An Investigation into Proteomic Constituents of Cerebrospinal Fluid in Patients with Chronic Peripheral Neuropathic Pain Medicated with Opioids- a Pilot Study

Royds, Jonathan; Cassidy, Hilary; Conroy, Melissa J.; Dunne, Margaret R.; Matallanas, David; Lysaght, Joanne; McCrory, Connail

doi:10.1007/s11481-020-09970-3

Cited by 2 publications

(2 citation statements)

References 101 publications

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“…TIMP-1 belongs to a family of cytokines that are expressed in response to multiple cytokine release in tissues and are well known for their role in extracellular remodeling by inhibiting matrix metalloproteinases ( 80 ). Identifying molecular profiles (preferably in serum, plasma or on circulating leukocytes) at well-defined disease stages in these peripheral neuropathies using transcriptomics ( 81 ), proteomics ( 82 ), flow cytometry or a combination thereof, supported by bioinformatics analyses to detect pathway similarities and differences, could advance current knowledge. This may lead to more disease-targeted personalized treatments and more precise objective disease measures in chronic neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Pro-inflammatory cytokines and leukocyte integrins associated with chronic neuropathic pain in traumatic and inflammatory neuropathies: Initial observations and hypotheses

Dong

Ubogu

2022

Front. Immunol.

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Leukocyte infiltration and persistence within peripheral nerves have been implicated in chronic nociception pathogenesis in murine peripheral neuropathy models. Endoneurial cytokine and chemokine expression contribute to leukocyte infiltration and maintenance of a pro-inflammatory state that delays peripheral nerve recovery and promotes chronic pain behaviors in these mice. However, there has been a failure to translate murine model data into safe and effective treatments for chronic neuropathic pain in peripheral neuropathy patients, or develop reliable biomarkers that may help diagnose or determine treatment responses in affected patients. Initial work showed that persistent sciatic nerve CD11b+ CD45+ leukocyte infiltration was associated with disease severity in three mouse models of inflammatory and traumatic peripheral neuropathies, implying a direct contributing role in disease pathogenesis. In support of this, CD11b+ leukocytes were also seen in the sural nerve biopsies of chronic neuropathic pain patients with three different peripheral neuropathies. Systemic CD11b antagonism using a validated function-neutralizing monoclonal antibody effectively treated chronic nociception following unilateral sciatic nerve crush injury (a representative traumatic neuropathy model associated with axonal degeneration and increased blood-nerve barrier permeability) and does not cause drug addiction behaviors in adult mice. These data suggest that CD11b could be an effective molecular target for chronic neuropathic pain treatment in inflammatory and traumatic peripheral neuropathies. Despite known murine peripheral neuropathy model limitations, our initial work suggests that 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. Studies aligning animal model investigation with observational data from well-characterized human peripheral neuropathies, including transcriptomics and proteomics, as well as animal model studies using a human clinical trial design should foster the identification of clinically relevant biomarkers and effective targeted treatments with limited addiction potential for chronic neuropathic pain in peripheral neuropathy patients.

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Section: Discussionmentioning

confidence: 99%

Pro-inflammatory cytokines and leukocyte integrins associated with chronic neuropathic pain in traumatic and inflammatory neuropathies: Initial observations and hypotheses

Dong

Ubogu

2022

Front. Immunol.

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“…The sensitivity, specificity, and wide dynamic range for detection of low-abundance secreted peptides makes MS exceptionally well suited for profiling as well as the structural and quantitative characterization of the peptidome in various models, and enables further discovery of pharmacological targets. Secretomics studies, most often based on liquid chromatography-MS/MS technology, have been applied to the analysis of neuropeptides in releasates from cell and organ cultures, brain microdialysates, and cerebrospinal fluid (Bernay et al, 2009;Yin et al, 2012;Tillmaand et al, 2015;Gahoi and Gautam, 2016;Al-Hasani et al, 2018;Beumer et al, 2020;Royds et al, 2021).…”

Section: A Decoding Chemical Signalingmentioning

confidence: 99%

Mass Spectrometry Approaches Empowering Neuropeptide Discovery and Therapeutics

Anapindi

Romanova

Checco

et al. 2022

Pharmacological Reviews

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The discovery of insulin in the early 1900s ushered in the era of research related to peptides acting as hormones and neuromodulators, among other regulatory roles. These essential gene products are found in all organisms, from the most primitive to the most evolved, and carry important biologic information that coordinates complex physiology and behavior; their misregulation has been implicated in a variety of diseases. The evolutionary origins of at least 30 neuropeptide signaling systems have been traced to the common ancestor of protostomes and deuterostomes. With the use of relevant animal models and modern technologies, we can gain mechanistic insight into orthologous and paralogous endogenous peptides and translate that knowledge into medically relevant insights and new treatments. Groundbreaking advances in medicine and basic science influence how signaling peptides are defined today.

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An Investigation into Proteomic Constituents of Cerebrospinal Fluid in Patients with Chronic Peripheral Neuropathic Pain Medicated with Opioids- a Pilot Study

Cited by 2 publications

References 101 publications

Pro-inflammatory cytokines and leukocyte integrins associated with chronic neuropathic pain in traumatic and inflammatory neuropathies: Initial observations and hypotheses

Pro-inflammatory cytokines and leukocyte integrins associated with chronic neuropathic pain in traumatic and inflammatory neuropathies: Initial observations and hypotheses

Mass Spectrometry Approaches Empowering Neuropeptide Discovery and Therapeutics

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