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

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.