This R21 application is designed to determine the impact of cerebellar damage on pain sensation and pain processing in the brain. Pain is a subjective experience comprised of sensory, affective, and cognitive dimensions. Human functional imaging studies investigating experimental and clinical pain consistently find cerebellar activation, though its functional implications are unclear. Initially thought to reflecta motor circuit response to pain, the characterization of cognitive and affective deficits following cerebellar damage in children and adults suggest a fundamental role in pain processing. We have also published work that suggests that the cerebellum may serve as a multimodal modulator of negative affect, a significant component in pain processing. However, as far as we know, a thorough investigation of changes in pain sensation following cerebellar tumor resection has never been reported. The hypothesis of this project is that the posterior cerebellum modulates affective brain circuits to down-regulate pain perception in response to noxious stimuli.
The specific aims are (1) to define the consequences of cerebellar tumor resection on pain perception with sensory testing, and (2) define the consequences of resection on pain processing in the brain with functional magnetic resonance imaging. Boston Children's Hospital will provide an ideal clinical research environment to efficiently recruit patients, and to evaluat them with sensory testing and neuroimaging. The long-term goal is to identify the role of the cerebellum in pain processing.
The discovery that the cerebellum modulates pain processing could aid in the development of novel therapies to treat pain. The proposed experiments are relevant to public health because they may lead to enhanced diagnostics and therapeutic treatments for chronic pain. The project is relevant to NCI's mission because the resulting findings could significantly improve quality of life in cancer patients suffering from pain.