Minocycline relieves neuropathic pain in rats with spinal cord injury via activation of autophagy and suppression of PI3K/Akt/mTOR pathway

Qiao, Leyan; Tang, Qian; An, Zhongzhe; Qin, Jun

doi:10.1016/j.jphs.2023.06.002

Cited by 8 publications

(2 citation statements)

References 27 publications

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“…On the one hand, overactivation of PI3K/Akt/mTOR signaling has been detected in models with nociceptive, neuropathic pain and opioid tolerance. 360 , 361 Mechanistically, Akt phosphorylates ASIC1a at the Ser25 site, which promotes its forward trafficking and membrane expression. 362 mTOR activation has been proved to facilitate reconstruction of nociceptive terminals following inflammation, diminishment of ACC synaptic protein involved in neuropathic pain perception.…”

Section: Molecular Mechanisms Of Pain Modulationmentioning

confidence: 99%

Pathology of pain and its implications for therapeutic interventions

Cao,

Xu,

Shi

et al. 2024

Sig Transduct Target Ther

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Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management is crucial for individuals suffering from pain. However, the current methods for pain assessment and treatment fall short of clinical needs. Benefiting from advances in neuroscience and biotechnology, the neuronal circuits and molecular mechanisms critically involved in pain modulation have been elucidated. These research achievements have incited progress in identifying new diagnostic and therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting the stage for the subsequent contents. The review next delves into the molecular mechanisms underlying pain disorders, including gene mutation, epigenetic modification, posttranslational modification, inflammasome, signaling pathways and microbiota. To better present a comprehensive view of pain research, two prominent issues, sexual dimorphism and pain comorbidities, are discussed in detail based on current findings. The status quo of pain evaluation and manipulation is summarized. A series of improved and innovative pain management strategies, such as gene therapy, monoclonal antibody, brain-computer interface and microbial intervention, are making strides towards clinical application. We highlight existing limitations and future directions for enhancing the quality of preclinical and clinical research. Efforts to decipher the complexities of pain pathology will be instrumental in translating scientific discoveries into clinical practice, thereby improving pain management from bench to bedside.

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Section: Molecular Mechanisms Of Pain Modulationmentioning

confidence: 99%

Pathology of pain and its implications for therapeutic interventions

Cao,

Xu,

Shi

et al. 2024

Sig Transduct Target Ther

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“…Additionally, we also include information about other properties of these substances that are not directly related to nociception but are useful from a clinical point of view. [42,70,71] ERK [72] MMP9 [73] CCI (mouse) [74,75] CCI (rats) [76,77] SCI (rats) [78] STZ (rats) [79] SNL (rats) [70] STZ (mouse) [80] iNOS [72,84] PI3K ↓ [84] morphine ↑ [26,74] Astaxanthin p38 [85] ERK [85] NF-κB [86] NR2B [87] ROS [88]…”

Section: Mapks and Neuropathic Painmentioning

confidence: 99%

Advances in Neuropathic Pain Research: Selected Intracellular Factors as Potential Targets for Multidirectional Analgesics

Ciapała,

Mika

2023

Pharmaceuticals

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Neuropathic pain is a complex and debilitating condition that affects millions of people worldwide. Unlike acute pain, which is short-term and starts suddenly in response to an injury, neuropathic pain arises from somatosensory nervous system damage or disease, is usually chronic, and makes every day functioning difficult, substantially reducing quality of life. The main reason for the lack of effective pharmacotherapies for neuropathic pain is its diverse etiology and the complex, still poorly understood, pathophysiological mechanism of its progression. Numerous experimental studies, including ours, conducted over the last several decades have shown that the development of neuropathic pain is based on disturbances in cell activity, imbalances in the production of pronociceptive factors, and changes in signaling pathways such as p38MAPK, ERK, JNK, NF-κB, PI3K, and NRF2, which could become important targets for pharmacotherapy in the future. Despite the availability of many different analgesics, relieving neuropathic pain is still extremely difficult and requires a multidirectional, individual approach. We would like to point out that an increasing amount of data indicates that nonselective compounds directed at more than one molecular target exert promising analgesic effects. In our review, we characterize four substances (minocycline, astaxanthin, fisetin, and peimine) with analgesic properties that result from a wide spectrum of actions, including the modulation of MAPKs and other factors. We would like to draw attention to these selected substances since, in preclinical studies, they show suitable analgesic properties in models of neuropathy of various etiologies, and, importantly, some are already used as dietary supplements; for example, astaxanthin and fisetin protect against oxidative stress and have anti-inflammatory properties. It is worth emphasizing that the results of behavioral tests also indicate their usefulness when combined with opioids, the effectiveness of which decreases when neuropathy develops. Moreover, these substances appear to have additional, beneficial properties for the treatment of diseases that frequently co-occur with neuropathic pain. Therefore, these substances provide hope for the development of modern pharmacological tools to not only treat symptoms but also restore the proper functioning of the human body.

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