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Updated: Jan 12, 2026

Cheek Injection Model for Simultaneous Measurement of Pain and Itch-related Behaviors
Published on: September 27, 2019
Phox2a in Lateral Spinal Nucleus Tac1-Positive Neurons Mediates Histamine-Independent Acute Itch
Yu-Ling Chen1,2, Zi-Ang Li1,3, Qing-Zhen Wang1,4
1Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, The Fourth Military Medical University, Xi'an, China.
Aims:
While acute itch comprises histamine-dependent and -independent subtypes, critical mechanisms underlying histamine-independent itch remain poorly understood. This study investigates the role of paired-like homeobox 2a (Phox2a) in tachykinin 1-positive (Tac1+) neurons of the lateral spinal nucleus (LSN) as a novel target for histamine-independent pruritus intervention.
Methods:
We combined chemogenetic manipulation (viral-mediated neuronal activation/inhibition), whole-cell patch-clamp recordings, immunohistochemistry, fluorescence in situ hybridization, Western blotting, and behavioral assays to investigate the role of LSNTac1 neurons and Phox2a in itch modulation.
Results:
LSNTac1 neurons were specifically activated during chloroquine (CQ)-induced histamine-independent itch. Chemogenetic activation of these neurons exacerbated scratching, whereas inhibition suppressed itch behavior. Notably, Phox2a, expressed in LSNTac1 neurons, was downregulated during CQ-induced itch. Overexpression of Phox2a in LSNTac1 neurons significantly alleviated CQ-evoked scratching and was accompanied by a reduction in spontaneous excitatory postsynaptic currents (sEPSCs) amplitude without a change in sEPSCs frequency.
Conclusions:
Our findings identify Phox2a in LSNTac1 neurons as a selective regulator of histamine-independent acute itch through presynaptic excitability. This highlights Phox2a as a novel therapeutic target for histamine-independent pruritus intervention.
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