ijms-logo

Journal Browser

Journal Browser

Pain and Inflammation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 December 2017) | Viewed by 45845

Special Issue Editor

Pharmazentrum Frankfurt, Dept. of Clinical Pharmacology, Goethe-University of Frankfurt, Theodor Stern Kai 7, Bd. 74, 4th Fl, 60590 Frankfurt am Main, Germany
Interests: nerve injury and neuropathic pain; pain and aging; central adaptations to chronic pain; multiple sclerosis; neuroinflammation; neuro-immunologic communication; redox signaling; nitric oxide; endocannabinoids and other lipid signaling molecules; progranulin; autophagy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A growing number of molecules have been suggested to contribute to the development of chronic inflammation and pain, and some of them bear some potential as drug targets based on rodent models. However, the mechanisms are not fully understood, and, traditionally, therapeutic approaches have mainly sought to antagonize the pro-inflammatory players of inflammation, with mixed success. More recently, molecular mechanisms that initiate the resolution of inflammation have opened a new avenue in pro-resolution strategies to treat complex chronic inflammatory diseases. However, resolution pathways are heterogeneous and probably tissue- and stimulus-specific. A better understanding of the balance between pro-inflammation and pro-resolution strategies addressing for example cell-to-cell receptor binding and bioactive lipid mediators are needed to develop novel therapeutic strategies.

In this Special Issue we invite original research and reviews in the field of pain and inflammation, particularly addressing molecular mechanisms of inflammation persistence versus resolution.

Prof. Dr. Irmgard Tegeder
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • resolution of inflammation
  • bioactive lipids
  • pain
  • immune cells
  • inflammasome
  • redox signaling
  • macrophage polarization

Published Papers (7 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

14 pages, 3474 KiB  
Communication
Proinflammatory Markers, Chemokines, and Enkephalin in Patients Suffering from Dry Eye Disease
by Pierre Nicolle, Hong Liang, Elodie Reboussin, Ghislaine Rabut, Elise Warcoin, Françoise Brignole-Baudouin, Stéphane Melik-Parsadaniantz, Christophe Baudouin, Antoine Labbe and Annabelle Reaux-Le Goazigo
Int. J. Mol. Sci. 2018, 19(4), 1221; https://doi.org/10.3390/ijms19041221 - 17 Apr 2018
Cited by 41 | Viewed by 5649
Abstract
Dry eye symptoms are among the leading complaints in ophthalmology. Dry eye disease (DED) is associated with significant pain affecting quality of life. Cellular and molecular mechanisms underlying ocular pain associated with DED are not fully understood. In this study, we investigated the [...] Read more.
Dry eye symptoms are among the leading complaints in ophthalmology. Dry eye disease (DED) is associated with significant pain affecting quality of life. Cellular and molecular mechanisms underlying ocular pain associated with DED are not fully understood. In this study, we investigated the ocular surface of patients with DED using in vivo confocal microscopy (IVCM) to quantify corneal nerve density and its relation with corneal inflammation. Gene expression of the proinflammatory markers HLA-DR, IL-6, CXCL12, and CCL2 and the receptors CXCR4 and CCR2, as well as PENK (enkephalin precursor), was therefore quantified in conjunctival impression cytology specimens. Thirty-two patients with DED and 15 age-matched controls were included. Subbasal nerve density was significantly lower in DED patients compared to controls. IVCM analysis revealed that DED patients had a significantly higher corneal dendritic cell density compared to controls. Conjunctival impression cytology analysis revealed that HLA-DR, IL-6, CXCR4, and CCL2/CCR2 mRNA levels were significantly increased in DED patients compared to controls, whereas PENK mRNA levels were significantly decreased. Similar results were obtained in vitro on immortalized human conjunctiva-derived epithelial cells challenged with osmotic stress that mimics the DED condition. These results demonstrate that proinflammatory molecules and endogenous enkephalin have opposite gene regulation during DED. Full article
(This article belongs to the Special Issue Pain and Inflammation)
Show Figures

Graphical abstract

20 pages, 3723 KiB  
Article
The Influence of Inflammation and Nerve Damage on the Neurochemical Characterization of Calcitonin Gene-Related Peptide—Like Immunoreactive (CGRP-LI) Neurons in the Enteric Nervous System of the Porcine Descending Colon
by Krystyna Makowska and Slawomir Gonkowski
Int. J. Mol. Sci. 2018, 19(2), 548; https://doi.org/10.3390/ijms19020548 - 12 Feb 2018
Cited by 25 | Viewed by 4878
Abstract
The enteric nervous system (ENS), localized in the wall of the gastrointestinal tract, regulates the functions of the intestine using a wide range of neuronally-active substances. One of them is the calcitonin gene-related peptide (CGRP), whose participation in pathological states in the large [...] Read more.
The enteric nervous system (ENS), localized in the wall of the gastrointestinal tract, regulates the functions of the intestine using a wide range of neuronally-active substances. One of them is the calcitonin gene-related peptide (CGRP), whose participation in pathological states in the large intestine remains unclear. Therefore, the aim of this study was to investigate the influence of inflammation and nerve damage using a double immunofluorescence technique to neurochemically characterize CGRP-positive enteric nervous structures in the porcine descending colon. Both pathological factors caused an increase in the percentage of CGRP-positive enteric neurons, and these changes were the most visible in the myenteric plexus after nerve damage. Moreover, both pathological states change the degree of co-localization of CGRP with other neurochemical factors, including substance P, the neuronal isoform of nitric oxide synthase, galanin, cocaine- and amphetamine-regulated transcript peptide and vesicular acetylcholine transporter. The character and severity of these changes depended on the pathological factor and the type of enteric plexus. The obtained results show that CGRP-positive enteric neurons are varied in terms of neurochemical characterization and take part in adaptive processes in the descending colon during inflammation and after nerve damage. Full article
(This article belongs to the Special Issue Pain and Inflammation)
Show Figures

Graphical abstract

13 pages, 2377 KiB  
Article
Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States
by Rou-Gang Xie, Wen-Guang Chu, San-Jue Hu and Ceng Luo
Int. J. Mol. Sci. 2018, 19(1), 161; https://doi.org/10.3390/ijms19010161 - 05 Jan 2018
Cited by 12 | Viewed by 5095
Abstract
Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current [...] Read more.
Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity. However, whether natural sensory neurons display different functional characteristics in terms of excitability and whether this excitability type undergoes plastic changes under pathological pain states have remained elusive. Here, by utilizing whole-cell patch clamp recordings, behavioral and pharmacological assays, we demonstrated that large dorsal root ganglion (DRG) neurons can be classified into three classes and four subclasses based on their excitability patterns, which is similar to mathematical models raised by Hodgkin. Analysis of hyperpolarization-activated cation current (Ih) revealed different magnitude of Ih in different excitability types of large DRG neurons, with higher Ih in Class 2-1 than that in Class 1, 2-2 and 3. This indicates a crucial role of Ih in the determination of excitability type of large DRG neurons. More importantly, this pattern of excitability displays plastic changes and transition under pathological pain states caused by peripheral nerve injury. This study sheds new light on the functional characteristics of large DRG neurons and extends functional classification of large DRG neurons by integration of transcriptomic and morphological characteristics. Full article
(This article belongs to the Special Issue Pain and Inflammation)
Show Figures

Graphical abstract

2697 KiB  
Article
Biglycan- and Sphingosine Kinase-1 Signaling Crosstalk Regulates the Synthesis of Macrophage Chemoattractants
by Louise Tzung-Harn Hsieh, Madalina-Viviana Nastase, Heiko Roedig, Jinyang Zeng-Brouwers, Chiara Poluzzi, Stephanie Schwalm, Christian Fork, Claudia Tredup, Ralf P. Brandes, Malgorzata Wygrecka, Andrea Huwiler, Josef Pfeilschifter and Liliana Schaefer
Int. J. Mol. Sci. 2017, 18(3), 595; https://doi.org/10.3390/ijms18030595 - 09 Mar 2017
Cited by 30 | Viewed by 6745
Abstract
In its soluble form, the extracellular matrix proteoglycan biglycan triggers the synthesis of the macrophage chemoattractants, chemokine (C-C motif) ligand CCL2 and CCL5 through selective utilization of Toll-like receptors (TLRs) and their adaptor molecules. However, the respective downstream signaling events resulting in biglycan-induced [...] Read more.
In its soluble form, the extracellular matrix proteoglycan biglycan triggers the synthesis of the macrophage chemoattractants, chemokine (C-C motif) ligand CCL2 and CCL5 through selective utilization of Toll-like receptors (TLRs) and their adaptor molecules. However, the respective downstream signaling events resulting in biglycan-induced CCL2 and CCL5 production have not yet been defined. Here, we show that biglycan stimulates the production and activation of sphingosine kinase 1 (SphK1) in a TLR4- and Toll/interleukin (IL)-1R domain-containing adaptor inducing interferon (IFN)-β (TRIF)-dependent manner in murine primary macrophages. We provide genetic and pharmacological proof that SphK1 is a crucial downstream mediator of biglycan-triggered CCL2 and CCL5 mRNA and protein expression. This is selectively driven by biglycan/SphK1-dependent phosphorylation of the nuclear factor NF-κB p65 subunit, extracellular signal-regulated kinase (Erk)1/2 and p38 mitogen-activated protein kinases. Importantly, in vivo overexpression of soluble biglycan causes Sphk1-dependent enhancement of renal CCL2 and CCL5 and macrophage recruitment into the kidney. Our findings describe the crosstalk between biglycan- and SphK1-driven extracellular matrix- and lipid-signaling. Thus, SphK1 may represent a new target for therapeutic intervention in biglycan-evoked inflammatory conditions. Full article
(This article belongs to the Special Issue Pain and Inflammation)
Show Figures

Figure 1

14421 KiB  
Article
Ketamine Analog Methoxetamine Induced Inflammation and Dysfunction of Bladder in Rats
by Qiang Wang, Qinghui Wu, Junpeng Wang, Yang Chen, Guihao Zhang, Jiawei Chen, Jie Zhao and Peng Wu
Int. J. Mol. Sci. 2017, 18(1), 117; https://doi.org/10.3390/ijms18010117 - 18 Jan 2017
Cited by 18 | Viewed by 7780
Abstract
The novel synthetic psychoactive ketamine analog methoxetamine is reportedly being used for recreational purposes. As ketamine use can result in urinary dysfunction, we conducted the present study to investigate how methoxetamine affects the bladder. A cystometry investigation showed that female Sprague-Dawley rats experienced [...] Read more.
The novel synthetic psychoactive ketamine analog methoxetamine is reportedly being used for recreational purposes. As ketamine use can result in urinary dysfunction, we conducted the present study to investigate how methoxetamine affects the bladder. A cystometry investigation showed that female Sprague-Dawley rats experienced increased micturition frequency bladder dysfunction after receiving a daily intraperitoneal injection of 30 mg/kg methoxetamine or ketamine for periods of 4 or 12 weeks. Histologic examinations of rat bladder tissue revealed damaged urothelium barriers, as well as evidence of inflammatory cell infiltration and matrix deposition. The drug-treated rats showed significantly upregulated levels of pro-inflammatory cytokines such as IL-1β, IL-6, CCL-2, CXCL-1, CXCL-10, NGF, and COX-2. In addition, interstitial fibrosis was confirmed by increased levels of collagen I, collagen III, fibronectin and TGF-β. Besides direct toxic effect on human urothelial cells, methoxetaminealso induced the upregulation related cytokines. Our results indicate that long term methoxetamine treatment can induce bladder dysfunction and inflammation in rats. Methoxetamine was confirmed to produce direct toxic and pro-inflammatory effects on human urothelial cells. Methoxetamine-associated bladder impairment may be similar to ketamine-induced cystitis. Full article
(This article belongs to the Special Issue Pain and Inflammation)
Show Figures

Figure 1

2077 KiB  
Article
R-Flurbiprofen Traps Prostaglandins within Cells by Inhibition of Multidrug Resistance-Associated Protein-4
by Ivonne Wobst, Lisa Ebert, Kerstin Birod, Marthe-Susanna Wegner, Marika Hoffmann, Dominique Thomas, Carlo Angioni, Michael J. Parnham, Dieter Steinhilber, Irmgard Tegeder, Gerd Geisslinger and Sabine Grösch
Int. J. Mol. Sci. 2017, 18(1), 68; https://doi.org/10.3390/ijms18010068 - 30 Dec 2016
Cited by 5 | Viewed by 6351
Abstract
R-flurbiprofen is the non-COX-inhibiting enantiomer of flurbiprofen and is not converted to S-flurbiprofen in human cells. Nevertheless, it reduces extracellular prostaglandin E2 (PGE2) in cancer or immune cell cultures and human extracellular fluid. Here, we show that R [...] Read more.
R-flurbiprofen is the non-COX-inhibiting enantiomer of flurbiprofen and is not converted to S-flurbiprofen in human cells. Nevertheless, it reduces extracellular prostaglandin E2 (PGE2) in cancer or immune cell cultures and human extracellular fluid. Here, we show that R-flurbiprofen acts through a dual mechanism: (i) it inhibits the translocation of cPLA to the plasma membrane and thereby curtails the availability of arachidonic acid and (ii) R-flurbiprofen traps PGE2 inside of the cells by inhibiting multidrug resistance–associated protein 4 (MRP4, ABCC4), which acts as an outward transporter for prostaglandins. Consequently, the effects of R-flurbiprofen were mimicked by RNAi-mediated knockdown of MRP4. Our data show a novel mechanism by which R-flurbiprofen reduces extracellular PGs at physiological concentrations, particularly in cancers with high levels of MRP4, but the mechanism may also contribute to its anti-inflammatory and immune-modulating properties and suggests that it reduces PGs in a site- and context-dependent manner. Full article
(This article belongs to the Special Issue Pain and Inflammation)
Show Figures

Graphical abstract

Review

Jump to: Research

660 KiB  
Review
Resilience and Vulnerability to Pain and Inflammation in the Hippocampus
by Verica Vasic and Mirko H. H. Schmidt
Int. J. Mol. Sci. 2017, 18(4), 739; https://doi.org/10.3390/ijms18040739 - 31 Mar 2017
Cited by 36 | Viewed by 8120
Abstract
Increasing evidence demonstrates the importance of hippocampal neurogenesis, a fundamental mechanism of neuroplasticity associated with cognition and emotion, in correlation to neurodegenerative and psychiatric disorders. Neuropsychiatric disorders are often a result of chronic stress or pain followed by inflammation; all these conditions manifest [...] Read more.
Increasing evidence demonstrates the importance of hippocampal neurogenesis, a fundamental mechanism of neuroplasticity associated with cognition and emotion, in correlation to neurodegenerative and psychiatric disorders. Neuropsychiatric disorders are often a result of chronic stress or pain followed by inflammation; all these conditions manifest cognitive deficits and impairments in neurogenesis. However, while some individuals are more susceptible to stress, others are able to adapt to new environments via mechanisms of resilience. In light of this emerging field and based on extensive research, the role of neurogenesis is summarized and presented as a potentially powerful therapeutic tool. Full article
(This article belongs to the Special Issue Pain and Inflammation)
Show Figures

Figure 1

Back to TopTop