Chronic musculoskeletal pains

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.

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.

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

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

Group Leader

Malin Ernberg

Research Group

PhD student: Sofia Louca, DDS

Collaborations

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.

Financing

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

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. 

Group Leader

Malin Ernberg

Research Group

PhD student: Hajer Jasim

Collaborations

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).  

Financing

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

Expression of peripheral pain receptors in chronic myalgia

This research group has developed a unique method to obtain muscle microbiopsies with only minor tissue damage. Our preliminary results indicate an up-regulation of 5-HT3A receptors in M-TMD, but this needs to be confirmed in a larger sample. In this project pain receptors, their mRNA levels and the proteomic signature will be explored in muscle biopsies. The focus will be on co-expression of 5-HT3A-receptors and TTX-insensitive sodium channels (NaV1.8 a-subunit), NR2B-receptors and SP, and the expression of TrkA/B and TRPV1, as well as their mRNA levels and the protein pattern in the masseter muscle. This will be investigated in healthy men and women, in patients with chronic jaw myalgia (TMD myalgia and fibromyalgia) as well as in a human experimental study of muscle hyperalgesia (NGF-injection).

Immunohistochemistry, in-situ hybridization and two-dimensional differential gel electrophoresis (2D-DIGE) with mass spectrometry for the identification of proteins will be used for the analyses.

Group Leader

Malin Ernberg

Research Group

PhD student: Abdelrahman Alhilou

Postdoc: Akiko Shimada

Collaborations

Academic collaboration: Assistant Professor Nikolaos Christidis (main supervisor), DDS, PhD, KaroIinska Institutet, Stockholm, Sweden; Senior Consultant Britt Hedenberg-Magnusson, DDS, PhD, Eastman Institute, Stockholm, Sweden; Associate Professor Bijar Ghafouri, PhD, Linköping University, Sweden; Professor Brian Cairns, MSci Pharm, PhD, University of British Columbia, Canada (co-supervisor).

Financing

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

Treatment of masticatory myofascial pain – efficacy and cost effectiveness

Therapeutic jaw exercises aim to attain relaxation in the jaw muscles and optimize jaw function. In the SBU report 2006, concerning chronic pain, it is concluded that the scientific evidence concerning physical treatment of pain in the orofacial region (including therapeutic jaw exercises) is inadequate. Chronic myofascial pain in the orofacial region can lead to large expenses for the community as well as for the individual patient. Thus, early cost-effective treatments are necessary to reduce health care costs and unnecessary suffering for the patients.

The experience of pain is one of the most subjective and complex feelings there is. Chronic masticatory myofascial pain has components of a sensory, affective and cognitive nature. No information is available about patients’ emotions and experiences concerning masticatory myofascial pain treated with therapeutic jaw exercises. A qualitative research method that takes emotional, psychological, social and existential aspects into account is the best method to investigate these phenomena.

Group Leader

Malin Ernberg

Research Group

PhD student: Erik Lindfors

Collaborations

National academic collaboration:  Professor Tomas Magnusson, DDS, PhD, Jönköping University, Sweden (co-supervisor).  

Financing

Uppsala Community Council

 

 

Odontology