"Pharmacology of salicin derivatives in sheep" : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Animal Science, Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand

Abstract

Content removed from thesis due to copyright reasons: Figure 1.20(e). S. viminalis. Retrieved from Valerie J.:http://gardeners-word.blogspot.co.uk/Sheep suffer from pain during various husbandry practices as well as during injury or diseases such as footrot. This pain could be potentially minimised with the use of analgesics such as non-steroidal anti-inflammatory drugs (NSAID). Unfortunately, there are very few registered NSAIDs for sheep. Thus, registered analgesics for cattle, for instance ketoprofen and meloxicam are used in sheep. Again, the high cost of analgesics and associated potential side effects such as reduced fertility, gastric irritation, gastric ulcers etc. evident in other species usually limits their use in sheep. Fear of residues in meat may stop some farmers from using analgesics. Considering these problems, this study was designed as a groundwork to explore a possible and potential use of natural, inexpensive analgesic for sheep. Salicylic acid, a derivative of salicin, is a NSAID used effectively in humans as an analgesic since ancient times in the form of willow bark and leaves. During this research study, the pharmacokinetics of salicylic acid in sheep was analysed after administration of the sodium salt of salicylic acid (sodium salicylate/NaS) intravenously and orally at different dose rates. The analgesic efficacy of salicylic acid in sheep was also studied after administration of sodium salicylate at different dose rates by measuring mechanical and thermal nociceptive thresholds. The minimum therapeutic plasma concentration of salicylic acid for analgesia in sheep ranged from 25 to 30 μg/mL, which was achieved for about 30 minutes by a 200 mg/kg intravenous dose of NaS. During this study it was discovered that thermal nociceptive threshold testing is unable to detect any analgesia from salicylic acid and ketoprofen in sheep. However, mechanical nociceptive threshold testing efficiently detected the analgesic effects of salicylic acid and the positive control, ketoprofen. The seasonal variation of willow salicin content (principal precursor of salicylic acid in willow) was studied over a year. The salicin in willows in New Zealand is higher during the summer months as compared to the winter months of the year, and appears greater in areas subject to drought. The analgesic efficacy of willow leaves can be assessed by feeding the willow leaves to lame sheep as they readily eat willow leaves. However, to assess the analgesia produced by willow in sheep, further research is warranted. Keywords: Salicin, sheep, salicylic acid, analgesia, HPLC, nociceptive testing, willow