Behavioral Changes and Morphological Plasticity in the Prefrontal Cortex during Neuropathic Pain

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Hughes, Hannah Alicia
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Chronic pain is a serious public health problem that is often intractable to known therapies. While cellular adaptations that occur in the periphery and spinal cord are fairly well-understood, less is known about adaptations that occur in the brain that alter how pain is perceived. Neuropathic pain is associated with the development of an affective state, and that state shapes ongoing cognitive and emotional processes. The first goal of this study was to evaluate the relationship between the onset of sensory pain and the development of the affective component. To evaluate these factors, we used the spared nerve injury (SNI) model for neuropathic pain in rats. Following SNI, we measured the pain threshold (allodynia) elicited by Von Frey filaments and evaluated ultrasonic vocalizations (USVs, 22KHz). We showed that there is an immediate and constant reduction in the pain threshold following SNI; however, USVs develop over time. This indicates that the affective component of pain develops after a prolonged period of sensory pain. Pain-related affect is mediated by the prefrontal cortex. The second goal of this study was to evaluate cellular adaptions that occur in the PFC that may contribute to the development of the affective component of pain. Immunocytochemical studies by collaborators show that there is increased expression of c-Fos in the contralateral prelimbic (PrL) region of rat prefrontal cortex following SNI, and that expression is colocalized to the expression of CaMKII. These results suggest that glutamatergic pyramidal cells are affected by SNI, and electrophysiological studies in these cells show that they are hyperexcitable. This study evaluated the dendritic spine population in PrL pyramidal cells following SNI. As a control experiment, we evaluated dendritic spines on pyramidal cells in the visual cortex. We showed an increase in the population of filopodia spines at day 30 and long thin spines at days 7 and 30 post-SNI. There was no change in the spine population in the visual cortex. Long thin spines have been referred to as “learning” spines because they are preferential sites for LTP, and this pain-induced increase in spine density may reflect a mechanism for “learning” of pain-related affect.
neuropathic pain, affect, dendritic spines,