SCOTTSDALE, AZ USA (UroToday.com) - In this panel session, Drs. Linda Watkins, Catherine Bushnell, and Anthony Ford presented their data on various aspects of the basic science behind pain.
Dr. Linda Watkins presented “Targeting glial activation for treating chronic pain and improving opioid efficacy.” Historically, peripheral nerves have been the target of pain treatments (i.e.. opioids). More recently, non-neural glial cells (microglia and astrocytes) have demonstrated an important role in chronic pain pathways. Glial cells have been shown to activate in pain states in numerous animal models. Additionally, animal models have also demonstrated that suppression of these glial cells reduces pain. The limited efficacy of opioids in current treatment regimens has been linked to opioid effect on toll-Like receptor 4, resulting in activation of glial based pain pathways. An application with the FDA for Investigational New Drug for the first drug developed for glial cell-targeted drug therapy is planned for submission this summer.
Dr. Catherine Bushnell presented “The brain’s role in perceiving and modifying chronic pain.” She reviewed data supporting MRI confirmation of increased function in specific regions of the brain in both interstitial cystitis and vulvodynia. Additionally, the resting brain state in patients with chronic pain disorders has been shown on MRI to be altered from normal controls. Interestingly, data has shown that patient emotional status does not affect the perceived severity of pain, but rather it affects the impact of their pain. Conversely, attention to pain (i.e., distracted from pain), has been shown to diminish the perception of the severity of pain. Cognitive behavioral therapy and yoga have been shown to improve the MRI findings in chronic pain states.
Dr. Anthony Ford presented “P2X3 antagonism in treatment of interstitial cystitis and bladder pain syndrome.” P2X are ATP-gated ion channels. P2X3 is a receptor subtype found almost exclusively in non-myelinated nerve channels (i.e., c-fibers). Initial animal studies utilizing P2X3 knockout mice demonstrated hyperalgesia to the bladder allowing for large bladder filling volumes. AF-219 is a first in class drug selective oral inhibitor of P2X3. Preliminary data from 9 trials in osteoarthritis and refractory chronic cough was reported a few months ago and demonstrated drug success. AF-219 is a non-narcotic, non-sedating drug without additive potential. The half-life of 8-9 hours allows for twice-a-day dosing. AF-130 is being studied as a more selective agent. AF-220 is being studied for increased CNS penetration. Clinical trials for chronic cough showed no effects on vital signs nor EKG changes. Preliminary data of their randomized controlled trial for treatment of moderate-to-severe IC/BPS are planned to be reported later in this meeting.
Moderated by Deborah R. Erickson, MD at the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU) Winter Meeting - February 24 - 28, 2015 - JW Marriott Camelback Inn Resort & Spa - Scottsdale, AZ USA
Linda R. Watkins, PhD - University of Colorado at Boulder, Boulder, CO USA
M. Catherine Bushnell, PhD - National Center for Complementary and Integrative Health, Bethesda, MD USA
Anthony Ford, PhD - Afferent Pharmaceuticals, Inc., San Mateo, CA USA
Reported for UroToday by Drew Freilich, MD. Dr. Freilich is a graduate of the University of Massachusetts Medical School and completed his urology residency at New York Medical College/Westchester Medical Center. He is currently a fellow in Female Urology, Neurourology and Reconstructive Urology at Medical University of South Carolina. He has authored more than 40 peer-reviewed articles, monographs, abstracts, and book chapters and abstracts. Dr. Freilich is a member of the American Urological Association and the Society for Urodynamics and Female Urology.