scholarly journals Protectin DX Attenuates Lumbar Radicular Pain of Non-compressive Disc Herniation by Autophagy Flux Stimulation via Adenosine Monophosphate-Activated Protein Kinase Signaling

2022 ◽  
Vol 12 ◽  
Author(s):  
Qing-xiang Zhao ◽  
Yi-hao Wang ◽  
Si-cong Wang ◽  
Song Xue ◽  
Zhen-xin Cao ◽  
...  

Background: Neuroinflammation plays a crucial role in initiating and sustaining lumbar radicular pain (LRP). Protectin DX (PDX) has been experimentally verified to possess pro-resolving properties and anti-inflammatory effects. This study aimed to observe the analgesic effects of PDX and its potential mechanisms in LRP rats with non-compressive lumbar disc herniation (NCLDH).Method: Only male rats were selected to avoid gender-related interferences. Rat models of NCLDH were established, and rats were randomly divided into four groups: the sham group, the vehicle group, the PDX (10 ng PDX) group, and the PDX (100 ng PDX) group. Changes in the mechanical withdrawal threshold and thermal withdrawal latency were observed for 7 days. The mRNAs of pro-inflammatory and anti-inflammatory mediators were evaluated via real-time polymerase chain reaction, whereas western blot and immunohistochemistry were separately conducted to assess the expression levels of autophagy-related proteins and adenosine monophosphate-activated protein kinase (AMPK) signaling.Results: Intrathecal delivery of PDX reduced interleukin (IL)-6 and IL-1β mRNA levels and facilitated mRNA transcription of transforming growth factor-β1, with attenuation of mechanical and thermal hyperalgesia in LRP rat models. With the application of nucleus pulposus to the dorsal root ganglion, autophagy flux and AMPK signaling were severely disrupted in the spinal dorsal horns, and intrathecal treatment with PDX could dose-dependently restore the dysfunction of autophagy flux and AMPK signaling.Conclusion: These data suggest that PDX possesses pro-resolving properties and exerts potent analgesic effects in LRP by affecting autophagy flux via AMPK signaling.

2014 ◽  
Vol 5 (3) ◽  
pp. 212-212
Author(s):  
Elina Iordanova Schistad ◽  
Line Melå Jacobsen ◽  
Cecilie Røe ◽  
Johannes Gjerstad

Abstract Aims Previous studies have suggested that many inflammatory cytokines, including interleukin (IL)-1α, may be associated with lumbar radicular pain after disc herniation. In the present study, we examined how variability of the IL-1α gene affects pain intensity and the pressure pain threshold (PPT) in patients with symptomatic disc herniation. Methods A total of 121 patients with lumbar radicular pain due to disc herniation were recruited from Oslo University Hospital, Norway, and followed up at 6 weeks and 12 months. The primary outcome measures were pain intensity scores for the lower back and legs using a visual analog pain scale (VAS) and PPT for the gluteal muscles. Genotyping was carried out using a predesigned TaqMan assay for IL-1α rs1800587. The effect of the IL-1α genotype on the VAS and PPT was analyzed by repeated measure analyses of variance. Results The IL-1α gene C>T polymorphism rs1800587 affected VAS and PPT scores in patients with symptomatic disc herniation. Patients with the CT/TT genotype reported a higher VAS leg pain intensity (p = 0.002) and also a lower PPT in the gluteal muscles (left p = 0.016; right p = 0.016) compared to patients with the CC genotype during 1 year of follow-up. Conclusions The present data show that the IL-1α CT/TT genotype rs1800587 may be associated with increased pain intensity, and corresponding reduced PPT during the first year after disc herniation.


2017 ◽  
Vol 7 (20;7) ◽  
pp. 633-670
Author(s):  
Chang Hong Park

Background: Lumbar radicular pain often results from lumbar disc herniation, spinal stenosis, or degenerative spondylolisthesis. Minimally invasive disc decompression procedures, such as nucleoannuloplasty or epiduroscopic neural decompression by laser, have been devised to treat such pain. Objective: The short-term outcomes of disc decompression by endoscopic epidural laser decompression (EELD) or transforaminal epiduroscopic laser annuloplasty (TELA) were compared in patients with lumbar radicular pain due to disc herniation. Study Design: A randomized, prospective trial. Setting: The Department of Anesthesiology and Pain Medicine at Spine Health Wooridul Hospital in Daegu, Korea. Methods: A total of 97 patients were enrolled in this study; 48 patients underwent EELD and 49 underwent TELA. The pain relief was evaluated at baseline and at 1, 3, and 6 months post-procedure via the numeric rating scale (NRS). The Oswestry Disability Index (ODI) was recorded at baseline and at the final follow-up. Postoperative wound pain was assessed over a 24-hour period. Complications and side effects were also recorded, as were operative times (from local anesthetic infiltration at entry sites to suturing of skin). Results: At post-treatment months 1, 3, and 6 the mean pain scores of patients were significantly lower (relative to pre-treatment baseline) regardless of the procedure used. However, the mean pain scores did not differ significantly by procedure (EELD vs TELA). As well, the number of patients who obtained relief from their pain and needed analgesics was not statistically significant. The irrigation volume was significantly higher in the TELA group. Two patients undergoing TELA procedures experienced headache during the procedures; however, no serious complications such as bleeding, dural/neural injuries, or infection were recorded for either group. Limitation: The observed significant reductions in pain (from baseline) lacked secondary outcome substantiation and given the mid follow-up period, no long-term follow-up results were monitored. Conclusion: Both EELD and TELA provide similar outcomes and are reasonable treatment options for carefully selected patients with lower back or radicular pain. Key words: Epiduroscopy, laser, annuloplasty, disc, herniation, TELA


2018 ◽  
Vol 48 (4) ◽  
pp. 1782-1792 ◽  
Author(s):  
Tianrong Ji ◽  
Chengwei Zhang ◽  
Linlin Ma ◽  
Qin Wang ◽  
Li Zou ◽  
...  

Background/Aims: Intracellular Ca2+ signaling plays an important role in the regulation of autophagy. However, very little is known about the role of Ca2+ influx, which is induced by plasma membrane Ca2+ channels. Our previous study showed that transient receptor potential canonical channel-6 (TRPC6), a major Ca2+ influx pathway in podocytes, was activated by hypoxia. Here, we investigated whether TRPC6 is involved in hypoxia-induced autophagy in cultured human podocytes. Methods: In the present study, an immortalized human podocyte cell line was used. Fluo-3 fluorescence was utilized to determine intracellular Ca2+ concentration ([Ca2+]i), and western blotting was used to measure autophagy and protein expression. Results: We found that blockade TRPC6 by using either TRPC6 siRNA or a TRPC6 blocker attenuated hypoxia-induced autophagy, while enhancement of TRPC6 activity with a TRPC6 activator enhanced hypoxia-induced autophagy. Furthermore, TRPC6-dependent Ca2+ signaling is responsible for hypoxia-induced autophagy since both an intracellular and extracellular Ca2+ chelator abolished hypoxia-induced autophagy. Moreover, we found that blockade of TRPC6 by using either TRPC6 siRNA or a TRPC6 blocker decreased the expression of adenosine monophosphate-activated protein kinase (AMPK), an important signaling molecule in Ca2+-dependent autophagy activation, which is activated under hypoxic conditions. These data suggest that the involvement of TRPC6 in hypoxia-induced autophagy is associated with AMPK signaling. Conclusion: TRPC6 is essential for hypoxia-induced autophagy in podocytes.


2015 ◽  
Vol 46 ◽  
pp. 132-136 ◽  
Author(s):  
Linda Margareth Pedersen ◽  
Elina Schistad ◽  
Line Melå Jacobsen ◽  
Cecile Røe ◽  
Johannes Gjerstad

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