Side Effects of Central Analgesic Drugs

Strong opioid analgesics, such as morphine, are the most widely used, centrally acting class of analgesics that are available in the clinic for the treatment of moderate to severe acute nociceptive pain and chronic cancer-related pain. However, strong opioid analgesics also evoke a broad array of side effects including sedation, respiratory depression, nausea and vomiting, pruritus, analgesic tolerance, constipation, and addiction/abuse liability, to name but a few. Due to the “opioid crisis” particularly in the United States, use of strong opioids to alleviate chronic noncancer pain is controversial due to unintentional respiratory depression and opioid misuse/abuse. Additionally, for patients with chronic cancer-related pain, constipation is a major cause of non-compliance. Hence, there is a large unmet medical need for novel, highly effective, safe, and well-tolerated strong opioid analgesics. In this chapter, we describe protocols currently used to evaluate important opioid-related centrally mediated adverse effects. These include protocols for assessing respiratory depression, sedation, constipation, physical dependence, and abuse liability using rodent and non-human primate models.