Evidence map›Paper›PMID 25261281›Full record

ArticleThe journal of headache and pain2014

Expression of 5-HT3 receptors and TTX resistant sodium channels (Na(V)1.8) on muscle nerve fibers in pain-free humans and patients with chronic myofascial temporomandibular disorders.

Nikolaos Christidis, Isabell Kang, Brian E Cairns, Ujendra Kumar, Xudong Dong, Annika Rosén, Sigvard Kopp, Malin Ernberg

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in The journal of headache and pain, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05720065 (Peripheral TMD Pain Mechanisms and the Effect by Botulinum Toxin A. A Randomized, Controlled, Double-blind Study), which is not on this map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.4field-weighted citation impact, top 19% 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.

NCT05720065 phase2recruitingnot on this mapstarted 2023, after this paper: background citation

Peripheral TMD Pain Mechanisms and the Effect by Botulinum Toxin A. A Randomized, Controlled, Double-blind Study

TypeinterventionalSponsorKarolinska InstitutetRan2023 to 2027Enrolled100ConditionsTemporomandibular DisordersArmsBotulinum toxin type A, Isotonic saline 0,9%
3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 37 citations in OpenAlex.

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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

8 authors at 2 institutions in 5 countries.

Nikolaos ChristidisOrofacial Pain and Jaw Function, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden. nikolaos.christidis@ki.se.
Isabell Kang
Brian E Cairns
Ujendra Kumar
Xudong Dong
Annika Rosén
Sigvard Kopp
Malin Ernberg
Karolinska Institutet · SEUniversity of British Columbia · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPrevious studies have shown that 5-HT3-antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT3-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (NaV) are involved in peripheral sensitization and found in trigeminal ganglion neurons innervating the rat masseter muscle. This study aimed to investigate the frequency of nerve fibers that express 5-HT3A-receptors alone and in combination with NaV1.8 sodium-channels in human muscles and to compare it between healthy pain-free men and women, the pain-free masseter and tibialis anterior muscles, and patients with myofascial temporomandibular disorders (TMD) and pain-free controls.

methodsThree microbiopsies were obtained from the most bulky part of the tibialis and masseter muscles of seven and six healthy men and seven and six age-matched healthy women, respectively, while traditional open biopsies were obtained from the most painful spot of the masseter of five female patients and from a similar region of the masseter muscle of five healthy, age-matched women. The biopsies were processed by routine immunohistochemical methods. The biopsy sections were incubated with monoclonal antibodies against the specific axonal marker PGP 9.5, and polyclonal antibodies against the 5-HT3A-receptors and NaV1.8 sodium-channels.

resultsA similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT3A-receptors. The expression of NaV1.8 by 5-HT3A positive nerve fibers associated with connective tissue was significantly higher than nerve fibers associated with myocytes (P < .001). In the patients, significantly more fibers per section were found with an average of 3.8 ± 3 fibers per section in the masseter muscle compared to 2.7 ± 0.2 in the healthy controls (P = .024). Further, the frequency of nerve fibers that co-expressed NaV1.8 and 5-HT3A receptors was significantly higher in patients (42.6%) compared to healthy controls (12.0%) (P < .001).

conclusionsThis study showed that the 5-HT3A-receptor is highly expressed in human masseter and tibialis muscles and that there are more nerve fibers that express 5-HT3A-receptors in the masseter of women with myofascial TMD compared to healthy women. These findings indicate that 5-HT3-receptors might be up-regulated in myofascial TMD and could serve as potential biomarkers of chronic muscle pain.

Indexed as

AdultChronic DiseaseFemaleHumansMaleMasseter MuscleMuscle, SkeletalNAV1.8 Voltage-Gated Sodium ChannelNerve FibersReceptors, Serotonin, 5-HT3Sodium Channel BlockersTemporomandibular Joint DisordersTetrodotoxinNAV1.8 Voltage-Gated Sodium ChannelReceptors, Serotonin, 5-HT3SCN10A protein, humanSodium Channel BlockersTetrodotoxin

Identifiers

PMID25261281
PMCPMC4182444
OpenAlexW2157956635

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.