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P2Y2 Receptors Mediate Masseter Muscle Mechanical Hypersensitivity in Rats

Authors Tariba Knežević P, Vukman R, Uhač M, Illeš D, Kovačević Pavičić D, Simonić-Kocijan S

Received 24 November 2019

Accepted for publication 7 May 2020

Published 3 June 2020 Volume 2020:13 Pages 1323—1333

DOI https://doi.org/10.2147/JPR.S239831

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr E Alfonso Romero-Sandoval


Petra Tariba Knežević,1,2 Robert Vukman,1,2 Mia Uhač,3 Davor Illeš,4 Daniela Kovačević Pavičić,1,2 Sunčana Simonić-Kocijan1,2

1Department of Prosthodontics, Faculty of Dental Medicine, University of Rijeka, Rijeka, Croatia; 2Department of Prosthodontics, Clinic of Dental Medicine, Clinical Hospital Center Rijeka, Rijeka, Croatia; 3Department of Orthodontics, Clinic of Dental Medicine, Clinical Hospital Center Rijeka, Rijeka, Croatia; 4Department of Removable Prosthodontics, School of Dental Medicine, University of Zagreb, Zagreb, Croatia

Correspondence: Sunčana Simonić-Kocijan
Department of Prosthodontics, Faculty of Dental Medicine, University of Rijeka, Krešimirova 40, Rijeka 51000, Croatia
Tel +385 51 345 633
Fax +385 51 345 630
Email suncanask@uniri.hr

Purpose: P2Y2 receptors (P2Y2Rs) are among the various receptors that play an important role in nociception. The goal of this research was to investigate possible P2Y2R expression changes in the trigeminal ganglion (TRG) in bilateral masseter muscle (MM) hypersensitivity following unilateral MM inflammation. The impact of unilateral intramasseteric administration of P2Y2R antagonist on bilateral MM hypersensitivity was also explored.
Materials and Methods: Bilateral MM hypersensitivity was provoked by unilateral intramasseteric injection of complete Freund’s adjuvant (CFA). The head withdrawal threshold (HWT) was assessed bilaterally 4 days later. Bilateral TRG and MM isolation were followed, and quantitative real-time polymerase chain reaction (qRT-PCR) and histopathological analysis were carried out on these tissues, respectively. The involvement of P2Y2Rs in nocifensive behavior was evaluated by administering two doses of P2Y2R antagonist AR-C118925 (0.2 or 1 mg/100 μL) in inflamed MM 4 days post-CFA administration. Bilateral HWT was assessed at different time points following antagonist injection.
Results: qRT-PCR analysis demonstrated P2Y2R up-regulation in TRG ipsilateral to the site of CFA administration. Compared to the controls, both doses of AR-C118925 injected ipsilateral to the TRG increased the bilateral HWT at 30, 60, 90, and 120 minutes after antagonist administration.
Conclusion: The findings suggest that P2Y2Rs may affect MM inflammatory hypersensitivity owing to its up-regulation in the TRG in MM inflammatory pain states.

Keywords: facial pain, masticatory muscles, temporomandibular disorders, trigeminal ganglion

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