Venlafaxine and Oxycodone Effects on Human Spinal and Supraspinal Pain Processing : a Randomized Cross-Over Trial

D. LELIC; I. W. D. FISCHER; A. E. OLESEN; C. D. MØRCH; F. G. ARGUISSAIN; J. A. BIURRUN MANRESA; A. DAHAN; A. M. DREWES

European Journal of Neuroscience

Wiley Online Library

Año: 2016 vol. 44 p. 2966 - 2974

1460-9568

Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have alsoshown a pain relieving effect, but for both SNRI and opioids, the specific mode of action in humans remains vague. This studyinvestigated how oxycodone and venlafaxine affect spinal and supraspinal pain processing. Twenty volunteers were included inthis randomized cross-over study comparing 5-day treatment with venlafaxine, oxycodone and placebo. As a proxy of the spinalpain transmission, the nociceptive withdrawal reflex (NWR) to electrical stimulation on the sole of the foot was recorded at the tib-ialis anterior muscle before and after 5 days of treatment. For the supraspinal activity, 61-channel electroencephalogram evokedpotentials (EPs) to the electrical stimulations were simultaneously recorded. Areas under curve (AUCs) of the EMG signals wereanalyzed. Latencies and AUCs were computed for the major EP peaks and brain source analysis was done. The NWR wasdecreased in venlafaxine arm ( P = 0.02), but the EP parameters did not change. Oxycodone increased the AUC of the EPresponse (P = 0.04). Oxycodone also shifted the cingulate activity anteriorly in the mid-cingulate-operculum network (P < 0.01),and the cingulate activity was increased while the operculum activity was decreased (P = 0.02). Venlafaxine exerts its effects onthe modulation of spinal nociceptive transmission, which may reflect changes in balance between descending inhibition anddescending facilitation. Oxycodone, on the other hand, exerts its effects at the cortical level. This study sheds light on how opioidsand SNRI drugs modify the human central nervous system and where their effects dominate.