Evidence map›Paper›PMID 32791212›Full record

ArticleBrain, behavior, and immunity2020

Spinal interleukin-6 contributes to central sensitisation and persistent pain hypersensitivity in a model of juvenile idiopathic arthritis.

Charlie H T Kwok, Annastazia E Learoyd, Julia Canet-Pons, Tuan Trang, Maria Fitzgerald

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain, behavior, and immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
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  15. Pain in Hemophilia: Unexplored Role of Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022
    Review
  16. Article
  17. Article
  18. Altered sensory innervation and pain hypersensitivity in a model of young painful arthritic joints: short- and long-term effects.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Charlie H T KwokPhysiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Comparative Biology and Experimental Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address: hongting.kwok@ucalgary.ca.
Annastazia E LearoydDepartment of Neuroscience, Physiology and Pharmacology, University College London, UK.
Julia Canet-PonsPhysiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Comparative Biology and Experimental Medicine, University of Calgary, Calgary, Alberta, Canada.
Tuan TrangPhysiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Comparative Biology and Experimental Medicine, University of Calgary, Calgary, Alberta, Canada.
Maria FitzgeraldDepartment of Neuroscience, Physiology and Pharmacology, University College London, UK.
University of Calgary · CAUniversity College London · GB

Funding

Versus Arthritis 21,322Versus Arthritis 21322
6 · The paper itself

Abstract

Pain is the most debilitating symptom in juvenile idiopathic arthritis. As pain correlates poorly to the extent of joint pathology, therapies that control joint inflammation are often inadequate as analgesics. We test the hypothesis that juvenile joint inflammation leads to sensitisation of nociceptive circuits in the central nervous system, which is maintained by cytokine expression in the spinal cord. Here, transient joint inflammation was induced in postnatal day (P)21 and P40 male Sprague-Dawley rats with a single intra-articular ankle injection of complete Freund's adjuvant. Hindpaw mechanical pain sensitivity was assessed using von Frey hair and weight bearing tests. Spinal neuron activity was measured using in vivo extracellular recording and immunohistochemistry. Joint and spinal dorsal horn TNFα, IL1β and IL6 protein expression was quantified using western blotting. We observed greater mechanical hyperalgesia following joint inflammation in P21 compared to P40 rats, despite comparable duration of swelling and joint inflammatory cytokine levels. This is mirrored by spinal neuron hypersensitivity, which also outlasted the duration of active joint inflammation. The cytokine profile in the spinal cord differed at the two ages: prolonged upregulation of spinal IL6 was observed in P21, but not P40 rats. Finally, spinal application of anti-IL-6 antibody (30 ng) reduced the mechanical hyperalgesia and neuronal activation. Our results indicate that persistent upregulation of pro-inflammatory cytokines in the spinal dorsal horn is associated with neuronal sensitisation and mechanical hyperalgesia in juvenile rats, beyond the progress of joint pathology. In addition, we provide proof of concept that spinal IL6 is a key target for treating persistent pain in JIA.

Indexed as

Arthritis, JuvenileInterleukin-6AnimalsCentral Nervous System SensitizationHyperalgesiaInflammationMalePainRatsRats, Sprague-DawleySpinal CordInterleukin-6Chronic painElectrophysiologyInflammationInterleukin-6Juvenile arthritisSensory behaviour

Identifiers

PMID32791212
PMCPMC7575902
OpenAlexW3048677422

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.