Projection from the parafascicular nucleus of the thalamus to the insular cortex mediate analgesia and anti-anxiety behaviors in mice

The parafascicular nucleus of the thalamus (PF), part of the intralaminar nuclei of the thalamus, plays critical roles in both motor and pain regulations. In this study, the projection from the ventral region of the PF to the dorsal area of the insular cortex (IC) were identified using a neuroanatomical approach. Then, chemogenetic inhibition or activation of the PF-IC neural pathway in the normal mice or in the spared nerve injury (SNI) model mice induced hyperalgesia and anxiety-like behaviors or alleviated hypersensitivity and anxiety-like behaviors, respectively. Additionally, a reduction in the intrinsic electrophysiological activity of the PF neurons projecting to the IC was recorded in 2-week SNI mice. Finally, the results of viral tracing and immunofluorescence histochemical staining demonstrated that the fibers and terminals projecting from the PF predominantly terminated on the parvalbumin-positive interneurons. These findings suggest that the activity of the PF-IC neuronal pathway is suppressed under neuropathic pain condition and that the activation of this pathway exhibits analgesic and anxiolytic effects in mice suffering from nerve injury.