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Lymphocyte opioid receptors as innovative biomarkers of osteoarthritic pain, for the assessment and risk management of opioid tailored therapy, before hip surgery, to prevent chronic pain and opioid tolerance/addiction development: OpMarkArt (Opioids-Markers-Arthroprosthesis) study protocol for a randomized controlled trial.

  • Malafoglia, Valentina1
  • Celi, Monica2
  • Muscoli, Carolina3
  • Ilari, Sara4
  • Lauro, Filomena4
  • Giancotti, Luigino Antonio4
  • Morabito, Chiara5
  • Feola, Maurizio2
  • Tarantino, Umberto2
  • Raffaeli, William6
  • 1 Institute for Research on Pain, ISAL Foundation, Torre Pedrera, RN, Italy. [email protected] , (Italy)
  • 2 Policlinico Foundation Tor Vergata, University of Tor Vergata, Rome, Italy. , (Italy)
  • 3 Institute of Research for Food Safety & Health (IRC_FSH), Department of Health Sciences, University 'Magna Graecia' of Catanzaro, Catanzaro, Italy. , (Italy)
  • 4 San Raffaele Roma S.r.l., Roccelletta di Borgia, Catanzaro, Italy. , (Italy)
  • 5 Department of Experimental Medicine, 'Sapienza' University of Rome, Rome, Italy. , (Italy)
  • 6 Institute for Research on Pain, ISAL Foundation, Torre Pedrera, RN, Italy. , (Italy)
Published Article
Springer (Biomed Central Ltd.)
Publication Date
Dec 19, 2017
DOI: 10.1186/s13063-017-2363-z
PMID: 29258584


The incidence of post-surgical chronic pain ranges between 20% and 40% in Europe. Osteoarthritis pain after prosthesis implantation is one of the most severe secondary syndromes, depending not only on surgery but also on organic changes before and after joints replacement. No data are available about risk factors. An excessive inflammatory response plays a central role but a best therapy is not defined yet. It is not clear whether opioid administration could influence post-surgical pain and lead to tolerance or addiction. Interestingly, the immune system, together with the nervous and peptidergic ones, is involved in hypersensibility. The connection across the three biological systems lies in the presence of opioid receptors on immune cells surface. Here, we show a method to analyze whether opioids could modulate lymphocytes, by proposing opioid receptors as biological markers to prevent chronic pain and opioid tolerance or addiction after hip surgery. After institutional independent ethics committee approval, 60 patients, in pain and undergoing hip surgery, will be enrolled in a single-blind, randomized, phase IV, pilot study. Pain treatment will be selected inside a class of non-steroidal anti-inflammatory drugs (NAISDs) or paracetamol or a class of opioids, into three medication arms: 25 mg tapentadol twice daily; 75 mg tapentadol twice daily; NSAIDs or paracetamol in accordance with surgeon's custom. For each group, we will collect blood samples before, during and after surgery, to apply molecular analysis. We will perform lymphocyte opioid receptors genes and proteins expression and functional analysis. Data will be statistically analyzed. This project has the potential to obtain a personalized diagnostic kit, by considering lymphocyte opioid receptors as biological markers. Starting from a simple blood sample, it will be possible to decide the best therapy for a single patient. Using a noninvasive approach, we expect to fix a daily standard dose and timing, before and after surgery, to bypass hip chronic pain and the insurgence of tolerance or addiction. The analysis of opioid receptors sensitivity will help to identify the best drug administration in each specific case (tailored therapy). ISRCTN, ISRCTN12559751 . Retrospectively registered on 23 May 2017.

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