Peripheral TMD Pain Mechanisms and the Effect by Botulinum Toxin A

Condition(s) studied

Investigational drug(s) / intervention(s)

Botulinum toxin type A: Randomized double-blind administration

Isotonic saline 0,9%: Randomized double-blind administration

Study summary

The goal of this clinical trial is to investigate the effect of botulinum toxin on neurons' plasticity in the masseter muscle in humans with and without painful myogenous temporomandibular disorders (TMDM). The main questions it aims to answer are:

* does treatment with botulinum toxin alter gene expressions, epigenetic signatures, and cells plasticity in the masseter muscles of TMDM patients?
* do any such changes differ between patients with local and regional TMDM?
* does treatment with botulinum toxin influence pain characteristics (intensity, frequency, and sensibility) and other variables in patients with TMDM and are there correlations between significantly changed expression of biomarkers and other variables?

Participants will be examined with a questionnaire, clinical examination (including quantitative sensory testing; QST), and microbiopsy sampling from one of the masseter (MM) and anterior tibialis (AT) muscles and are then randomized to treatment with botulinum toxin or control (isotonic saline). Follow-ups occur after one and three months for all patients, and six months with questionnaire, clinical examination, and collection of post-treatment microbiopsies to see if botulinum toxin alter peripheral molecular events and clinical variables.

Eligibility

Primary outcome measure(s)

• Change of gene expression measured with bulk RNA-seq — 1-6 months
  Gene expression in the anterior tibialis muscle (internal control) will be subtracted from the masseter and the patients will then be clustered according to DEGs and compared to baseline.
• Change of RNA expression measured with single-cell RNA (scRNA) seq/spatial trnascriptomics. — 1-6 months
  ScRNA-seq will be analyzed by SEURAT
• Change of expression of sensory neuron markers measured with IHC — 1-6 months
  The expression will be measured as the change of frequency (%) of selected sensory neuron markers.
• Change of proteome measured with proteomics — 1-6 months
  The expression wil be measured with two-dimensional gel electrophoresis, followed by liquid chromatography-tandem mass spectrometry and protein network analyses.
• Change of proteome measured with affinity-based proteomics. — 1-6 months
  The protein expression will be measured with affinity proteomics using Olink platforms will be done, which enables analysis of several hundreds of proteins in one analysis

Trial sites (1)

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