Pain responses to protease-activated receptor-2 stimulation in the spinal cord of naïve and arthritic rats.

ABSTRACT

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 naïve animals, and an antagonist (GB83) in different models of joint pain. Saline or FLIGRL (10 nmol) were injected intrathecally in naïve 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 µL each) into the right knee joint of male Wistar rats (24 h recovery). Chronic inflammatory joint pain was modelled by intraarticular injection of Freund's complete adjuvant (FCA; 50 µL; 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 µL); 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.