An Investigation into Proteomic Constituents of Cerebrospinal Fluid in Patients with Chronic Peripheral Neuropathic Pain
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ORIGINAL ARTICLE
An Investigation into Proteomic Constituents of Cerebrospinal Fluid in Patients with Chronic Peripheral Neuropathic Pain Medicated with Opioids- a Pilot Study Jonathan Royds 1 & Hilary Cassidy 2,3 & Melissa J. Conroy 4,5 & Margaret R. Dunne 4,5 & David Matallanas 2 & Joanne Lysaght 4,5 & Connail McCrory 1 Received: 1 July 2020 / Accepted: 30 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The pharmacodynamics of opioids for chronic peripheral neuropathic pain are complex and likely extend beyond classical opioid receptor theory. Preclinical evidence of opioid modulation of central immune signalling has not been identified in vivo in humans. Examining the cerebrospinal fluid (CSF) of patients medicated with opioids is required to identify potential pharmacodynamic mechanisms. We compared CSF samples of chronic peripheral neuropathic pain patients receiving opioids (n = 7) versus chronic peripheral neuropathic pain patients not taking opioids (control group, n = 13). Baseline pain scores with demographics were recorded. Proteome analysis was performed using mass spectrometry and secreted neuropeptides were measured by enzyme-linked immunosorbent assay. Based on Gene Ontology analysis, proteins involved in the positive regulation of nervous system development and myeloid leukocyte activation were increased in patients taking opioids versus the control group. The largest decrease in protein expression in patients taking opioids were related to neutrophil mediated immunity. In addition, notably higher expression levels of neural proteins (85%) and receptors (80%) were detected in the opioid group compared to the control group. This study suggests modulation of CNS homeostasis, possibly attributable to opioids, thus highlighting potential mechanisms for the pharmacodynamics of opioids. We also provide new insights into the immunomodulatory functions of opioids in vivo. Keywords Opioids . Cerebrospinal fluid . Neuroimmune interface . Neuropathic pain . Chronic pain . Proteomics
Introduction Opiates have been used to treat pain for centuries. The modern development of synthetic opioids with different specific
* Jonathan Royds [email protected] 1
Department of Pain Medicine, St. James Hospital, Dublin and School of Medicine, Trinity College Dublin, Dublin 8, Ireland
2
Systems Biology Ireland, School of Medicine, University College Dublin, Dublin 4, Ireland
3
School of Biomolecular and Biomedical Sciences, University College Dublin, Dublin 4, Ireland
4
Department of Surgery, Trinity Translational Medicine Institute, St. James’s Hospital and Trinity College Dublin, Dublin 8, Ireland
5
Trinity St James’s Cancer Institute, St James’s Hospital Dublin, Dublin 8, Ireland
properties has led to their extensive use in acute, chronic and cancer pain (Ballantyne 2003; Rosenblum et al. 2008; O'Brien et al. 2017). Developments in opioid therapies have focused on reduction in serious side effects and have been largely unsuccessful, particularly in the management of chro
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