Tapentadol effects on brain response to pain in sensitized patients with knee osteoarthritis

Objective: Pain sensitization, in the form of knee tenderness and anatomically spread hyperalgesia, is notably common in patients with knee OA and is often refractory to conventional interventions. Tapentadol, as an opioid receptor agonist and noradrenaline reuptake inhibitor, has been proposed as a...

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Bibliographic Details
Authors: Pujol Martí, Jesús, 1981-, Martínez-Vilavella, Gerard, Doreste, Andrea, Blanco Hinojo, Laura, 1981-, Ojeda Morillo, Fabiola Alejandra, Llorente-Onaindia, J., Polino, Luciano, Deus, Joan, Monfort Faure, Jorge
Format: article
Status:Versión aceptada para publicación
Publication Date:2022
Country:España
Institution:Universitat Pompeu Fabra
Repository:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/53692
Online Access:http://hdl.handle.net/10230/53692
http://dx.doi.org/10.1093/rheumatology/keab761
Access Level:Open access
Keyword:Brain activation
Functional MRI
Opioids
Osteoarthritis
Pain sensitization
Sensory cortex
Description
Summary:Objective: Pain sensitization, in the form of knee tenderness and anatomically spread hyperalgesia, is notably common in patients with knee OA and is often refractory to conventional interventions. Tapentadol, as an opioid receptor agonist and noradrenaline reuptake inhibitor, has been proposed as a potentially effective symptomatic treatment for pain-sensitized OA patients. We empirically tested whether tapentadol could attenuate brain response to painful stimulation on the tender knee using functional MRI. Methods: Painful pressure stimulation was applied to the articular interline and the tibial surface, a commonly sensitized site surrounding the joint. Thirty patients completed the crossover trial designed to compare prolonged release tapentadol and placebo effects administered over 14 days. Results: We found no effects in the direction of the prediction. Instead, patients administered with tapentadol showed stronger activation in response to pressure on the tender site in the right prefrontal cortex and somatosensory cortices. The somatosensory effect was compatible with the spread of neural activation around the knee cortical representation. Consistent with the functional MRI findings, the patients showed higher clinical ratings of pain sensitization under tapentadol and a significant positive association was identified between the number of tapentadol tablets and the evoked subjective pain. Conclusion: The tapentadol effect paradoxically involved both the spread of the somatosensory cortex response and a stronger activation in prefrontal areas with a recognized role in the appraisal of pain sensations. Further studies are warranted to explore how OA patients may benefit from powerful analgesic drugs without the associated risks of prolonged use.