Journal ArticleDOI
An Investigation into Proteomic Constituents of Cerebrospinal Fluid in Patients with Chronic Peripheral Neuropathic Pain Medicated with Opioids- a Pilot Study
Jonathan Royds,Hilary Cassidy,Melissa J. Conroy,Margaret R. Dunne,David Matallanas,Joanne Lysaght,Connail McCrory +6 more
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TLDR
Modulation of CNS homeostasis, possibly attributable to opioids, is suggested, thus highlighting potential mechanisms for the pharmacodynamics of opioids and providing new insights into the immunomodulatory functions of opioids in vivo.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.read more
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Mass Spectrometry Approaches Empowering Neuropeptide Discovery and Therapeutics
TL;DR: This review outlines modern technologies that enable neuropeptide discovery and characterization, and highlights lessons from nature made possible by neuropePTide research in relevant animal models that is being adopted by the pharmaceutical industry.
Journal ArticleDOI
Pro-inflammatory cytokines and leukocyte integrins associated with chronic neuropathic pain in traumatic and inflammatory neuropathies: Initial observations and hypotheses
TL;DR: The data suggest that CD11b could be an effective molecular target for chronic neuropathic pain treatment in inflammatory and traumatic peripheral neuropathies, and early expression of pro-inflammatory cytokines, such as tissue inhibitor of metalloproteinases-1 may predict subsequent chronic nociception development following unilateral sciatic nerve crush injury.
References
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