scholarly journals LncRNA-UC.25+ ShRNA Alleviates P2Y14 Receptor Mediated Diabetic Neuropathic Pain Via STAT1

2022 ◽  
Author(s):  
Baoguo Wu ◽  
Congfa Zhou ◽  
Zehao Xiao ◽  
Gan Tang ◽  
Hongmin Guo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
P38 Mapk ◽  
Clinical Manifestations ◽  
P2y Receptors ◽  
P2y12 Receptor ◽  
Inflammatory Factors ◽  
Diabetic Neuropathic Pain ◽  
Spinal Cord Neurons ◽  
Mapk Phosphorylation

Abstract Diabetic neuropathic pain (DNP) is a common complication of diabetes, and its complicated pathogenesis as well as clinical manifestations has brought great troubles to clinical treatment. The spinal cord is an important part of regulating the occurrence and development of DNP. Spinal microglia can regulate the activity of spinal cord neurons and have a regulatory effect on chronic pain. P2Y12 receptor is involved in DNP. P2Y14 and P2Y12 receptor belong to the Gi subtype of P2Y receptors, but there is no report that P2Y14 receptor is involved in DNP. Closely related to many human diseases, the dysregulation of lncRNA has the effect of promoting or inhibiting the occurrence and development of diseases. The aim of this research is to investigate the function of spinal cord P2Y14 receptor in type 2 DNP and to understand the function as well as the possible mechanism of lncRNA-UC.25+ (UC.25+) in rat spinal cord P2Y14 receptor-mediated DNP. Our results showed that P2Y14 shRNA can reduce the expression of P2Y14 in DNP rats, thereby restraining the activation of microglia, decreasing the expression of inflammatory factors and the level of p38 MAPK phosphorylation. At the same time, UC.25+ shRNA can down-regulate the expression of P2Y14 receptor, reduce the release of inflammatory factors, and diminish the p38 MAPK phosphorylation, indicating that UC.25+ can alleviate spinal cord P2Y14 receptor-mediated DNP. The RNA immunoprecipitation result showed that UC.25+ enriched STAT1 and positively regulated its expression. The chromatin immunoprecipitation result indicated that STAT1 combined to the promoter region of P2Y14 receptor and positively regulated the expression of P2Y14 receptor. Therefore, we infer that UC.25+ may alleviate DNP in rats by regulating the expression of P2Y14 receptor in spinal microglia via STAT1.

scholarly journals Tetrahydropalmatinee alleviates diabetic neuropathic pain by inhibiting the inflammation via p38-MAPK signaling pathway in microglia

2021 ◽  
Author(s):  
Lianzhi Cheng ◽  
Junlong Ma ◽  
Aijuan Jiang ◽  
Kai Cheng ◽  
Fanjing Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Inflammatory Factors ◽  
Specific Marker ◽  
Diabetic Neuropathic Pain ◽  
Tnf Α

Abstract Object: Exploring the effect of Tetrahydropalmatine (THP) on diabetic neuropathic pain (DNP) and its possible mechanism. Methods: The type 2 diabetic (T2DM) rat models were prepared by high-fat and high-sugar feeding combined with a single small-dose intraperitoneal injection of streptozotocin (STZ). When the mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) of T2DM model rats decreased to less than 85% which were judged as DNP-bearing rats. After treatment with or without THP, the protein expression of hypertonic glycerol reactive kinase (p38), phosphorylated hypertonic glycerol-responsive kinase (p-p38) and OX42 (a specific marker of microglia) were detected by Western Blot and and the mRNA content of p38 and OX42 were detected by qRT-PCR. The expression of pro-inflammatory factors IL-1β, IL-6, TNF-α, as well as chemotactic factors and their receptors including CXCL1, CXCR2, CCL2 and CCR2 in spinal tissues were detected by ELISA. Serum FINS and GSP content were also detected by ELISA. Double-label immunofluorescence were used to observe the expression of OX42 and p-p38 in the spinal dorsal horn. Results: Results showed that THP inhibited microglial activation of spinal in DNP rats. And after THP intervention, the MWT and TWL of DNP rats decreased, the expression of p38, p-p38 and OX42 in the spinal cord tissues of rats was significantly reduced while the mRNA of p38 and OX42 also reduced. The expression of IL-1β, IL-6, TNF-α, CXCL1, CXCR2, CCL2 and CCR2 in the spinal cord tissues of rats was significantly reduced (P < 0.01). At the same time, THP significantly proved FINS, but did not affect FBG and GSP in DNP rats. Conclusions: THP significantly alleviates pain symptoms in DNP rats, and this effect may be achieved by inhibiting the inflammatory response caused by the activation of microglia mediated by the p38-MAPK signaling pathway.

scholarly journals EGCG Prevents the Loss of Pontine Noradrenergic Neurons Induced by Diabetes: A Role in Diabetic Neuropathic Pain

2012 ◽  
Vol 18 (S5) ◽  
pp. 5-6 ◽  
Author(s):  
Carla Morgado ◽  
João Silva ◽  
André Miranda ◽  
Patrícia Pereira-Terra ◽  
Diogo Raposo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Diabetic Rats ◽  
Pain Modulation ◽  
Diabetic Patients ◽  
Spontaneous Pain ◽  
Noradrenergic Neurons ◽  
Diabetic Neuropathic Pain ◽  
Descending Pain Modulation ◽  
Pain Responses

Diabetes is a major health problem with an alarming increasing prevalence, and is the most frequent cause of neuropathy worldwide. Neuropathy affects 50–60% of diabetic patients, being a major life-quality impairment for a quarter of these patients. Diabetic neuropathic pain (DNP) is characterized by spontaneous pain, mechanical hyperalgesia and tactile allodynia and is accompanied by functional and neurochemical changes at the peripheral nerves, spinal cord and supraspinal pain control areas. Regarding the effects of diabetic neuropathy in the central somatossensory system, it was shown that streptozotocin (STZ)-diabetic rats present spontaneous hyperactivity and hyperexcitability of spinal nociceptive neurons, which may be subserving the exacerbated pain responses. The spinal functional changes and pain may be due to increased peripheral input(2), changes in spinal nociceptive modulatory mechanisms and altered supraspinal descending pain modulation. Noradrenergic descending pain modulation seems to be impaired since STZ-diabetic rats present decreased numbers of noradrenergic neurons at the A5 and A7 pontine cell groups, along with lower levels of noradrenaline at the spinal cord and higher behavioral responses to pain. This is consistent with the strong noradrenergic projection from A5 and A7 neurons to the spinal dorsal horn and the modulation of nociceptive transmission by local release of noradrenaline. The mechanisms underlying the decrease in noradrenergic neurons in the brainstem during diabetes remain unclear. Our recent findings that diabetes induces oxidative stress damage in neurons from those areas, lead us to hypothesize that it may contribute to their loss. Thereafter, with the present study we aimed to evaluate the effects of Epigallocathechin Gallate (EGCG), a potent antioxidant present in green tea, on spinal noradrenaline levels, on A5 and A7 noradrenergic neurons and on behavioral pain responses of STZ-diabetic rats.

Central regulation of pain in patients with joint disease and approaches to therapy

2016 ◽  
Vol 88 (12) ◽  
pp. 159-164 ◽  
Author(s):  
E S Filatova ◽  
Sh F Erdes ◽  
E G Filatova
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Structural Changes ◽  
Mixed Model ◽  
Combined Therapy ◽  
Clinical Manifestations ◽  
Pain Syndrome ◽  
Joint Disease ◽  
Spinal Cord Neurons ◽  
Number Of Patients

The paper reviews investigations studies that have demonstrated that chronic pain syndrome is mixed in rheumatic diseases. The nervous system is involved in its pathogenesis with different frequency and different mechanisms. Under the influence of afferent pain impulses from damaged joints, there are changes in the excitability of spinal cord neurons, which is called central sensitization (CS). A number of patients have enhanced CS and clinical manifestations as neuropathic sensitive phenomena. The mixed model of the development of chronic pain in joint diseases and its presence along with nociceptive (inflammatory) and neuropathic pain components may explain the discrepancy between joint inflammatory and structural changes and pain intensity, the presence of distant pain and sensitive disorders in the areas outside the joint, and sometimes the efficiency of anti-inflammatory therapy. The presence of the neuropathic pain component serves as a rationale for combined therapy by adding centrally acting drugs, such as anticonvulsants.

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