Effect of intra-articular versus systemic anti-inflammatory drugs in a rabbit model of temporomandibular joint inflammation.
OBJECTIVE
In an attempt to better understand the time course of inflammatory mediator production or release in inflammatory joint disease, a rabbit model of acute temporomandibular joint (TMJ) inflammation was established. This model was used to evaluate the effects of specific anti-inflammatory agents administered either systemically (intraperitoneal, IP) or locally (intra-articular, IA) on the modulation of in vivo tissue levels of two prototypic inflammatory mediators, prostaglandin E2 (PGE2) and bradykinin (BK).


METHODS
An experimental model of inflammation was created by administering carrageenan (carra) into one joint and an equivalent volume of saline (control) into the contralateral joint of 42 male New Zealand White rabbits. The development of hyperthermia was assessed by placement of a microthermister probe into the joint space. The inflammatory mediators, immunoreactive PGE2 (iPGE2) and BK (iBK), were recovered with microdialysis probes, and samples were assayed in conjunction with specific pharmacologic interventions. In the first part of the study, the time course for the release or production of iBK and iPGE2 was determined. In the second part, the effects of IP versus IA administration of dexamethasone and a nonsteroidal anti-inflammatory drug, ketorolac tromethamine, were compared. Dexamethasone and ketorolac were administered at 3 hours and 1 hour, respectively, before the peak release of the inflammatory mediators.


RESULTS
The onset of IA hyperthermia, an index of inflammation, was evident by 90 minutes post-carra and reached a maximum of 1.2 degrees C above core temperature by 150 minutes post-carra. Intra-articular levels of iPGE2 and iBK peaked at 240 minutes (3.35+/-1.9 nmol/L) and 270 minutes (0.45+/-0.29 nmol/L), respectively, after the induction of inflammation in the superior joint space. iBK levels within the superior joint space were significantly decreased by dexamethasone and ketorolac. Ketorolac (50 microg) decreased iBK and iPGE2 levels when given IA or IP. With dexamethasone (3 mg), the levels of iBK were significantly reduced, and iPGE2 levels were not changed.


CONCLUSIONS
This study shows that the rabbit model of TMJ inflammation, with concurrent collection of iBK and iPGE2 via microdialysis, is a reproducible and reliable method to investigate the time course of inflammatory mediator release and their modulation by either the local or systemic administration of anti-inflammatory medications.
Swift
J Q
JQ
Division of Oral and Maxillofacial Surgery, University of Minnesota, School of Dentistry, Minneapolis 55455, USA.
Roszkowski
M T
MT
Alton
T
T
Hargreaves
K M
KM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy* / Q000378:metabolism; D001920:Bradykinin / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D005334:Fever / Q000378:metabolism; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism; D007270:Injections, Intra-Articular; D007274:Injections, Intraperitoneal; D020911:Ketorolac Tromethamine; D008297:Male; D017551:Microdialysis; D011817:Rabbits; D015203:Reproducibility of Results; D013705:Temporomandibular Joint Disorders / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors; D014046:Tolmetin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005938:Glucocorticoids; D018836:Inflammation Mediators; D020911:Ketorolac Tromethamine; D003907:Dexamethasone; D014046:Tolmetin; D015232:Dinoprostone; D001920:Bradykinin