Neuropeptides in temporomandibular joint arthritis

Involvement of the peripheral and central nervous systems in the pathophysiology of arthritis has been suggested and neuropeptides are thought to participate in the mediation and modulation of the inflammatory process.

The main objective of the clinical studies was to investigate the relationship between the presence of neuropeptides in the synovial fluid of the temporomandibular joint (TMJ) and the stomatognathic symptoms and signs, including the intra-articular temperature (IAT), in patients with TMJ arthritis. In addition, intra-articular treatment with glucocorticoids was evaluated by examining the neuropeptide Y (NPY) concentrations in the arthritic TMJ and corresponding symptoms and signs. An experimental animal model of TMJ arthritis was conducted to study the peripheral and central effects of induced monoarthritis in the rat TMJ on the NPY concentrations in TMJ tissue and selected brain regions.

Patients with TMJ arthritis and general inflammatory joint disease were subjected to arthrocentesis to enable joint fluid sampling, intra-articular temperature recordings and administration of glucocorticoids. The clinical parameters also included pain (assessed with a visual analog scale), hyperalgesia (determined by a pressure pain threshold), mandibular mobility (indirectly reflected by the mouth opening capacity) and occlusal signs of TMJ tissue destruction. The concentrations of neurokinin A- (NKA-), substance P- (SP-), calcitonin generelated peptide- (CGRP-) and NPY-like immunoreactivity (-LI) were determined with the use of competitive radioimmunoassay technique.

NKA-LI, SP-LI, CGRP-LI and NPY-LI were found in concentrations above the plasma level in the synovial fluid of the rheumatoid TMJ. Changes in the IAT corresponded to changes in joint fluid NPY-LI and CGRP-LI and the patients with intra-articular hypothermia had the highest joint fluid concentrations of NPY-LI. Moreover, the IAT was found to be positively correlated to the joint fluid concentrations of SP-LI. Pain, hyperalgesia, restricted mouth opening and occlusal signs of TMJ tissue destruction were associated with the high concentrations of CGRP-LI and NPY-LI. Interestingly, TMJ pain and hyperalgesia were found to be negatively correlated to the high concentrations of SP-LI. Intra-articular glucocorticoid treatment of the arthritic TMJ was associated with a short-term decrease in joint fluid NPY-LI in conjunction with a general improvement of the TMJ symptoms and signs.

Monoarthritis in the rat TMJ induced a uni- and/or bilateral decrease in NPY-LI in the TMJ tissue 1, 5 and 10 weeks after inoculation. Concomitant changes in central NPY expression were observed in the hippocampus, the hypothalamus and the pituitary brain regions. It may be concluded that SP, CGRP and NPY are present in the joint fluid of the arthritic TMJ fluid and it is suggested that these neuropeptides may participate in the mediation and modulation of TMJ arthritis involving the peripheral, central and sympathetic nervous systems.

List of scientific papers

I. Appelgren A, Appelgren B, Eriksson S, Kopp S, Lundeberg T, Nylander M, Theodorsson E (1991). Neuropeptides in temporomandibular joints with rheumatoid arthritis: a clinical study. Scand J Dent Res. 99(6):519-521.
https://pubmed.ncbi.nlm.nih.gov/1722347

II. Appelgren A, Appelgren B, Kopp S, Lundeberg T, Theodorsson E (1993). Relation between the intra-articular temperature of the temporomandibular joint and the presence of neuropeptide Y-like immunoreactivity in the joint fluid. A clinical study. Acta Odontol Scand. 51(1):1-8.
https://pubmed.ncbi.nlm.nih.gov/8451918

III. Appelgren A, Appelgren B, Kopp S, Lundeberg T, Theodorsson E (1993). Relation between intra-articular temperature of the arthritic temporomandibular joint and presence of calcitonin gene-related peptide in the joint fluid. A clinical study. Acta Odontol Scand. 51(5):285-91.
https://pubmed.ncbi.nlm.nih.gov/8279269

IV. Appelgren A, Appelgren B, Kopp S, Lundeberg T, Theodorsson E (1995). Neuropeptides in the arthritic TMJ and symptoms and signs from the stomatognathic system with special consideration to rheumatoid arthritis. J Orofac Pain. 9(3):215-25.
https://pubmed.ncbi.nlm.nih.gov/8995921

V. Alstergren P, Appelgren A, Appelgren B, Kopp S, Lundeberg T, Theodorsson E (1996). The effect on joint fluid concentration of neuropeptide Y by intra-articular injection of glucocorticoid in temporomandibular joint arthritis. Acta Odontol Scand. 54(1):1-7.
https://pubmed.ncbi.nlm.nih.gov/8669234

VI. Appelgren A, Appelgren B, Kopp S, Lundeberg T, Theodorsson E (1998). Substance P-associated increase of intra-articular temperature and pain threshold in the arthritic TMJ. J Orofac Pain. 12(2):101-7.
https://pubmed.ncbi.nlm.nih.gov/9656887

VII. Appelgren A, Appelgren B, Carleson J, Kopp S, Theodorsson E, Lundeberg T. Central and peripheral changes in neuropeptide Y-like immunoreactivity following adjuvant monoarthritis in the rat temporomandibular joint. [Manuscript]