Ondansetron does not block paracetamol-induced analgesia in a mouse model of fracture pain

Abstract

Background: The aim of this study was to assess any interaction between ondansetron and paracetamol on a model of post-fracture pain in mice. Methods: In protocol A, after fracture of the tibia, mice were assigned to four groups: paracetamol 30 mg kg−1, paracetamol 50 mg kg−1, paracetamol 100 mg kg−1, or a saline vehicle i.p. In protocol B, after fracture of the tibia, mice were randomized to receive either paracetamol (100 mg kg−1) plus saline (vehicle), paracetamol (100 mg kg−1) plus ondansetron (1 mg kg−1), paracetamol (100 mg kg−1) plus ondansetron (2 mg kg−1), saline plus ondansetron (2 mg kg−1), or saline plus saline i.p. Three tests were used to assess pain behaviour: von Frey filament application, hot-plate test, and a subjective pain scale. Rescue analgesia with morphine was administered as necessary. Results: In protocol A, paracetamol (100 mg kg−1)-treated animals had less mechanical nociception, thermal nociception, and a lower subjective pain scale rating, when compared with those receiving paracetamol at 30 or 50 mg kg−1 or saline [ED50 paracetamol=46.3 (6.34) mg kg−1]. No difference was found between paracetamol (30 mg kg−1) and saline-treated animals. In protocol B, the mechanical withdrawal threshold, the thermal withdrawal latency, and the subjective pain scale were lower after injection of paracetamol (100 mg kg−1)+saline, paracetamol (100 mg kg−1)+ondansetron (1 mg kg−1), and paracetamol (100 mg kg−1)+ondansetron (2 mg kg−1), whereas in mice receiving saline+ondansetron (2 mg kg−1) or saline+saline, there was no difference. Conclusion: We found that paracetamol 100 mg kg−1 blocked the development of hyperalgesia and allodynia after fracture pain and ondansetron did not modify the antinociceptive effect of paracetamol in this model.