Neuronal plasticity at remote sites causes neuropathic pain after SCI

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DESCRIPTION (provided by applicant): Spinal cord injury (SCI) often impairs sensory systems causing chronic allodynia and hyperalgesia, two common forms of neuropathic pain. While the recovery of motor systems appears to be exponentialy related to axonal sparing at the epicenter, the recovery of normal sensation appears to be an all or none response. In contusion SCI models, profound hypersensitization occurs with greater than 90% axonal loss at the lesion epicenter and is similar in intensity to the pain produced in classic peripheral nerve injury models. The mechanism of neuropathic pain development has been studied extensively following peripheral nerve injury (PNI), while little is known about the mechanism underlying pain development after central trauma. Recent studies show novel remodeling of descending motor systems after SCI that elicited profound locomotor recovery. Using similar transynaptic labeling and functional magnetic resonance imaging techniques, we will determine the anatomical integrity or novel plasticity of the ascending pain pathways. Preliminary data from our laboratory suggest that profound microglial activation not only occurs within the superficial dorsal horn ten segments caudal to the SCI lesion, but also correlates strongly to the development of chronic hypersensitivity after SCI. Though these data suggest that glia play a significant role in the development of hypersensitivity after SCI, it also suggests that there may be profound effects on the sensory neurons due to glial-neuronal communication and/or an alteration of the local environment where sensory processing occurs. The purpose of this proposal is to ascertain whether sensory changes that occur after spinal cord injury are a result of anatomical and functional changes that occur away from the lesion site in supraspinal regions that are involved in the processing of pain and sensory information such as the ventroposterolateral nucleus of the thalamus Potential changes in these regions may ultimately cause hypersensitivity or the perception of pain. This proposal would show for the first time an anatomical and functional pathway (either the original spared or novel pathway) exists that relays pain and sensory information after SCI. It will provide a basis for targeting future mechanistic studies which will ultimately lead to better, more efficacious treatments for the neuropathic pain which occurs after human SCI.