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


CONCLUSIONS
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.
Department of Anaesthesiology and Intensive Care, Toulouse University Hospital, Toulouse, France. minville.v@chu-toulouse.fr
V
V
Minville
O
O
Fourcade
J X
JX
Mazoit
J P
JP
Girolami
I
I
Tack
D000082:Acetaminophen / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017294:Ondansetron / Q000494:pharmacology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D013978:Tibial Fractures / Q000150:complications*
D018712:Analgesics, Non-Narcotic; D000932:Antiemetics; D012702:Serotonin Antagonists; D000082:Acetaminophen; D017294:Ondansetron