Affective tactile stimulation ameliorates chronic pain and comorbid anxiety by modulating hippocampal CA1 oscillations and functional connectivity.

Chronic pain is a multidimensional experience influenced by biological, psychological, and social factors. It frequently culminates in a reciprocal "pain-emotion" vicious cycle involving comorbid anxiety and depression. This study investigated the therapeutic potential of affective tactile stimulation in a rat model of chronic inflammatory pain with anxiety, focusing on the afferent pathways and the regulatory role of the hippocampal CA1 region. Through behavioral assays and optogenetic interventions, we demonstrated that affective tactile stimulation partially ameliorates pain hypersensitivity, exerts a mild modulatory effect on peripheral inflammatory responses, and effectively alleviates anxiety-like behaviors. Mechanistically, affective tactile stimulation appears to integrate sensory information within the tactile cortex to modulate neural activity in the hippocampal CA1, a key regulatory hub. Enhanced CA1 neuronal activity was found to correlate closely with symptom improvement. Furthermore, our results suggest that oscillatory enhancement in the theta and delta bands, alongside functional connectivity remodeling, might play a critical role in these effects. These findings provide a neurobiological foundation for the clinical application of affective tactile stimulation in managing chronic inflammatory pain and associated affective disorders.