behavior/neurological
• mutants showed a 50% reduction in the activity-dependent facilitation ("wind-up") of a spinal nociceptive reflex evoked by electrical stimulation of afferent nociceptive fibers
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• intradermal injection of capsaicin (1.6 mg), which activates polymodal nociceptors responding to heat, evoked diminished nocifensive behaviors in mutant mice relative to wild-type
• intradermal injection of formalin (2.5%), evoked significantly reduced nocifensive behaviors in the early and late phase of the model
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hypoalgesia
(
J:63271
)
• in the hot plate assay, mutant mice exhibited marked hypoalgesia in response to mildly painful heat stimuli (52.5 and 55.5C); no difference was observed with more painful stimuli (58.5C)
• in the tail-flick assay, mutants displayed normal acute nociception in response to a noxious heat stimulus relative to wild-type
• in addition, the noxious heat sensitivity of two functional classes of isolated nociceptors (differentiated by their IB4 binding) appeared normal
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immune system
• in the carrageenan-induced pleurisy model, invasion of polymorphonuclear leukocytes into inflamed tissue was markedly reduced; in contrast, endothelial permeabilization and mononuclear cell infiltration appeared unaffected
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• mice exhibit a partially attenuated hypotensive response to LPS compared to wild-type mice
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cardiovascular system
N |
• homozygous mutant mice were viable, fertile and normotensive
• notably, homozygotes displayed a significant reduction in the hypotensive response to lipopolysaccharide injection (a model for sepsis) during the first 35 min but not thereafter
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