In anaesthetized spinal cats, the release of immunoreactive substance P in the spinal cord during development of an acute inflammation in one knee joint was studied with antibody microprobes. The microprobes bore antibodies directed to the C- or N-terminus of substance P. With the normal knee joint, innocuous mechanical stimuli (flexion, pressure) did not result in spinal release of immunoreactive substance P. Following injection of kaolin and carrageenan into a knee, evidence for release of substance P following joint stimulation was found in 7 of 10 cats. Such release did not occur for several hours after joint injection and was detected predominantly in the superficial dorsal horn, the dorsal columns and at the dorsal surface of the spinal cord. In some experiments release was detected in the deep dorsal horn and upper ventral horn. Release of immunoreactive substance P required periods of mechanical stimulation such as flexion of, or pressure to, the inflamed joint. The failure to detect central release of substance P from stimulation of normal joints, and the release of substance P, after a delay, from inflamed joints, suggest that the fibres releasing this compound require sensitization by inflammatory mediators before they are excited by joint stimuli.
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