An attention-demanding hunting paradigm engages the superior colliculus-zona incerta circuit mediating analgesia in male mice
Source: Nature communications
Authors: Xue Zhang, Xiao-Juan Liu, Cui Yin, Qiangqiang Zhou, Jiaqi Zhang, Liwei Wang, Jun-Li Cao, Cheng Xiao, Chunyi Zhou, Publication Date: Tue, 19 May 2026 06:00:00 -0400
Nat Commun. 2026 May 19;17(1):4419. doi: 10.1038/s41467-026-73206-w.
ABSTRACT
Attention distraction mitigates pain, yet its neural basis remains elusive. We established cricket hunting as an attention-demanding paradigm that alleviates acute and chronic pain in male mice. Activity tagging revealed that cricket hunting activated a subset of glutamatergic neurons in the superior colliculus (SC). Selective stimulation of these hunting-activated neurons alleviated chronic hyperalgesia, primarily mediated by their projections to the zona incerta (ZI). Notably, repeated engagement, either through the hunting paradigm or by repeatedly activating hunting-activated SC-ZI projections, induced sustained analgesia (lasting at least 6 hours), linked to potentiated glutamatergic inputs to ZI GABAergic neurons. Furthermore, SC-ZI projections originating from SC neurons expressing tachykinin precursor 1 (Tac1) selectively elevated neuropathic pain thresholds via substance P release and neurokinin 1 (NK1) receptor-dependent excitatory synaptic transmission onto ZI GABAergic neurons. Together, we show that a specific SC-ZI circuit drives attention-induced analgesia, highlighting the SCTac1-ZI pathway as a therapeutic target for chronic pain.
PMID:42156761 | PMC:PMC13187426 | DOI:10.1038/s41467-026-73206-w
Pubmed ID: pubmed:42156761
Identifiers: pmid:42156761, pmc:PMC13187426, doi:10.1038/s41467-026-73206-w,
Paper chosen by Allan Basbaum
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Continuing the studies that examined the influence of attention/distraction on pain, here the authors used cricket hunting to distract male mice. Cricket hunting was associated with activation of a subset of glutamatergic neurons in the superior colliculus, stimulation of which reduced chronic pain. The inhibition derived from a substance P-expressing subset of the SC projections to GABAergic inhibitory neurons in the zona incerta. Whether activation of this pathway can translate to different pain models remains to be determined.