The ventral tegmental area (VTA) and the rostromedial tegmental nucleus (RMTg) each contribute to opiate reward and each receive inputs from the laterodorsal tegmental and pedunculopontine tegmental nuclei, the two principle brainstem cholinergic cell groups. We compared the contributions of VTA or RMTg muscarinic cholinergic receptors to locomotion induced by morphine infusions into the same sites. VTA co-infusion of atropine completely blocked VTA morphine-induced locomotion providing additional support for the important role of VTA muscarinic cholinergic receptors in the stimulant effects of opiates. By contrast, RMTg co-infusion of atropine increased RMTg morphine-induced locomotion. Furthermore, RMTg co-infusion of the M3-selective antagonist 4-DAMP, but not the M4-selective antagonist Tropicamide, strongly increased RMTg morphine-induced locomotion. RMTg infusions of 4-DAMP, but not of Tropicamide, by themselves strongly increased drug-free locomotion. Muscarinic cholinergic receptors in the RMTg thus also contribute to the stimulant effects of morphine, but in a way opposite to those in VTA. We suggest that the net effect of endogenous cholinergic input to the RMTg on drug-free and on RMTg morphine-induced locomotion is inhibitory.
Summary of Background Data. The impact of not achieving ideal realignment in the global alignment and proportion (GAP) score in adult spinal deformity (ASD) correction on clinical outcomes is understudied at present. Objective. To identify the clinical impact of failing to achieve GAP proportionality in ASD surgery. Study Design. Retrospective cohort. Methods. Operative ASD patients with fusion to S1/pelvis and with pre-(BL) and 2-year (2Y) data were included. Patients were assessed for matching their 6-week (6W) age-adjusted alignment goals.1 Patients were stratified by age-adjusted match at 6W postoperatively (Matched) and 6W GAP proportionality (proportioned: GAP-P; moderately disproportioned: GAP-MD; severely disproportioned: GAP-SD). Groups were assessed for differences in demographics, surgical factors, radiographic parameters, and complications occurring by 2Y. Multivariable logistic regression was used to assess independent effects of not achieving GAP proportionality on postoperative outcomes for Matched and Unmatched patients. Results. Included: One hundred twenty three ASD patients. At baseline, 39.8% were GAP-SD, and 12.2% GAP-SD at 6W. Of 123 patients, 51.2% (n =63) had more than or equal to one match at 6W. GAP-SD rates did not differ by being Matched or Unmatched (P = 0.945). GAP-SD/Unmatched patients had higher rates of reoperation, implant failure, and PJF by 2Y postop (all P <0.05). Regressions controlling for age at BL, levels fused, and CCI, revealed 6W GAP-SD/Unmatched patients had higher odds of reoperation (OR: 54 [3.2–899.9]; P =0.005), implant failure (OR: 6.9 [1.1–46.1]; P =0.045), and PJF (OR: 30.1 [1.4–662.6]; P =0.031). Compared to GAP-P or GAP-MD patients, GAP-SD/ Matched patients did not have higher rates of reoperation, implant failure, or junctional failure (all P >0.05). The regression results for both Matched and Unmatched cohorts were consistent when proportionality was substituted by the continuous GAP score. Conclusion. In ASD patients who meet age-adjusted realignment goals, GAP proportionality does not significantly alter complication rates. However, GAP proportionality remains an important consideration in patients with sub-optimal age- adjusted alignment. In these cases, severe global disproportion is associated with higher rates of reoperation, implant failure, rod fracture, and junctional failure.
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