Journal ArticleDOI
Microglial interleukin-1β in the ipsilateral dorsal horn inhibits the development of mirror-image contralateral mechanical allodynia through astrocyte activation in a rat model of inflammatory pain.
Hoon Seong Choi,Dae Hyun Roh,Seo Yeon Yoon,Jiyoung Moon,Sheu Ran Choi,Soon Gu Kwon,Suk Yun Kang,Ho Jae Han,Hyun-Woo Kim,Alvin J. Beitz,Seog Bae Oh,Jang Hern Lee +11 more
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Results suggest that spinal IL-1&bgr; derived from activated microglia temporarily suppresses astrocyte activation, which can ultimately prevent the development of contralateral MA under inflammatory conditions, and imply that microglial IL- 1&b gr; plays an important role in regulating the induction of inflammatory MIP.Abstract:
Damage on one side of the body can also result in pain on the contralateral unaffected side, called mirror-image pain (MIP). Currently, the mechanisms responsible for the development of MIP are unknown. In this study, we investigated the involvement of spinal microglia and interleukin-1β (IL-1β) in the development of MIP using a peripheral inflammatory pain model. After unilateral carrageenan injection, mechanical allodynia (MA) in both hind paws and the expression levels of spinal Iba-1, IL-1β, and GFAP were evaluated. Ipsilateral MA was induced beginning at 3 hours after carrageenan injection, whereas contralateral MA showed a delayed onset occurring 5 days after injection. A single intrathecal (i.t.) injection of minocycline, a tetracycline derivative that displays selective inhibition of microglial activation, or an interleukin-1 receptor antagonist (IL-1ra) on the day of carrageenan injection caused an early temporary induction of contralateral MA, whereas repeated i.t. treatment with these drugs from days 0 to 3 resulted in a long-lasting contralateral MA, which was evident in its advanced development. We further showed that IL-1β was localized to microglia and that minocycline inhibited the carrageenan-induced increases in spinal Iba-1 and IL-1β expression. Conversely, minocycline or IL-1ra pretreatment increased GFAP expression as compared with that of control rats. However, i.t. pretreatment with fluorocitrate, an astrocyte inhibitor, restored minocycline- or IL-1ra-induced contralateral MA. These results suggest that spinal IL-1β derived from activated microglia temporarily suppresses astrocyte activation, which can ultimately prevent the development of contralateral MA under inflammatory conditions. These findings imply that microglial IL-1β plays an important role in regulating the induction of inflammatory MIP.read more
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Microglia induce the transformation of A1/A2 reactive astrocytes via the CXCR7/PI3K/Akt pathway in chronic post-surgical pain
Ting Li,Tongtong Liu,Xuhui Chen,Li Li,Miaomiao Feng,Yue Zhang,Li Wan,Chuanhan Zhang,Wenlong Yao +8 more
TL;DR: Results indicated that microglia induce the transformation of astrocytes to the A1 phenotype in the spinal cord via downregulation of the CXCR7/PI3K/Akt signaling pathway during CPSP.
Journal ArticleDOI
Hypoxic Stress and Inflammatory Pain Disrupt Blood-Brain Barrier Tight Junctions: Implications for Drug Delivery to the Central Nervous System.
TL;DR: What is currently known with regard to BBB disruption following a hypoxic or inflammatory insult in vivo is looked at and potential mechanisms involved in altering tight junction components at the BBB are discussed.
Journal ArticleDOI
Interleukin‐1beta released by microglia initiates the enhanced glutamatergic activity in the spinal dorsal horn during paclitaxel‐associated acute pain syndrome
Xisheng Yan,Fen Li,Dylan W. Maixner,Ruchi Yadav,Mei Gao,Mourad Wagdy Ali,Shelley B. Hooks,Han-Rong Weng,Han-Rong Weng +8 more
TL;DR: The study indicates that IL‐1β is a crucial molecule used by microglia to alter functions in astrocytes and neurons upon activation of TLR4 in the genesis of P‐APS, and targeting the signaling pathways regulating the production and function of IL‐ 1β frommicroglia is a potential avenue for the development of analgesics for the treatment of P-APS.
Journal ArticleDOI
CD200R1 agonist attenuates glial activation, inflammatory reactions, and hypersensitivity immediately after its intrathecal application in a rat neuropathic pain model.
Miriam Hernangómez,Ilona Klusáková,Ilona Klusáková,Marek Joukal,Ivana Hradilová-Svíženská,Ivana Hradilová-Svíženská,Carmen Guaza,Petr Dubový,Petr Dubový +8 more
TL;DR: Intrathecal administration of the CD200R1 agonist CD200Fc induces very rapid suppression of neuroinflammatory reactions associated with glial activation and neuropathic pain development, which may constitute a promising and novel therapeutic approach for the treatment of neuropathicPain.
References
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Journal ArticleDOI
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