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Basolateral amygdala astrocytes modulate of diabetic neuropathic pain and may be a potential therapeutic target for koumine
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  • Jingshan Lu,
  • Lan Yang,
  • Jian Chen,
  • Fangfang Xiong,
  • Ping Cai,
  • Xinyao Wang,
  • Bojun Xiong,
  • Zehong Chen,
  • Li Chen,
  • Jian Yang,
  • Changxi Yu
Jingshan Lu
Fujian Medical University

Corresponding Author:[email protected]

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Lan Yang
Fujian Medical University
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Jian Chen
Fujian Medical University
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Fangfang Xiong
Fujian Medical University
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Ping Cai
Fujian Medical University
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Xinyao Wang
Fujian Medical University
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Bojun Xiong
Fujian Medical University
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Zehong Chen
Fujian Medical University
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Li Chen
Fujian Medical University
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Jian Yang
Fujian Medical University
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Changxi Yu
Fujian Medical University
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Abstract

Background and Purpose: New remedies are required for the treatment of diabetic neuropathic pain (DNP) due to insufficient efficacy of available therapies. Here, we used chemogenetic approaches combined with in vivo pharmacology to elucidate the role of BLA astrocytes in DNP pathogenesis and provide new insights into DNP therapeutic strategies. Experimental Approach: A streptozotocin-induced DNP model was established. Designer receptors exclusively activated by designer drugs (DREADDs) were used to regulate the activity of astrocytes. Mechanical hyperalgesia was assessed using the electronic von Frey test. Anxiety-like behaviors were detected by open field and elevated plus maze tests. Astrocytic activity was detected by immunofluorescence, and cytokine content was determined by ELISA. Key Results: BLA astrocytes were regulated by DREADDs, and inhibition of BLA astrocytes attenuated mechanical allodynia and anxiety-like behavior in DNP rats. Contrastively, temporary activation of BLA astrocytes induced allodynia without anxious behavior in naive rats. In addition, we found that koumine alleviates mechanical allodynia and anxiety-like behavior in DNP rats, inhibits the activation of BLA astrocytes and suppresses the inflammatory response. Furthermore, persistent activation of BLA astrocytes by chemogenetic mimics chronic pain, and koumine can alleviate its pain hypersensitivity and anxiety-like behavior. Conclusion and Implications: DREADDs bidirectionally regulate the activity of BLA astrocytes, which proves for the first time the role of BLA astrocytes activation in the pathogenesis of DNP and represents a novel therapeutic strategy for DNP. Koumine ameliorated DNP, perhaps by inhibiting the activation of BLA astrocytes and reveal KM as a potential candidate for treating DNP.
28 Apr 2022Submitted to British Journal of Pharmacology
04 May 2022Submission Checks Completed
04 May 2022Assigned to Editor
16 May 2022Reviewer(s) Assigned
06 Jun 2022Review(s) Completed, Editorial Evaluation Pending
09 Jun 2022Editorial Decision: Revise Minor
30 Aug 20221st Revision Received
30 Aug 2022Submission Checks Completed
30 Aug 2022Assigned to Editor
10 Sep 2022Reviewer(s) Assigned
30 Sep 2022Review(s) Completed, Editorial Evaluation Pending
07 Oct 2022Editorial Decision: Revise Minor
20 Oct 20222nd Revision Received
22 Oct 2022Submission Checks Completed
22 Oct 2022Assigned to Editor
22 Oct 2022Review(s) Completed, Editorial Evaluation Pending
28 Oct 2022Reviewer(s) Assigned
05 Dec 2022Editorial Decision: Accept