Prolonged alteration of vasoconstrictor and vasodilator responses in rat knee joints by adjuvant monoarthritis

Abstract

SUMMARYBoth neurogenic influences and the regulatory neuropeptide substance P (SP) have been implicated in the development of joint inflammation. Using the laser Doppler perfusion imaging technique to quantify relative changes in joint blood flow, the effects of nerve stimulation and topical SP application were examined in normal and chronically inflamed rat knee joints. Synovial inflammation was induced by unilateral intra-articular injection of Freund's complete adjuvant and experiments were carried out 1 week and 3 weeks later. Normal knees showed a frequency-dependent vasoconstriction in response to saphenous nerve stimulation over the range of 5-30 Hz and a dose-dependent vasodilatation in response to SP administration. These vasoactive responses were completely abolished in the chronically inflamed knee joint, the abolition persisting throughout the investigation. Since articular cartilage is critically dependent on synovial fluid formation for its nutrition, loss of neurovascular control of the synovial microcirculation could contribute to the degenerative changes that commonly accompany chronic inflammatory joint diseases.

Effects of Adrenoceptor Antagonists on the Cutaneous Blood Flow Increase Response to Sympathetic Nerve Stimulation in Rats with Persistent Inflammation.

“…Along the same line as the present observation, McDougall et al reported the vasoconstriction response to electrical stimulation of sympathetic or saphenous nerves was diminished in rats with CFA-induced knee joint inflammation [13,14]. The vasoconstriction response to SS was reduced in rats with carrageenan inflammation as well [15].…”

“…The vasoconstriction response to electrical stimulation of the sympathetic or saphenous nerve was diminished in a model of chronic inflammation induced by complete Freund's adjuvant (CFA) in rats [13,14]. Lam and Ferrell also reported the vasoconstriction response to electrical stimulation of the sympathetic nerve was reduced in carrageenan inflammation rats [15].…”

Calcium channel blockers attenuate chronic inflammation in rat knee joints

“…This procedure is an accepted model for induction of chronic inflammations that produce rheumatoid arthritis like inflammatory reactions in human (Morgan et al, 1978;McDougall et al, 1995).…”

“…Finally, the animals were humanely killed by the high dose of urethane. The blood flow of biological zero level (BZL) of joint's tissue were recorded to subtract from the measured level during the experiment (McDougall et al, 1995).…”

Substance P Is Involved in the Cutaneous Blood Flow Increase Response to Sympathetic Nerve Stimulation in Persistently Inflamed Rats

“…For example, Lundberg et al reported that electrical stimulation of the sympathetic nerve caused cutaneous vasodilatation in patients with obstructive vascular disease [5]. McDugall et al reported that the vasoconstriction response to electrical stimulation of sympathetic or saphenous nerves was diminished in rats with complete Freund's adjuvant (CFA)-induced knee joint inflammation [6,7]. Reduced vasoconstriction response to sympathetic nerve stimulation was also observed in rats with carrageenan inflammation [8].…”