Intrathecal Injection of SIRT1-modified Human Mesenchymal Stem Cells Alleviates Neuropathic Pain in Rat
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Intrathecal Injection of SIRT1-modified Human Mesenchymal Stem Cells Alleviates Neuropathic Pain in Rat Jun Tian 1 & Tieying Song 2
&
Hong Wang 2 & Wenli Wang 3 & Zaiwang Zhang 4 & Ruyu Yan 5 & Xiaojing Ma 2 & Yue Hu 6
Received: 20 July 2020 / Accepted: 23 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Accumulating evidence has elucidated that human mesenchymal stem cells (hMSCs) exert profound analgesic effects on numerous animal models of neuropathic pain, including drug-induced peripheral nerves, diabetes-induced neuropathy, and chronic constriction injury. We aimed to address whether forcing expression of sirtuin 1 (SIRT1) can enhance the efficacy of hMSCs on alleviation of pain sensation. A rat model of chronic constriction injury (CCI) mimicking peripheral nerve injury was incorporated in the study. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) testing were used to measure pain-related behavior. Our results demonstrated that SIRT1 was decreased post-CCI surgery. Compared to hMSCs-control implantation, the hMSCs-SIRT1 (hMSCs overexpressing SIRT1) implantation exhibited superior effects on reducing proinflammatory cytokine levels in serum and spinal dorsal horn, while ameliorating neuropathic pain in CCI rat. Engineering hMSCs such as overexpressing SIRT1 may serve as a promising strategy for the treatment of patients with neuropathic pain. Keywords Neuropathic pain . hMSCs . SIRT1 . HMGB1/TLR4 pathway . Chronic constriction injury
Introduction Neuropathic pain occurs when the somatosensory nervous system is damaged from nerve disease or injury, which impedes transmit sensation from impacted nerves to the brain, leading to a series of neurological conditions, including peripheral nerve injury pain, postherpetic neuralgia, amputation, and trigeminal neuralgia (Cavalli et al. 2019; Costigan et al. 2009). Numerous pathological mechanisms contribute to the development of
* Tieying Song [email protected] 1
Department of Neurosurgery, The First Hospital of Shijiazhuang, Shijiazhuang 050000, China
2
Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang 050000, China
3
Department of Gynaecology, Maternal and Child Health Care Hospital of Shijiazhuang, Shijiazhuang 050000, China
4
Department of Anesthesiology, The Bethune International Peace Hospital of P.L.A., Shijiazhuang 050000, China
5
Department of Anesthesiology, Shijiazhuang Hospital of Traditional Chinese Medicine, Shijiazhuang 050000, China
6
Department of Gynaecology, The First Hospital of Shijiazhuang, Shijiazhuang 050000, China
neuropathic pain, including peripheral diabetic neuropathy, viral infection–induced neuropathies, chemotherapy-promoted peripheral neuropathies, and injuries to the brain or spinal cord (Campbell and Meyer 2006). Patients with neuropathic pain may present various signs and symptoms, which can be generally characterized into hyperalgesia (enhanced perception of the stimuli that cause pain), and allodynia (hypersensitive responses
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