Pain Responses to Protease-Activated Receptor-2 Stimulation in the Spinal Cord of Naive and Arthritic Rats

F Lucena, JJ McDougall

Departments of Pharmacology and Anesthesia, Dalhousie University, Halifax, Canada

Neuroscience Letters

There is strong evidence showing that the activation of peripheral proteinase-activated receptors type 2 (PAR-2) can initiate hyperalgesic and inflammatory responses in the joint. However, to date, there is no report of functional spinal PAR-2 receptors in arthritis models. The primary aim of this study was to evaluate the activity of PAR-2 receptors at the spinal cord by using a potent agonist (FLIGRL) in na•ve animals, and an antagonist (GB83) in different models of joint pain. Saline or FLIGRL (10_nmol) were injected intrathecally in na•ve animals and nociceptive behaviour was evaluated over a 24_h time period by von Frey hair algesiometry. Paw withdrawal threshold decreased from 3 to 24_h and this allodynic effect was blocked by GB83 (90_nmol; i.p.). Acute inflammatory joint pain was induced by injecting 0.5% kaolin/carrageenan (50_microL each) into the right knee joint of male Wistar rats (24_hr recovery). Chronic inflammatory joint pain was modelled by intraarticular injection of FreundÕs complete adjuvant (FCA; 50_microL; 7 days recovery) or chronic osteoarthritis pain by sodium monoiodoacetate (MIA; 3_mg; 14 days recovery). Animals were then treated with either intrathecal vehicle or 10_nmol of GB83 (10_microL); joint pain was evaluated throughout the subsequent 3_h period. The acute inflammatory pain induced by kaolin/carrageenan was not affected by treatment with GB83. Conversely, both chronic arthritis models demonstrated increased hind paw withdrawal threshold after spinal injection of the PAR-2 antagonist. Based on these results, spinal PAR-2 receptors are involved in joint nociceptive processing in chronic but not acute arthritic conditions.

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