Optimizing the dosing interval of buprenorphine in a multimodal postoperative analgesic strategy in the rat: minimizing side-effects without affecting weight gain and food intake

Abstract

Buprenorphine is commonly used as ( part of ) postoperative analgesic treatment with dosage dependent side-effects such as pica behaviour. No strict consensus exists about the optimal dosing interval of buprenorphine, as its duration of action has been described as being in the range of 6 -12 h. In this study, dosing intervals of 8 h (thrice-a-day) and 12 h (twice-a-day) for buprenorphine in a multimodal analgesic strategy (concurrent administration of a non-steroidal anti-inflammatory drug) were compared on food intake, weight and side-effects (gnawing on plastic Petri dishes and growth rate, indicative of pica behaviour) in rats. The food intake and weight of both intervals were comparable, as the animals from the twice-a-day group did not lose more weight or consumed less food during the analgesic period. The rats from the thrice-a-day group suffered from more side-effects, as the growth rate was decreased and more plastic was gnawed on. It is recommended to carefully evaluate analgesic and side-effects when using buprenorphine. When side-effects are observed, the possibility of increasing the dosing interval of buprenorphine should be explored. In this study, increasing the dosing interval of buprenorphine in a multimodal analgesic regimen resulted in reduced unwanted side-effects, without increasing weight loss or decreasing food intake. Although this is suggestive of provision of comparable analgesia, future studies including more pain-related readout parameters to assess the effect of the dosing interval on analgesic efficacy are recommended.

Dopaminergic neurotransmission in ventral and dorsal striatum differentially modulates alcohol reinforcement

“…Cannulas were fixed to the skull using stainless steel screws and antibiotic cement (Simplex ™ P bone cement with tobramycin, Stryker Nederland B.V., The Netherlands). Anaesthesia and analgesia protocols were as previously published (Schaap et al ., , ). Briefly, rats were anaesthetized with fentanyl (0.25 mg/kg, IP – Fentanyl Janssen ® ; Janssen‐Cilag B.V., The Netherlands) and dexmedetomidine (0.15 mg/kg, IP – Dexdomitor ® ; Pfizer Animal Health B.V., The Netherlands) in their home cage.…”

Preanesthesia, Anesthesia, Analgesia, and Euthanasia

“…Optimal analgesia may be best achieved with a multimodal approach incorporating preemptive analgesia (Gaertner et al, 2008;Zegre Cannon et al, 2011;Flecknell, 2009;Penderis and Franklin, 2005;Schaap et al, 2012). Optimal analgesia may be best achieved with a multimodal approach incorporating preemptive analgesia (Gaertner et al, 2008;Zegre Cannon et al, 2011;Flecknell, 2009;Penderis and Franklin, 2005;Schaap et al, 2012).…”

“…Due to their small size and high metabolic rate, rodents may require a buprenorphine dose frequency of 2-4 times daily (Gades et al, 2008(Gades et al, , 2000Deng et al, 2000;Roughan and Flecknell, 2002;Yu et al, 2006). While lower doses are not associated with significant side effects, in the rat, pica and possibly long-term weight reductions have been reported at higher doses or with prolonged dosing schedules ( (Schaap et al, 2012;Bomzon, 2006). 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).…”

“…Ketamine-xylazine intramuscular injection resulted in significant muscle necrosis; to a lesser degree lesions were identified in the abdominal musculature after IP injection (Smiler et al, 1990;Wellington et al, 2013). Its side-effects, such as pica, can be minimized by altering the dose schedule and utilizing a multimodal approach (Schaap et al, 2012). Pentobarbital, where available, is less reliable but can be useful for non-recovery applications.…”

Efficacy of Intrathecal Morphine in a Model of Surgical Pain in Rats

“…However, pica has been cited as a reason for withholding morphine and other opioids such as buprenorphine in rats [16,17]. The incidence of pica-type behaviour depends on several factors such as dose, frequency of opioid administration, strain of rat and type of bedding [17,18]. In rodents, respiratory depression, another commonly quoted side effect following opioid use appears to have little clinical significance in rodents [19,20].…”