Abstract
The mechanisms underlying endotoxin-induced hyperalgesia remain unknown. We aimed to study the mechanisms underlying the sensitizing action of lipopolysaccharide (LPS) on intestinal afferent responses to mechanical and chemical stimuli. Extracellular recordings of jejunal afferent nerve discharge were obtained from pentobarbitone-anaesthetized rats. Lipopolysaccharide (6 mg kg(-1), i.v.) stimulated a short-term, transient (<30 min) increase in chemosensitivity to systemic 5-HT (6 microg kg(-1)) and responses to mechanical distension and a delayed but maintained (>30 min) increase in spontaneous afferent discharge. Naproxen (10 mg kg(-1)) and the prostaglandin receptor antagonist AH6809 (1 mg kg(-1)) significantly attenuated both the short-term sensitization to mechanical distension and 5-HT and the long-term increase in baseline afferent firing following LPS. In contrast, the iNOS inhibitor aminoguanidine (15 mg kg(-1)) and the L-type calcium channel antagonist nifedipine (1 mg kg(-1)) both prolonged the period of afferent sensitization to distension and 5-HT without influencing the augmented baseline-firing rate. omega-Conotoxin GVIA attenuated the increase in afferent discharge to LPS, without any change in mechano- and chemosensitivity. The long-term (>30 min) increase in afferent firing following systemic LPS involves neurogenic release of prostanoids. The short-term (<30 min) sensitization also appears to depend on prostanoid release, while nitric oxide production may serve to down-regulate LPS-induced afferent hypersensitivity.
Published Version
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