Src/p38 MAPK pathway in spinal microglia is involved in mechanical allodynia induced by peri-sciatic administration of recombinant rat TNF-α

Li, Yuying; Wei, Xu-Hong; Lu, Zhenhe; Chen, Jinsheng; Huang, Qingyang; Gong, Qingjuan

doi:10.1016/j.brainresbull.2013.05.002

Cited by 14 publications

(10 citation statements)

References 34 publications

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“…MAPK signalling pathways (such as those involving extracellular signal-regulated kinase (ERK), p38 and JUN N-terminal kinases (JNK)) in glia have an important role in intracellular signalling, leading to the activation of transcription factors, such as nuclear factor-κB (NF-κB), that promote the expression of a wide array of genes encoding pro-inflammatory products (such as cytokines and brain-derived neurotrophic factor (BDNF)). In various models of peripheral pain, spinal microglia show increased phosphorylation of SRC family kinases (namely, SRC, LYN and FYN), which are upstream of ERK 28,87,88. Furthermore, specific inhibition of SRC family kinases in microglia attenuates nerve injury-induced allodynia by preventing long-term potentiation in spinal dorsal C-fibres 88,89 .…”

Section: The Neuroimmune Interface In Pathological Painmentioning

confidence: 99%

Pathological pain and the neuroimmune interface

et al. 2014

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Reciprocal signalling between immunocompetent cells in the central nervous system (CNS) has emerged as a key phenomenon underpinning pathological and chronic pain mechanisms. Neuronal excitability can be powerfully enhanced both by classical neurotransmitters derived from neurons, and by immune mediators released from CNS-resident microglia and astrocytes, and from infiltrating cells such as T cells. In this Review, we discuss the current understanding of the contribution of central immune mechanisms to pathological pain, and how the heterogeneous immune functions of different cells in the CNS could be harnessed to develop new therapeutics for pain control. Given the prevalence of chronic pain and the incomplete efficacy of current drugs — which focus on suppressing aberrant neuronal activity — new strategies to manipulate neuroimmune pain transmission hold considerable promise.

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Section: The Neuroimmune Interface In Pathological Painmentioning

confidence: 99%

Pathological pain and the neuroimmune interface

et al. 2014

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“…Studies have demonstrated that elevated TNF-α and its receptor are found at the sites of nerve damage in the classic chronic constriction injury (CCI) animal model of neuropathic pain [18–21]. Administration of exogenous TNF-α can also induce allodynia in rodents [22–26], while the administration of TNF-α antagonists has been found to decrease behaviors suggestive of pain and hyperalgesia in rodents following CCI [27–30]. …”

Section: Targeting Pro-inflammatory Cytokinesmentioning

confidence: 99%

Targeting cytokines for treatment of neuropathic pain

Hung

Lim

Doshi

2017

Scandinavian Journal of Pain

149

120

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AbstractBackgroundNeuropathic pain is a challenging condition often refractory to existing therapies. An increasing number of studies have indicated that the immune system plays a crucial role in the mediation of neuropathic pain. Exploration of the various functions of individual cytokines in neuropathic pain will provide greater insight into the mechanisms of neuropathic pain and suggest potential opportunities to expand the repertoire of treatment options.MethodsA literature review was performed to assess the role of pro-inflammatory and antiinflammatory cytokines in the development of neuropathic pain. Both direct and indirect therapeutic approaches that target various cytokines for pain were reviewed. The current understanding based on preclinical and clinical studies is summarized.Results and conclusionsIn both human and animal studies, neuropathic pain has been associated with a pro-inflammatory state. Analgesic therapies involving direct manipulation of various cytokines and indirect methods to alter the balance of the immune system have been explored, although there have been few large-scale clinical trials evaluating the efficacy of immune modulators in the treatment of neuropathic pain. TNF-α is perhaps the widely studied pro-inflammatory cytokine in the context of neuropathic pain, but other pro-inflammatory (IL-1β, IL-6, and IL-17) and anti-inflammatory (IL-4, IL-10, TGF-β) signaling molecules are garnering increased interest. With better appreciation and understanding of the interaction between the immune system and neuropathic pain, novel therapies may be developed to target this condition.

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“…The upregulation of multiple inflammatory factors (IL-1β, IL-6, interleukin-17 (IL-17), and TNF-α) can be found in the model of NP [ 14 ]. The intrathecal injection of TNF-α can directly induce hyperalgesia in rodents [ 41 , 42 ]. Therefore, we used an animal model of NP induction through the intrathecal injection of TNF-α in the present study.…”

Section: Discussionmentioning

confidence: 99%

Daphnetin Improves Neuropathic Pain by Inhibiting the Expression of Chemokines and Inflammatory Factors in the Spinal Cord and Interfering with Glial Cell Polarization

et al. 2023

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Neuropathic pain (NP) is a common pain disease that seriously affects the quality of life and physical and mental health of patients. Daphnetin is extracted from the Daphne giraldii Nitsche and has the structure of 7,8-dihydroxy coumarin. As a natural product, daphnetin displays a wide range of pharmacological activities, such as analgesia and anti-inflammatory activities, but whether it is able to improve NP through anti-inflammatory effects is unknown. Therefore, this paper intends to investigate the mechanism of daphnetin in improving NP rats affected by the intrathecal injection of tumor necrosis factor-α (TNF-α) from the perspective of anti-inflammation. Our results showed that daphnetin significantly improved hyperalgesia in NP rats. Daphnetin inhibited the activation and polarization of glial cells and neurons in the spinal cord of NP rats and reduced the expression of mRNA and protein of inflammatory factors and chemokine pairs in the spinal cord. Daphnetin inhibited the polarization of human microglia cell 3 (HMC3) cells and human glioma cells (U251) cells toward M1 microglia and A1 astrocytes, respectively, and induced the conversion of M1 microglia and A1 astrocytes to M2 microglia and A2 astrocytes, respectively. In conclusion, daphnetin ameliorates NP by inhibiting the expression of inflammatory factors and chemokines and the polarization of glial cells in the spinal cord of NP rats. This study provides a theoretical basis for the treatment of NP with daphnetin to expand the clinical application of daphnetin.

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Src/p38 MAPK pathway in spinal microglia is involved in mechanical allodynia induced by peri-sciatic administration of recombinant rat TNF-α

Cited by 14 publications

References 34 publications

Pathological pain and the neuroimmune interface

Pathological pain and the neuroimmune interface

Targeting cytokines for treatment of neuropathic pain

Daphnetin Improves Neuropathic Pain by Inhibiting the Expression of Chemokines and Inflammatory Factors in the Spinal Cord and Interfering with Glial Cell Polarization

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