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

Abstract

Objective Pain sensitization, in the form of knee tenderness and anatomically spread hyperalgesia, is notably common in patients with knee osteoarthritis 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 osteoarthritis patients. We empirically tested whether tapentadol could attenuate brain response to painful stimulation on the tender knee using functional MRI. Methods Pressure painful 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 osteoarthritis patients may benefit from powerful analgesic drugs without the associated risks of prolonged use. EudraCT-[2016–005082-31].

Effects of remifentanil on brain responses to noxious stimuli during deep propofol sedation

“…31 Brain activation in this group includes all relevant brain structures processing the sensorydiscriminative, emotional-affective, and cognitive-evaluative components of pain. The pattern is consistent with previous evidence from our group, 12,32 meta-analyses and reviews, 8,10,11 and multivariate pattern analyses. 33,34 Brain activation at low doses involved the sensorimotor cortex at the level of the thumb cortical representation, supplementary motor area, and anterior cingulate cortex.…”

“…The largest effect of intense focal pressure is to stimulate mechanical nociceptors in peripheral nerves 41 and activate the relevant pain-related areas in the brain. 12,32,42 Therefore, a large response suppression might be expected when high doses of a potent opioid 43 are used. In contrast, brain responses to less selective stimuli might be only partially eliminated.…”

Distinctive alterations in the functional anatomy of the cerebral cortex in pain-sensitized osteoarthritis and fibromyalgia patients

“…Differences in the response to treatments further support distinct pathophysiological mechanisms for pain sensitization in both situations. For example, anti-in ammatory drugs are analgesic in osteoarthritis through the inhibition of nociceptive sensitization [73,74], whereas opioids, powerful analgesic agents, may paradoxically favor pain sensitization [19], presumably by promoting the release of in ammatory mediators in the nervous system [75]. In bromyalgia, conventional analgesic/anti-in ammatory drugs are generally not effective [76].…”

“…Sample selection and inclusion criteria have been previously described [2,18,19]. In short, the included osteoarthritis patients showed a radiological and clinical diagnosis of knee osteoarthritis based upon the American Rheumatism Association criteria [20] and pain sensitization affecting the knee de ned by combining clinical and experimental (pain thresholds) evidence (see below) [2,19].…”

“…Sample selection and inclusion criteria have been previously described [2,18,19]. In short, the included osteoarthritis patients showed a radiological and clinical diagnosis of knee osteoarthritis based upon the American Rheumatism Association criteria [20] and pain sensitization affecting the knee de ned by combining clinical and experimental (pain thresholds) evidence (see below) [2,19]. Fibromyalgia patients met the American College of Rheumatology criteria for bromyalgia [21] and were consecutively recruited during clinical follow-up to make up a homogeneous sample with severe and durable symptoms [18].…”