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Calcitonin gene-related peptide in temporomandibular inflammation

thesis
posted on 2024-09-02, 16:25 authored by Joakim Carleson

Calcitonin gene-related peptide (CGRP) is an important biological mediator and cell-signalling molecule, involved in modulation of the immune system, inflammatory response and pain modulation. During pain and inflammation, sensory nerves are activated, and sensory neuropeptides such as CGRP is released from peripheral and central nerve endings.

The function of CGRP is to participate in the mediation and modulation of the inflammatory process. Therefore, the main objective was to investigate the relationship, between the concentrations of CGRP in synovial fluid and tissue of the temporomandibular joint (TMJ), the masseter muscles (MA), plasma (PL), trigeminal ganglia (TG), hippocampus (HC), hypothalamus-pituitary axis (HP) and cerebrospinal fluid (CSF), in rats with induced temporomandibular inflammation. Also, pre-treatment with capsaicin or surgical denervation was evaluated, in addition to, animal behaviour.

Rats were subjected either to an intra-articular or muscular, injection of substance P (SP), interleukin 1-alpha (IL-1alpha) or heat killed Mycobacterium Butyricum in paraffin Oil (Freund's adjuvant (FA). Acute and chronics experiments were conducted. Clinical parameters, such as degree of swelling, cutaneous temperature, skin colour and scratching behaviour, were used as assessment, apart from analysis of the concentration of CGRP-like immunoreactivity (CGRPLI), determined with the use of competitive radio immunoassay technique, high performance liquid chromatography, immunohistochemistry and modified protein assays.

Two, 6 and 24 hrs after induced acute unilateral TMJ inflammation, with SP or IL-1alpha the concentrations of CGRP-LI were elevated in TMJ perfusates and in the CSF. One and 12 hrs after unilateral FA induced TMJ inflammation, the concentrations of CGRP-LI were bilaterally elevated in TMJ perfusates, and were higher in monoarthritic rats compared to polyarthritic rats. The concentrations of CGRP-LI were higher on the contralateral side, after 1 hour, and bilaterally higher, after 12 hours, in the monoarthritic group compared to the polyarthritic group during FA induced TMJ inflammation.

In plasma, the concentrations of CGRP-LI decreased 1 and 12 hrs after FA induction in the polyarthritic animals, and after 1 hr in the monoarthritic rats, compared to controls. However, no changes were seen in the concentrations of CGRP-LI in the plasma of the SP or IL-1alpha treated rats. In the CSF, the concentrations of CGRP-LI increased 2, 6 and 24 hrs after SP or IL-1alpha induced TMJ inflammation and I and 12 hrs after FA induced polyarthritis, but were left unchanged in the monoarthritic group.

In bilateral chronic TMJ inflammation, the levels of CGRP-LI were higher, bilaterally, in TMJ and TG, compared to controls. In unilateral chronic TMJ inflammation and in masseter myositis, the concentrations of CGRP-LI were higher compared to controls. Also, the levels were higher on the contralateral side compared to the ipsilateral side, along with a concomitant increase in nociceptive behaviour.

A unilateral denervation of the TMJ, with capsaicin or surgery, decreased the concentrations of CGRP-LI in the TMJ and TG, both in intact and arthritic rats, compared to ipsi- and contralateral sides. The concentrations of CGRP-LI in the TMJ and TG, correlated.

The increased concentrations of CGRP-LI in the TMJs and the MAs after induced acute and chronic inflammation with associated nociceptive behaviour, demonstrate that CGRP is involved in the mediation and the modulation of the inflammatory process in temporomandibular inflammation.

List of scientific papers

I. Carleson J, Alstergren P, Appelgren A, Appelgren B, Kopp S, Theodorsson E, Lundeberg T (1996). "A model for experimental induction of acute temporomandibular joint inflammation in rats: effects of substance P(SP) on neuropeptide-like immunoreactivity. " Life Sci 59(15): 1193-201
https://pubmed.ncbi.nlm.nih.gov/8845005

II. Carleson J, Alstergren P, Appelgren A, Appelgren B, Kopp S, Theodorsson E, Lundeberg T (1996). "A model for the study of experimentally induced temporomandibular arthritis in rats: the effect of human recombinant interleukin-1 alpha on neuropeptide-like immunoreactivity. " J Orofac Pain 10(1): 9-14
https://pubmed.ncbi.nlm.nih.gov/8995911

III. Carleson J, Alstergren P, Appelgren A, Appelgren B, Kopp S, Srinivasan GR, Theodorsson E, Lundeberg T (1996). "Effects of adjuvant on neuropeptide-like immunoreactivity in experimentally induced temporomandibular arthritis in rats. " Arch Oral Biol 41(7): 705-12
https://pubmed.ncbi.nlm.nih.gov/9015573

IV. Carleson J, Bileviciute I, Theodorsson E, Appelgren B, Appelgren A, Yousef N, Kopp S, Lundeberg T (1997). "Effects of adjuvant on neuropeptide-like immunoreactivity in the temporomandibular joint and trigeminal ganglia. " J Orofac Pain 11(3): 195-9
https://pubmed.ncbi.nlm.nih.gov/9610308

V. Carleson J, Kogner P, Bileviciute I, Theodorsson E, Appelgren A, Appelgren B, Kopp S, Yousef N, Lundeberg T (1997). "Effects of capsaicin in temporomandibular joint arthritis in rats. " Arch Oral Biol 42(12): 869-76
https://pubmed.ncbi.nlm.nih.gov/9460541

VI. Carleson J, Lundeberg T, Appelgren B (2001). "Bilateral increases of Calcitonin gene-related peptide in experimentally induced unilateral rat masseter myositis." J Orofac Pain (Submitted)

History

Defence date

2001-06-01

Department

  • Department of Physiology and Pharmacology

Publication year

2001

Thesis type

  • Doctoral thesis

ISBN-10

91-628-4838-0

Number of supporting papers

6

Language

  • eng

Original publication date

2001-05-11

Author name in thesis

Carleson, Joakim

Original department name

Department of Physiology and Pharmacology

Place of publication

Stockholm

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