Expression of peripheral pain receptors in chronic myalgia

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

  • Nikolaos Christidis

Projects

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 TMD myalgia, 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.

The microbiopsies are obtained through the skin-surface overlaying the superficial masseter muscle. 30 min before this procedure topical anesthesia (EMLA®, 25mg lidocaine and 25 mg prilocaine, AstraZeneca, Södertälje, Sweden) will be placed over the skin at the area to be penetrated. A Bard®TruGuide™ coaxial needle (BARD Norden, Helsingborg, Sweden) will be inserted to a depth of 10 mm and used to guide the biopsy instrument (Bard® Monopty® disposable core biopsy instrument with a penetration depth of 11 mm and a diameter of 18G).

Example of high power (40 x) photomicrographs for a masseter section from one healthy woman, showing fibers positively labeled for PGP 9.5 (A), NR2B (B), and Substance P (C). (D) is the composite image. Calibration bar: 100 μm.

Members

  • Abdelrahman Alhilou, PhD student
  • Akiko Shimada, Postdoc

Collaborations

Professor Malin Ernberg (co-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 (co-supervisor), MSci Pharm, PhD, University of British Columbia, Canada.

Financing

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

Prevalence of TMD in children and adolescents

The previous studies regarding the prevalence of orofacial pain in children are all based on self-reports or on patients already referred to a specialist clinic. No study has examined a random sample of children/adolescents from the general population or any possible correlation between psychosocial status, socioeconomic status and general health and TMD.

In this study 500 randomly selected children and adolescents will be examined using the validated research diagnostic criteria for TMD (RDC/TMD) Axis I (clinical diagnosis) and Axis II for the psychosocial status, socioeconomic status and general health, also the Youth Health Report will be used.

  • Amal Al-Khotani, PhD student

Collaborations

 Professor Malin Ernberg (co-supervisor), DDS, PhD; Assistant Professor Aron Naimi-Akbar (co-supervisor), DDS, PhD, both at KaroIinska Institutet, Stockholm, Sweden; Senior Dental Officer Britt Hedenberg-Magnusson (co-supervisor), DDS, PhD, Eastman Institute, Stockholm, Sweden; Senior Dental Officer Emad AbdulRahman Al-Badawi (co-supervisor), DDS, PhD, North Jeddah Specialty Dental Center, Ministry of Health, Saudi Arabia.

Financing

Karolinska Institutet, and the Government of Saudi Arabia.

Evaluation of different treatment modalities in children with TMD pain

One of the most commonly used treatments for TMD are occlusal appliances and the use of occlusal appliances in managing TMD pain is supported by evidence in the literature, but only for adults. In addition, there are no reports if occlusal appliances affect the mandibular growth.

In order to investigate the effectiveness of different treatment modalities in children with TMD-pain and any possible side-effects we will investigate the effectiveness of a soft occlusal appliance compared to standardized jaw exercises in children with TMD myalgia on pain-reduction and mandibular growth as well as compared to either standardized jaw exercises or non-steroidal anti-inflammatory drugs (NSAIDs) as a treatment of TMJ arthralgia.

Figure: The use of occlusal appliances in managing TMD pain is supported by evidence in the literature, but only for adults.

  • Nina Monsef, Masters student

Collaborations

Senior Dental Officer Georgios Tsilingaridis (co-supervisor), DDS, PhD, Eastman Institute, Stockholm; Senior Dental Officer Britt Hedenberg-Magnusson (co-supervisor), DDS, PhD, Eastman Institute, Stockholm, Sweden; Senior Dental Officer Malin Collin, DDS, PhD, Eastman Institute, Stockholm; Associate Professor Agneta Karsten (co-supervisor), DDS, PhD, KaroIinska Institutet, Stockholm, Sweden.

Financing

Folktandvården AB

Sensory-motor regulation of human biting behavior in painful orofacial conditions

Several reports have indicated that the periodontal mechanoreceptors, which are activated when force is applied on the tooth, have an important role in the control of jaw muscles during chewing. Periodontal receptors of the anterior teeth are important in manipulative tasks during the initial part of mastication, like holding and positioning food for biting. Muscle spindles regulate contraction of the muscle and also allow the brain to determine the mandibular position and movement. Mechanisms affecting the muscle spindles seem to affect the ability to bite and chew. It is of great interest to investigate if and how pain in the orofacial region, mediated by the trigeminal nerve, affects the ability to bite and chew. If the ability to bite and chew is impaired, then also the ability to get the necessary nourishment will be affected, leading to even more severe conditions. Consequently, the aim is to investigate how acute and chronic temporomandibular pain affects the human biting behavior. The procedure used to investigate the biting behavior is developed by our research group. 

Figure: Illustration from the equipment developed by our research group to investigate the biting behavior in normal state, in acute and chronic pain from the temporomandibular muscles and joints.

  •  Samaa Al-Sayegh, Master student

Collaborations

Assistant Professor Krister Svensson (co-supervisor) DDS, PhD, KaroIinska Institutet, Stockholm, Sweden; Senior Dental Officer Lars Fredriksson (co-supervisor), DDS, PhD, Eastman Institute, Stockholm, Sweden; Assistant Professor Anastasios Grigoriadis (co-supervisor) DDS, PhD, KaroIinska Institutet, Stockholm, Sweden; Annie Borgwardt DDS, Eastman Institute, Stockholm, Sweden.

Financing

This project is part of the part of the National clinical research school in odontology and funded by Folktandvården AB, the Swedish Dental Society.

Odontology