Oral Biol Res.  2024 Jun;48(2):37-44. 10.21851/obr.48.02.202406.37.

Peripheral NLR family pyrin domain-containing 3 protein pathway participates in the development of orofacial inflammatory pain in rats

• Kim MD
• Kim YM
• Son JY
• Ju JS
• Ahn DK

• KMID: 2557489
• DOI: http://doi.org/10.21851/obr.48.02.202406.37

Abstract

The study aimed to investigate the role of peripheral NLR family pyrin domain-containing 3 protein (NLRP3) in inflammatory pain development in the orofacial area. Male Sprague–Dawley rats were used in experiments, with orofacial formalin-induced pain behavior and complete Freund’s adjuvant (CFA)-induced thermal hyperalgesia as chronic inflammatory pain models. Administration of 5% formalin produced biphasic nociceptive behavior, and subcutaneous pretreatment with MCC950 (50 and 100 μg/50 μL), an NLRP3 inhibitor, remarkably attenuated nociceptive behavior during the second phase. Subcutaneous CFA injection induced thermal hyperalgesia 1 day after injection, which persisted for 7 days. Five days after CFA injection, subcutaneous treatment with MCC950 (50 and 100 μg/50 μL) significantly attenuated thermal hyperalgesia. Additionally, subcutaneous injection of BMS-986299 (50 and 100 μg/50 μL), an NLRP3 agonist, induced significant nociceptive behavior for 1 hour in naïve rats. Pretreatment with an interleukin-1β (IL-1β) receptor antagonist blocked the nociceptive behavior produced by subcutaneous injection of BMS-986299 (100 μg/50 μL); however, treatment with a hypoxia-inducible factor 1α inhibitor did not. These findings suggest the involvement of the peripheral NLRP3 and IL-1β pathway in chronic inflammatory pain development in the orofacial area, highlighting the potential of blocking this pathway as a strategy for developing future inflammatory pain treatment drugs.

Keyword

Facial pain; Formaldehyde; Interleukin-1beta; NLR family pyrin domain-containing 3 protein; Tigeminal nerve