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.
Mechanisms of Chronic Pain in Women (Ursula Wesselmann, M.D., Ph.D).
Dr. Wesselmann has a long-standing interest in the neurobiological mechanisms of chronic pain syndromes in women. She is a clinical neurologist and experimental neuro-physiologist with sub-specialty training in pain management. Over the last 20 years NIH-funded studies in her translational research laboratory have focused on the common theme of (1) elucidating peripheral and central pain mechanisms via neurophysiological, neuroanatomical and psychophysical paradigms in health and disease, specifically in females and (2) phenotyping subgroups of patients with pain syndromes based on different pathophysiological mechanisms, with the goal of identifying novel treatment strategies for these different phenotypes based on the underlying pathophysiology. Her current research, in collaboration with Dr. P. Czakanski (Depts. Of Anesthesiology and Obstetrics & Gynecology), focuses on neurophysiological, psychosocial and autonomic factors that contribute to the onset and maintenance of chronic urological (interstitial cystitis) and gynecological (vulvodynia) pain syndromes in women. A new area of research investigation is to determine the biological, psychological, and socio-cultural variables contributing to pain and pain-related disability in women treated for breast cancer. The long-term goal of her research program is to translate new discoveries into clinical practices that improve the ability to diagnose and treat women experiencing chronic pain.
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.
Inflammation-Induced Opioidergic Antinocieption (Alan Randich, Ph.D. - Adjunct Faculty).
Since retiring from Psychology, Dr. Randich (Professor Emeritus) has continued his collaborative research projects with Drs. Ness and Robbins in Anesthesiology, and 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 interactions between TRPA1 and opioid receptors is being examined in both behavioral and neurophysiological experiments.
Phenotype Identification in Pain Populations (Laurence Bradley, Ph.D. and Georg Deutsch, Ph.D. - 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.