Human Studies

Neurobiological mechanisms can be involved in early programming of pain sensitization. We aimed to investigate the association between early-life pain experience and pre-adolescence spinal pain. We conducted a study of 29,861 pre-adolescents (age 11-14) from the Danish National Birth Cohort. As indicators of early-life pain, we used infantile colic and recurrent otitis media, reported by mothers when their children were 6 and 18 months. Self-reported spinal pain (neck, middle back, and/or low back pain) was obtained in the 11-year follow-up, classified according to severity. Associations between early-life pain and spinal pain in pre-adolescents were estimated using multinomial logistic regression models. To account for sample selection, inverse probability weighting was applied. Children experiencing pain in early life were more likely to report severe spinal pain in pre-adolescence. The association appeared stronger with exposure to two pain exposures (relative risk ratio, 1.31; 95% CI, 1.02-1.68) rather than one (relative risk ratio, 1.14; 95% CI, 1.05-1.24). We observed similar results when using headache and abdominal pain as outcome measures, underpinning a potential neurobiological or psychosocial link in programming of pain sensitization.Conclusion: Experience of early-life pain is seemingly associated with spinal pain in pre-adolescence. The study highlights that early-life painful experiences can influence programming future pain responses. What is Known: • Spinal pain in pre-adolescents is common, causes marked discomfort and impairment in everyday life, and may be an important predictor of spinal pain later in life. • Neurobiological mechanisms have been suggested as involved in early programming of pain sensitization. What is New: • Pain exposure in early postnatal life in terms of infantile colic and recurrent otitis media is associated with spinal pain in pre-adolescence; thus, experience of such painful conditions in the early postnatal period may seemingly influence programming of future pain sensation.

Chronic pain is a common and severely disabling disease whose treatment is often unsatisfactory. Insights into the brain mechanisms of chronic pain promise to advance the understanding of the underlying pathophysiology and might help to develop disease markers and novel treatments. Here, we systematically exploited the potential of electroencephalography (EEG) to determine abnormalities of brain function during the resting state in chronic pain. To this end, we performed state-of-the-art analyses of oscillatory brain activity, brain connectivity and brain networks in 101 patients of either sex suffering from chronic pain. The results show that global and local measures of brain activity did not differ between chronic pain patients and a healthy control group. However, we observed significantly increased connectivity at theta (4 – 8 Hz) and gamma (> 60 Hz) frequencies in frontal brain areas as well as global network reorganization at gamma frequencies in chronic pain patients. Furthermore, a machine learning algorithm could differentiate between patients and healthy controls with an above-chance accuracy of 57%, mostly based on frontal connectivity. These results suggest that increased theta and gamma synchrony in frontal brain areas are involved in the pathophysiology of chronic pain. While substantial challenges concerning the reproducibility of the findings and the accuracy, specificity and validity of potential EEG-based disease markers remain to be overcome, our study indicates that abnormal frontal synchrony at theta and gamma frequencies might be promising targets for non-invasive brain stimulation and/or neurofeedback approaches.

Many people with HIV (PWH) experience chronic pain that limits daily function and quality of life. PWH with chronic pain have commonly been prescribed opioids, sometimes for many years, and it is unclear if and how the management of these legacy patients should change in light of the current US opioid epidemic. Guidelines, such as the Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain (CDCG), provide recommendations for the management of such patients but have yet to be translated into easily implementable interventions; there is also a lack of strong evidence that adhering to these recommendations improves patient outcomes such as amount of opioid use and pain levels. Herein we describe the development and preliminary testing of a theory-based intervention, called TOWER (ard Saf Opioid Prescribing), designed to support HIV primary care providers in CDCG-adherent opioid prescribing practices with PWH who are already prescribed opioids for chronic pain. TOWER incorporates the content of the CDCG into the theoretical and operational framework of the Information Motivation and Behavioral Skills (IMB) model of health-related behavior. The development process included elicitation research and incorporation of feedback from providers and PWH; testing is being conducted via an adaptive feasibility clinical trial. The results of this process will form the basis of a large, well-powered clinical trial to test the effectiveness of TOWER in promoting CDCG-adherent opioid prescribing practices and improving outcomes for PWH with chronic pain.

To evaluate whether diabetic polyneuropathy (DPN) follows the hypothesis for the course of nerve fiber damage reflected by symptoms progressing from pure small through mixed to large nerve fiber symptoms with or without symptoms of loss of function of small nerve fibers.