The antinociceptive efficacy of buprenorphine administered through the drinking water of rats

Abstract

SummaryPostoperative pain management in laboratory animals is important for animal welfare and required under law in many countries. Frequent injection of analgesics to rodents after surgery is stressful for the animals and labour-intensive for animal care personnel. An alternative dosing scheme such as administration of analgesics in the drinking water would be desirable. However, the efficacy of a chronic oral analgesic treatment via this route has not yet been documented. This study investigated the antinociceptive efficacy of buprenorphine administered ad libitum via the drinking water of laboratory rats. The antinociceptive efficacy of buprenorphine in drinking water was compared with repeated subcutaneous injections. A comparison was also made between buprenorphine in drinking water and the combination of one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water. Antinociception was assessed by use of an analgesiometric model measuring the rats' latency time to withdrawal from a noxious heat stimulus applied to the plantar surface of the paw. Results revealed that buprenorphine in drinking water (0.056 mg/mL) induced significant increases in paw withdrawal latency times during a three-day period of administration with a maximal effect at 39 h after the start of buprenorphine administration. One single injection of buprenorphine (0.1 mg/kg s.c.) followed by buprenorphine in the drinking water (0.056 mg/mL) induced an earlier onset of antinociception than buprenorphine in drinking water alone. In contrast, buprenorphine (0.1 mg/kg s.c.) injected every 8 h over a period of three days did not result in significant increases in paw withdrawal latency times. In conclusion, our results suggest that one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water may be a viable treatment option for the relief of pain in laboratory rats, but at the doses used in this study in pain-free rats it was associated with a decrease in water intake and some behavioural changes.

Evaluating analgesic efficacy and administration route following craniotomy in mice using the grimace scale

“…We do not believe that prolonging the presurgical sucralose consumption period would have increased analgesic efficacy because previous studies have shown that 15 h of voluntary buprenorphine ingestion was required to reach similar or higher blood concentrations than subcutaneous administration 24 . Previous studies have suggested that the willingness of the animal to ingest water may enhance inter-subject variation 29 , but that does not apply here as there was comparable water Table 1. University of Toronto recommendations for dose, route and frequency of mouse analgesics following surgery.…”

Correlation between body weight changes and postoperative pain in rats treated with meloxicam or buprenorphine

“…Variations in analgesic efficacy, evaluated according to tail withdrawal latencies, have been noted among various strains of adult male rats 19. Intriguingly, repeated injected doses of 0.1 mg buprenorphine per kg body weight can elicit antinociceptive tolerance in male rats 20. In our study, we chose to administer buprenorphine s.c. every 12 h, as this administration frequency and route are common in US laboratory animal research protocols that use buprenorphine.…”

“…In our study, we chose to administer buprenorphine s.c. every 12 h, as this administration frequency and route are common in US laboratory animal research protocols that use buprenorphine. Oral dosing of buprenorphine is complicated by changes in water consumption in the absence of operative procedures 20.…”

Preanesthesia, Anesthesia, Analgesia, and Euthanasia

“…Strain and sex of rodents can also modulate response to opiates (Jablonski et al, 2001;Avsaroglu et al, 2007Avsaroglu et al, , 2008Cotroneo et al, 2012;Wright-Williams et al, 2013). Although usually given as an injection, in some studies orally administered buprenorphine was efficacious in alleviating postoperative pain, however, its utility may be limited in duration of analgesia and by reliable consumption of the food stuffs or water into which it is compounded (Flecknell et al, 1999a;Martin et al, 2001;Jablonski and Howden, 2002;Thompson et al, 2004Thompson et al, , 2006Jessen et al, 2007;Goldkuhl et al, 2010a,b;Leach et al, 2010b;Kalliokoski et al, 2011;Abelson et al, 2012). Additionally, sustained release and transdermal formulations of buprenorphine are emerging as potentially viable and practical opiate delivery systems (Park et al, 2008;Foley et al, 2011;Carbone et al, 2012a).…”