Influence of tapentadol and oxycodone on the spinal cord and brain using electrophysiology: a randomized, placebo‐controlled trial

AIMS: The aim of this study was to investigate the effects of tapentadol and oxycodone using the nociceptive withdrawal reflex and sensory evoked potentials. METHODS: Twenty‐one healthy volunteers completed a cross‐over trial with oxycodone (10 mg), tapentadol (50 mg) extended‐release tablets, or placebo treatment administered orally BID for 14 days. Electrical stimulations were delivered on the plantar side of the foot to evoke a nociceptive withdrawal reflex at baseline and post‐interventions. Electromyography, recorded at tibialis anterior, and electroencephalography were recorded for analysis of: number of reflexes, latencies, and area under the curve of the nociceptive withdrawal reflex as well as latencies, amplitudes and dipole sources of the sensory‐evoked potential. RESULTS: Tapentadol decreased the odds ratio of eliciting nociceptive withdrawal reflex by −0.89 (P = .001, 95% confidence interval [CI] −1.46, −0.32), whereas oxycodone increased the latency of the N1 component of the sensory‐evoked potential at the vertex by 12.5 ms (P = .003, 95% CI 3.35, 21.69). Dipole sources revealed that the anterior cingulate component moved caudally for all three interventions (all P < .02), and the insula components moved caudally in both the oxycodone and tapentadol arms (all P < .03). CONCLUSION: A decrease in the number of nociceptive withdrawal reflex was observed during tapentadol treatment, possibly relating to the noradrenaline reuptake inhibition effects on the spinal cord. Both oxycodone and tapentadol affected cortical measures possible due to μ‐opioid receptor agonistic effects evident in the dipole sources, with the strongest effect being mediated by oxycodone. These findings could support the dual effect analgesic mechanisms of tapentadol in humans as previously shown in preclinical studies.