Chapter 28 Sites of action of opiates in production of analgesia

Yaksh, Tony L.; Al-Rodhan, Nayef R. F.; Jensen, Troels Staehelin

doi:10.1016/s0079-6123(08)62803-4

Cited by 128 publications

(57 citation statements)

References 92 publications

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“…A similar effect was demonstrated in the rat tail flick test following microinjection of carbachol into various amygdaloid nuclei, including the CE and the medial (ME) nuclei (15,16). Microinjection of morphine into the corticomedial subdivision of the amygdala is effective in the flinch-jump (17,18) and hot plate (19) tests. Microinjection of opioids into the CE (9,(20)(21)(22)(23)(24)(25) or of serotonin (26) into the basomedial part of the amygdala also induces antinociception.…”

Section: Introductionsupporting

confidence: 53%

Antinociception induced by stimulating amygdaloid nuclei in rats: changes produced by systemically administered antagonists

Oliveira

Prado

1998

Braz J Med Biol Res

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The antinociceptive effects of stimulating the medial (ME) and central (CE) nuclei of the amygdala in rats were evaluated by the changes in the latency for the tail withdrawal reflex to noxious heating of the skin. A 30-s period of sine-wave stimulation of the ME or CE produced a significant and short increase in the duration of tail flick latency. A 15-s period of stimulation was ineffective. Repeated stimulation of these nuclei at 48-h intervals produced progressively smaller effects. The antinociception evoked from the ME was significantly reduced by the previous systemic administration of naloxone, methysergide, atropine, phenoxybenzamine, and propranolol, but not by mecamylamine, all given at the dose of 1.0 mg/kg. Previous systemic administration of naloxone, atropine, and propranolol, but not methysergide, phenoxybenzamine, or mecamylamine, was effective against the effects of stimulating the CE. We conclude that the antinociceptive effects of stimulating the ME involve at least opioid, serotonergic, adrenergic, and muscarinic cholinergic descending mechanisms. The effects of stimulating the CE involve at least opioid, ß-adrenergic, and muscarinic cholinergic descending mechanisms.Correspondence

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Section: Introductionsupporting

confidence: 53%

Antinociception induced by stimulating amygdaloid nuclei in rats: changes produced by systemically administered antagonists

Oliveira

Prado

1998

Braz J Med Biol Res

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“…The main antinociceptive zone identified by microinjections of opioids was reported to lie within the caudal ventrolateral column (Yaksh et al, 1988). Presynaptic inhibition by opioids was quite uniform throughout the lateral and ventrolateral PAG, consistent with a role in antinociception.…”

Section: Discussionmentioning

confidence: 84%

Inhibition by opioids acting on μ‐receptors of GABAergic and glutamatergic postsynaptic potentials in single rat periaqueductal gray neurones in vitro

Chieng¹,

Christie²

1994

British J Pharmacology

102

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1 Membrane properties of rat periaqueductal gray neurones were investigated by use of intracellular recordings from single neurones in brain slices. Morphological properties and anatomical location of each impaled neurone were characterized by intracellular staining with biocytin. The present paper considers the properties of electrically-evoked and spontaneous postsynaptic potentials impinging on periaqueductal gray neurones, and the actions of opioids on postsynaptic potentials in neurones which were not directly hyperpolarized by opioids. The preceding paper considers neurones which were hyperpolarized by opioids. 2 Electrical stimulation in the vicinity of impaled neurones evoked postsynaptic potentials having fast (duration at half-maximal amplitude 37 ± 2 ms, n = 65) and in some cases slow (duration at halfmaximal amplitude 817 ± 187 ms, n = 3) components. Amplitudes of evoked potentials were dependent on stimulus voltage, membrane potential, and were abolished during superfusion with solutions containing tetrodoxotoxin (100 nM to 1 gM, n = 5) or Co2" (4 mM, n = 2).3 Fast postsynaptic potentials were mediated predominantly by activation of glutamate and GABAA receptors. The GABAA-receptor antagonist, bicucuilline (30 AM), inhibited postsynaptic potentials by 44 ± 8% (n = 14). The non-NMDA-receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (10 PM), inhibited postsynaptic potentials by 48 ± 6% (n = 16). Combined superfusion of bicuculline (30 AM) and 6-cyano-7-nitroquinoxaline-2,3-dione (10 M) inhibited postsynaptic potentials by 93 + 1% (n = 8). Additional superfusion of the NMDA-receptor antagonist, (± )-2-amino-5-phosphonovaleric acid (50 tM) inhibited synaptic potentials by 94 ± 1% (n = 3). 4 Slow inhibitory postsynaptic potentials were observed in 12% (8/65) of neurones. They reversed polarity between -100 and -11O mV, and were abolished by superfusion with spiperone (1 LM, n = 2), but not the a2-antagonist, idazoxan (3 LM, n = 2).5 Selective A-receptor agonists inhibited fast postsynaptic potentials in all neurones tested which were not directly hyperpolarized by opioids. Met-enkephalin (30 AM) and Tyr-D-Ala-Gly-MePhe-Glyol (3 rM) inhibited postsynaptic potentials by 53 ± 3% and 49 ± 3%, respectively. This effect was completely antagonised by naloxone (1 LM, n = 3). A small inhibition produced by the selective 6-receptor agonist, Tyr-D-Pen-Gly-Phe-D-Pen-enkephalin (3 ELM, 26 ± 4%, n = 14), was antagonized by naloxone (1 PM), but not by the selective 6-receptor antagonist, naltrindole (10 nM), suggesting non-specific it-receptor activation by this agonist. The selective K-receptor agonist, U50488H (3 AM), also consistently inhibited postsynaptic potentials by 45 ± 15% (n = 4). However, this effect was not fully reversed by naloxone (1 AM) suggesting a non-specific action. 6 Both glutamatergic and GABAergic components of fast postsynaptic potentials were inhibited by Met-enkephalin (10 or 30 AM). Met-enkephalin inhibited postsynaptic potentials by 55 ± 5% (n = 12) in the presence of 6-cyano-7-nit...

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“…This relay is subject to modulation by spinal interneurons and supraspinal projections originating in the periaqueductal gray (PAG) and rostroventral medulla. Opiate analgesics such as morphine bind preferentially to -opioid receptors (MORs) and trigger antinociception by inhibiting neuronal targets, including supraspinal GABAergic interneurons, primary afferent neurons, and secondary dorsal horn neurons (Yaksh et al, 1988;Yaksh, 1997).…”

Section: Introductionmentioning

confidence: 99%

Spinal G-Protein-Gated K⁺Channels Formed by GIRK1 and GIRK2 Subunits Modulate Thermal Nociception and Contribute to Morphine Analgesia

Marker¹,

Stoffel²,

Wickman³

2004

J. Neurosci.

134

142

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G-protein-gated potassium (K ϩ ) channels are found throughout the CNS in which they contribute to the inhibitory effects of neurotransmitters and drugs of abuse. Recent studies have implicated G-protein-gated K ϩ channels in thermal nociception and the analgesic action of morphine and other agents. Because nociception is subject to complex spinal and supraspinal modulation, however, the relevant locations of G-protein-gated K ϩ channels are unknown. In this study, we sought to clarify the expression pattern and subunit composition of G-protein-gated K ϩ channels in the spinal cord and to assess directly their contribution to thermal nociception and morphine analgesia. We detected GIRK1 (G-protein-gated inwardly rectifying K ϩ channel subunit 1) and GIRK2 subunits, but not GIRK3, in the superficial layers of the dorsal horn. Lack of either GIRK1 or GIRK2 was correlated with significantly lower expression of the other, suggesting that a functional and physical interaction occurs between these two subunits. Consistent with these findings, GIRK1 knock-out and GIRK2 knock-out mice exhibited hyperalgesia in the tail-flick test of thermal nociception. Furthermore, GIRK1 knock-out and GIRK2 knock-out mice displayed decreased analgesic responses after the spinal administration of higher morphine doses, whereas responses to lower morphine doses were preserved. Qualitatively similar data were obtained with wild-type mice after administration of the G-proteingated K ϩ channel blocker tertiapin. We conclude that spinal G-protein-gated K ϩ channels consisting primarily of GIRK1/GIRK2 complexes modulate thermal nociception and mediate a significant component of the analgesia evoked by intrathecal administration of high morphine doses.

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Chapter 28 Sites of action of opiates in production of analgesia

Cited by 128 publications

References 92 publications

Antinociception induced by stimulating amygdaloid nuclei in rats: changes produced by systemically administered antagonists

Antinociception induced by stimulating amygdaloid nuclei in rats: changes produced by systemically administered antagonists

Inhibition by opioids acting on μ‐receptors of GABAergic and glutamatergic postsynaptic potentials in single rat periaqueductal gray neurones in vitro

Spinal G-Protein-Gated K⁺Channels Formed by GIRK1 and GIRK2 Subunits Modulate Thermal Nociception and Contribute to Morphine Analgesia

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Chapter 28 Sites of action of opiates in production of analgesia

Cited by 128 publications

References 92 publications

Antinociception induced by stimulating amygdaloid nuclei in rats: changes produced by systemically administered antagonists

Antinociception induced by stimulating amygdaloid nuclei in rats: changes produced by systemically administered antagonists

Inhibition by opioids acting on μ‐receptors of GABAergic and glutamatergic postsynaptic potentials in single rat periaqueductal gray neurones in vitro

Spinal G-Protein-Gated K+Channels Formed by GIRK1 and GIRK2 Subunits Modulate Thermal Nociception and Contribute to Morphine Analgesia

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Spinal G-Protein-Gated K⁺Channels Formed by GIRK1 and GIRK2 Subunits Modulate Thermal Nociception and Contribute to Morphine Analgesia