treated with lipopolysaccharide (LPS) to induce CCI, and then treated with lidocaine or 3-MA (autophagy inhibitor). CCK-8 was performed to detect cell proliferation. Western blot and enzyme-linked immunosorbent assay were performed to detect the level of protein and inflammatory factor. CCI rats exhibited a decrease of MWT and TWL, which was effectively abolished by lidocaine. Lidocaine enhanced the number of LC3/GFAP-positive cells in CCI rats. Moreover, lidocaine inhibited the expression of GFAP and p62, and enhanced LC3-II/LC3-I expression in the LPS-treated astrocytes. Lidocaine inhibited the level of TNF-α and IL-1β in the LPS-treated astrocytes. The influence conferred by lidocaine was effectively abolished by 3-MA. In conclusion, our work demonstrates that lidocaine activates autophagy of astrocytes and ameliorates CCI-induced NP. Thus, our study provides a further experimental basis for the mechanism of lidocaine to alleviate NP.


2018 ◽  
Vol 1 (21;1) ◽  
pp. 33-40 ◽  
Author(s):  
Luo Fang

Background: Several studies in recent years have confirmed that the direct application of pulsed radiofrequency (PRF) on peripheral nerve compression points can alleviate hyperalgesia in animal models of neuropathic pain (NP). However, the mechanism underlying the treatment of peripheral nerves by PRF is unclear. Objectives: We aim to observe changes in pain behavior after the application of PRF on the ligation site of the sciatic nerves (SNs) of rats with chronic constriction injury (CCI) and to investigate the effects of PRF on the transcription and translation levels of glial cell line-derived neurotrophic factor (GDNF) in nerve tissues at the treatment site. Study Design: A randomized, experimental trial. Setting: Experimental Animal Center, Beijing Tiantan Hospital. Methods: Ninety-six adult male Sprague-Dawley rats were randomly divided into 4 groups: sham-sham (SS) group, sham-PRF (SP) group, CCI-sham (CS) group, and CCI-PRF (CP) group. The right SNs of rats in the CS and CP group were ligated to establish the CCI model. The right SNs in the SS and SP groups were isolated and exposed but without being ligated. On the fourteenth day after CCI/sham operation, PRF treatment was performed on the midpoint of the ligation sites of the SN in the CP group and the corresponding sites in the SP group. The electrode was only placed at the ligation sites of the SN in the CS group and the corresponding sites in the SS group without current being applied. The 50% paw withdrawal threshold (50%PWT) and thermal withdrawal latency (TWL) of rats in all of the groups were measured. The transcription and translation levels of GDNF of the PRF/sham treatment sites were measured before and after treatment by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays (ELISAs). Results: The 50%PWT value of the hind paws of rats in the CP group gradually increased on day 6 after the PRF treatment and was significantly higher than that in the CS group (6 days after treatment P < 0.05; 14 days after treatment P < 0.01). The TWL value in the CP group was higher than that in the CS group 2 days after treatment (P < 0.05) and was significantly higher (P < 0.01) from day 6 until the end of the experiment. On the day 6 and 14 after PRF treatment, the mRNA and protein expression levels of GDNF at the ligation sites of the SNs of rats in the CP group were higher than both the levels before treatment and those in the CS group (P < 0.01). Limitations: The efficacy of PRF treatment in the CCI model was only tested within 14 days, and the changes in GDNF levels were only tested at 3 time-points before and after treatment. Conclusions: The direct application of PRF on SN ligation sites in the CCI model can safely and effectively alleviate NP. One of the mechanisms of this effect could be the upregulation of the transcription and translation of GDNF in compressed SNs. Key words: Pulsed radiofrequency, chronic constriction injury, sciatic nerve, 50% paw withdrawal threshold, thermal withdrawal latency, glia cell line-derived neurotrophic factor, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay


2020 ◽  
Vol 19 (5) ◽  
pp. 989-994
Author(s):  
Wentong Xu ◽  
Xueli Zhu ◽  
Gonghao Zhan ◽  
Liangyu Sheng ◽  
Yanwei Chen

Purpose: To investigate the therapeutic effect of vitexin on neuropathic pain (NP) in a mouse model of chronic constriction injury (CCI).Methods: The CCI model was established by four chronic ligatures in the sciatic nerve. Vitexin was intraperitoneally administered (10 mg/kg, once daily) for 21 days. Mechanical withdrawal threshold (MWT) and paw withdrawal latency (PWL) were determined before and after the establishment of CCI model. The spinal cords were collected to measure mRNA levels by reverse-transcriptase polymerase chain reaction (RT-PCR) enzyme-linked immunosorbent assay (ELISA). Western blot was used to examine protein expression levels.Results: Vitexin reversed the CCI-induced reduction in MWT and PWL values, indicating that it lowered mechanical hypersensitivity response and hyperalgesia caused thermal stimulation (p < 0.05). The elevated levels of IL-6, IL-1β, and TNFα observed in CCI-treated mice were also inhibited by vitexin, suggesting that it suppressed pro-inflammatory cytokines. Moreover, vitexin attenuated CCI-induced activation of NF-κB signaling in CCI-treated mice (p < 0.05).Conclusion: Vitexin alleviates NP by inhibiting pro-inflammatory cytokines and NF-κB signaling in CCItreated mice. Thus, it is a potential target for NP treatment. Keywords: Vitexin, Neuropathic pain, Chronic constriction injury, Mechanical hypersensitivity, Hyperalgesia, NF-κB


2019 ◽  
Vol 89 (4) ◽  
pp. 630-636
Author(s):  
Mine Gecgelen Cesur ◽  
V. Ozgen Ozturk ◽  
Beral Afacan ◽  
F. Burcu Sirin ◽  
Afra Alkan ◽  
...  

ABSTRACT Objectives: To evaluate the Interleukin-4 (IL-4), bone-specific alkaline phosphatase (BALP), and C-telopeptide of type I collagen (CTX-I) levels in peri-miniscrew crevicular fluid (PMCF) during orthodontic tooth movement between 75 and 150 g of distalization force. Materials and Methods: Thirty miniscrews were placed bilaterally between the maxillary second premolars and first molars. The right and the left maxillary canines were moved distally using either 75 or 150 g of force. PMCF samples were collected before loading (T0); at 2 hours (T1) and 24 hours (T2) later; and on days 7 (T3), 14 (T4), 21 (T5), 30 (T6), and 90 (T7) after force application. Enzyme-linked immunosorbent assay kits were used to determine BALP, CTX-I, and IL-4 levels. Results: There was no significant difference between the force groups at all time points with respect to BALP, CTX-I, and IL-4 levels (P &gt; .05). There was no significant difference among time points for the two force groups in terms of BALP and IL-4 levels (P &gt; .05). The CTX-I level at T3 was significantly higher than at T0 for both force groups (P &lt; .05). Conclusions: Both 75 g and 150 g of orthodontic force are within optimal force limits, and there is no difference in biochemical markers of bone turnover.


2021 ◽  
pp. 155982762110304
Author(s):  
Mallory R. Marshall ◽  
Alexander H. K. Montoye ◽  
Michelle R. Conway ◽  
Rebecca A. Schlaff ◽  
Karin A. Pfeiffer ◽  
...  

As pregnancy progresses, physical changes may affect physical activity (PA) measurement validity. n = 11 pregnant women (30.1 ± 3.8 years) wore ActiGraph GT3X+ accelerometers on the right hip, right ankle, and non-dominant wrist for 3–7 days during the second and third trimesters (21 and 32 weeks, respectively) and 12 weeks postpartum. Data were downloaded into 60-second epochs from which stepping cadence was calculated; repeated-measures analysis of variance was used to determine significant differences among placements. At all time points, the wrist accelerometer measured significantly more daily steps (9930–10 452 steps/d) and faster average stepping cadence (14.5–14.6 steps/min) than either the hip (4972–5944 steps/d, 7.1–8.6 steps/min) or ankle (7161–8205 steps/d, 10.3–11.9 steps/min) placement, while moderate- to vigorous-intensity activity at the wrist (1.2–1.7 min/d) was significantly less than either hip (3.0–5.9 min/d) or ankle (6.1–7.3 min/d). Steps, cadence, and counts were significantly lower for the hip than the ankle at all time points. Kappa calculated for agreement in intensity classification between the various pairwise comparisons ranged from .06 to .41, with Kappa for hip–ankle agreement (.34–.41) significantly higher than for wrist–ankle (.09–.11) or wrist–hip (.06–.16). These data indicate that wrist accelerometer placement during pregnancy likely results in over counting of PA parameters and should be used with caution.


2018 ◽  
Vol 10 ◽  
pp. 117957351880358 ◽  
Author(s):  
Ashish Kumar Gupta ◽  
Komal Rani ◽  
Surabhi Swarnkar ◽  
Gaurav Khunger Kumar ◽  
Mohd Imran Khan ◽  
...  

Aim of the Study: Parkinson’s disease and schizophrenia are disease end points of dopaminergic deficit and hyperactivity, respectively, in the mid brain. Accordingly, current medications aim to restore normal dopamine levels, overshooting of which results in adverse effects of psychosis and extra-pyramidal symptoms, respectively. There are currently no available laboratory tests to guide treatment decisions or help predict adverse side effects of the drugs. The aim was to therefore explore the possibility of using apolipoprotein E as a biomarker to monitor pharmacological intervention in dopamine dictated states of Parkinson’s disease and schizophrenia for optimum therapy. Methods: Naïve and treated, Parkinson’s disease and schizophrenic patients were recruited from neurology and psychiatry clinics. Serum of healthy volunteers was collected as controls. Serum concentrations of apolipoprotein E was estimated by enzyme-linked immunosorbent assay (ELISA). Pathway analysis was carried out to delineate the interactions of apolipoprotein E in Parkinson’s disease and schizophrenia. Results: Apolipoprotein E levels are higher in Parkinson’s disease patients as compared with schizophrenic samples ( P < .05). Also, post-treatment apolipoprotein E levels in both disease states were at par with levels seen in healthy controls. The interactions of apolipoprotein E validate the results and place the differential expression of the protein in Parkinson’s disease and schizophrenia in the right perspective. Conclusion: Apolipoprotein E concentration across the dopaminergic spectrum suggests that it can be pursued not only as a potential biomarker in schizophrenia and Parkinson’s disease, but can also be an effective tool for clinicians to determine efficacy of drug-based therapy.


2019 ◽  
Vol 10 (1) ◽  
pp. 175-179 ◽  
Author(s):  
Xianhai Fang ◽  
Huacheng Zhou ◽  
Shaopeng Huang ◽  
Jinfeng Liu

Abstract Background This study determined the role of miR-1906 in neuropathic pain and proliferation in neuronal cells using a chronic constriction injury (CCI)-induced neuropathic pain (NP) rat model. Methodology NP was induced by CCI. Animals were divided into a sham group, an NP group, and a miR-1906 mimic group, which received 500 nmol/kg of a miR-1906 mimic intrathecally for 10 consecutive days following surgery. The effect of miR-1906 agomir was determined by estimating the thermal and mechanical withdrawal latency; an enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proinflammatory mediators. Western blotting and reverse-transcription polymerase chain reaction (RT-PCR) were used to determine protein expression in the spinal tissues of the CCI-induced neuropathic pain rat model. Results Administration of miR-1906 agomir increased the mechanical and thermal withdrawal latency period and the levels of inflammatory mediators compared with the NP group. Western blotting showed that treatment with miR-1906 agomir attenuated the levels of Akt, mTOR, TLR-4, and PI3K proteins in the spinal tissues of the CCI-induced neuropathic pain model. TLR-4 and NF-κB gene expression was lower in the miR-1906 agomir group than in the NP group. Conclusion miR-1906 gene stimulation reduced neuropathic pain by enhancing Akt/nTOR/PI3K and TLR-4/NF-κB pathway regulation.


2017 ◽  
Vol 3 (20;3) ◽  
pp. E451-E454 ◽  
Author(s):  
Stephanie Jones

Pudendal neuralgia (PN) is a result of pudendal nerve entrapment or injury, also called “Alcock syndrome.” Pain that develops is often chronic, and at times debilitating. If conservative measures fail, invasive treatment modalities can be considered. The goal of this case report is to add to a small body of literature that a pulsed radiofrequency (PRF) ablation can be effectively used to treat PN and to show that high resolution MR neurography imaging can be used to detect pudendal neuropathy. Case Presentation: We present a case of a 51-year-old woman with 5 years of worsening right groin and vulva pain. Various medication trials only lead to limited improvement in pain. The first diagnostic right pudendal nerve block was done using 3 mL of 0.25% bupivacaine with 6mg of betamethasone using a transgluteal technique and a target of the right ischial spine; this procedure resulted in ~8 hours of > 50% pain relief. The patient was then referred for MR neurography of the lumbosacral plexus. This study revealed increased signal of the right pudendal nerve at the ischial spine and in the pudendal canal, findings consistent with the clinical picture of PN. Six weeks after the initial block, the patient underwent a second right transgluteal pudendal nerve block, utilizing 3 mL of 0.25% bupivacaine with 40 mg of triamcinolone acetonide; this procedure resulted in ~8 hours of 100% pain relief. Satisfied with these results the patient decided to undergo pudendal nerve PRF ablation for possible long-term relief. For this therapeutic procedure, a right transgluteal approach was again utilized. PRF ablation was performed for 240 seconds at 42° Celsius. Following this ablation the patient reported at least 6 weeks of significant (> 50%) pain relief. Discussion and Conclusion: In this paper we presented a case of successful treatment of PN with PRF ablation and detection of pudendal neuropathy on MR neurography. We believe that transgluteal PRF ablation for PN might be an effective, minimally invasive option for those patients that have failed conservative management. MR neurography employed in this case is not only helpful in confirming the diagnosis of PN but could also be useful in ruling out other causes of pelvic pain, such as genitofemoral neuropathy, endometriosis, adenomyosis, or pelvic mass lesion. To conclude, transgluteal PRF ablation can serve as a viable treatment option for mitigating symptoms of pudendal neuropathy and MR neurography is useful in confirming a clinically suspected diagnosis of PN. Key words: Pelvic pain, pudendal neuralgia, MR neurography, pulsed radiofrequency ablation, transgluteal technique, Alcock canal syndrome


Author(s):  
Francesca Saluzzo ◽  
Paola Mantegani ◽  
Valeria Poletti De Chaurand ◽  
Virginia Quaresima ◽  
Federica Cugnata ◽  
...  

Our study provides a fresh perspective on the possible employment of SARS-CoV-2 LFA antibody tests. We developed an in-depth, large-scale analysis comparing LFA performance to enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (ECLIA) and evaluating their sensitivity and specificity in identifying COVID-19 patients at different time points from symptom onset.


2018 ◽  
Vol 46 (6) ◽  
pp. 2423-2435
Author(s):  
Domna Dorotheou ◽  
Marie-Luce Bochaton-Piallat ◽  
Catherine Giannopoulou ◽  
Stavros Kiliaridis

Objective This study was performed to explore the expression of α-smooth muscle actin (α-SMA) in the periodontal ligament (PDL) of young and adult rats during post-emergent tooth eruption in opposed and unopposed teeth at two time points: 3 and 15 days after antagonist loss. Methods Four-week-old (n = 20) and 22-week-old (n = 20) male Wistar rats were used. The right maxillary molar crowns were cut down. PDL samples were isolated from the first mandibular molars at two time points: 3 and 15 days after cut-down of the right maxillary molars. Quantitative reverse-transcription polymerase chain reaction and immunohistochemical staining were performed to detect differences in α-SMA expression in the PDL tissues of unopposed versus opposed molars. Results α-SMA was upregulated in the PDL of the unopposed molars in the 3-day group of young rats. The region around the root apex of the unopposed molars in this group exhibited strong immunostaining for α-SMA. The expression level and immunoreactivity of α-SMA did not differ in both time points in young controls and among all the adult groups. Conclusion α-SMA-positive myofibroblasts are implicated in post-emergent tooth eruption of unopposed molars of young animals.


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