Chronic pain is a hallmark of osteoarthritis (OA), yet little is known about its properties and representation in the brain. Here we use fMRI combined with psychophysics to study knee pain in 14 OA patients and 9 healthy controls. Mechanical painful pressure stimuli were applied to the knee in both groups and ratings of evoked pain and related brain activity examined. We observe that psychophysical properties and brain activation patterns of evoked pain are essentially the same between OA patients and healthy subjects, and between worse and better OA knees. In OA patients, stimulus-related brain activity could be distinguished from brain activity associated with spontaneous pain. The former activated brain regions commonly observed for acute painful stimuli in healthy subjects, while the spontaneous pain of OA engaged prefrontal-limbic regions closely corresponding to areas observed for spontaneous pain in other chronic pain conditions, such as chronic back pain and post-herpetic neuralgia. Arthritis-related clinical characteristics of knee OA also mapped to prefrontal-limbic regions. In a subgroup of patients (n = 6) we examined brain activity changes for a 2-week, repeat measure, cyclooxygenase-2 inhibitor (valdecoxib) therapy. Treatment decreased spontaneous pain for the worse knee and clinical characteristics of OA, and increased blood and csf levels of the drug which correlated positively with prefrontal-limbic brain activity. These findings indicate dissociation between mechanically induced and spontaneous OA knee pain, the latter engaging brain regions involved in emotional assessment of the self, and challenge the standard clinical view regarding the nature of OA pain.

Traumatic brain injury (TBI) has been called “the most complicated disease of the most complex organ of the body” and is an increasingly high-profile public health issue. Many patients report long-term impairments following even “mild” injuries, but reliable criteria for diagnosis and prognosis are lacking. Every clinical trial for TBI treatment to date has failed to demonstrate reliable and safe improvement in outcomes, and the existing body of literature is insufficient to support the creation of a new classification system. Concussion, or mild TBI, is a highly heterogeneous phenomenon, and numerous factors interact dynamically to influence an individual’s recovery trajectory. Many of the obstacles faced in research and clinical practice related to TBI and concussion, including observed heterogeneity, arguably stem from the complexity of the condition itself. To improve understanding of this complexity, we review the current state of research through the lens provided by the interdisciplinary field of systems science, which has been increasingly applied to biomedical issues. The review was conducted iteratively, through multiple phases of literature review, expert interviews, and systems diagramming and represents the first phase in an effort to develop systems models of concussion. The primary focus of this work was to examine concepts and ways of thinking about concussion that currently impede research design and block advancements in care of TBI. Results are presented in the form of a multi-scale conceptual framework intended to synthesize knowledge across disciplines, improve research design, and provide a broader, multi-scale model for understanding concussion pathophysiology, classification, and treatment.

Purpose Research into the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome has primarily focused on markers of peripheral dysfunction. We present the first neuroimaging investigation to our knowledge to characterize brain function and anatomy in chronic prostatitis/chronic pelvic pain syndrome. Materials and Methods We collected data from 19 male patients with chronic prostatitis/chronic pelvic pain syndrome, and 16 healthy age and gender matched controls. Functional magnetic resonance imaging data were obtained from 14 patients with chronic prostatitis/chronic pelvic pain syndrome as they rated spontaneous pain inside the scanner. Group differences (16 patients per group) in gray matter total volume and regional density were evaluated using voxel-based morphometry, and white matter integrity was studied with diffusion tensor imaging to measure fractional anisotropy. Functional and anatomical imaging outcomes were correlated with the clinical characteristics of chronic prostatitis/chronic pelvic pain syndrome. Results Spontaneous pelvic pain was uniquely characterized by functional activation within the right anterior insula, which correlated with clinical pain intensity. No group differences were found in regional gray matter volume, yet density of gray matter in pain relevant regions (anterior insula and anterior cingulate cortices) positively correlated with pain intensity and extent of pain chronicity. Moreover the correlation between white matter anisotropy and neo-cortical gray matter volume was disrupted in chronic prostatitis/chronic pelvic pain syndrome. Conclusions We provide novel evidence that the pain of chronic prostatitis/chronic pelvic pain syndrome is associated with a chronic pelvic pain syndrome specific pattern of functional brain activation and brain anatomical reorganization. These findings necessitate further investigations into the role of central mechanisms in the initiation and maintenance of chronic prostatitis/chronic pelvic pain syndrome.

Despite increasing public awareness and a growing body of literature on the subject of concussion, or mild traumatic brain injury, an urgent need still exists for reliable diagnostic measures, clinical care guidelines, and effective treatments for the condition. Complexity and heterogeneity complicate research efforts and indicate the need for innovative approaches to synthesize current knowledge in order to improve clinical outcomes. Methods from the interdisciplinary field of systems science, including models of complex systems, have been increasingly applied to biomedical applications and show promise for generating insight for traumatic brain injury. The current study uses causal-loop diagramming to visualize relationships between factors influencing the pathophysiology and recovery trajectories of concussive injury, including persistence of symptoms and deficits. The primary output is a series of preliminary systems maps detailing feedback loops, intrinsic dynamics, exogenous drivers, and hubs across several scales, from micro-level cellular processes to social influences. Key system features, such as the role of specific restorative feedback processes and cross-scale connections, are examined and discussed in the context of recovery trajectories. This systems approach integrates research findings across disciplines and allows components to be considered in relation to larger system influences, which enables the identification of research gaps, supports classification efforts, and provides a framework for interdisciplinary collaboration and communication—all strides that would benefit diagnosis, prognosis, and treatment in the clinic.

BackgroundThe 5% Lidocaine patch is used for treating chronic neuropathic pain conditions such as chronic back pain (CBP), diabetic neuropathy and complex regional pain syndrome, but is effective in a variable proportion of patients. Our lab has reported that this treatment reduces CBP intensity and associated brain activations when tested in an open labelled preliminary study. Notably, effectiveness of the 5% Lidocaine patch has not been tested against placebo for treating CBP. In this study, effectiveness of the 5% Lidocaine patch was compared with placebo in 30 CBP patients in a randomised double-blind study where 15 patients received 5% Lidocaine patches and the remaining patients received placebo patches. Functional MRI was used to identify brain activity for fluctuations of spontaneous pain, at baseline and at two time points after start of treatment (6 hours and 2 weeks).ResultsThere was no significant difference between the treatment groups in either pain intensity, sensory and affective qualities of pain or in pain related brain activation at any time point. However, 50% patients in both the Lidocaine and placebo arms reported a greater than 50% decrease in pain suggesting a marked placebo effect. When tested against an untreated CBP group at similar time points, the patch treated subjects showed significantly greater decrease in pain compared to the untreated group (n = 15).ConclusionsThese findings suggest that although the 5% Lidocaine is not better than placebo in its effectiveness for treating pain, the patch itself induces a potent placebo effect in a significant proportion of CBP patients.