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The involvement of claustrum/insular cortex-locus coeruleus neural pathway in modulating neuropathic pain in mice

PAN Lyu-La^1,2, GONG Tao³, LI Zi-Ang^1,2, QIU Xin-Tong², ZHANG Ming-Ming², LI Yun-Qing^1,2,3,*

¹Basic Medical School, Zhengzhou University, Zhengzhou 450001, China；²Department of Anatomy and K.K. Leung Brain Research Centre, School of Basic Medicine, Air Force Military Medical University, Xi'an 710032, China；³Department of Anatomy, Baotou medical college, Baotou 014000, China

Abstract

To investigate the fiber connections between the claustrum (CLA)/insular cortex (IC) and the locus coeruleus (LC), as well as the role of this neural pathway in neuropathic pain, morphological techniques, patch-clamp recording, and chemogenetics were used in this study, to observe the CLA/IC-LC neural pathway in mice, the effects of neuropathic pain stimuli on the electrophysiological properties of CLA/IC neurons, and the impact of regulating the pathway on pain behaviors, respectively. The results showed that: (1) After injecting anterograde tracing virus into the CLA/IC, anterogradely labeled fibers and terminals were observed in the ipsilateral LC. When retrograde tracers were injected into the LC, retrogradely labeled neurons were observed in both the ipsilateral CLA/IC, whereas fewer labeled neurons were observed in the contralateral side; (2) In the neuropathic pain state, the presynaptic release of neurotransmitters from CLA/IC-LC projection neurons was increased, postsynaptic receptor responses were enhanced, and the number of action potential discharges was elevated; (3) Specific inhibition of the CLA/IC-LC neural pathway induced pain responses in sham-operated mice; specific activation of this pathway alleviated pain-related behaviors in neuropathic pain mice. The present results indicate the existence of functional projection from the CLA/IC to the LC. Under neuropathic pain condition, the CLA/IC-LC pathway exhibits enhanced neuronal activity, and selective activation of this pathway produces significant analgesic effects against neuropathic pain.

Key words: Locus coeruleus; claustrum; insular cortex; neuropathic pain

Received: 　　Accepted:

Corresponding author: 李云庆　　E-mail:

DOI: 10.13294/j.aps.2026.0018

Citing This Article：

PAN Lyu-La, GONG Tao, LI Zi-Ang, QIU Xin-Tong, ZHANG Ming-Ming, LI Yun-Qing. The involvement of claustrum/insular cortex-locus coeruleus neural pathway in modulating neuropathic pain in mice. Acta Physiol Sin 2026; 78 (1): 148-158 (in Chinese with English abstract).