The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)
Behavioral Insights into Nociceptor Function: A Systematic Approach to Understanding Postsurgical and Neuropathic Pain Mechanisms in Rats
Author ORCID Identifier
Date of Graduation
Doctor of Philosophy (PhD)
Edgar T. Walters, Ph.D.
Carmen W. Dessauer, Ph.D.
Annemieke Kavelaars, Ph.D.
Patrick M. Dougherty, Ph.D.
Shane R. Cunha, Ph.D.
Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.
Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly lit chamber by crossing sharp probes. Most studies employing the MC test habituate rodents to the device and measure the latency to escape the bright light. We found reducing habituation caused rats to repeatedly return to the light chamber when probes were absent, presumably as part of their exploratory behavior. We asked whether combining motivations to avoid the bright light and to explore the device would reveal a conflicting, pain-related reluctance of rats to cross noxious probes. Rats with a thoracic spinal cord injury (SCI), lumbar spinal nerve transection, or chronic constriction injury of the sciatic nerve, as well as their sham controls, exhibited heightened pain-avoidance behavior compared to uninjured controls. These findings have important implications for investigations into behavioral and neuronal alterations contributing to postsurgical and neuropathic pain.
Many C-fiber nociceptors generate OA in vivo in rats with SCI and ongoing pain. Probable nociceptors continue to generate OA in vitro after dissociation. We used whole-cell recordings from isolated dorsal root ganglion neurons and novel algorithms that analyze irregular changes in membrane potential (MP) to define neurophysiological alterations underlying SCI-induced nociceptor OA. In a distinct type of probable nociceptor, SCI caused 3 chronic alterations that promote OA: 1) depolarization of resting MP, 2) reduction in the voltage threshold for action potential generation, and 3) enhancement of depolarizing spontaneous fluctuations (DSFs) in MP. In vitro modeling of acute inflammation by combining serotonin with artificial depolarization also potentiated DSFs and OA. These findings reveal nociceptor specializations for generating OA during ongoing pain.
postoperative pain, spontaneous pain, pain-avoidance behavior, nociceptor, spontaneous activity, neural injury, spinal cord injury, inflammation, membrane potential, depolarizing spontaneous fluctuations
Behavioral Neurobiology Commons, Behavior and Ethology Commons, Cellular and Molecular Physiology Commons, Laboratory and Basic Science Research Commons, Nervous System Diseases Commons, Pathological Conditions, Signs and Symptoms Commons