Protease-activated receptor 2 antagonist potentiates analgesic effects of systemic morphine in a rat model of bone cancer pain

Reg Anesth Pain Med. 2015 Mar-Apr;40(2):158-65. doi: 10.1097/AAP.0000000000000211.

Abstract

Background and objectives: Bone cancer pain affects the quality of life of cancer patients. This study was aimed at investigating the analgesic effects of combined therapies with an antagonist of proteinase-activated receptor (PAR) 2 and morphine on pain-related behaviors in a rat model of bone cancer pain.

Methods: Female Wistar rats were inoculated intramedullarily with Walker 256 cells into their tibias. The analgesic effects of intraperitoneal treatment with morphine and/or intrathecal with the PAR2 antagonist, FSLLRY-NH2, on bone cancer pain-related behaviors in rats were examined.

Results: Treatment with morphine at 3 or 10 mg/kg significantly improved limb-use and weight-bearing scores and reduced the number of spontaneous flinches in rats. Treatment with FSLLRY-NH2 at 10 mmol/L also significantly improved limb use and weight bearing scores, and reduced the number of spontaneous flinches in rats. Combination a sub-analgesic dose of FSLLRY-NH2 (0.1 mmol/L) and morphine further elevated limb-use and weight-bearing scores and reduced the number of flinches compared with the effects of morphine alone in rats.

Conclusions: Our data indicate that the combination of morphine and FSLLRY-NH2 has potent analgesic effects on bone cancer pain and our findings may aid in design of new strategies for the treatment of bone cancer pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Bone Neoplasms / complications*
  • Carcinoma 256, Walker
  • Drug Synergism
  • Female
  • Injections, Intraperitoneal
  • Morphine / pharmacology*
  • Neoplasm Transplantation
  • Oligopeptides / therapeutic use*
  • Pain Measurement
  • Pain, Intractable / drug therapy*
  • Rats
  • Rats, Wistar
  • Receptor, PAR-2 / antagonists & inhibitors*

Substances

  • Analgesics, Opioid
  • H-Phe-Ser-Leu-Leu-Arg-Tyr-NH2
  • Oligopeptides
  • Receptor, PAR-2
  • Morphine