Neuronal interleukin-1 receptors mediate pain in chronic inflammatory diseases

Chronic pain is a major comorbidity of chronic inflammatory diseases. Here, we report that the cytokine IL-1β, which is abundantly produced during multiple sclerosis (MS), arthritis (RA), and osteoarthritis (OA) both in humans and in animal models, drives pain associated with these diseases. We found that the type 1 IL-1 receptor (IL-1R1) is highly expressed in the mouse and human by a subpopulation of TRPV1+ dorsal root ganglion neurons specialized in detecting painful stimuli, termed nociceptors. Strikingly, deletion of the Il1r1 gene specifically in TRPV1+ nociceptors prevented the development of mechanical allodynia without affecting clinical signs and disease progression in mice with experimental autoimmune encephalomyelitis and K/BxN serum transfer–induced RA. Conditional restoration of IL-1R1 expression in nociceptors of IL-1R1–knockout mice induced pain behavior but did not affect joint damage in monosodium iodoacetate–induced OA. Collectively, these data reveal that neuronal IL-1R1 signaling mediates pain, uncovering the potential benefit of anti–IL-1 therapies for pain management in patients with chronic inflammatory diseases.

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Mechanism of interleukin-1?-induced calcitonin gene-related peptide production from dorsal root ganglion neurons of neonatal rats

Journal of Neuroscience Research ◽

10.1002/jnr.10651 ◽

2003 ◽

Vol 73 (2) ◽

pp. 188-197 ◽

Cited By ~ 40

Author(s):

Lingfei Hou ◽

Wenjing Li ◽

Xian Wang

Keyword(s):

Dorsal Root Ganglion ◽

Dorsal Root ◽

Interleukin 1 ◽

Calcitonin Gene Related Peptide ◽

Dorsal Root Ganglion Neurons ◽

Neonatal Rats ◽

Related Peptide ◽

Calcitonin Gene ◽

Ganglion Neurons

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Astrocyte-derived TGF-beta 2 and NGF differentially regulate neural recognition molecule expression by cultured astrocytes.

The Journal of Cell Biology ◽

10.1083/jcb.115.2.473 ◽

1991 ◽

Vol 115 (2) ◽

pp. 473-484 ◽

Cited By ~ 86

Author(s):

B Saad ◽

D B Constam ◽

R Ortmann ◽

M Moos ◽

A Fontana ◽

...

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Adhesion Molecule ◽

Interleukin 1 ◽

Dorsal Root Ganglion Neurons ◽

Tgf Beta ◽

Beta 2 ◽

Ganglion Neurons ◽

Culture Supernatants ◽

Recognition Molecule

Because of the importance of neural recognition molecules expressed by glial cells to mediate interactions with neurons, growth factors and cytokines known to be functional during morphogenesis and in diseases of the nervous system were studied for their effects on recognition molecule expression by cultured immature and mature astrocytes from several brain regions. In cultures of immature astrocytes, transforming growth factors-beta 1 (TGF-beta 1) and -beta 2 (TGF-beta 2) and nerve growth factor (NGF) increased expression of the neural adhesion molecule L1, leading to a glia-mediated L1-specific increase in neurite outgrowth of dorsal root ganglion neurons on the astrocyte substrate. L1 expression induced by TGF-beta was inhibited by addition of antibodies to NGF, suggesting that TGF-beta influences L1 expression by modulating production of NGF by astrocytes. TGF-beta 1 and -beta 2 decreased expression of N-CAM by immature astrocytes. Since N-CAM expression was not affected by NGF and antibodies to NGF did not abolish the TGF-beta-induced decrease in N-CAM expression, NGF did not appear to be the mediator for regulating expression of N-CAM. Expression of the adhesion molecule on glia (AMOG) was not affected by any factor. NGF and TGF-beta 2 in latent form, but not TGF-beta 1 were found in the culture supernatants. Addition of interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), platelet-derived growth factor (PDGF), or basic fibroblast growth factor (bFGF) to the cultures did not change recognition molecule expression. REcognition molecule expression by mature astrocytes was not found to be modified by any of the factors tested. In view of the observation that levels of L1 and N-CAM expression correlated with the presence of TGF-beta 2 and NGF in the culture supernatants of immature astrocytes, an autocrine regulatory mechanism for recognition molecule expression by these cells is suggested to play a crucial role in regulation of neuron-glia interactions.

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Rational antimicrobal therapy of inflammatory diseases of the pelvic organs

HEALTH OF WOMAN ◽

10.15574/hw.2020.147.26 ◽

2020 ◽

pp. 26-30

Author(s):

T.H. Romanenko ◽

◽

G.M. Zhaloba ◽

N.V. Yesyp ◽

◽

...

Keyword(s):

Pelvic Pain ◽

Inflammatory Diseases ◽

Statistical Significance ◽

Clinical Signs ◽

Reference Intervals ◽

Reproductive Age ◽

Combination Drug ◽

Chronic Inflammatory Diseases ◽

Pelvic Organs ◽

Duration Of Hospitalization

The objective: to evaluate the efficacy of Tazpen® (piperacillin/tazobactam) for the treatment of chronic inflammatory diseases of the pelvic organs. Materials and methods. 67 women of reproductive age with exacerbation of chronic inflammatory diseases the pelvic organs (salpingitis, salpingoophoritis) were examined. Antimictobal therapy was different in two groups: first that include 35 patients was treated with third generation cephalosporine ceftriaxone (2.0 grams daily: 1.0 gram each 12 hours intravenously), for the second group with 32 women Tazpen® (piperacillin/tazobactam) was prescribed (4.5 grams each 6–8 hours intravenously). Efficacy assessment was based on analysis of duration the hospitalization and the pain level according to The Visual Analogue Scale (VAS) on the admission day, 3rd, 6th day and the day of discharge, duration of hyperthermia, leucocyte level with number of band neutrophils on the admission day, 3rd day and the day of discharge. Results. Clinical signs of exacerbation of chronic inflammatory diseases of the pelvic organs included general weakness, hyperthermia, pelvic pain, pathological discharges, dyspareunia. During the treatment the intensity of pelvic pain decreased, difference of pain levels according to VAS between two groups of study was statistically significant on the 6th day of hospitalization and the day of discharge, that accounts 33.7±1.9 mmand 29.7±2.4 mmon the 6th day in first and second group respectfully, and on the day of discharge –14.0±0.8 mmin first group and 8.8±1.3 mmin second group (p<0.05). Duration of hyperthermia from the day of admission was 3.09±0.17 days in the group of ceftriaxone that is statistically greater than in the group of Tazpen – 2.16±0.21 days (p<0.05).The number of leukocytes and band neutrophils were measured before the treatment, this marker was also decreased in the process of treatment and reached reference intervals on the day of the discharge in both groups. Duration of hospitalization differed in two groups with statistical significance: it accounted 10.71±0.42 days in the first group, treated with ceftriaxone, and 7.34±0.32 days in the second group, treated with piperacillin/tazobactam. One patient (2.9%) from the first group has developed such complication as tubo-ovarian abscess while no one from the second group had such complication. Conclusions. Combination drug Tazpen® (piperacillin/tazobactam) demonstrate comparable or even superior efficacy of treatment of chronic inflammatory diseases of the pelvic organs in comparison with medications of classical schemes. Diminished systemic indicators of inflammatory process alongside with decreased duration of hospitalization evidences the perspective of widening the clinical indicators for Tazpen® prescription and shows an importance of further clinical researches. Key words: chronic inflammatory diseases of the pelvic organs, pelvic pain, broad-spectrum antibiotics, piperacillin, tazobactam, treatment.

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