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

Abstract

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 following: saline, ethanol, dimethylsulfoxide (DMSO), morphine, ketoprofen, ketorolac, or DFU (a cyclooxygenase-2 inhibitor). After drug treatment, mice underwent intracolonic administration of 50 microL 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.

Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function

“…DFU is a highly selective PGHS-2 inhibitor in vitro (12). The selectivity of the dosage regimen that we used has been reported previously (43)(44)(45) and was confirmed in this study (Supplemental Figure 1).…”

Development and characterisation of a novel animal model of prostate inflammation-induced chronic pelvic pain

“…Also, since the inflammation is induced in the prostate and the response to heat or mechanical stimuli was measured from the skin in the pelvic areaa, the measured parameter should be considered as secondary hyperalgesia, which is taken as a measure of primary hyperalgesia or the pain in the inflammed prostate. Occurrence of secondary hyperalgesia or allodynia in 'referred' areas of the inflamed tisue or organ has been previously reported in animals and humans (Zhang et al, 2002;Radhakrishnan et a., 2003;Vera-Portocarrero et al, 2003;Stawowy et al, 2004;Rodrigues et al, 2005;Shin et al, 2006).…”

Urinary Bladder Function and Somatic Sensitivity in Vasoactive Intestinal Polypeptide (VIP)−/− Mice

“…In addition to mechanical sensitivity testing in mice, we also observed mice for nociceptive behaviors beginning 30 min after CYP treatment (Laird et al, 2000;Hu et al, 2005) for WT and VIP -/-mice. After treatment, rodents were observed every 30 min for 5 min for a total duration of 4 h. The number and type of the following behaviors was recorded, assigned points and a cumulative point score of all observed behaviors was quantified for each time point (Laird et al, 2000;Shin et al, 2006): (1) normal (score 0); (2) piloerection (score 2); (3) strong piloerection (score 3); (4) labored breathing (score 4); licking of the abdomen (score 5) and (6) stretching or contraction of the abdomen (score 6). All somatic testing and behavioral scoring was performed in a blinded manner with respect to treatment and mouse strain.…”