Buprenorphine via drinking water and combined oral-injection protocols for pain relief in mice

Abstract

Buprenorphine is the opioid most commonly used in laboratory mice. To maintain therapeutic serum levels, repeated injections are required. Oral self-administration is an alternative but has been criticized to be unreliable. Here we analyse voluntary intake and water/injection combinations for their reliability to achieve effective drug supply. Mice were assigned to one of five groups: a) naïve (N); b) buprenorphine via water for 24 h (W); c) buprenorphine via two injections during light, and via water during dark phase (IW2); d) buprenorphine via three subcutaneous injections during light phase and water for 24 h (IW3) or e) surgery plus buprenorphine via three subcutaneous injections during light phase and water for 24 h (S). Drinking frequency, water and food intake, activity, body mass progression, blood serum concentrations and behavioral pain indicators were determined. Water intake was not decreased due to buprenorphine or surgery. Administration of buprenorphine resulted in an increase of activity in IW3 animals and a decrease in body mass. Food intake decreased in IW2, IW3 and S mice. All treatment groups showed mean serum concentrations higher than the targeted value throughout dark phase.

Voluntary intake of paracetamol-enriched drinking water and its influence on the success of embryo transfer in mice

“…Furthermore, the uptake of paracetamol with the drinking water might be decreased after anaesthesia and surgery, but data obtained in this study and from other publications (Cesarovic et al, 2010;Sauer et al, 2016) show, that no relevant alteration of drinking behaviour occurred after inhalation anaesthesia with or without surgery. However, in case of doubts regarding uptake of the drug in the immediate post-anaesthetic phase, one may administer the analgesic then as a single bolusinjection to compensate for a suspected delay in drinking after the intervention.…”

“…Low water intake during the pre-operative phase could have been due to the still unfamiliar taste of the water, and to generally lower water intake at the beginning of the light period. Water consumption during the day time tends to be less and more sporadic than during night time due to circadian rhythmicity (Sauer et al, 2016).…”

The IMPROVE Guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments)

“… 116 However, medication of food or water has more variable effects, and it is important to ensure that the analgesic is reliably consumed, in sufficient quantity. 117 For example, intake of analgesics in water may be unreliable for animals that are less mobile, or where the taste of the water is altered by adding the drug. Administration in food and water may be ineffective, since food and water consumption are greatly influenced by diurnal rhythms, and animals may receive ineffective doses during the light phase of their photoperiod.…”

Side effects of pain and analgesia in animal experimentation

“…Moreover, latency to ingestion as well as the total amount ingested by the animals, especially during the resting phase, is difficult to anticipate and is clearly variable for each individual. Thus, voluntary ingestion protocols might be applicable only when pain is mild, or in combination with drug injections, at least during the resting phase of rodents 24 .…”

“…Voluntary oral administration of analgesia is another promising approach that avoids the negative effects of handling. Several routes of oral administration have been described, such as mixing analgesics with flavored gelatine 21 , Nutella 22 , regular diet 23 or drinking water 24 . These studies in mice and rats have shown that several analgesics are efficient when administered orally and voluntarily.…”