title: Intra-articular (IA) ropivacaine microparticle suspensions reduce pain, inflammation, cytokine, and substance p levels significantly more than oral or IA celecoxib in a rat model of arthritis.
abstract: Current therapeutic treatment options for osteoarthritis entail significant safety concerns. A novel ropivacaine crystalline microsuspension for bolus intra-articular (IA) delivery was thus developed and studied in a peptidoglycan polysaccharide (PGPS)-induced ankle swelling rat model. Compared with celecoxib controls, both oral and IA, ropivacaine IA treatment resulted in a significant reduction of pain upon successive PGPS reactivation, as demonstrated in two different pain models, gait analysis and incapacitance testing. The reduction in pain was attended by a significant reduction in histological inflammation, which in turn was accompanied by significant reductions in the cytokines IL-18 and IL-1β. This may have been due to inhibition of substance P, which was also significantly reduced. Pharmacokinetic analysis indicated that the analgesic effects outlasted measurable ropivacaine levels in either blood or tissue. The results are discussed in the context of pharmacologic mechanisms both of local anesthetics as well as inflammatory arthritis.
authors.affiliation: Baxter Healthcare Corporation, Medication Delivery, Global R&D, 25212 W. Illinois Route 120, Round Lake, IL, 60073, USA, barrett_rabinow@baxter.com.
authors.forename: Barrett
authors.initials: B
authors.lastname: Rabinow
authors.forename: Jane
authors.initials: J
authors.lastname: Werling
authors.forename: Alison
authors.initials: A
authors.lastname: Bendele
authors.forename: Jerome
authors.initials: J
authors.lastname: Gass
authors.forename: Roy
authors.initials: R
authors.lastname: Bogseth
authors.forename: Kelly
authors.initials: K
authors.lastname: Balla
authors.forename: Paul
authors.initials: P
authors.lastname: Valaitis
authors.forename: Audrey
authors.initials: A
authors.lastname: Hutchcraft
authors.forename: Sabine
authors.initials: S
authors.lastname: Graham
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000008:administration & dosage*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068579:Celecoxib / Q000008:administration & dosage*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007270:Injections, Intra-Articular; D008297:Male; D008863:Microspheres; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D000077212:Ropivacaine; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D016207:Cytokines; D013373:Substance P; D000077212:Ropivacaine; D000068579:Celecoxib