Pain Treatment Division Research
The Pain Treatment Division has an established but expanding program associated with the characterization and identification of pain-related processes arising in deep tissue structures. Recent expansions have included the recruitment of faculty interested in the exacerbation of pain which is produced by stress and the tracking of outcomes related to pain treatment interventions. Collaboration with adjunct faculty has expanded further the investigations of this small but growing portion of Anesthesiology Department research endeavors.
Active Research Protocols
Mechanisms of Urologic-Gastroenterologic Pain (Timothy Ness, M.D., Ph.D.)
In NIH-funded studies, truly translational studies related to urinary bladder and colorectal sensation are being performed by measuring psychophysical responses in humans and parallel studies in rodents. Dr. Ness with collaborators (Drs. Randich and Robbins) have determined that developmental mechanisms related to visceral hypersensitivity can be initiated by early-in-life inflammatory events that lead to altered neurophysiological processing as adults. These observations are now supported by epidemiological studies. The precise interplay between excitatory and inhibitory influences that exist at a spinal level are being dissected out using behavioral, neurophysiological (spinal dorsal horn, medullary and thalamic extracellular neuronal studies) and immunohistochemical (c-fos induction) studies in this programmatic line of research. Psychophysical studies have identified deficiencies in endogenous pain control systems related to counterirritation - similar deficits have been identified in preclinical experimental models.
In NIH-funded studies, two recently recruited researchers with primary appointments in Anesthesiology but training in Neurology (Wesselmann) and Obstetrics & Gynecology (Czakanski) have unique capabilities to perform translational research and have done so by combining psychophysical and epidemiological studies in humans with laboratory investigations in rodents using model systems developed by these investigators. Effects of abuse at early developmental stages, an observation supported by epidemiological studies, is being investigated in the rodent systems.
Mechanisms of Stress-Induced Hyperalgesia (Meredith Robbins, Ph.D.).
In NIH-funded studies Dr. Robbins, a PhD trained in Psychology with postdoctoral training in neurophysiology, is leading investigations into the molecular and behavioral consequences of experimentally-induced stress using rodent models. She has identified that a previously ignored endogenous peptide family, urocortins, and their associated receptor, CRFR2, are pivotal to increases in visceral sensitivity that are induced by experimental stress. Using ablative techniques and molecular-cell biological endpoints (Western blot analysis, ELISA measure, immunohistochemistry) the up or down regulation of spinal neuropeptide content and receptor number in response to environmental stressors is being identified and parallel responses in visceral and somatic sensitivity models assessed. In collaborative studies with Ness, central nervous system mechanisms of this stress-induced hyperalgesia that involve the amygdala are being identified using a experiments that lead to either abolition (neuroablative procedures) or augmenting (intracerebral implantations) effects.
Outcomes Research in Pain Medicine (Thomas Vetter, M.D., M.P.H.)
In this newly-initiated project, Dr. Vetter is probing and creating databases that allow for an assessment of the efficacy of current and novel therapies for pain treatment. Using support from insurance companies (BCBS-Alabama) and his training in public health, Dr. Vetter is pioneering the development of this sorely needed component of pain medicine which has functioned in a virtual vacuum of information related to evidence-based practice. As Director of the entire Division of Pain Treatment, he is ideally situated to implement research strategies related to clinical care. Integrated with on-campus research entities such as the Center for Outcomes Research and UAB's internationally recognized excellence in Public Health research, this new enterprise has a high probability for growth and the generation of clinically valuable data.
Functional Imaging of Analgesia and Sedation (Michael Froelich, M.D., M.S.)
NIH-funded anesthesiologist, Dr. Froelich is the central member of a team of 10 researchers from six departments who are contrasting and comparing the central nervous system effects of analgesics and anesthetics thereby determining mechanisms of sedation, antinociception and amnesia. By utilizing parallel measures in human subjects with psychophysical measures, saccadic eye movements determinations and state-of-the-art functional imaging of brain (single-positron emission tomography & functional MRI imaging) it has become possible to identify specific subregions of the brain responsible for the differing subcomponents of general anesthesia. Recent collaboration with pain clinician Dr. Jason McKeown which was funded by ASRA-PM has allowed expansion of these studies to include subjects with painful disorders such as complex regional pain syndrome - type I.
Inflammation-Induced Opioidergic Antinocieption (Alan Randich - Adjunct Faculty).
NIH-funded researcher, Dr. Randich (Psychology) with collaborative assistance from Anesthesiology (Co-PI on this project is Ness & Robbins is Co-Investigator), has identified the activation of a descending modulatory system that can be activated by the induction of visceral inflammation. Not present in superficial (cutaneous) model systems, this system appears to suppress excessive expression of nociceptive responses evoked by deep tissue stimuli (joint, muscle, viscera) and involves an opioidergic mechanism as it is reversed by naloxone. This system appears to be deficient in chronically hypersensitive animals. Probing the molecular basis of this reactive system has utilized Western blot and ELISA analysis of endogenous opioid agonist and receptor expression. Most recently, a role for the rostral ventromedial medulla has been identified using both electrostimulatory and neuroablative procedures and behavioral and neurophysiological endpoints. Dr. Randich's research endeavors are intimately intermixed with those of Ness and Robbins despite the physical location of his laboratory in a separate building (Campbell Hall).
Phenotype Identification in Pain Populations (Drs. Bradley and Deutsch - Adjunct Faculty)
NIH-funded researcher, Dr. Bradley (Medicine-Rheumatology/Immunology) with collaborators Drs. Deutsch (Radiology-Nuclear Medicine), Ness and Froelich (Anesthesiology), have expanded current studies of patients with fibromyalgia and/or irritable bowel syndrome to include patients with the diagnosis of painful bladder syndrome. Parallel quantitative sensory testing studies and regional cerebral bloodflow studies using Continuous Arterial Spin-Label functional MRI technologies are probing whether there exist phenotypic subtypes within these clinical populations based on alterations in sensory testing and altered baseline and evoked regional cerebral bloodflow measures. It is notable that animal studies by Randich (in projects noted above) have identified subpopulations within preclinical models of bladder pain.