Tactile stimulation reverses painful stimuli outcomes via PVN-VTA oxytocin circuitry and dopaminergic regulation.

Abstract

Newborn mammals often encounter painful stimuli (PS)-such as trampling, retrieval by parental incisors, or conspecific aggression-that can disrupt neural and behavioral development. Parental tactile care, including licking and grooming, is thought to buffer these effects, but the underlying mechanisms remain unclear. Using mandarin voles, a highly social species, we showed that postnatal back brushing, a proxy for affiliative tactile stimulation, reversed the negative impact of early tail pinching on emotional and social behaviors. Back brushing notably reversed the reduction in activities of oxytocin (OXT) neurons in the paraventricular nucleus (PVN) and activities of the ventral tegmental area (VTA) induced by early tail pinching. Chemogenetic and optogenetic activation of PVN-VTA OXT neuron terminals reduced anxiety, increased sociality, and enhanced dopamine (DA) release in the nucleus accumbens (NAc) of animals with PS. These effects were reversed by oxytocin receptor (OXTR) antagonism in the VTA. Conversely, inhibition of this circuit produced opposite effects. At the molecular level, brushing reversed PS-induced hypermethylation of Drd1, Drd2, and Nr3c1, as well as broader transcriptomic shifts in the NAc. Our findings uncover a tactile-oxytocin-dopamine pathway underlying resilience to early-life pain and highlight conserved mechanisms through which social touch supports emotional brain development.