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Endogenous opiates, the enkephalins, have been identified in the brain and intestine. Their physiological role in the gut has yet to be determined, but since opiates have anti-diarrhoeal actions it was thought possible that they might be involved in the control of mucosal ion transport in addition to their known effects on motility. This possibility was studied using the lq'in vitro' technique of Ussing and Zerahn. Morphine (10^-6 to 10^-4M) induced a significant fall in potential difference (PD) and short-circuit current (I_sc) across stripped rabbit ileal mucosa, with no change in tissue resistance. A maximal electrical response was dependent on the presence of Na, Cl and HCO₃ in the bathing medium. A significant increase in Cl absorption due to a decrease in serosa to mucosa flux was provoked in response to morphine (2 x 10^-5M), accompanied by an increase in residual ion flux (J^R/_net), possibly due to HCO₃ secretion. Na transport was unaffected. Dextromoramide (10^-5M) mimicked the response to morphine, but the inactive isomer laevomoramide (10^-5M) had no effect. Naloxone (10^-6M) inhibited the response to morphine (2 x 10^-5M) and this inhibition was competitive in nature supporting the existence of mucosal opiate receptors. The enkephalin analogue Me-Tyr-D-Met-Gly-Phe-Pro-NH₂ also decreased the PD and I_sc and produced a similar increase in Cl absorption and J^R/_net. This analogue had a more rapid action and provoked a response at a lower dose (10^-8M) than morphine. Tetrodotoxin (10^-7M) inhibited the response to morphine (10^-4M) but blockade of cholinergic, α and β adrenergic and dopaminergic mechanisms had no effect. Morphine (10^-4M) inhibited the secretion produced by three secretagogues, prostaglandin E₂ (10^-5M), acetylcholine (10^-4M) and cholera toxin (1 μg/ml). Adenyl cyclase and cyclic AMP levels were unaffected by morphine, but the electrical response to morphine was increased by omitting Ca^+ + from the medium. Thus these studies provide evidence for the presence of mucosal opiate receptors which may have a physiological role, and demonstrate that opiates enhance Cl absorption and inhibit secretion provoked by three secretagogues. The mechanism of action may be related to an antagonism to intracellular calcium.

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Tonsillectomy is one of the most commonly performed surgeries in North America. Guidelines exist for surgical candidacy for pediatric patients, but to date, there exists significant controversy and no clear guidelines advising physicians on treating pain post-tonsillectomy. Pain is the most frequent and potentially morbid complication of tonsillectomy, as it triggers return visits to physicians and hospitals following surgery, and can result in the need for hospital admission for hydration and pain control. In fact, a main point of controversy surrounds the use of a large class of analgesics known as non-steroidal anti-inflammatory drugs (NSAIDs), due to the potential for increased risk of bleeding as a result of their anti-platelet activity. However, NSAIDs have been shown to have a notable analgesic benefit in other surgical fields without conferring a significant bleeding risk. Moreover, they are known for their opioid-sparing effect, which is favored due to the many side-effects of opioids. Therefore, we undertook a systematic review of the literature to investigate the question of analgesic benefit for NSAIDs compared to other analgesics, and found that they were not different than opioids at treating post-tonsillectomy pain. However, the evidence available to answer this question was often flawed, warranting further investigation into this question. We were also especially interested in investigating commonly used analgesics such as ibuprofen and acetaminophen, so we devised a protocol that included these two medications. This protocol compares ibuprofen and acetaminophen to acetaminophen alone and seeks to show a significant opioid-sparing effect for ibuprofen. Ultimately, this topic is important because of the frequency with which tonsillectomies are performed and the importance of pain control following this procedure. / Thesis / Master of Science (MSc) / Tonsillectomy is the surgery that completely removes the tonsil from the throat, and many children and adults undergo this procedure for various reasons including infections, sleeping problems and other. This surgery has several side effects including pain, dehydration and bleeding. Pain is the most frequent of all these side effects, and can result in significant disturbances in the recovery experience, as well as cause the patient to require hospital visits and admission. Therefore pain control is important, and can be achieved incorporating medications such as non-steroidal anti-inflammatory drugs into the post-operative analgesic regimen. We investigated the role that these medications can play in relieving pain in this setting, and found that these are no different than opioids, such as morphine and codeine, the latter of which have many side-effects including breathing problems, constipation, itchiness, nausea, and others. However, there wasn't enough evidence to make definitive conclusions regarding the amount of opioids that can be avoided with the use of non-steroidal anti-inflammatory drug. Therefore, we designed a protocol for a randomized study to better understand this area that is so far little understood. The results of this study could help optimize pain control measures following tonsillectomy, and change the practice of surgeons favoring an evidence-based approach.

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