The Role of Spino-Parabrachial Neurons in post-SCI Affective Pain

Neuropathic pain develops in over 80% of spinal cord injury (SCI) patients. Negative affective disorders, such as anxiety and depression, are highly comorbid with neuropathic pain and SCI. However, these emotional components of pain have not been studied in the context of SCI, nor have they been linked to spinal plasticity below the level of injury. Projection neurons in lamina I of the spinal cord relay pain information to the parabrachial nucleus (Pb), and Pb neurons project to the amygdala. While considered the neural correlate of affective pain, it is unclear as to whether the spino-Pb-amygdaloid pathway can be anatomically delineated from the sensory-discriminative spinothalamic pathway in the mouse. We hypothesize that the affective and discriminative pathways from lumbar cord are distinct in the mouse, and that incomplete SCI causes an increased cellular activity of spared lamina I spino-Pb projections to facilitate the development of negative affective behaviors. Combined retrograde tracing from the Pb and thalamus revealed no overlap in lamina I projection neurons at lumbar spinal levels, allowing for selective control. Following incomplete SCI, a subset of mice with mechanical hypersensitivity displayed a cognitive aversiveness to pain and a trend towards increased anxiety-like behaviors. Intracellular recordings from lamina I spino-Pb neurons revealed higher input resistances in mice displaying pain behaviors, suggesting an increased responsiveness to sensory input. This work provides the foundation for cell-specific manipulations to elucidate the functional roles of spino-Pb neurons in post-SCI affective pain.M.S., Neuroscience -- Drexel University, 201