Pain
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Inflammation enhances release of neuropeptides from sensory nerve terminals in the spinal cord, and this may contribute to the development of hyperalgesia. In a similar manner, proinflammatory prostaglandins also augment peptide release from sensory neurons. To ascertain whether the inflammation-induced increase in peptide release from spinal cord slices is mediated by production of these eicosanoids, we examined whether intrathecal administration of nonsteroidal antiinflammatory drugs (NSAIDS) could attenuate the effects of inflammation. ⋯ Systemic administration of the same amount of ketorolac did not attenuate the effect of inflammation on peptide release. Intrathecal administration of 16 nmol/h (S)-ibuprofen, before and throughout the inflammation, also significantly attenuated the increase in evoked neuropeptide release associated with inflammation, whereas (R)-ibuprofen was ineffective. These results suggest that inhibition of cyclooxygenase at the level of the spinal cord attenuates the augmentation of neuropeptide release induced by peripheral inflammation, and provide further evidence for an action of prostaglandins at central terminals of sensory neurons during inflammation.
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The present study was undertaken to examine the involvement of descending pain modulatory systems from the brainstem rostral ventromedial medulla (RVM) in modulating visceral hyperalgesia produced by intracolonic instillation of zymosan. Three hours after intracolonic zymosan, the visceromotor response (VMR) to noxious colorectal distension (CRD, 80 mmHg, 20s) was increased significantly. This hyperalgesia was attenuated in a dose-dependent manner by the selective NMDA receptor antagonist APV (10-30 fmol, 1 microl) microinjected into the RVM. ⋯ In contrast to the effects of APV and L-NAME, administration of the non-NMDA receptor antagonist DNQX into the RVM further enhanced the already facilitated VMR to CRD in zymosan-treated rats. Taken together, these data suggest that zymosan-produced visceral hyperalgesia is influenced by two descending pain modulatory systems: a facilitatory system mediated by activation of NMDA receptors in the RVM and production of nitric oxide, and an inhibitory system mediated by activity at non-NMDA receptors in the RVM. The unmasking of one system by selective blockade of the other suggests simultaneous activation of both by colonic inflammation.