scholarly journals Lysophosphatidic Acid Receptor 1- and 3-Mediated Hyperalgesia and Hypoalgesia in Diabetic Neuropathic Pain Models in Mice

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1906
Author(s):  
Hiroshi Ueda ◽  
Hiroyuki Neyama ◽  
Yosuke Matsushita

Lysophosphatidic acid (LPA) signaling is known to play key roles in the initiation and maintenance of various chronic pain models. Here we examined whether LPA signaling is also involved in diabetes-induced abnormal pain behaviors. The high-fat diet (HFD) showing elevation of blood glucose levels and body weight caused thermal, mechanical hyperalgesia, hypersensitivity to 2000 or 250 Hz electrical-stimulation and hyposensitivity to 5 Hz stimulation to the paw in wild-type (WT) mice. These HFD-induced abnormal pain behaviors and body weight increase, but not elevated glucose levels were abolished in LPA1−/− and LPA3−/− mice. Repeated daily intrathecal (i.t.) treatments with LPA1/3 antagonist AM966 reversed these abnormal pain behaviors. Similar abnormal pain behaviors and their blockade by daily AM966 (i.t.) or twice daily Ki16425, another LPA1/3 antagonist was also observed in db/db mice which show high glucose levels and body weight. Furthermore, streptozotocin-induced similar abnormal pain behaviors, but not elevated glucose levels or body weight loss were abolished in LPA1−/− and LPA3−/− mice. These results suggest that LPA1 and LPA3 play key roles in the development of both type I and type II diabetic neuropathic pain.

2017 ◽  
Vol 49 (5) ◽  
pp. 1025-1033 ◽  
Author(s):  
Gerardo Ordaz-Ochoa ◽  
Aureliano Juárez-Caratachea ◽  
Rosa Elena Pérez-Sánchez ◽  
Rafael María Román-Bravo ◽  
Ruy Ortiz-Rodríguez

1998 ◽  
Vol 1998 ◽  
pp. 188-188 ◽  
Author(s):  
S.E.M. Snijders ◽  
K. O'Farrell ◽  
M. P. Boland ◽  
P. Dillon ◽  
M. Diskin ◽  
...  

Efficient milk production in Ireland in both spring and autumn calving herds is very much dependent on compact calving. This requires an early resumption of ovarian activity, high submission rate, and pregnancy rate to service. Since 1984 there has been an increase in the genetic merit of Irish dairy herds. High genetic merit animals have reduced reproductive performance due to the demands of high milk yield (Nebel and McGilliard, 1993) and the loss of body weight and body condition (Butler and Smith, 1989). However, little comparative data on the reproductive performance of dairy cows of different genetic merit are available. The objective of this study was therefore, to determine the relationship between genetic merit of dairy cows and follicular growth patterns, milk production, body weight loss, insulin and glucose levels in early lactation.


2012 ◽  
Vol 506 (1) ◽  
pp. 104-106 ◽  
Author(s):  
Eugene H. Liu ◽  
Chunmei Li ◽  
Malathi Govindasamy ◽  
Hong Jye Neo ◽  
Tat Leang Lee ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Weifeng Ji ◽  
Haiying Huang ◽  
Ji Chao ◽  
Wuchao Lu ◽  
Jianyou Guo

Objective. The present investigation examined the neuroprotective effect ofAgaricus brasiliensis(AbS) against STZ-induced diabetic neuropathic pain in laboratory rats. STZ-induced diabetic rats were administered orally with AbS. Body weight, serum glucose, and behavioral parameters were measured before and at the end of the experiment to see the effect of AbS on these parameters. After 6 weeks of treatments, all animals were sacrificed to study various biochemical parameters. Treatment with AbS 80 mg/kg in diabetic animals showed significant increase in body weight, pain threshold, and paw withdrawal threshold and significant decrease in serum glucose, LPO and NO level, Na-K-ATPase level, and TNF-αand IL-1βlevel as compared to vehicle treated diabetic animals in dose and time dependent manner. AbS can offer pain relief in PDN. This may be of potential benefit in clinical practice for the management of diabetic neuropathy.


2019 ◽  
Vol 31 (3) ◽  
pp. 208
Author(s):  
Dian Widya Damaiyanti ◽  
Pratiwi Soesilowati ◽  
Ira Arundina ◽  
Rima Parwati Sari

Introduction: Gold sea cucumber (Stichopus hermanii) is a marine organism that contains omega-3 and glycosaminoglycan for enhancing collagen needed in the healing process. This study was aimed to determine the effectiveness of gold sea cucumber extracts in accelerating the healing process of oral traumatic ulcer in Wistar rats, in terms of the correlation between collagen type I expression, ulcer diameter, and body weight loss. Methods: Twenty Wistar rats (Rattus norvegicus) was divided into four groups and treated with gold sea cucumber extracts with the concentration of 80%, 40%, and 20% in the form of 0.1 ml gel daily. The negative control group received no treatment. Ulceration of the lower lip of labial mucosa was induced by a burnisher. The animals were observed for 7 days, during which they were weighed and the ulcers diameter was measured. The rats were then sacrificed after 7 days of treatment. Histometric analysis of collagen type I expression was also performed. Data obtained were analysed for differences between the group with one-way ANOVA test and the correlation was analysed with the Pearson test. Results: The significant differences (p < 0.05) between treatment groups was found in the ulcer diameters and the collagen type I expression. The most decreased ulcer diameter and the highest collagen type I expression detected in the group of treatment with a concentration of 80% — no significant differences found in the weight loss between-groups (p > 0.05). Strong correlation was also found between the expression of collagen type I and diameter of ulcer (Pearson correlation = 0.599, p = 0.05), however, no correlation found between weight loss with the expression of collagen type I (Pearson correlation = -0.102, p = 0.66), and the ulcer diameter (Pearson correlation = 0.022, p = 0.92). Conclusion: Gold sea cucumber had a potential benefit to be used as a traumatic ulcer healing medicament. Water extract of gold sea cucumber able to accelerate traumatic ulcer healing by enhancing the production of collagen type I and reduce the diameter of ulcer. There is a strong correlation between collagen type 1 expression and diameter of ulcer, and a weak correlation found between body weight loss and collagen type I expression, also with reducing ulcer diameter.Keywords: Gold sea cucumber, Stichopus hermanii, healing process, traumatic ulcer.


2021 ◽  
Vol 22 (16) ◽  
pp. 8519
Author(s):  
Lisha Joshi ◽  
Ioanna Plastira ◽  
Eva Bernhart ◽  
Helga Reicher ◽  
Alexander Triebl ◽  
...  

Increasing evidence suggests that systemic inflammation triggers a neuroinflammatory response that involves sustained microglia activation. This response has deleterious consequences on memory and learning capability in experimental animal models and in patients. However, the mechanisms connecting systemic inflammation and microglia activation remain poorly understood. Here, we identify the autotaxin (ATX)/lysophosphatidic acid (LPA)/LPA-receptor axis as a potential pharmacological target to modulate the LPS-mediated neuroinflammatory response in vitro (the murine BV-2 microglia cell line) and in vivo (C57BL/6J mice receiving a single i.p. LPS injection). In LPS-stimulated (20 ng/mL) BV-2 cells, we observed increased phosphorylation of transcription factors (STAT1, p65, and c-Jun) that are known to induce a proinflammatory microglia phenotype. LPS upregulated ATX, TLR4, and COX2 expression, amplified NO production, increased neurotoxicity of microglia conditioned medium, and augmented cyto-/chemokine concentrations in the cellular supernatants. PF8380 (a type I ATX inhibitor, used at 10 and 1 µM) and AS2717638 (an LPA5 antagonist, used at 1 and 0.1 µM) attenuated these proinflammatory responses, at non-toxic concentrations, in BV-2 cells. In vivo, we demonstrate accumulation of PF8380 in the mouse brain and an accompanying decrease in LPA concentrations. In vivo, co-injection of LPS (5 mg/kg body weight) and PF8380 (30 mg/kg body weight), or LPS/AS2717638 (10 mg/kg body weight), significantly attenuated LPS-induced iNOS, TNFα, IL-1β, IL-6, and CXCL2 mRNA expression in the mouse brain. On the protein level, PF8380 and AS2717638 significantly reduced TLR4, Iba1, GFAP and COX2 expression, as compared to LPS-only injected animals. In terms of the communication between systemic inflammation and neuroinflammation, both inhibitors significantly attenuated LPS-mediated systemic TNFα and IL-6 synthesis, while IL-1β was only reduced by PF8380. Inhibition of ATX and LPA5 may thus provide an opportunity to protect the brain from the toxic effects that are provoked by systemic endotoxemia.


1993 ◽  
Vol 83 (8) ◽  
pp. 457-461 ◽  
Author(s):  
JP Burke ◽  
MR Fenton ◽  
W Young ◽  
L Donatiello

This study is an attempt to assess the role of dietary supplementation in the treatment and prevention of diabetic peripheral neuropathy. The authors developed an animal model system to study this problem. Animals given streptozotocin to induce a type I diabetic state showed elevated glucose levels and decreased body weight. Analysis of the sciatic nerve revealed a decrease in nerve conduction velocity and Na(+)-K(+)-ATPase activity. The activity of protein kinase C, another component of the nerve transmission process, was also affected by the diabetic state. The dietary intervention of polyunsaturated fatty acids seemed to revert some of these changes toward normal.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Sun ◽  
Rui Zhang ◽  
Xiaowei Xue ◽  
Qunli Wu ◽  
Dan Yang ◽  
...  

Jinmaitong (JMT) is a compound prescription of traditional Chinese medicine that has been used to treat diabetic neuropathic pain (DNP) for many years. Here, we investigated the effects of JMT on the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and pyroptosis in Dorsal root ganglia (DRG) of diabetic rats. Streptozotocin (STZ)-induced diabetic rats were gavaged with JMT (0.88 g/kg/d) or alpha-lipoic acid (ALA, positive control, 0.48 mmol/kg/d) for 12 weeks. Distilled water was administered as a vehicle control to both diabetic and non-affected control rats. Blood glucose levels and body weights were measured. Behavioral changes were tested with mechanical withdrawal threshold (MWT) and tail-flick latency (TFL) tests. Morphological injury associated with DRG was observed with hematoxylin and eosin (H&amp;E) and Nissl’s staining. mRNA and protein levels of NLRP3 inflammasome components (NLRP3, ASC, caspase-1), downstream IL-1β and gasdermin D (GSDMD) were evaluated by immunohistochemistry, quantitative real time-PCR and western blot. The results showed that JMT had no effect on blood glucose levels and body weights, but significantly improved MWT and TFL behavior in diabetic rats, and attenuated morphological damage in the DRG tissues. Importantly, JMT decreased the mRNA and protein levels of components of NLRP3 inflammasome, including NLRP3, ASC and caspase-1. JMT also down-regulated the expression of IL-1β and GSDMD in the DRG of DNP rats. In addition, ALA treatment did not perform better than JMT. In conclusion, JMT effectively relieved DNP by decreasing NLRP3 inflammasome activation and pyroptosis, providing new evidence supporting JMT as an alternative treatment for DNP.


2019 ◽  
Vol 28 (6) ◽  
pp. 84-92
Author(s):  
Edgar Romualdo Esquivel-Gutiérrez ◽  
Lilia Alcaraz-Meléndez ◽  
Roberto Hernández-Herrera ◽  
Amada Torres ◽  
Carmen Rodríguez-Jaramillo

Turnera diffusa (damiana) grows wild in Baja California Sur (BCS), Mexico. It is traditionally used for its aphrodisiac effects and for diabetes treatment. Two varieties (var.) have been identified: diffusa and aphrodisiaca. To evaluate the effects of water-ethanol extracts from both varieties, measurements on blood glucose, body weight, biochemical parameters, and cell blood counts were performed in a diabetic rat model. Oxidative stress was also evaluated when var. diffusa was administered. No significant reductions in blood glucose levels, in biochemical parameters, or in cell blood counts with any variety of damiana were observed; however, it helped diabetic animals to keep their body weight. Damiana var. diffusa did not modify the mitochondrial nitric oxide levels and superoxide dismutase activity; however, thiobarbituric acid reactive species diminished. In conclusion, damiana can be utilized reliably in the management of diabetes because of its antioxidant potential; it promoted body weight loss in healthy animals and helped to preserve it in diabetes.


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