Review ArticlesThe Shared Neuroanatomy and Neurobiology of Comorbid Chronic Pain and PTSD Therapeutic ImplicationsScioli-Salter, Erica R. PhD*,†; Forman, Daniel E. MD‡; Otis, John D. PhD*,§; Gregor, Kristin PhD*; Valovski, Ivan MD∥; Rasmusson, Ann M. MD¶Author Information *Research Division ∥Department of Anesthesiology, VA Boston Healthcare System, Jamaica Plain Departments of †Psychiatry §Psychiatry and Psychology, Boston University School of Medicine ‡New England Geriatric Research, Education, and Clinical Center, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School ¶Department of Psychiatry, National Center for PTSD, Women’s Health Science Division, VA Boston Healthcare System, Boston University School of Medicine, Boston, MA This publication was, in part, based on the grant narrative of my Career Development Award (CDA-2) through the VA Rehabilitation, Research and Development Service (VARR&D). The authors declare no conflict of interest. Reprints: Erica R. Scioli-Salter, PhD, Research Division, VA Boston Healthcare System, 12C-5, 150 South Huntington Avenue, Boston, MA 02130 (e-mail: firstname.lastname@example.org). Received December 9, 2013 Received in revised form August 22, 2014 Accepted April 24, 2014 The Clinical Journal of Pain: April 2015 - Volume 31 - Issue 4 - p 363-374 doi: 10.1097/AJP.0000000000000115 Buy Metrics Abstract Chronic pain and posttraumatic stress disorder (PTSD) are disabling conditions that affect biological, psychological, and social domains of functioning. Clinical research demonstrates that patients who are affected by chronic pain and PTSD in combination experience greater pain, affective distress, and disability than patients with either condition alone. Additional research is needed to delineate the interrelated pathophysiology of chronic pain and PTSD, with the goal of facilitating more effective therapies to treat both conditions more effectively; current treatment strategies for chronic pain associated with PTSD have limited efficacy and place a heavy burden on patients, who must visit various specialists to manage these conditions separately. This article focuses on neurobiological factors that may contribute to the coprevalence and synergistic interactions of chronic pain and PTSD. First, we outline how circuits that mediate emotional distress and physiological threat, including pain, converge. Secondly, we discuss specific neurobiological mediators and modulators of these circuits that may contribute to chronic pain and PTSD symptoms. For example, neuropeptide Y, and the neuroactive steroids allopregnanolone and pregnanolone (together termed ALLO) have antistress and antinociceptive properties. Reduced levels of neuropeptide Y and ALLO have been implicated in the pathophysiology of both chronic pain and PTSD. The potential contribution of opioid and cannabinoid system factors also will be discussed. Finally, we address potential novel methods to restore the normal function of these systems. Such novel perspectives regarding disease and disease management are vital to the pursuit of relief for the many individuals who struggle with these disabling conditions. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.