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Pain that persists beyond the time required for tissue healing and pain that arises in the absence of tissue injury, collectively referred to as nociplastic pain, are poorly understood phenomena mediated by plasticity within the central nervous system. The parabrachial nucleus (PBN) is a hub that relays aversive sensory information and appears to play a role in nociplasticity. Here, by preventing PBN Calcaneurons from releasing neurotransmitters, we demonstrate that activation of Calcaneurons is necessary for the manifestation and maintenance of chronic pain. Additionally, by directly stimulating Calcaneurons, we demonstrate that Calcaneuron activity is sufficient to drive nociplasticity. Aversive stimuli of multiple sensory modalities, such as exposure to nitroglycerin, cisplatin, or lithium chloride, can drive nociplasticity in a Calca-neuron-dependent manner. Aversive events drive nociplasticity in Calcaneurons in the form of increased activity and excitability; however, neuroplasticity also appears to occur in downstream circuitry.