Soft tactile stimulation engages CGRP neurons in the parabrachial nucleus

Gentle tactile stimulation is associated with positive affect and social bonding, yet the central circuits engaged by such stimuli remain incompletely understood. The lateral parabrachial nucleus (lePB) is a key hub in ascending affective sensory pathways and is robustly activated by aversive stimuli, including pain. Here, we examined neuronal activation in the lePB and the subparafascicular nucleus, parvocellular part (SPFp), following tactile stimulation in mice. Behavioral analyses confirmed that the soft touch stimuli used were not aversive: mice displayed low aversive facial grimace scores during brushing and von Frey stimulation compared with noxious heat, and showed a preference for a soft tactile environment in a place preference assay. Neuronal activation was assessed using c-Fos immunohistochemistry following exposure to brushing-based soft touch, a fur-roll paradigm, innocuous punctate touch (von Frey), or noxious heat. Soft touch robustly increased c-Fos expression in the lePB compared with home cage controls, whereas innocuous punctate touch did not. Notably, activation produced by brushing was comparable to that induced by noxious heat. Using Calca^Cre mice, we further found that soft touch recruited a subset of CGRP-expressing neurons in the lePB. In contrast, tactile stimulation did not strongly increase overall c-Fos expression in the SPFp. These findings demonstrate that soft tactile stimulation can engage neuronal populations within the parabrachial nucleus, including CGRP neurons frequently associated with aversive processing. The results broaden the range of sensory stimuli known to engage these populations and suggest that they contribute to processing somatosensory signals beyond aversive stimuli.