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.
Minville
V
V
Department of Anaesthesiology and Intensive Care, Toulouse University Hospital, Toulouse, France. minville.v@chu-toulouse.fr
Fourcade
O
O
Mazoit
J X
JX
Girolami
J P
JP
Tack
I
I
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