Investigating movement-induced corticospinal modulation of pain in fibromyalgia using simultaneous brain and spinal cord functional magnetic resonance imaging
Description: Chronic pain affects approximately every third and sixth person in the United States and Switzerland, respectively. Around 75% have daily pain which is treatment-resistant and accompanies them for decades, together with depression and even suicidal thoughts. Many patients also resort to illicit drugs to find pain relief. Direct health care costs of chronic pain are tremendous for our society and are further excelled by productivity losses. Chronic widespread pain is the cardinal symptom of fibromyalgia (FM) which is a debilitating pain disorder, afflicting an increasing number of patients with a prevalence of 7.3% to 12.9% across countries. Pain and tenderness are often accompanied by fatigue, sleep disturbances, and altered cognition. While physical and exercise therapy have been found to relieve pain, its mechanisms remain understudied and FM still lacks effective and reliable treatment options. There is an urgent need to better understand the neurobiological correlates underlying pain chronification and modulation and translate that knowledge into safe and effective therapies. As stated in the National Institute on Drug Abuse (NIDA) Strategic Plan, “we need to identify biomarkers of pain severity that can be used to evaluate new treatments and to further personalized interventions.”I propose a research project that uses simultaneous brain-spinal cord (SC) functional magnetic resonance imaging (fMRI) to fully characterize central nervous system (CNS) mechanisms of chronic pain and pain modulation and to develop improved corticospinal biomarkers of FM which might represent a major step towards accomplishing the NIDA goals. I aim (i) to characterize the intricate interplay between brain and SC neuronal networks during corticospinal modulation of pain through active movement (i.e., gripping task) in healthy controls (HC), (ii) to investigate aberrant nociceptive signaling and identify fMRI biomarkers of chronic pain and pain modulation in FM, and (iii) to correlate changes in activity and brain-SC connectivity with disease-related clinical impairments and questionnaire-derived patient-reported measures for improved classification and phenotyping of FM.We will use innovative brain-SC fMRI at 3T to uncover the effects of right-hand gripping-induced corticospinal projections on the spinal processing of noxious heat stimulations applied to C6 dermatome of the right volar forearm in female FM patients and sex- and age-matched HC (n=25 each). Activation maps and brain-SC connectivity will be analyzed using sophisticated data processing pipelines and statistical models performed in FSL and Spinal Cord Toolbox. Brain-SC activity measures indicative of chronic pain and altered descending pain modulation will be associated with behavioral effects of pain modulation (i.e., subjective pain rating) and clinical disability measures in FM. We expect to see gripping-induced reductions in thermal pain ratings in HC which are less prominent or absent in FM, paralleled by increased fMRI activity within the spinal dorsal horn and pain-related brain regions in FM compared to HC. We anticipate that these changes and altered cortical-spinal dorsal horn connectivity in FM are correlated with clinical symptom severity and that identifying such fMRI biomarkers of pain might advance classification and phenotyping of FM.The findings of this study have the potential to advance our understanding of pathological CNS mechanisms and functional reorganization involved in central pain and deficient descending modulation of pain in FM. I am confident that identification of objective fMRI biomarkers of pain could be used for improved diagnosis and classification of FM and to track the disease course and predict treatment response. This said, they could also be implemented as surrogate biomarkers in future clinical trials. Knowledge of these aberrant CNS mechanisms could potentially be translated to other chronic pain conditions and ultimately be used to develop clinically useful pain treatment strategies and improve patients’ quality of life.
Amount: CHF 183,200
Funding type: fellowship
Funder scheme: Postdoc.Mobility
Start date: 2023-08-01
End date: 2025-08-31
Investigator: Pfyffer, Dario
Institution: Institution abroad - United States of America
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Funded outputs count: 7
Funder award ID: 214211
OpenAlex ID: G1237762206