title: Spinal neuronal correlates of tapentadol analgesia in cancer pain: a back-translational approach.
abstract: BACKGROUND
  Pain is a common and highly debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of multiple mechanisms including both inflammatory and neuropathic processes and also some unique changes. Strong opioids are a mainstay of treatments but side effects are problematic and can compromise optimal pain control. Tapentadol is a novel dual-action drug, both stimulating inhibitory μ-opioid receptors (MOR) and mediating noradrenaline reuptake inhibition (NRI) leading to activation of the inhibitory α-2 adrenoceptor. It has been demonstrated to treat effectively both acute and chronic pain. We here demonstrate the efficacy in a model of cancer-induced bone pain.
  
  
  METHODS
  MRMT-1 mammary carcinoma cells were inoculated into the tibia of 6-week-old rats and 2 weeks after, the neuronal responses to a wide range of peripheral stimulation were evaluated. The recordings were made from wide-dynamic range neurons in lamina V of the dorsal horn before and after administration of tapentadol as well as antagonists of the two mechanisms, naloxone or atipamezole.
  
  
  RESULTS
  We found marked inhibitions of the neuronal activity with efficacy against mechanical, thermal and electrically evoked activity following tapentadol administration. In addition, the effects of the drug were fully reversible by naloxone and partly by atipamezole, supporting the idea of MOR-NRI dual actions.
  
  
  CONCLUSIONS
  These findings add to the mechanistic understanding of cancer-induced bone pain and support the sparse clinical data indicating a possible use of the drug as a therapeutic alternative for cancer patients with metastatic pain complication.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Falk
authors.forename: R
authors.initials: R
authors.lastname: Patel
authors.forename: A
authors.initials: A
authors.lastname: Heegaard
authors.forename: S
authors.initials: S
authors.lastname: Mercadante
authors.forename: A H
authors.initials: AH
authors.lastname: Dickenson
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000627:therapeutic use; D000698:Analgesia / Q000379:methods; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004594:Electrophysiology / Q000379:methods; D008297:Male; D009369:Neoplasms / Q000150:complications*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D010636:Phenols / Q000494:pharmacology*; D011788:Quality of Life; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D000077432:Tapentadol
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D010636:Phenols; D017450:Receptors, Opioid, mu; D000077432:Tapentadol