Background: Chronic pain is prevalent among patients with rare diseases (RDs). However, little is understood about how biopsychosocial mechanisms may be integrated in the unique set of clinical features and therapeutic challenges inherent in their pain conditions. Methods: This review presents examples of major categories of RDs with particular pain conditions. In addition, we provide translational evidence on clinical and scientific rationale for psychosocially- and neurodevelopmentally-informed treatment of pain in RD patients. Results: Neurobiological and functional overlap between various RD syndromes and pain states suggests amalgamation and mutual modulation of the respective conditions. Emotional sequelae could be construed as an emotional homologue of physical pain mediated via overlapping brain circuitry. Given their clearly defined genetic and molecular etiologies, RDs may serve as heuristic models for unraveling pathophysiological processes inherent in chronic pain. Conclusions: Systematic evaluation of chronic pain in patients with RD contributes to sophisticated insight into both pain and their psychosocial correlates, which could transform treatment.

By unconscious or covert processing of pain we refer to nascent interactions that affect the eventual deliverance of pain awareness. Thus, internal processes (viz., repeated nociceptive events, inflammatory kindling, reorganization of brain networks, genetic) or external processes (viz., environment, socioeconomic levels, modulation of epigenetic status) contribute to enhancing or inhibiting the presentation of pain awareness. Here we put forward the notion that for many patients, ongoing sub-conscious changes in brain function are significant players in the eventual manifestation of chronic pain. In this review, we provide clinical examples of nascent or what we term pre-pain processes and the neurobiological mechanisms of how these changes may contribute to pain, but also potential opportunities to define the process for early therapeutic interventions.

Endometriosis, a condition in which uterine tissue grows outside the uterus, is a debilitating disease, affecting millions of women and costing the United States approximately $78 billion annually in pain- related disability. It is also the leading cause of chronic pelvic pain (CPP), which is often unresponsive to existing treatments. Adolescent women with the disease are at particular risk as there are often significant diagnostic delays, which in turn can exacerbate pain. Research and treatment guidelines for adolescents with endometriosis are largely based on studies for adult women due to the limited number of studies focusing on adolescents. The current paper critically reviews the literature as it pertains to endometriosis pathophysiology, mechanisms contributing to CPP, and treatment implications and recommendations with a focus on gaps related to adolescents.

Assessing clinical pain and metrics related to function or quality of life predominantly relies on patient reported subjective measures. These outcome measures are generally not applicable to the preclinical setting where early signs pointing to analgesic value of a therapy are sought, thus introducing difficulties in animal to human translation in pain research. Evaluating brain function in patients and respective animal model(s) has the potential to characterize mechanisms associated with pain or pain-related phenotypes and thereby provide a means of laboratory to clinic translation. This review summarizes the progress made towards understanding of brain function in clinical and preclinical pain states elucidated using an imaging approach as well as the current level of validity of translational pain imaging. We hypothesize that neuroimaging can describe the central representation of pain or pain phenotypes and yields a basis for the development and selection of clinically relevant animal assays. This approach may increase the probability of finding meaningful new analgesics that can help satisfy the significant unmet medical needs of patients.

Chronic pain and depression are two frequently co-occurring and debilitating conditions. Even though the former is treated as a physical affliction, and the latter as a mental illness, both disorders closely share neural substrates. Here, we review the association of pain with depression, especially when symptoms are lateralized on either side of the body. We also explore the overlapping regions in the forebrain implicated in these conditions. Finally, we synthesize these findings into a model, which addresses gaps in our understanding of comorbid pain and depression. Our lateralized pain-depression dyad model suggests that individuals diagnosed with depression should be closely monitored for pain symptoms in the left hemibody. Conversely, for patients in pain, with the exception of acute pain with a known source, referrals in today's pain centers for psychological evaluation should be part of standard practice, within the framework of an interdisciplinary approach to pain treatment.

Concussion (mild traumatic brain injury (mTBI)) is a significant pediatric public health concern. Despite increased awareness, a comprehensive understanding of the acute and chronic effects of concussion on central nervous system structure and function remains incomplete. Here we review the definition, epidemiology, and sequelae of concussion within the developing brain, during childhood and adolescence, with current data derived from studies of pathophysiology and neuroimaging. These findings may contribute to a better understanding of the neurological consequences of traumatic brain injuries, which in turn, may lead to the development of brain biomarkers to improve identification, management and prognosis of pediatric patients suffering from concussion. (C) 2012 Elsevier Ltd. All rights reserved.