Abstract
Introduction
Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat severe and moderate pain, but for both of them the mechanisms in humans remain unclear. This study aimed to explore how oxycodone (opioid) and venlafaxine (SNRI) modulate spinal and supraspinal sensory processing.
Methods
Twenty volunteers were included in this randomized, double blinded, three-way (placebo, oxycodone, venlafaxine), cross-over study. Spinal and full scalp cortical evoked potentials (EPs) to median nerve stimulation were recorded before and after five days of treatment. Assessment of central effects of the three treatments involved: 1) amplitudes and latencies of spinal EPs (spinal level), 2) amplitudes and latencies of the P14 potential (subcortical level), 3) amplitudes and latencies of early and late cortical EPs (cortical level), 4) brain sources underlying early cortical EPs and 5) brain networks underlying the late cortical EPs.
Results
In the venlafaxine arm, the spinal P11 and the late cortical N60-80 latencies were reduced by 1.8%(95%CI:1.7,1.9%) and 5.7%(95%CI:5.3,6.1%), whereas the early cortical P25 amplitude was decreased by 7.1%(95%CI:6.1,8.7%). Oxycodone increased the sub-cortical P14 (+25%(95%CI:22.2,28.6%)), early cortical N30 (+12.9%(95%CI:12.5,13.2%)) amplitudes and the late cortical N60-80 latency (+2.9%(95%CI:1.9,4.0%)). The brainstem and primary somatosensory cortex source strengths were increased by 66.7%(95%CI:62.5,75.0%) and 28.8%(95%CI:27.5,29.6%) in oxycodone arm, whereas the primary somatosensory cortex strength was decreased in venlafaxine arm by 18.3%(95%CI:12.0,28.1%).
Conclusions
Opioids and SNRI drugs exert different central effects. This study contributes to the much needed human models of the mechanisms of drugs with effects on the central nervous system.
Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat severe and moderate pain, but for both of them the mechanisms in humans remain unclear. This study aimed to explore how oxycodone (opioid) and venlafaxine (SNRI) modulate spinal and supraspinal sensory processing.
Methods
Twenty volunteers were included in this randomized, double blinded, three-way (placebo, oxycodone, venlafaxine), cross-over study. Spinal and full scalp cortical evoked potentials (EPs) to median nerve stimulation were recorded before and after five days of treatment. Assessment of central effects of the three treatments involved: 1) amplitudes and latencies of spinal EPs (spinal level), 2) amplitudes and latencies of the P14 potential (subcortical level), 3) amplitudes and latencies of early and late cortical EPs (cortical level), 4) brain sources underlying early cortical EPs and 5) brain networks underlying the late cortical EPs.
Results
In the venlafaxine arm, the spinal P11 and the late cortical N60-80 latencies were reduced by 1.8%(95%CI:1.7,1.9%) and 5.7%(95%CI:5.3,6.1%), whereas the early cortical P25 amplitude was decreased by 7.1%(95%CI:6.1,8.7%). Oxycodone increased the sub-cortical P14 (+25%(95%CI:22.2,28.6%)), early cortical N30 (+12.9%(95%CI:12.5,13.2%)) amplitudes and the late cortical N60-80 latency (+2.9%(95%CI:1.9,4.0%)). The brainstem and primary somatosensory cortex source strengths were increased by 66.7%(95%CI:62.5,75.0%) and 28.8%(95%CI:27.5,29.6%) in oxycodone arm, whereas the primary somatosensory cortex strength was decreased in venlafaxine arm by 18.3%(95%CI:12.0,28.1%).
Conclusions
Opioids and SNRI drugs exert different central effects. This study contributes to the much needed human models of the mechanisms of drugs with effects on the central nervous system.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | British Journal of Clinical Pharmacology |
| Vol/bind | 83 |
| Udgave nummer | 4 |
| Sider (fra-til) | 764-776 |
| Antal sider | 13 |
| ISSN | 0306-5251 |
| DOI | |
| Status | Udgivet - apr. 2017 |