Diffuse noxious inhibitory controls and nerve injury: restoring an imbalance between descending XXXX inhibitions and facilitations.

@entity1 @entity3160 @entity3974 @entity17087 @entity18891 @entity20708 @entity4480 @entity750 @entity1154 @entity35 @entity5161 @entity1063 @entity22571
Diffuse noxious inhibitory controls (DNICs) utilize descending inhibitory controls through poorly understood brain stem pathways. The @entity1 counterpart, conditioned pain modulation, is reduced in @entity1 with neuropathy aligned with animal data showing a loss of descending inhibitory @entity1063 controls together with a gain of 5-HT3 receptor-mediated facilitations after neuropathy. We investigated the pharmacological basis of @entity17087 and whether it can be restored after neuropathy. Deep dorsal horn neurons were activated by von Frey filaments applied to the hind paw, and @entity17087 was induced by a pinch applied to the ear in @entity5161 -anaesthetized animals. Spinal nerve ligation was the model of neuropathy. Diffuse noxious inhibitory control was present in control @entity35 but abolished after neuropathy. a2 adrenoceptor mechanisms underlie @entity17087 because the antagonists, @entity3160 and @entity22571 , markedly attenuated this descending inhibition. We restored @entity17087 in spinal nerve ligated animals by blocking 5-HT3 descending facilitations with the antagonist @entity3974 or by enhancing @entity1063 modulation through the use of @entity18891 (a @entity1063 reuptake inhibitor, NRI) or @entity20708 ( -opioid receptor agonist and NRI). Additionally, ondansetron enhanced @entity17087 in normal animals. Diffuse noxious inhibitory controls are reduced after peripheral nerve injury illustrating the central impact of neuropathy, leading to an imbalance in descending excitations and inhibitions. Underlying noradrenergic mechanisms explain the relationship between conditioned pain modulation and the use of @entity20708 and @entity4480 (a @entity750 , NRI) in @entity1 . We suggest that pharmacological strategies through manipulation of the @entity1154 system could be used to enhance @entity17087 in @entity1 by blocking descending facilitations with ondansetron or enhancing @entity1063 inhibitions, so possibly reducing chronic pain.
