Basolateral amygdala astrocytes modulate diabetic neuropathic pain and may be a potential therapeutic target for koumine

Jing‐Shan Lu; Lan Yang; Jian Chen; Fang‐Fang Xiong; Ping Cai; Xin‐Yao Wang; Bo‐Jun Xiong; Ze‐Hong Chen; Li Chen; Jian Yang; Chang‐Xi Yu

doi:10.1111/bph.16011

journal article Jan 10, 2023

Basolateral amygdala astrocytes modulate diabetic neuropathic pain and may be a potential therapeutic target for koumine

Jing‐Shan Lu

Lan Yang

Jian Chen

Fang‐Fang Xiong Ping Cai Xin‐Yao Wang Bo‐Jun Xiong Ze‐Hong Chen Li Chen

Jian Yang

Chang‐Xi Yu

British Journal of Pharmacology Vol. 180 No. 10 pp. 1408-1428 · Wiley

View at Publisher Save 10.1111/bph.16011

Abstract

Background and PurposeNew 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 basolateral amygdala (BLA) astrocytes in DNP pathogenesis and provide new insights into therapeutic strategies for DNP.Experimental ApproachA streptozotocin‐induced DNP model was established. Designer receptors exclusively activated by designer drugs (DREADDs) were used to regulate astrocyte activity. Mechanical hyperalgesia was assessed using the electronic von Frey test. Anxiety‐like behaviours were detected using open field and elevated plus maze tests. Astrocytic activity was detected by immunofluorescence, and cytokine content was determined by ELISA.Key ResultsBLA astrocytes were regulated by DREADDs, and inhibition of BLA astrocytes attenuated mechanical allodynia and pain‐related negative emotions in DNP rats. In contrast, temporary activation of BLA astrocytes induced allodynia without anxious behaviours in naive rats. In addition, koumine (KM) alleviated mechanical allodynia and anxiety‐like behaviours in DNP rats, inhibited the activation of BLA astrocytes and suppressed the inflammatory response. Furthermore, persistent activation of BLA astrocytes through chemogenetics mimicked chronic pain, and KM alleviated the pain hypersensitivity and anxiety‐like behaviours.Conclusion and ImplicationsDREADDs bidirectionally regulate the activity of BLA astrocytes, which proves for the first time the role of BLA astrocyte activation in the pathogenesis of DNP and represents a novel therapeutic strategy for DNP. KM ameliorates DNP, perhaps by inhibiting the activation of BLA astrocytes and reveal KM as a potential candidate for treating DNP.

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References

68

[1]

10.1038/nature15698

[2]

10.1007/s40265-020-01259-2

[3]

10.1111/bph.15538

[4]

10.1111/bph.15539

[5]

10.1111/bph.14112

[6]

10.1078/0944-7113-00050

[7]

10.1038/s41386-018-0127-4

[8]

10.1016/j.neuron.2015.06.005

[9]

10.1016/j.pharep.2017.09.002

[10]

10.1016/j.neuron.2006.09.021

[11]

10.1007/s11418-017-1070-0

[12]

10.1016/0304-3959(93)90059-x

[13]

10.1111/bph.15868

[14]

10.1002/glia.22349

[15]

10.1097/j.pain.0000000000001386

[16]

10.1007/s13311-020-00905-7

[17]

Diabetic neuropathy

Eva L. Feldman, Brian C. Callaghan, Rodica Pop-Busui et al.

Nature Reviews Disease Primers 10.1038/s41572-019-0092-1

[18]

Neuropathic Pain: From Mechanisms to Treatment

Nanna Brix Finnerup, Rohini Kuner, Troels Staehelin Jensen

Physiological Reviews 10.1152/physrev.00045.2019

[19]

10.1016/j.neuroscience.2018.08.010

[20]

10.1016/s0304-3959(99)00024-x

[21]

10.1073/pnas.1602070113

[22]

10.1038/s41593-019-0528-7

[23]

10.1038/s41593-020-0632-8

[24]

10.1016/j.sjpain.2017.08.002

[25]

10.1016/j.phrs.2018.10.027

[26]

10.1038/s41583-019-0218-1

[27]

10.1038/nrd4334

[28]

10.1186/s12950-019-0217-z

[29]

10.1155/2018/9347696

[30]

10.1016/j.phymed.2021.153640

[31]

10.1016/j.jep.2014.01.003

[32]

10.1007/s00429-021-02235-6

[33]

10.1016/j.drudis.2013.10.018

[34]

Estrogen alleviates neuropathic pain induced after spinal cord injury by inhibiting microglia and astrocyte activation

Jee Youn Lee, Hae Young Choi, Bong-Gun Ju et al.

Biochimica et Biophysica Acta (BBA) - Molecular Ba... 10.1016/j.bbadis.2018.04.006

[35]

10.1186/s12974-019-1524-2

[36]

10.1371/journal.pone.0070921

[37]

10.1016/j.brainres.2010.10.044

[38]

10.1111/bph.15178

[39]

10.1016/j.neuron.2020.08.012

[40]

10.1007/s00213-012-2867-x

[41]

10.1523/jneurosci.2566-20.2021

[42]

10.1002/j.1532-2149.2012.00255.x

[43]

10.1016/j.neuron.2019.03.042

[44]

10.1016/j.ejphar.2020.173039

[45]

10.3390/ijms20225729

[46]

10.1136/bmj.g1799

[47]

The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research

Nathalie Percie du Sert, Viki Hurst, Amrita Ahluwalia et al.

PLOS Biology 10.1371/journal.pbio.3000410

[48]

10.2174/1566523221666210211102435

[49]

10.1016/j.neuron.2016.01.040

[50]

10.1016/j.neuroscience.2017.12.009

Showing 50 of 68 references

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References

Details

Published: Jan 10, 2023
Vol/Issue: 180(10)
Pages: 1408-1428
License: View

Authors

J

Jing‐Shan Lu

Department of Pharmacology, School of Pharmacy Fujian Medical University Fuzhou China; Fujian Center for Safety Evaluation of New Drug Fujian Medical University Fuzhou China

L

Lan Yang