Despite the profound clinical significance of individual differences in pain, remarkably little is known about the basic brain mechanisms that support such differences. Portions of this inter-individual variation in subjective reports of pain may be due to physical factors such as brain connectivity. Other components arise from psychological disposition and may involve factors such as cognitive control, impulsivity, depression, and anxiety. Finally, demographic variables such as sex and ethnicity may also substantially contribute to individual differences in pain sensitivity.
Surprisingly little is known about the brain mechanisms by which these factors influence the construction of the pain experience at the level of a single individual. Thus, the fundamental aim of the proposed research is to delineate the brain mechanisms that give rise to individual differences in pain sensitivity. We are acquiring both functional and structural MRI data from a large number of volunteers.
Recruitment was designed to obtain a true community sample in order to facilitate generalizability of findings. As such, this research involves individuals of differing socio-economic levels, obese individuals, individuals with active depression and anxiety, as well as those in excellent physical and mental health. Participants also undergo extensive sensory testing and psychological evaluation in order to fully characterize their pain phenotype. Multiple regression statistical analyses is used to identify brain regions related to inter-individual differences in sensitivity in both structural and functional neuroimaging data.
Techniques such as psychophysiological interaction analyses are used to test hypotheses about the influence of functional connectivity on pain sensitivity. The identification of brain mechanisms that support individual differences in pain sensitivity contributes substantially to our basic understanding of brain mechanisms of pain and will critically evaluate our existing notions that every individual processes nociceptive information in the same way. The results from these studies will provide a solid rationale for the development of individualized pain treatment strategies.
Brain Mechanisms of response to migraine treatment
Neuroimaging and quantitative sensory testing (QST) are techniques that can provide insight into the biological basis for pain treatment effects.
This project studies migraine, which affects > 6 million youth in the U.S. Cochrane reviews show that psychological therapies for pediatric headache result in better outcomes than control conditions (56% improved vs. 22% in 714 participants), and our CBT+Amitriptyline Study found that 66% of youth with chronic migraine had a 50% reduction in headache days compared to 36% in an education control+Amitriptyline (AMI) group. Despite this evidence base, the neural mechanisms supporting the efficacy of CBT for pain remain poorly understood. The lack of mechanistic understanding is a barrier to treatment utilization, particularly given the time, effort, and expense for pediatric migraine patients to receive CBT vs. conventional pharmacological therapy (which in a national trial reduced headache days similar to placebo pill: AMI 52% of participants improved; Placebo 61%).
We are recruiting 240 youth ages 10 to 17 with migraine to undergo functional MRI and QST before and after 8 weeks of either CBT, placebo, or AMI to determine 1) if CBT engages brain mechanisms which are distinct from those engaged by pill-based therapy (placebo & AMI). 2) Are poorer baseline pain modulatory mechanisms measured by QST predictive of greater headache day reduction from CBT vs. pill-based therapy? 3) Assess whether brain changes at 8 weeks in those who receive CBT play a mediational role when outcomes are assessed at a 3 month follow-up 4) Test if these findings from are supported when other pain contextual variables (anxiety, depression, sleep) are included in the statistical models; 5) Compare neuroimaging between placebo and AMI.
All analyses will include age, sex, pubertal status, and brain structural connectivity in the statistical models to assess developmental variables. Pediatric medical and behavioral clinicians can use mechanistic insights from translational investigations such as this project to enhance the care they provide to youth with migraine.
Brain Mechanisms of Pediatric Complex Regional Pain Syndrome (CRPS)