Proinflammatory cytokines and their receptors as druggable targets to alleviate pathological pain

Kalpachidou, Theodora; Riehl, Lydia; Schöpf, Clemens L; Uçar, Buket; Kress, Michaela

doi:10.1097/j.pain.0000000000002737

Cited by 10 publications

(3 citation statements)

References 390 publications

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“…Noteworthy femaleselective BPs including cytokine/chemokine production and signaling as well as angiogenesis. The contribution of various cytokine/chemokines in nociception and inflammation (103)(104)(105) is widely established and our data showed that the number of cytokine/chemokines altered in female neurons was higher than in males (i.e. 14 in females versus 3 in males).…”

Section: Discussionmentioning

confidence: 63%

Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice

Ibrahim

Wang

et al. 2023

Preprint

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While sex-specific prevalence of orofacial pain is established, mechanisms of sex-dependent orofacial pain are widely understudied. To this end, a significant gap in knowledge exists about comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased state of males and females. Using RNA sequencing of FACS sorted retro-labeled sensory neurons innervating tongue tissue, we determined changes in transcriptomic profiles in males and female mice under naive as well as tongue-tumor bearing conditions Our data revealed the following interesting findings: 1) Tongue tissue of female mice was innervated with higher number of trigeminal neurons compared to males; 2) Naive female neurons innervating the tongue exclusively expressed immune cell markers such as Csf1R, C1qa and others, that werent expressed in males. This was validated by Immunohistochemistry. 3) Male neurons were more tightly regulated than female neurons upon tumor growth; 4) While very few differentially expressed genes (DEGs) overlapped between males and females post-tumor growth, several biological processes (BPs) were similar between two sexes. However, additional distinct processes were sex-specific; 5) Post-tumor growth, male DEGs contained an equal mix of transcription factors, ligands, growth factors, receptors and channels, whereas female DEGs predominantly contained channels/receptors, enzymes, cytokines and chemokines. Taken together, this is the first study to characterize the effect of sex as well as of tongue-tumor on global gene expression, biological pathways and molecular function of tongue-innervating sensory neurons.

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Section: Discussionmentioning

confidence: 63%

Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice

Ibrahim

Wang

et al. 2023

Preprint

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“…1 ). Pro-inflammatory cytokines such as IL-6, IL-1β, and TNFα can bind to their receptors on nociceptors to cause excitation and sensitization [ 86 , 87 ]. The complement system is part of the innate immune system, its activation can lead to immune cell recruitment and inflammation, and it is linked to the production of persistent pain through its ability to sensitize nociceptors [ 88 , 89 ].…”

Section: Resultsmentioning

confidence: 99%

Neuroimmune Mechanisms Underlying Post-acute Sequelae of SARS-CoV-2 (PASC) Pain, Predictions from a Ligand-Receptor Interactome

2023

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Purpose of Review Individuals with post-acute sequelae of SARS-CoV-2 (PASC) complain of persistent musculoskeletal pain. Determining how COVID-19 infection produces persistent pain would be valuable for the development of therapeutics aimed at alleviating these symptoms. Recent Findings To generate hypotheses regarding neuroimmune interactions in PASC, we used a ligand-receptor interactome to make predictions about how ligands from PBMCs in individuals with COVID-19 communicate with dorsal root ganglia (DRG) neurons to induce persistent pain. In a structured literature review of -omics COVID-19 studies, we identified ligands capable of binding to receptors on DRG neurons, which stimulate signaling pathways including immune cell activation and chemotaxis, the complement system, and type I interferon signaling. The most consistent finding across immune cell types was an upregulation of genes encoding the alarmins S100A8/9 and MHC-I. Summary This ligand-receptor interactome, from our hypothesis-generating literature review, can be used to guide future research surrounding mechanisms of PASC-induced pain.

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“…In the growing field of neuroimmunology of pain, Michaela Kress and coauthors review several inflammatory cytokines and their roles in the pathophysiology of pain as well as potential therapeutic targets. 6 In an upcoming journal issue, plenary lecturer Diana Bautista is expected to present a review on neuroimmune mechanisms that subserve itch and inflammation. In a relatively new area of study, Isaac Chiu discusses exciting cutting-edge research on the interactions between external infectious organisms and the nociceptive system that further reveals novel pain mechanisms and possibly new treatment avenues.…”

mentioning

confidence: 99%

An introduction to the biennial review of pain

Gilron¹,

Keefe²

2022

Pain

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Proinflammatory cytokines and their receptors as druggable targets to alleviate pathological pain

Cited by 10 publications

References 390 publications

Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice

Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice

Neuroimmune Mechanisms Underlying Post-acute Sequelae of SARS-CoV-2 (PASC) Pain, Predictions from a Ligand-Receptor Interactome

An introduction to the biennial review of pain

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