Comparison of the peripheral and central effects of the opioid agonists loperamide and morphine in the formalin test in rats
Section snippets
Subjects
Male Sprague–Dawley rats (Harlan Sprague Dawley, Indianapolis, IN) weighing 180–220 g were used. Rats were housed up to eight per cage in a large colony room, and provided with food and water ad libitum with a 12-h light/dark cycle. Each animal was used only once. All procedures were approved by the Eli Lilly Institutional Animal Care and Use Committee.
Formalin test
The methods used were based on the automated method of Jett and Michelson (1996) as modified by Shannon and Lutz (2000). All testing took place
Subcutaneous administration of loperamide and morphine
In animals administered vehicle SC 30 min before formalin, there was an initial peak in the number of events during the first 5-min block after formalin, followed by a decrease in the number of events in the second 5-min block, and subsequently an increase again in blocks 3–9 (Fig. 1, open circles). When loperamide was administered SC 30 min before formalin, it produced a dose- and time-dependent analgesic effect in the formalin test in rats (Fig. 1). Loperamide (1.0–10 mg/kg SC) was
Discussion
The major finding of the present studies was that the opioid agonists loperamide and morphine produced antihyperalgesia after subcutaneous administration in the formalin test in rats, most likely by acting at peripheral opioid receptors. Loperamide, which does not penetrate into the brain in appreciable amounts (Heykants et al., 1974, Wuster and Herz, 1978, Schinkel et al., 1996), was efficacious in reducing formalin-induced nocifensive behaviors. Moreover, the quaternary opioid antagonist
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Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain
2021, NeuropharmacologyCitation Excerpt :The second phase is also influenced by supraspinal-mediated descending inhibition of spinal nociception (Basbaum and Fields, 1984; Detweiler et al., 1995; Manning and Franklin, 1998; Manning et al., 1994; Matthies and Franklin, 1992). Morphine has been shown to suppress responses in both phases of the test ((Martin et al., 2003; Sevostianova et al., 2003; Shannon and Lutz, 2002) and this study) in wild type mice; while MOR-KO mice display an enhanced formalin response with a more robust second phase upon a 2% formalin injection (Zhao et al., 2003). Demonstrating morphine antinociceptive tolerance in the formalin test has been more challenging (Abbott et al., 1981, 1982; Connell et al., 1994; Detweiler et al., 1995).
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2018, Neurobiology of PainCitation Excerpt :To explore this approach we chose the brain sparing MOR agonist loperamide (Guan et al., 2008; Kumar et al., 2012; Nozaki-Taguchi and Yaksh, 1999). Loperamide produces analgesia in adult models of inflammatory (Shannon and Lutz, 2002), cancer, and neuropathic pain (Chung et al., 2012; Guan et al., 2008) by acting on the peripheral opioid receptors (DeHaven-Hudkins et al., 1999; Guan et al., 2008). Accordingly, MORs in the periphery are critically involved in the analgesic effects of opioids (Taddese et al., 1995; Wang et al., 2010).
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