A XXXX (NK1) antagonist enhances the widespread osteoporotic effects of sciatic nerve section.

@entity3604 @entity604 @entity170 @entity16325 @entity26957 @entity128 @entity79 @entity35
The long-term effects of sciatic nerve section on @entity79 ( @entity79 ) were studied using dual-energy X-ray absorptiometry (DEXA) in skeletally mature @entity35 . Unilateral sciatic neurectomy caused the rapid loss of cancellous bone in the proximal and distal femur and tibia in the ipsilateral hindlimb and, to a lesser extent, in the contralateral intact hindlimb. The reduction in @entity79 rapidly progressed for 4 weeks after sciatic section and then gradually stabilized with no evidence of recovery at 12 weeks. The development of @entity170 in the contralateral intact hindlimb was a novel finding. There was no evidence of disuse in the normal contralateral hindlimb after unilateral sciatic section; grid-crossing activity over a 24-h interval was unchanged and there was no reduction in weight bearing on the contralateral normal hindpaw during the stance phase of ambulation. Unilateral peripheral nerve lesions have well-documented effects on substance P content and function in the corresponding contralateral intact nerve. We hypothesized that after sciatic section a reduction in substance P signaling might contribute to @entity604 in the contralateral hindlimb. Daily administration of the @entity16325 (NK1) antagonist @entity26957 for 2 weeks caused significant loss of cancellous bone in the denervated and the contralateral hindlimb, evidence that substance P signaling sustained bone density after nerve section. After sciatic neurectomy there was a 33% reduction in sciatic nerve stimulation-evoked extravasation in the contralateral intact hindlimb, indicating transmedian inhibition of substance P signaling after @entity128 . Furthermore, there was a 50% reduction in the substance P content in both tibias after unilateral sciatic section. Collectively, these data support the hypothesis that a widespread reduction in substance P content in bone contributes to the @entity3604 and that residual substance P signaling maintains bone integrity after nerve section in both the denervated and contralateral intact hindlimb.
