Preclinical comparison of antinociceptive effects between ibuprofen, diclofenac, naproxen, and acetaminophen on acid-stimulated body stretching and acid-depressed feeding behaviors in rats

Behav Pharmacol. 2022 Dec 1;33(8):567-574. doi: 10.1097/FBP.0000000000000704. Epub 2022 Oct 18.


Pain is a major problem that burdens the health and economy of societies worldwide. Nonsteroidal anti-inflammatory drugs (NSAIDs) are over-the-counter medications that are widely indicated for mild to moderate pain conditions. Clinically, the selection of a medication among this class is mainly based according to both patient's and doctor's previous experiences. Herein, we studied differences in therapeutic efficacies among the most commonly prescribed NSAIDs and acetaminophen in inflammatory pain rat model. Body stretching and food consumption behaviors were assessed after intraperitoneal administration of lactic acid. Initially, different concentrations of lactic acid were evaluated in adult male rats in both behavioral models. Acid concentrations of 1.8 and 3.2% were selected to assess the effects of ibuprofen, diclofenac, naproxen, and acetaminophen in body stretching and feeding behaviors, respectively. In the feeding study, food restriction for 1-24 h prior to feeding studies was assessed at first, and 24 h was selected for further tests. Acetaminophen (100 mg/kg), diclofenac (10 mg/kg), ibuprofen (10-32 mg/kg), and naproxen (3.2-10 mg/kg) significantly decreased acid-stimulated body stretching. Likewise, acetaminophen (100 mg/kg), diclofenac (10 mg/kg), and ibuprofen (32 mg/kg) increased food consumption significantly after 3.2% lactic acid. There were no significant differences between different test drugs efficacies in both stretching and feeding behaviors. In conclusion, feeding behavior provides a good appraisal for pain and analgesic drugs in preclinical studies. There were comparable efficacies between all tested medications in both lactic acid-stimulated body stretching and -depressed feeding behaviors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen* / pharmacology
  • Acetaminophen* / therapeutic use
  • Analgesics / therapeutic use
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Diclofenac / pharmacology
  • Diclofenac / therapeutic use
  • Feeding Behavior
  • Ibuprofen* / pharmacology
  • Lactic Acid
  • Male
  • Naproxen / therapeutic use
  • Pain / drug therapy
  • Rats


  • Ibuprofen
  • Acetaminophen
  • Naproxen
  • Diclofenac
  • Anti-Inflammatory Agents, Non-Steroidal
  • Analgesics
  • Lactic Acid