Stable Rat Model of Mechanical Allodynia in Diabetic Peripheral Neuropathy: The Role of Nerve Compression

2018 ◽  
Vol 34 (04) ◽  
pp. 264-269 ◽  
Author(s):  
Chenlong Liao ◽  
Min Yang ◽  
Pengfei Liu ◽  
Wenxiang Zhong ◽  
Wenchuan Zhang

Background Preclinical studies involving animal models are essential for understanding the underlying mechanisms of diabetic neuropathic pain. Methods Rats were divided into four groups: two controls and two experimental. Diabetes mellitus was induced by streptozotocin (STZ) injection in two experimental groups. The first group involved one sham operation. The second group involved one latex tube encircling the sciatic nerve. The vehicle-injection rats were used as two corresponding control groups: sham operation and encircled nerves. By the third week, STZ-injected rats with encircled nerves were further divided into three subgroups: one involving continuing observation and the other two involving decompression (removal of the latex tube) at different time points (third week and fifth week). Weight and blood glucose were monitored, and behavioral analysis, including paw withdrawal threshold (PWT) and latency, was performed every week during the experimental period (7 weeks). Results Hyperglycemia was induced in all STZ-injected rats. A significant increase in weight was observed in the control groups when compared with the experimental groups. By the third week, more STZ-injected rats with encircled nerves developed mechanical allodynia than those without (P < 0.05), while no significant difference was noted (P > 0.05) on the incidence of thermal hyperalgesia. Mechanical allodynia, but not thermal hyperalgesia, could be ameliorated by the removal of the latex tube at an early stage (third week). Conclusion With the combined use of a latex tube and STZ injection, a stable rat model of painful diabetic peripheral neuropathy (DPN) manifesting both thermal hyperalgesia and mechanical allodynia has been established.

1998 ◽  
Vol 86 (3) ◽  
pp. 584-587 ◽  
Author(s):  
Masahiko Shibata ◽  
Satoshi Wakisaka ◽  
Takaya Inoue ◽  
Tadao Shimizu ◽  
Ikuto Yoshiya

1998 ◽  
Vol 86 (3) ◽  
pp. 584-587 ◽  
Author(s):  
Masahiko Shibata ◽  
Satoshi Wakisaka ◽  
Takaya Inoue ◽  
Tadao Shimizu ◽  
Ikuto Yoshiya

2012 ◽  
Vol 20 (5) ◽  
pp. 980-987 ◽  
Author(s):  
Leonice Fumiko Sato Kurebayashi ◽  
Juliana Rizzo Gnatta ◽  
Talita Pavarini Borges ◽  
Maria Júlia Paes da Silva

AIMS: randomized clinical trial aimed at evaluating the auriculotherapy in reducing stress levels in 75 nursing professionals and analyze the coping domains that have changed after treatment. METHODOLOGY: volunteers were divided into 3 groups (Control, Needles and Seeds) and received eight sessions at Shenmen, Kidney and Brainstem points. The Control Group didn't receive any intervention. RESULTS: ANOVA test showed statistical differences in stress levels for Needle/Control Groups in the third and fourth assessments, according to Stress Symptoms List when compared the three groups in four assessments. For the Inventory of Folkman/Lazarus, a significant difference was obtained for Spacing domain between needle/control. In analysis within the same group, differences were found for Confrontation in fourth assessment between Needle/Control Groups and for Social Support in the third one between Seeds/Control Groups. CONCLUSION: The auriculotherapy decreased stress levels, changed Coping domains after treatment, suggesting that both Auriculotherapy with needles and seeds can produce positive impact to improve strategy Coping in the nursing team. However, more studies are needed to conceive the extent of the technique.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Zhou ◽  
Ruxue Lei ◽  
Chuanyi Zuo ◽  
Yunqing Yue ◽  
Qin Luo ◽  
...  

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.


Burns ◽  
2014 ◽  
Vol 40 (4) ◽  
pp. 759-771 ◽  
Author(s):  
Marcie Fowler ◽  
John L. Clifford ◽  
Thomas H. Garza ◽  
Terry M. Slater ◽  
Helen M. Arizpe ◽  
...  

2020 ◽  
Vol 8 (1) ◽  
pp. e001004 ◽  
Author(s):  
Joo-Shin Tan ◽  
Chou-Ching Lin ◽  
Gin-Shin Chen

ObjectiveEffective treatment methods for diabetic peripheral neuropathy are still lacking. Here, a focused ultrasound (FUS) technique was developed to improve blood flow in diabetic peripheral vessels and potentially treat diabetic peripheral neuropathy.Research design and methodsMale adult Sprague-Dawley rats at 4 weeks poststreptozotocin injections were adopted as models for diabetic neuropathic rats. For single FUS treatment, blood perfusion in the skin of the pad of the middle toe was measured before, during, and after the medial and lateral plantar arteries were treated by FUS. For multiple FUS treatments, blood perfusion measurements, von Frey and hot plate testing and nerve conduction velocity measurements were performed before ultrasonic treatment on the first day of each week, and the microvascular and neural fiber densities in the pad of the toe were measured on the first day of the last week.ResultsThe blood perfusion rate significantly increased for 7–10 min in the control and neuropathic rats after a single ultrasound exposure. Multiple ultrasound treatments compared with no treatments significantly increased blood perfusion at the second week and further enhanced perfusion at the third week in the neuropathic rats. Additionally, the paw withdrawal force and latency significantly increased from 34.33±4.55 g and 3.96±0.25 s at the first week to 39.10±5.02 g and 4.77±0.71 s at the second week and to 41.13±2.57 g and 5.24±0.86 s at the third week, respectively. The low nerve conduction velocity in the diabetic rats also improved after the ultrasound treatments. Additionally, ultrasound treatments halted the decrease in microvessel and neural fiber densities in the skin of the diabetic toes. Histologic analysis indicated no damage to the treated arteries or neighboring tissue.ConclusionsFUS treatment can increase upstream arterial blood flow in diabetic feet, ameliorate the decrease in downstream microvessel perfusion and halt neuropathic progression.


2017 ◽  
Vol 243 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Li Zhuang ◽  
Ke Li ◽  
Gaowei Wang ◽  
Tao Shou ◽  
Chunlin Gao ◽  
...  

Bone cancer pain (BCP) is a severe type of hyperpathic pain occurring with primary bone tumors or advanced cancers which metastasize to bones. BCP can detrimentally reduce quality of life and presents a challenge to modern medicine. Studies have shown that exogenous H2S may act as a neuroprotectant to protect against some diseases in central nervous system. The preset study aimed to investigate the antinociceptive effect of H2S in BCP. We first measured the changes of serum H2S in patients with BCP and analyzed the relationship between them, then investigated the effect of H2S preconditioning on BCP, and explored the mechanism in rat model. Our results revealed that serum H2S level was negatively correlated with pain scores. In the rat model of BCP, preconditioning with H2S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. The mechanism of H2S preconditioning may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. Impact statement Bone cancer pain (BCP) significantly decreases the life quality of patients or their life expectancy and causes a severe health burden to the society. However, as the exact mechanism of BCP is still poorly understood, no effective treatment has been developed yet. There are some pain medicines now, but they have some inevitable side effects. Additional therapeutic strategies are urgently needed. First, we revealed that preconditioning with H2S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. Second, the mechanism of H2S preconditioning was elucidated. It may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. This novel finding may significantly help us to understand the difference between the roles of endogenous H2S and exogenous H2S in the development of BCP and present us a new strategy of pain management.


Author(s):  
Haritha Pasupulati ◽  
Satyanarayana S. V. Padi ◽  
Sujatha Dodoala ◽  
Prasad V. S. R. G. Koganti

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.


2021 ◽  
Author(s):  
Qi Wang ◽  
Tingting Han ◽  
Ruihe Lai ◽  
Dalong Zhang ◽  
Yao Diao ◽  
...  

Abstract BackgroundTo explore the mechanism of nicotine mediated improvement of cognitive impairment in an established ischemic rat model. MethodsEndothelin-1 (ET-1) was injected into the left thalamic region in adult male Sprague-Dawley (SD) rats to establish ischemia model. 6 groups of rats (6 rats in each group) were then treated with nicotine, nicotine+DHβE, DHβE, AG490, nicotine +AG490 and saline respectively via intraperitoneal injection for 9 days. Another sham operation group was treated with saline as above. Morris Water Maze (MWM) test was performed for 6 consecutive days starting on the 4th day after operation to detect the cognitive function of rats in each group. 2-[18F]-A-85380 microPET imaging was performed on day 10 to evaluate the changes of α4β2 nAChRs in different brain regions of rats. Real-time PCR and Western blot were used to detect the amount of α4β2 nAChRs, JAK2, STAT3 and inflammatory factors in thalamus of rats in each group. ResultsThe results of MWM test showed the spatial learning and memory abilities of rats in the nicotine and sham operation groups were significantly better than the saline treating group in this ischemic rat model (p<0.05). There was no significant difference in other groups (p>0.05). MicroPET imaging showed more uptake of 2-[18F]-A-85380 in the nicotine, nicotine+AG490 and sham operation groups than in saline treating group, while there was no significant difference found in other groups (p>0.05). The expression of α4- and β2-nAChR in nicotine, nicotine+AG490 and sham operation groups was significantly higher than the saline treating group (p<0.05). In the nicotine group, the expression of p-JAK2 and p-STAT3 in left thalamus of rats was significantly higher than the saline treating group (p<0.05), and the expression of IL-1β and IL-6 protein was found to be lower than the saline treating group (p<0.05). While the expression of p-JAK2, p-STAT3 and inflammatory factors was not significantly different in all the other groups (p>0.05). ConclusionThe study suggests nicotine inhibits the expression of inflammatory factors by activating α4β2 nAChRs through the activation of JAK2-STAT3 signaling pathway to improve cognitive impairment in ischemic rats.


2021 ◽  
Author(s):  
Pegah Mohammadzadeh ◽  
Elnaz Shaseb ◽  
Zohreh Sanaat ◽  
Parvin Sarbakhsh ◽  
Nasrin Gholami ◽  
...  

Abstract Purpose Peripheral neuropathy is a complication of taxane that in severe cases can limit the optimal treatment. The aim of this study was to evaluate the efficacy of memantine in prevention of docetaxel induced peripheral neuropathy in patients with breast cancer. Methods In this randomized clinical trial, 40 women between the ages of 18 and 64 years with non-metastatic breast cancer (stages I to III) were included (registry number: IRCT20160310026998N9 and registry date: 26 March 2019). All patients were treated with the AC-T regimen (with docetaxel). Patients in intervention group received memantine at a dose of 20 mg for 8 weeks at the beginning of the first cycle of docetaxel. Patients in control group did not take any medication for neuropathy prevention. To assess the neuropathy, DN4 and CTCAE questionnaires were used at baseline, one months, three months and six months after the intervention. Results The DN4 questionnaire score was remarkably less in memantine group in follow up one (p-value: 0.033) and three (p < 00.1). The CTCAE follow up score did not change during study. The Neuropathy duration and Neuropathy onset, were shown significant difference between the intervention and control groups, p = 0.050 and p = 0.001, respectively. From 40 patients, 8 (40%) in memantine group and 2 (10%) in control group, did not experience any kind of neuropathy. Conclusion Data showed that prophylactic administration of memantine 20 mg/day has been effective in prevention of severity and incidence of docetaxel induced neuropathy in patients with breast cancer.


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