Neuropathic pain often manifests as hypersensitivity to cold, also known as cold allodynia. The underlying neural circuitries in the brain have yet to be explored. Here, using chemotherapy-induced cold hypersensitivity as a model, we sought to understand the role of the connections between the brainstem parabrachial nucleus (PBN) and the parafascicular thalamus (PF). PBN is a well-known gateway for nociceptive information from the spinal cord to the rest of the brain, while PF is instrumental in mediating motor behavior through its connections with the motor cortex and the striatum. In a series of experiments, we demonstrate that the PBN-PF circuitry drives behavioral responses to pain. At the same time, synaptic plasticity in the same circuits is necessary for the persistent pain caused by neuropathy.