Metformin attenuates diabetic neuropathic pain via AMPK/NF-κB signaling pathway in dorsal root ganglion of diabetic rats

Cao, Xiao-Jun; Wu, Rui; Qian, Heya; Chen, Xiang; Xu, Guang–Yin; Sun, Ye-Zi; Zhang, Ping-An

doi:10.1016/j.brainres.2021.147663

Cited by 18 publications

(15 citation statements)

References 28 publications

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“… 110 , 111 There is considerable evidence that metformin also has beneficial effects on neuroprotection and hyperalgesia. 5 , 112 Metformin can reduce inflammatory response and oxidative stress and regulate autophagy response and the activation or expression of NaV1.7 and TRPA1 channels to play analgesic and antihyperalgesia roles by activating AMPK. Metformin's analgesia is also partially explained by the reduction in MGO and IR.…”

Section: Discussionmentioning

confidence: 99%

“… 36 Recently, studies have shown that the downregulated AMPK is closely related to pain symptoms and metformin can relieve pain by activating AMPK. 3 , 5 , 10 , 36 …”

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 99%

“…Metformin attenuated mechanical allodynia through downregulating NF‐κB expression in L4‐6 DRG neurons, and the expression of NF‐κB was controlled by P‐AMPK. 5 …”

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 99%

“… 3 Metformin is an antihyperglycemic drug widely used in patients with type 2 diabetes mellitus (T2DM) and has been reported to have analgesic potential. 4 Studies have shown that metformin can relieve neuropathic pain caused by diabetes 5 , 6 or chemotherapeutic drugs, 7 , 8 low back pain, 9 , 10 osteoarthritis, 11 , 12 postoperative pain 13 , 14 and inflammatory pain 15 , 16 through activating adenosine 5′monophosphate‐activated protein kinase (AMPK). Metformin also has the ability to remove methylglyoxal (MGO), 17 a metabolite associated with PDPN.…”

Section: Introductionmentioning

confidence: 99%

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Is metformin a possible treatment for diabetic neuropathy?

Wei

Wei²,

Huang

et al. 2022

Journal of Diabetes

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Metformin is a hypoglycemic drug widely used in the treatment of type 2 diabetes. It has been proven to have analgesic and neuroprotective effects. Metformin can reverse pain in rodents, such as diabetic neuropathic pain, neuropathic pain caused by chemotherapy drugs, inflammatory pain and pain caused by surgical incision. In clinical use, however, metformin is associated with reduced plasma vitamin B12 levels, which can further neuropathy. In rodent diabetes models, metformin plays a neuroprotective and analgesic role by activating adenosine monophosphate‐activated protein kinase, clearing methylgloxal, reducing insulin resistance, and neuroinflammation. This paper also summarized the neurological adverse reactions of metformin in diabetic patients. In addition, whether metformin has sexual dimorphism needs further study.

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Section: Discussionmentioning

confidence: 99%

“… 36 Recently, studies have shown that the downregulated AMPK is closely related to pain symptoms and metformin can relieve pain by activating AMPK. 3 , 5 , 10 , 36 …”

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 99%

“…Metformin attenuated mechanical allodynia through downregulating NF‐κB expression in L4‐6 DRG neurons, and the expression of NF‐κB was controlled by P‐AMPK. 5 …”

Section: Effects and Mechanisms Of Metformin On Pdpnmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Is metformin a possible treatment for diabetic neuropathy?

Wei

Wei²,

Huang

et al. 2022

Journal of Diabetes

View full text Add to dashboard Cite

show abstract

“…( 40 ) reported that the use of insulin is an independent risk factor for DPN in patients with type 2 diabetes. On the other hand, metformin possibly attenuated neuropathic pain in a diabetic rat model ( 57 ). According to UK biobank data, the use of metformin had low odds of causing musculoskeletal pain in patients with type 2 diabetes ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

Scores of peripheral neuropathic pain predicting long-term mortality in patients with type 2 diabetes: A retrospective cohort study

2022

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ObjectivesDiabetic peripheral neuropathic pain (DPNP) is a prevalent chronic complication in patients with diabetes. Using a questionnaire is helpful for DPNP screening in outpatients. In this retrospective cohort, we aimed to examine whether DPNP diagnosed based on scoring questionnaires could predict long-term mortality in outpatients with type 2 diabetes.MethodsWe enrolled 2318 patients who had joined the diabetes pay-for-performance program and completed the annual assessments, including both the identification pain questionnaire (ID pain) and Douleur Neuropathique en 4 questionnaire (DN4), between January 2013 and October 2013. Information on registered deaths was collected up to August 2019.ResultsThere was high consistency in the scores between the ID pain and DN4 (r = 0.935, P < 0.001). During the median follow-up of 6.2 years (interquartile range: 5.9−6.4 years), 312 patients deceased. Patients with an ID pain score of ≥ 2 had a higher mortality risk than those with a score of < 2 (hazard ratio [HR] = 1.394, 95%CI: 1.090−1.782), and patients with a DN4 score of ≥ 4 had a higher mortality risk than those with a score of < 4 (HR = 1.668, 95% confidence interval [CI]: 1.211−2.297). Patients consistently diagnosed with DPNP by the ID pain and DN4 had a significantly higher mortality risk (HR = 1.713, 95% CI: 1.223−2.398, P = 0.002), but not those discrepantly diagnosed with DPNP (P = 0.107), as compared with those without DPNP.ConclusionsBoth the ID pain and DN4 for DPNP screening were predictive of long-term mortality in patients with type 2 diabetes. However, a discrepancy in the diagnosis of DPNP weakened the power of mortality prediction.

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