Albumin-Oleic Acid Treatment of Spinal Cord Injury Figure 4. Albumin-Oleic Acid Promotes Phasic Inhibition of Early and Late Tibialis Anterior Reflex Activity following SCI. Analysis of the first and second phase of Tibialis Anterior (TA) reflex temporal summation in na¨ıve animals (Fig. 4A) and those with SCI 28 days after T9 spinal contusion (Cont) revealed that the synergistic phasic inhibitory effect of Albumin-Oleic acid produced with the high-frequency electrical conditioning stimulation when normalized to the first phase of the pre-conditioned response was present during both the early and late phases of temporal summation (Fig. 4C), but not in the group treated with Saline (Sal, Fig. 4B) or in na¨ıve animals (Fig. 4A). Furthermore activation of phasic inhibition of absolute integrated TA reflex activity measured during both phases of temporal summation revealed that Alb-OA treatment significantly inhibited nociceptive activity to below the normal value observed in na¨ıve animals during the early phase (Fig. 4D). Statistical analysis was performed with a one-way ANOVA supported by a post-hoc Bonferroni test (* - p,0.05; ** - p,0.01, ***-p,0.001). doi:10.1371/journal.pone.0026107.g004 5-HT supersensitivity which has been implicated as a pathophys- iological mechanism of change in nociception [18] and motor function [17] following SCI. At the lumbar spinal level inhibition of nociceptive TA reflex temporal summation with Alb-OA was reflected also by a decrease in the number of lumbar dorsal horn neurons with phosphorylated NR1 receptors. The NR1 NMDA receptor subtype is present within the dorsal horn [67] and on motoneurones [68], and specific variants of this receptor are upregulated after contusion SCI [69]. Temporal summation of nociceptive flexor reflex activity can be pharmacologically blocked with NMDA antagonists following ischemic SCI [70], and NR1 phosphorylation is related to central spinal sensitisation to noxious stimuli [71]. Importantly the relationship between descending inhibitory systems and reduction of pNR1 activation has been demonstrated recently with the application of monoaminergic agonists following NMDA administration [72], suggesting the hypothesis that increased descending serotoninergic tract function promoted by Alb-OA PLoS ONE | www.plosone.org 9 October 2011 | Volume 6 | Issue 10 | e26107