KEY POINTS: Despite the clinical importance of pre-emptive @entity1337 , the mechanisms by which it @entity158 associated with central sensitization are poorly understood. We find that @entity3575 and the a2-adrenoceptor agonist @entity6948 ( @entity9170 ) differ significantly in their modulatory actions on noxious mechanical and noxious heat-evoked nociception in vivo. Unlike @entity3575 , @entity9170 modified descending control of nociception by decreasing the threshold for descending inhibition and/or increasing the threshold for descending facilitation. @entity9170 exhibited after-actions on activities of thalamus in prolongation of noxious heat-evoked paw withdrawal latency that persisted for at least 7  days. This study provides insight into the organization of thalamic modulation in pre-emptive @entity1337 . ABSTRACT: We investigated and compared the antinociceptive effects of intraperitoneal administration of @entity3575 (2-60   g  kg(-1) ) and @entity6948 ( @entity9170 , 1-10   g  kg(-1) ; a highly selective a2-adrenoceptor agonist) in the regulation of nociception assessed by measuring noxious paw withdrawal reflexes in @entity35 . @entity3575 elevated noxious mechanical paw withdrawal threshold and prolonged paw withdrawal heat latency within 1-1.5  h (P  <  0.05). @entity9170 failed to affect the mechanical paw withdrawal threshold, yet significantly prolonged the paw withdrawal heat latency in a bi-phasic manner; a short transient 1-1.5  h period followed by a second, slowly developing increase in latency that persisted for at least 7  days (P  <  0.05). Lesion of the @entity5487 ( @entity5487 ) did not influence @entity3575 -induced antinociceptive effects, indicating peripheral and spinal antinociceptive mechanisms. By contrast, the @entity9170 -induced second, but not the first, phase of the prolonged paw withdrawal heat latency was significantly blocked by the lesion of either @entity5487 or thalamic ventromedial (VM) nuclei, and was attenuated by intracerebral administration of either @entity22571 (a2-adrenoceptor antagonist) or @entity10098 (5-HT1A receptor antagonist) into the VM nuclei (P  <  0.05). Upon intramuscular 5.8% saline-induced @entity925 , pre-emptive injection of @entity3575 enhanced @entity1931 and blocked @entity6167 , whereas @entity9170 significantly prevented the occurrence of @entity1931 and enhanced @entity6167 . It is suggested that @entity9170 , but not @entity3575 , significantly enhances descending inhibition and/or decreases descending facilitation to modulate @entity158 and nociception. The present study provides novel insight into thalamus-mediated mechanisms in pre-emptive @entity1337 .

Pre-emptive @entity1337 and its supraspinal mechanisms: enhanced descending inhibition and decreased descending facilitation by XXXX .

@entity1931 :: ('MESH:D006930', 'Disease') :: ['mechanical hyperalgesia'] @entity9170 :: ('D003907', 'Chemical') :: ['Dex'] @entity1337 :: ('MESH:D000699', 'Disease') :: ['analgesia'] @entity6167 :: ('MESH:D018883', 'Disease') :: ['heat hypoalgesia'] @entity5487 :: ('MESH:D014854', 'Disease') :: ['dorsolateral funiculus', 'DLF'] @entity158 :: ('MESH:D010146', 'Disease') :: ['attenuates pain', 'pain'] @entity10098 :: ('MESH:C090413', 'Chemical') :: ['WAY-100635'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity6948 :: ('MESH:D020927', 'Chemical') :: ['dexmedetomidine'] @entity925 :: ('MESH:D063806', 'Disease') :: ['muscle nociception'] @entity3575 :: ('MESH:D005283', 'Chemical') :: ['fentanyl', 'Fentanyl'] @entity22571 :: ('MESH:C050701', 'Chemical') :: ['atipamezole']
@entity6948 :: (MESH:D020927,Chemical) :: ['dexmedetomidine']
