Figure 1.
(A) MIA Sensitization timeline with recording on a single day between 14–17 days post injection (B) Protocol on the day of recording. Black arrows denote time points at which dried blood spot samples were taken for drug exposure measurement.
Table 1.
Assay Capability Tool.
Table 2.
Assay Capability Tool applied to the joint rotation assay.
Figure 2.
Spinal cord neuron responses to knee joint rotation.
For each of (A), (B) and (C) the top trace shows the rotation stimulus set with rotation angle increasing in 20 degree steps and extending at least 40 degrees above the tonic firing threshold. The middle trace shows the PSTH of the response to the rotation set. White arrow denotes phasic threshold, black arrow denotes tonic threshold and bin width = 0.05 ms. The bottom trace shows the neural waveform during the joint rotation stimulus set. (A) Response from a cell showing no ongoing spike activity and high response threshold (B) A cell showing little ongoing spike activity, low threshold and extended firing after stimulus offset (C) A cell showing high ongoing spike activity with a low response threshold.
Figure 3.
Effects of oxycodone on spinal dorsal horn neuronal activity.
Each row shows the results for an exploratory endpoint with ANCOVA adjusted means on the left (error bars ± sem) and the ratios of adjusted means for oxycodone/saline on the right (error bars ±95%CI). Ratio graphs focus on 0, 30, 60 and 90 minutes, the time points at which a following cohort of animals was determined to have (mean±sem) 0±0 nM, 44±6 nM, 217±24 nM and 70±12 nM free plasma concentration of oxycodone respectively. The 90 minute time point is after a 30 minute infusion of 20 mg/kg/hr naloxone with no oxycodone infused. (A) tonic spike count during the six seconds following phasic spiking (B) phasic spiking during the first one second after rotation onset (C) ongoing activity quantified during the 120 seconds preceding each stimulus set (D) afterdischarge during the 120 seconds following the last rotation of each set.
Figure 4.
Effects of naproxen on spinal dorsal horn neuronal activity.
Each row shows the results for an exploratory endpoint with ANCOVA adjusted means on the left (error bars ± sem) and the ratios of adjusted means for naproxen/saline on the right (error bars ±95%CI). Ratio graphs focus on 0, 30, and 60 minutes, the time points at which these animals were determined to have (mean±sem) 0±0 nM, 165±28 nM and 697±45 nM free plasma concentration of naproxen respectively and 90 minutes which is after 30 minutes of no infusion resulting in 567±34 nM free plasma concentration. (A) tonic spike count during the six seconds following phasic spiking (B) phasic spiking during the first one second after rotation onset (C) ongoing activity quantified during the 120 seconds preceding each stimulus set and (D) afterdischarge during the 120 seconds following the last rotation of each set.