This proposal is based on our recent imaging studies in children that show our ability to image functional and anatomical changes in a pediatric model of Complex Regional Pain Syndrome (CRPS). CRPS may develop following relatively minor trauma to the limbs. Patients typically present with limb pain and stiffness, hypersensitivity, and functional loss. Unlike adult CRPS, however, pediatric CRPS will usually resolve completely and thus provides a unique model of chronic pain reversal. Our preliminary findings suggest that even minor trauma to a limb may result in significant neural (i.e., structural and functional) changes in the pediatric brain over time, persisting well into and beyond the recovery period. This may well be a distinctive feature of pediatric CRPS and serves as a central focus of this investigation. The overarching goal of the research proposed is to determine whether such changes to the pediatric brain are reversible;and if so, what role this biological process may play in elucidating adult CRPS and in developing more effective therapies for both populations. Against this backdrop, we will investigate neural plasticity using imaging techniques in a longitudinal study of pediatric CRPS patients (in pain and in early pain-free states) and in a cross-sectional study of recovered CRPS patients and healthy controls (up to 24 months following symptomatic recovery).
The specific aims are (1) To measure the functional (fMRI) changes in the brains of CRPS patients (ages 14-16) first during the painful state, and then, during the early recovery (within 3 months) state, comparing these changes to those noted in age/gender matched controls;(2) To define plasticity of changes in cortical thickness and white matter tracts (using diffusor tensor imaging - DTI) in pediatric patients ages 14-16 with CRPS affecting their leg during their painful and early recovered states, vs. age/gender matched controls;(3) To measure the same functional (as in Aim 1) and anatomical changes (as in Aim 2) in a cross sectional study of cohorts of recovered CRPS patients at 6, 12 and 24 months following their recovery;we will compare these changes with age- gender matched controls.
Each aim will test specific hypotheses related to the functional and anatomical changes that take place in pediatric CRPS population.

Public Health Relevance

This unique multidisciplinary effort will dovetail with the broader objectives of the NIH Pain Consortium by (1) significantly improving insights into the pathophysiology of both adult and pediatric CRPS;and (2) placing critical emphasis on translational applications leading to more responsive treatments, the elimination of unwanted pain, accelerated recoveries, shorter and less costly hospitalizations, and enhanced quality of life.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Babcock, Debra J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Hospital Boston
United States
Zip Code
Simons, L E; Pielech, M; Erpelding, N et al. (2014) The responsive amygdala: treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome. Pain 155:1727-42
Becerra, Lino; Sava, Simona; Simons, Laura E et al. (2014) Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome. Neuroimage Clin 6:347-69
Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa et al. (2014) Rapid treatment-induced brain changes in pediatric CRPS. Brain Struct Funct :
Erpelding, Nathalie; Sava, Simona; Simons, Laura E et al. (2014) Habenula functional resting-state connectivity in pediatric CRPS. J Neurophysiol 111:239-47
Linnman, Clas; Becerra, Lino; Lebel, Alyssa et al. (2013) Transient and persistent pain induced connectivity alterations in pediatric complex regional pain syndrome. PLoS One 8:e57205
Shelton, L; Becerra, L; Borsook, D (2012) Unmasking the mysteries of the habenula in pain and analgesia. Prog Neurobiol 96:208-19
Borsook, David (2012) Neurological diseases and pain. Brain 135:320-44
Shelton, L; Pendse, G; Maleki, N et al. (2012) Mapping pain activation and connectivity of the human habenula. J Neurophysiol 107:2633-48
Pendse, Gautam V; Borsook, David; Becerra, Lino (2011) A simple and objective method for reproducible resting state network (RSN) detection in fMRI. PLoS One 6:e27594