Soft tactile stimulation engages parabrachial circuits traditionally associated with aversion

Abstract

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 likewise associated subparafascicular nucleus, parvocellular part (SPFp), following different tactile stimulation paradigms in mice. Behavioral analyses confirmed that the soft touch stimuli used in this study 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 Fos immunohistochemistry following exposure to brushing-based soft touch, a fur-roll paradigm, innocuous punctate touch (von Frey), or noxious heat. Soft touch protocols robustly increased Fos expression in the lePB compared with home cage controls, whereas innocuous punctate touch did not. Notably, the magnitude of activation produced by brushing-based stimuli was comparable to that induced by noxious heat. Using CalcaCre mice, we further found that soft touch recruited a subset of CGRP-expressing neurons in the lePB. In contrast, tactile stimulation produced only modest activation in the SPFp and did not strongly increase overall Fos expression in this region. Together, these findings demonstrate that affective tactile stimulation can engage neuronal populations within ascending parabrachial circuits, including CGRP neurons traditionally associated with nociceptive processing, suggesting that these pathways may encode the salience or affective significance of somatosensory stimuli rather than exclusively aversive input.