Peripheral muscle pain biomarkers in chronic muscle pain

Chronic musculoskeletal pains have significant impact on quality of life; in addition, annual costs to society in terms of lost work days and sick leave are great.

Temporomandibular disorders (TMD) is a collective term embracing chronic musculoskeletal conditions affecting the temporomandibular joint (TMJ) or the masticatory muscles (myalgia). TMD has a prevalence of 5%–10% and is more prevalent in women than in men. In children prevalences as high as 20% has been reported. Masticatory myalgia is the most common pain condition in the orofacial are and is frequently accompanied by restricted jaw opening, pain upon chew­ing, pain referral, and headache and, thus, reduces patients’ quality of life.

Principal Investigator

  • Malin Ernberg, Professor

Project: Peripheral muscle pain biomarkers in chronic muscle pain

This project is based on the hypothesis that mechanical overloading and disturbed local blood flow may lead to local ischemia and peripheral release of algesic substances (“inflammatory soup”) that may induce and maintain muscle pain and thus be of importance for the pathogenesis of chronic myalgia. In several sub-projects the role of peripheral pain biomarkers for chronic myalgia is explored.

Project: Pain genes and muscle biomarkers in TMD myalgia

Here, we will use microdialysis to further investigate the role of algogenic inflammatory and markers as well as genetic biomarkers in the pathophysiology underlying TMD myalgia in clinical and experimental studies.

Close-up of patient with a thin tube that goes into his cheek and another one that goes out of the cheek.
Intramuscular microdialysis of the masseter. This is a method developed by us that allows the collection of different substances from the extracellular environment in-vivo. Photo: Sofia Louca

Previous studies have shown that there is an increased muscle level of 5-HT in patients with chronic myalgia and a positive correlation to muscle pain and tenderness. 5-HT participates in pain mediation via the 5-HT3 receptor when it is released peripherally from platelets due to tissue damage or ischemia. The 5-HT3 receptors are suggested to be involved both in central and peripheral perception and processing of pain as well as in inflammation.

Blocking of the 5-HT3 receptor reduces experimental and clinical pain, but with a large inter-individual variation in the efficacy, which might be due to genetic factors. Recently several polymorphisms that influence pain perception have been identified. However, the role of genes coding for the 5-HT3 receptor and their role in pain mediation and efficacy of 5-HT3 antagonists in chronic myalgia has not yet been explored


  • Sofia Louca, PhD student


National academic collaborations: Professor Thomas List, DDS, PhD, Malmö University, Sweden (co-supervisor); Professor Martin Schalling, MD, PhD (co-supervisor); Assistant Professor Nikolaos Christidis, DDS, PhD (co-supervisor); Professor Peter Svensson, DDS, PhD, all at Karolinska Institutet, Stockholm, Sweden.


Swedish Research Council, Karolinska Institutet, Stockholm Community Council, Swedish Dental Association, Swedish Rheumatism Association.

Project: Molecular biomarkers in saliva in health and pain states

The overall aim is to investigate if saliva can be used to sample algogenic substances that can serve as molecular biomarkers for diagnosing TMD.

Studies have suggested that peripheral release of 5HT and glutamate may be involved in the pathogenesis of chronic myalgia, including myofacial TMD. There is further evidence suggesting that 5-HT, nerve growth factor (NGF), substance P (SP), calcitonin gene-related peptide (CGRP) and brain derived neurotrophic factor (BDNF) saliva levels are increased in patients with chronic migraine and headache.

Saliva contains an extensive collection of potential biomarkers that could play important roles for the pathophysiology of orofacial pain. Saliva is often neglected as a body fluid of diagnostic value, even though generally well accepted by the patients. This is due to lack of a standardized collection procedure.

Results from a saliva test
The protein expression in saliva of a patients with TMD myalgia and an age and sex-matched healthy control. Several proteins in the patient show another pattern compared to the control, being either up- or down-regulated Photo: Hajer Jasim


  • Hajer Jasim, PhD 


National academic collaboration: Associate Professor Bijar Ghafouri, PhD, Linköping University, Sweden (co-supervisor); Associate Professor Jochen Schwenk, PhD, Royal Institute of Technology, Stockholm, Sweden (co-supervisor), Senior Consultant Britt Hedenberg-Magnusson, Eastman Institute, Stockholm, Sweden (co-supervisor).


Karolinska Institutet, Stockholm Community Council, Swedish Dental Association, Swedish Rheumatism Association.