Loken, L. S. | bioRxiv Science

bioRxiv2026

Soft tactile stimulation engages parabrachial circuits traditionally associated with aversion

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.

neuroscience↗

bioRxiv2021

A topographical and physiological exploration of C-tactile afferents and their response to menthol and histamine.

Numerous microneurography studies in the human peroneal nerve have suggested that CT afferents are lacking in the more distal parts of the limbs. Here we recorded from unmyelinated low-threshold mechanosensitive afferents in the peroneal and radial nerves, with the most distal receptive fields located on the proximal phalanx of the third finger for the superficial branch of the radial nerve, and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regard to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, were similar in CT units across the antebrachial, radial and peroneal nerves. Moreover, we found that while CT afferents are readily found during microneurography of the arm nerves, they appear to be much more sparse in the lower leg compared to C nociceptors. We continued to explore CT afferents with regard to their chemical sensitivity and found that they could not be activated by topical application to their receptive field of either the cooling agent menthol or the pruritogen histamine. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, including a lack of responsiveness to heat, these findings add to the growing body of research suggesting that CT afferents constitute a unique class of sensory afferents with highly specialized mechanisms for transducing gentle touch.

neuroscience↗