The inflammatory response to injury consists of the activation of several protective mechanisms involving different cellular systems. Among the mechanisms and systems that exert their effects rapidly, peptide transmitters released from peripheral endings of primary sensory neurons (evoking neurogenic inflammation) play a major role in the response to tissue injury. Noxious stimuli may directly activate sensory nerves to release proinflammatory neuropeptides. More recently, evidence has accumulated suggesting that indirect mechanisms leading to sensory neuropeptide release are also activated in relevant models of pathophysiological conditions. Tachykinin NK1 and NK2 receptor antagonists reduced the plasma extravasation in the trachea and nasal mucosa and the bronchoconstriction caused by antigen challenge in sensitized guinea-pigs. Blockade of kinin B2 receptors with the selective antagonist HOE-140 had a similar inhibitory effect. The magnitude of the inhibition observed with the kinin receptor antagonist alone was similar to that caused by a combination a tachykinin and kinin receptor antagonists. This suggests activation of a common final pathway by these two groups of mediators. Pharmacological and biochemical evidence suggests that in the airways of sensitized guinea-pigs, kinins released by the anaphylactic reaction stimulate the release of tachykinins from sensory nerves, thus contributing to their proinflammatory action.Key words: kinins, tachykinins, neurogenic inflammation, antigen challenge, airways, nitric oxide.
An isobolographic analysis of the effects of N-methyl-D-aspartate and NK1 tachykinin receptor antagonists on inflammatory hyperalgesia in the rat