1991
DOI: 10.1093/oxfordjournals.bmb.a072501
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Mechanisms of the analgesic actions of opiates and opioids

Abstract: It is now clear that there are three sub-types of the opiate receptor, mu, delta and kappa. Evidence for differential roles of these sub-types in pain modulation is accumulating since the advent of relatively selective agonists and more recently, antagonists for the three receptors. The actions of opioids in the spinal cord is reasonably well understood and there is increasing knowledge of supraspinal sites of action, peripheral analgesic effects in inflammatory states and in the interactions between opioid an… Show more

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Cited by 140 publications
(53 citation statements)
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“…Although a spinal mechanism has previously been implicated in the analgesic actions of all three classes of opioid receptors (29), whether spinally projecting 5-HT neurons are involved remains unclear. Our data delineate the role of spinal 5-HT in opioid analgesia and reveal that 5-HT neurons are required for MOR-and DOR-induced spinal analgesia, but not for KOR-induced spinal analgesia.…”
Section: Discussionmentioning
confidence: 99%
“…Although a spinal mechanism has previously been implicated in the analgesic actions of all three classes of opioid receptors (29), whether spinally projecting 5-HT neurons are involved remains unclear. Our data delineate the role of spinal 5-HT in opioid analgesia and reveal that 5-HT neurons are required for MOR-and DOR-induced spinal analgesia, but not for KOR-induced spinal analgesia.…”
Section: Discussionmentioning
confidence: 99%
“…Activation of pre-synaptic opioid receptors reduces intracellular cyclic adenosine monophosphate (cAMP) concentration and calcium ion influx, inhibiting the release of the excitatory neurotransmitters, glutamate and substance P. At the post-synaptic neuron, opioid binding produces a hyperpolarisation of the neuronal membrane, thereby reducing the probability of an action potential being generated. Opioids also affect supraspinal structures of pain processing, especially the thalamus and limbic system 72 . The emotional assessment of pain is altered via these higher centres, so that it is still perceived but no longer experienced as unpleasant or threatening.…”
Section: Current Treatment Optionsmentioning
confidence: 99%
“…When stimulated, these postsynaptic opioid receptors hyperpolarize the membrane of dorsal horn neurons, thereby reducing activity in nociceptive pathways. 57,61 Studies with agonists of the delta opioid receptors have highlighted their potential as analgesics possessing fewer of the side effects usually associated with morphine. However, experience with kappa receptor agonists, to date, has been disappointing.…”
Section: Opioidsmentioning
confidence: 99%
“…The exact role of the kappa receptors in the production of supraspinal analgesia is the subject of debate, with varying opinions ventured in the literature. 61,64,65 Opioids also act peripherally as analgesic agents. Mu receptor agonists prevent the nociceptor sensitization induced by inflammatory mediators, such as prostaglandin E 2 (PGE 2 ).…”
Section: Opioidsmentioning
confidence: 99%