Recent studies indicate that sustained opioid administration produces increased expression of spinal dynorphin, which promotes enhanced sensitivity to non-noxious and noxious stimuli. Such increased " @entity158 " may manifest behaviorally as a decrease in spinal antinociceptive potency. Here, the possibility of similar mechanisms in the antinociception of spinal cannabinoids was explored. Response thresholds to non-noxious mechanical and noxious thermal stimuli were assessed. Antinociception was determined using the 52 degrees C tail-flick test. @entity19 received repeated @entity10024 , its inactive enantiomer, @entity10024 or vehicle (i.th., bid, 5 days). @entity10024 , but not @entity10024 or vehicle, produced a time-related increased sensitivity to non-noxious and noxious stimuli. @entity10024 , but not @entity10024 or vehicle, elicited a significant increase in lumbar spinal dynorphin content at treatment day 5. Increased sensitivity to mechanical and thermal stimuli produced by @entity10024 was reversed to baseline levels by i.th. @entity3390 or dynorphin antiserum; control serum had no effect. @entity10024 , but not @entity10024 or vehicle, produced dose-related antinociception and repeated administration resulted in antinociceptive tolerance. While @entity3390 and dynorphin antiserum did not alter acute antinociception produced by @entity10024 , these substances significantly blocked antinociceptive tolerance when given immediately prior to @entity10024 challenge on day 5. Daily @entity3390 pretreatments, prior to @entity10024 injection, also produced a significant block of antinociceptive tolerance. These data suggest that like opioids, repeated spinal administration of a cannabinoid @entity14650 agonist elicits @entity158 , which results in increased expression of spinal dynorphin. Manipulations that block cannabinoid-induced @entity158 also block the behavioral manifestation of cannabinoid tolerance.

Pronociceptive effects of spinal dynorphin promote cannabinoid-induced XXXX and antinociceptive tolerance.

@entity19 :: ('10090', 'Species') :: ['Mice'] @entity10024 :: ('MESH:C070417', 'Chemical') :: ['WIN 55,212-3', 'WIN 55,212-2'] @entity14650 :: ('12801(Tax:10090)', 'Gene') :: ['CB1'] @entity158 :: ('MESH:D010146', 'Disease') :: ['pain', 'abnormal pain'] @entity3390 :: ('MESH:D016291', 'Chemical') :: ['MK-801']
@entity158 :: (MESH:D010146,Disease) :: ['pain']
