Nonsteroidal Antiinflammatory Drugs Suppress Pain-Related Behaviors, but Not Referred Hyperalgesia of Visceral Pain in Mice

Visceral pain is characterized by spontaneous pain and referred hyperalgesia. After inducing visceral pain in mice using intracolonic mustard oil administration, we examined the effects of various nonsteroidal antiinflammatory drugs (NSAIDs) on pain-related behavior and on Evans blue dye extravasation. Animals were given one of the followingsaline, ethanol, dimethylsulfoxide (DMSO), morphine, ketoprofen, ketorolac, or DFU (a cyclooxygenase-2 inhibitor). After drug treatment, mice underwent intracolonic administration of 50 μL 1.5% mustard oil. Spontaneous pain-related responses were assessed for the next 20 min. The frequency of withdrawal responses to the application of von Frey hairs to the abdomen, foot, and tail was determined. After completion of the behavioral tests, Evans blue was injected into the animals via the tail vein. Two hours later, the colon was removed postmortem and Evans blue content was measured. Spontaneous pain behaviors were significantly less in animals administered 3 and 10 mg/kg morphine, 50 mg/kg ketorolac, 100 mg/kg ketoprofen, and 20 mg/kg DFU (P < 0.05). Response frequencies to the application of von Frey hairs were lower in mice administered 3 and 10 mg/kg morphine (P < 0.05) but were not affected by ketorolac, ketoprofen, or DFU treatment. Colonic Evans blue content was smaller in mice given 100 mg/kg ketoprofen and 20 mg/kg DFU (P < 0.05). We concluded that NSAIDs reduced pain behavior and inflammation but had little effect on referred hyperalgesia.