Defining the peripheral plasticity of nociceptive afferents following spinal cord injury and physical therapy intervention.

The focus of this dissertation is to explore the peripheral plasticity of nociceptive afferents following spinal cord injury (SCI) and whether it is exacerbated or induced when physical therapy-based muscle stretching, a therapy we have shown to be detrimental to locomotor recovery in rodents, is implemented post-SCI. Chapter I provides a brief introduction on sensory afferents with particular emphasis on nociceptive afferents and their multifaceted role within the peripheral and central nervous systems. Chapter II describes SCI epidemiology and common sensory related complications that occur in patients as well and pharmaco- and physical therapies that are employed post-SCI. Chapter III explores nociceptor-related mechanisms that may contribute to the described stretching phenomenon by combining clinically common drugs (baclofen, ibuprofen, acetaminophen, or morphine) with hindlimb muscle stretching following SCI in rodents. Chapter IV utilizes intraneural injections of viral vector to explore the peripheral plasticity of nociceptive afferents after a complete (transection) SCI around anatomical landmarks within skeletal muscle such as motor axons and motor endplates, blood vessels, and tendon. In Chapter V, the foundational discoveries found in Chapter IV are explored in the context of an incomplete, contusion SCI. Furthermore, we implement physical therapy muscle stretching acutely post-SCI for 6 weeks to determine if peripheral nociceptor sprouting is modulated. Finally, Chapter VI speculates on the potential relationship between sensory and motor plasticity post-SCI. The clinical implications of nociceptor sprouting are also addressed and its potential role as a driver in sequelae such as neuropathic pain, muscle spasticity, and muscle fatigue.