Parabrachial inputs to the parafascicular thalamus drive sensory and affective-motivational responses to cold-allodynia in mice.

Tonic pain engages both sensory and affective-motivational processes, which are partially mediated by the medial thalamus. However, the circuit mechanisms by which distinct medial thalamic subnuclei contribute to pain-related behaviors remain poorly understood. Taking advantage of intersectional viral genetics, in vivo imaging, and ex vivo physiology, we find that the neurons in the parafascicular (PF) nuclei of the medial thalamus receive monosynaptic inputs from the lateral parabrachial nuclei (LPBN) in mice. The PF neurons downstream LPBN (PFpost-LPBN) are nociceptive, sensitized by peripheral neuropathy, and acutely aversive; when activated, they drive both sensory and affective-motivational responses to cold allodynia. In contrast, the LPBN target neurons in the intralaminar centromedian thalamus (CMpost-LPBN), another nociceptive nucleus of the medial thalamus, are primarily involved in the affective-motivational aspects of pain. Together, these findings show that LPBN projections to two closely related medial thalamic nuclei differentially shape behavioral responses to cold hypersensitivity associated with peripheral neuropathy.