Roles of AMPK and Its Downstream Signals in Pain Regulation

Wang, Shenglan; Dai, Yi

doi:10.3390/life11080836

Cited by 10 publications

(19 citation statements)

References 162 publications

(228 reference statements)

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“…Decreased AMPK activity is related to many types of pain, including neuropathic pain. In contrast, activation of AMPK activity may reduce inflammatory reactions and pain levels [ 42 ]. When cells are in a hypoglycemic environment, AMPK activity may decrease, resulting in pain.…”

Section: Discussionmentioning

confidence: 99%

“…When cells are in a hypoglycemic environment, AMPK activity may decrease, resulting in pain. Increasing glucose concentration in a timely manner may alleviate pain [ 42 ]. Other researchers have proposed that glucose indirectly inhibits the capsaicin-sensitive receptor (transient receptor potential vanilloid receptor-1, TRPV-1) and blocks the secretion of substance P and calcitonin gene-related peptide (CGRP), which are pro-nociceptive substances involved in neurogenic inflammation [ 43 , 44 , 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

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Mechanism of Glucose Water as a Neural Injection: A Perspective on Neuroinflammation

Chen

Lam

et al. 2022

Life

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The entrapment of peripheral nerves is associated with chronic neuroinflammation and neuropathic pain, and perineural injection therapy with glucose is emerging as an effective treatment for peripheral entrapment neuropathy. However, the mechanism underlying the pharmacological effect of glucose on nerves remains unclear. One of the hypothesized mechanisms is that glucose reduces neurogenic inflammation. Therefore, we investigated the effects of high glucose concentrations on cytokine-induced neuroinflammation in vitro. Human SH-SY5Y neuronal cells were challenged with 10 ng/mL TNF-α for 16 h and subsequently treated with different glucose concentrations (0–25 mM) for 24 h. Cell viability was evaluated using the diphenyltetrazolium bromide assay, and proinflammatory cytokine levels were assessed using ELISA and quantitative PCR. In addition, mRNA levels of NF-κB and cyclooxygenase-2 were analyzed using quantitative PCR. Exposure to 10 ng/mL TNF-α resulted in decreased viability of SH-SY5Y cells and significant upregulation of IL-6, IL-1β, NF-κB, and cyclooxygenase-2. Subsequent exposure to high glucose levels (25 mM) markedly reduced the upregulation of IL-6, IL-1β, cyclooxygenase-2, and NF-κB, and restored the functional metabolism of SH-SY5Y cells, compared with that of the normal glucose control. Our findings suggest that high glucose concentrations can mitigate TNF-α-induced NF-κB activation, upregulation of proinflammatory cytokines, and metabolic dysfunction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mechanism of Glucose Water as a Neural Injection: A Perspective on Neuroinflammation

Chen

Lam

et al. 2022

Life

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“…Moreover, the elevated extracellular glucose concentration could hyperpolarize C-fibers to stabilize their activation [38]. Adenosine monophosphate protein kinase (AMPK) is a key enzyme regulating cell metabolism, and decreased AMPK activity is associated with neuropathic pain and vice versa [39,40]. AMPK activity may decrease with hypoglycemia and return to normal with elevated glucose, which may be associated with pain reduction [40].…”

Section: Discussionmentioning

confidence: 99%

“…Adenosine monophosphate protein kinase (AMPK) is a key enzyme regulating cell metabolism, and decreased AMPK activity is associated with neuropathic pain and vice versa [39,40]. AMPK activity may decrease with hypoglycemia and return to normal with elevated glucose, which may be associated with pain reduction [40]. Elevated glucose may be neuroprotective in other ways.…”

Section: Discussionmentioning

confidence: 99%

The Effectiveness of Hydrodissection with 5% Dextrose for Persistent and Recurrent Carpal Tunnel Syndrome: A Retrospective Study

Chao

Reeves

Lam

et al. 2022

JCM

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Patients with failure of primary surgery for carpal tunnel syndrome (CTS) present a frustrating clinical problem because there are no relevant treatment guidelines, and the effect of current conservative management or revision surgery is unsatisfactory. Hydrodissection with 5% dextrose is emerging as an effective treatment for primary CTS and may be an effective alternative treatment method for persistent or recurrent post-surgical CTS. We retrospectively investigated the long-term effectiveness of hydrodissection with 5% dextrose for persistent or recurrent CTS. Thirty-six of forty consecutively-treated patients with either persistent or recurrent symptoms of CTS after surgery, who were treated with ultrasound-guided hydrodissection of the median nerve using 10 mL of 5% dextrose, were available to provide outcome data by a structured phone interview at least six months after treatment completion. Symptom relief ≥ 50% represented an effective outcome, while symptom relief < 50% was rated as a poor outcome. Nearly 2/3 (61.1%) of patients reported an effective outcome after a mean of 3.1 injections, with a post-injection follow-up mean of 33 (6–67) months. A non-significant trend toward a more frequently-effective outcome was observed in those with recurrent versus persistent symptoms following CTS (76.9% vs. 52.2%, p = 0.165). However, a significantly higher percentage of those with recurrent symptoms reported an excellent outcome, defined as a greater than 70% improvement (8/13 [61.6%] vs. 3/23 [13%], p = 0.006). The percentage of patients achieving an effective outcome was not significantly different between <2, 2–4, and >4 years of post-treatment follow-up (36.4% vs. 77.8% vs. 57.1%; p = 0.077). Hydrodissection with 5% dextrose may result in a clinically important and durable benefit in those experiencing persistent or recurrent CTS after surgery.

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“…AMPK, as a serine/threonine kinase, is associated with various types of pain and is a potential target for pain management. 28 AMPK activation by AICAR, metformin and resveratrol phosphorylated at Thr172, resultes in 1000-fold activation of AMPK activity, and alleviates inflammatory pain, nerve injury, painful diabetic neuropathy and cancer pain in experimental animal models. 29 , 30 In CIA induced inflammatory pain model mice, AMPK activator AICAR produces an analgesic effect and inhibites the level of proinflammatory cytokine IL-1β.…”

Section: Discussionmentioning

confidence: 99%

Emodin alleviates arthritis pain through reducing spinal inflammation and oxidative stress

et al. 2022

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Chronic pain is the predominant problem for rheumatoid arthritis patients, and negatively affects quality of life. Arthritis pain management remains largely inadequate, and developing new treatment strategies are urgently needed. Spinal inflammation and oxidative stress contribute to arthritis pain and represent ideal targets for the treatment of arthritis pain. In the present study, collagen-induced arthritis (CIA) mouse model was established by intradermally injection of type II collagen (CII) in complete Freund’s adjuvant (CFA) solution, and exhibited as paw and ankle swelling, pain hypersensitivity and motor disability. In spinal cord, CIA inducement triggered spinal inflammatory reaction presenting with inflammatory cells infiltration, increased IL-1β expression, and up-regulated NLRP3 and cleaved caspase-1 levels, elevated spinal oxidative level presenting as decreased Nrf2 expression and SOD activity. To explore potential therapeutic options for arthritis pain, emodin was intraperitoneally injected for three days on CIA mice. Emodin treatment statistically elevated mechanical pain sensitivity, suppressed spontaneous pain, recovered motor coordination, decreased spinal inflammation scores and expression levels of IL-1β, increased spinal Nrf2 expression and SOD activity. Further, AutoDock data showed that emodin bind to AMPK through two electrovalent bonds. And emodin treatment increased the phosphorylated AMPK at threonine 172. In summary, emodin treatment activates AMPK, suppresses NLRP3 inflammasome response, elevates antioxidant response, inhibits spinal inflammatory reaction and alleviates arthritis pain.

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Roles of AMPK and Its Downstream Signals in Pain Regulation

Cited by 10 publications

References 162 publications

Mechanism of Glucose Water as a Neural Injection: A Perspective on Neuroinflammation

Mechanism of Glucose Water as a Neural Injection: A Perspective on Neuroinflammation

The Effectiveness of Hydrodissection with 5% Dextrose for Persistent and Recurrent Carpal Tunnel Syndrome: A Retrospective Study

Emodin alleviates arthritis pain through reducing spinal inflammation and oxidative stress

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