Peripheral Neurokinin-1 Receptors Contribute to Kaolin-Induced Acute Monoarthritis in Rats

Abstract

Objective: intra-articular co-injection of kaolin with carrageenan (CGN) in rodents is widely used as an experimental model of arthritis. However, the ability of kaolin to cause arthritis and related immune responses when administered alone is unclear. We evaluated the contribution of prostanoids and sensory C-fibres (and their neuropeptide substance P) to kaolin-induced inflammation in the rat knee. Methods: Wistar rats, 8-10 weeks old, received an intra-articular injection of kaolin (1-10 μg/joint) or saline into the knee joint. Knee inflammation, proinflammatory cytokines, pain behaviour and secondary tactile allodynia were assessed over 5 h, when synovial leukocyte counts, histopathological changes and proinflammatory cytokine levels were evaluated. Results: The intra-articular injection of kaolin caused a dose- and time-dependent knee swelling and impairment of motion that were associated with secondary tactile allodynia, elevated concentrations of IL-1β, IL-6 and TNFα, leukocyte infiltration, and histopathological changes in the ipsilateral hindpaw. The neurokinin-1 (NK₁) receptor antagonist SR140333 or neonatal treatment with capsaicin markedly reduced the inflammatory parameters, cytokines and allodynia but failed to significantly inhibit the impaired motion. The cyclo-oxygenase inhibitor indomethacin partially inhibited knee oedema and allodynia but did not affect the leukocyte influx, myeloperoxidase activity or impaired motion in the kaolin-injected rat. Conclusions: We show the first evidence that intra-articular injection of kaolin without CGN produced severe acute monoarthritis. This was highly dependent on substance P (released from C-fibres) and NK₁ receptor activation, which stimulated local production of proinflammatory cytokines. This model may be of critical importance for mechanistic studies and screening new anti-inflammatory/analgesic drugs.

Genoprotective, antioxidant, antifungal and anti-inflammatory evaluation of hydroalcoholic extract of wild-growing Juniperus communis L. (Cupressaceae) native to Romanian southern sub-Carpathian hills

“…The kaolin induced inflammation model lead to the increase of proinflammatory cytokines e.g. f IL-1β, IL-6 and TNFα [ 55 ]. Studies showed that flavonoids [ 56 , 57 ] and quercitin [ 58 , 59 ] downregulates the expression of proinflammatory cytokines.…”

Transmission pathways and mediators as the basis for clinical pharmacology of pain

“…Studies have shown that administration of NK1 receptor antagonists decrease pain sensation in rats with induced monoarthritis [176, 177]. Uematsu et al [176] induced inflammation in rats, then conducted histological analysis of rodent cartilage.…”

“…Research suggests that pain transmission pathways may play a significant role in this process. For example, neurokinin has been shown to both decrease inflammatory pain and joint cartilage destruction in rats [176, 177]. Preventing joint destruction in this case may also prevent osteoarthritis-related pain.…”