The Role of Spinal Cord CX3CL1/CX3CR1 Signalling in Chronic Pain

Montague-Cardoso, Karli; Mrózková, Petra; Malcangio, Marzia

doi:10.1007/s43152-020-00006-9

Cited by 5 publications

(7 citation statements)

References 48 publications

(63 reference statements)

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“…CX3CR1 is therefore known as the fractalkine receptor or G-protein coupled receptor 13 (GRP13). There is a vast body of literature that suggests a pro-nociceptive role of microglial CX3CR1 in spinal and supraspinal sites in chronic pain conditions [62; 88]. This is contrary to the association found in our study.…”

Section: Resultscontrasting

confidence: 99%

Understanding Painful versus Non-Painful Dental Pain in Male and Female Patients: A Transcriptomic Analysis of Human Biopsies

Patel

Eskander

Chang

et al. 2023

Preprint

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Dental pain from apical periodontitis is an infection induced-orofacial pain condition that presents with diversity in pain phenotypes among patients. While 60% of patients with a full-blown disease present with the hallmark symptom of mechanical allodynia, nearly 40% of patients experience no pain. Furthermore, a sexual dichotomy exists, with females exhibiting lower mechanical thresholds under basal and diseased states. Finally, the prevalence of post-treatment pain refractory to commonly used analgesics ranges from 7-19% (2 million patients), which warrants a thorough investigation of the cellular changes occurring in different patient cohorts. We, therefore, conducted a transcriptomic assessment of periapical biopsies (peripheral diseased tissue) from patients with persistent apical periodontitis. Surgical biopsies from symptomatic male (SM), asymptomatic male (AM), symptomatic female (SF), and asymptomatic female (AF) patients were collected and processed for bulk RNA sequencing. Using strict selection criteria, our study found several unique differentially regulated genes (DEGs) between symptomatic and asymptomatic patients, as well as novel candidate genes between sexes within the same pain group. Specifically, we found the role of cells of the innate and adaptive immune system in mediating nociception in symptomatic patients and the role of genes involved in tissue homeostasis in potentially inhibiting nociception in asymptomatic patients. Furthermore, sex-related differences appear to be tightly regulated by macrophage activity, its secretome, and/or migration. Collectively, we present, for the first time, a comprehensive assessment of peripherally diseased human tissue after a microbial insult and shed important insights into the regulation of the trigeminal system in female and male patients.

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Section: Resultscontrasting

confidence: 99%

Understanding Painful versus Non-Painful Dental Pain in Male and Female Patients: A Transcriptomic Analysis of Human Biopsies

Patel

Eskander

Chang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…CX3CR1 is therefore known as the fractalkine receptor or G-protein coupled receptor 13 (GRP13). There is a vast body of literature that suggests a pro-nociceptive role of microglial CX3CR1 in spinal and supraspinal sites in chronic pain conditions [ 73 , 74 ]. This is contrary to the association found in our study.…”

Section: Resultsmentioning

confidence: 99%

Understanding painful versus non-painful dental pain in female and male patients: A transcriptomic analysis of human biopsies

Patel,

Eskander,

Fang-Mei Chang

et al. 2023

PLoS ONE

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Dental pain from apical periodontitis is an infection induced-orofacial pain condition that presents with diversity in pain phenotypes among patients. While 60% of patients with a full-blown disease present with the hallmark symptom of mechanical allodynia, nearly 40% of patients experience no pain. Furthermore, a sexual dichotomy exists, with females exhibiting lower mechanical thresholds under basal and diseased states. Finally, the prevalence of post-treatment pain refractory to commonly used analgesics ranges from 7–19% (∼2 million patients), which warrants a thorough investigation of the cellular changes occurring in different patient cohorts. We, therefore, conducted a transcriptomic assessment of periapical biopsies (peripheral diseased tissue) from patients with persistent apical periodontitis. Surgical biopsies from symptomatic male (SM), asymptomatic male (AM), symptomatic female (SF), and asymptomatic female (AF) patients were collected and processed for bulk RNA sequencing. Using strict selection criteria, our study found several unique differentially regulated genes (DEGs) between symptomatic and asymptomatic patients, as well as novel candidate genes between sexes within the same pain group. Specifically, we found the role of cells of the innate and adaptive immune system in mediating nociception in symptomatic patients and the role of genes involved in tissue homeostasis in potentially inhibiting nociception in asymptomatic patients. Furthermore, sex-related differences appear to be tightly regulated by macrophage activity, its secretome, and/or migration. Collectively, we present, for the first time, a comprehensive assessment of peripherally diseased human tissue after a microbial insult and shed important insights into the regulation of the trigeminal system in female and male patients.

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“…Indeed, recent reviews on the topic of FKN and chronic pain discuss the advantages of using a non-promiscuous axis as a specific therapeutic target, supported by convincing preclinical evidence of the axis' role in animal models of pain. The preclinical data encourages the exploration of clinical conditions in patients, to support the axis' translation into clinical benefits ( 65 , 66 ).…”

Section: Direct Evidence Of Chemokines In Trigeminal Painmentioning

confidence: 99%

“…C-X3-C motif chemokine ligand 1 (CX3CL1), or fractalkine (FKN), belongs to the CX3C chemokine family and signals only through its receptor CX3CR1, contrary to other promiscuous chemokines. FKN is the only member of the CX3C subfamily of chemokines, and its involvement in chronic pain has been of interest as a therapeutic target ( 64 , 65 ). Indeed, recent reviews on the topic of FKN and chronic pain discuss the advantages of using a non-promiscuous axis as a specific therapeutic target, supported by convincing preclinical evidence of the axis' role in animal models of pain.…”

Section: Direct Evidence Of Chemokines In Trigeminal Painmentioning

confidence: 99%

Chemokines and Pain in the Trigeminal System

2021

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Chemotactic cytokines or chemokines are a large family of secreted proteins able to induce chemotaxis. Chemokines are categorized according to their primary amino acid sequence, and in particular their cysteine residues that form disulphide bonds to maintain the structure: CC, CXC, CX3C, and XC, in which X represents variable amino acids. Among their many roles, chemokines are known to be key players in pain modulation in the peripheral and central nervous systems. Thus, they are promising candidates for novel therapeutics that could replace current, often ineffective treatments. The spinal and trigeminal systems are intrinsically different beyond their anatomical location, and it has been suggested that there are also differences in their sensory mechanisms. Hence, understanding the different mechanisms involved in pain modulation for each system could aid in developing appropriate pharmacological alternatives. Here, we aim to describe the current landscape of chemokines that have been studied specifically with regard to trigeminal pain. Searching PubMed and Google Scholar, we identified 30 reports describing chemokines in animal models of trigeminal pain, and 15 reports describing chemokines involved in human pain associated with the trigeminal system. This review highlights the chemokines studied to date at different levels of the trigeminal system, their cellular localization and, where available, their role in a variety of animal pain models.

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The Role of Spinal Cord CX3CL1/CX3CR1 Signalling in Chronic Pain

Cited by 5 publications

References 48 publications

Understanding Painful versus Non-Painful Dental Pain in Male and Female Patients: A Transcriptomic Analysis of Human Biopsies

Understanding Painful versus Non-Painful Dental Pain in Male and Female Patients: A Transcriptomic Analysis of Human Biopsies

Understanding painful versus non-painful dental pain in female and male patients: A transcriptomic analysis of human biopsies

Chemokines and Pain in the Trigeminal System

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