In vivo profiling of four centrally administered opioids for antinociception, constipation and respiratory depression: Between‐colony differences in Sprague Dawley rats

Abstract

Outbred rodent stocks including Sprague Dawley rats, are known for their genetic diversity and so they are often used to develop animal models of human disease. Although between-colony differences in pharmaco-behavioural studies have been published previously, a direct head-to-head comparison study, whereby all research was performed in the same laboratory by the same experimenter utilising the supraspinal route of drug administration in the same strain of rat, is lacking. Herein, we report our head-to-head comparison study, involving assessment of antinociception, constipation and respiratory depression evoked by single bolus intracerebroventricular (ICV) doses of morphine, buprenorphine, DPDPE and U69,593 using male Sprague Dawley rats sourced from a different breeding colony (BC2) from that (BC1) used by us previously. Our data show that there are marked differences in the potency rank order for morphine and buprenorphine between rats sourced from BC2 and BC1. Although ICV morphine evoked a bell-shaped dose-response curve in the constipation test for rats from both colonies, this occurred at higher doses for rats from BC2. In conclusion, our head-to-head comparison shows considerable between-colony differences for the same rat strain, in the potency rank order of two clinically important strong opioid analgesics given by the ICV route.

Improving Stereotaxic Neurosurgery Techniques and Procedures Greatly Reduces the Number of Rats Used per Experimental Group—A Practice Report

“…Some drugs acting on the central nervous system can have delayed effects that can impact the animal’s behavior and well-being. For example, compounds like buprenorphine [ 25 ] or fentanyl offer effective pain relief properties but can also cause nausea [ 42 ] and a decrease of intestinal motility [ 43 , 44 ]. Some anesthesia methods can cause excessive salivation and bronchial secretion.…”

Impact of Pharmacy-Led Education Regarding Multimodal Acute Pain Management on Medical Residents’ Prescribing of Opioids

“…4,5 As such, the benefit vs risk of opioid use must be carefully weighed when prescribing for acute pain. 1,5,6…”

“…1 As higher doses of opioids are taken, incidences of side effects, euphoria, tolerance, abuse, and addiction are increased as well. [2][3][4][5] Common opioid side effects include constipation, nausea, vomiting, dizziness, headache, and somnolence, with the most serious side effect manifested as respiratory depression when taken in excessive amounts or in combination with other central nervous system (CNS) depressants. 4,5 As such, the benefit vs risk of opioid use must be carefully weighed when prescribing for acute pain.…”

“…[2][3][4][5] Common opioid side effects include constipation, nausea, vomiting, dizziness, headache, and somnolence, with the most serious side effect manifested as respiratory depression when taken in excessive amounts or in combination with other central nervous system (CNS) depressants. 4,5 As such, the benefit vs risk of opioid use must be carefully weighed when prescribing for acute pain. 1,5,6 Emerging practice guidelines recommend the use of a multimodal approach to target pain through different mechanisms of action using drug classes such as nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, partial µ receptor agonist opioids, and opioids.…”

“…4,5 As such, the benefit vs risk of opioid use must be carefully weighed when prescribing for acute pain. 1,5,6 Emerging practice guidelines recommend the use of a multimodal approach to target pain through different mechanisms of action using drug classes such as nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, partial µ receptor agonist opioids, and opioids. [6][7][8] Using various classes of medications provides a synergistic analgesic effect.…”