Evidence for the involvement of descending noradrenergic pathways in the antinociceptive effect of baclofen

Sawynok, Jana; Dickson, C.

doi:10.1016/0006-8993(85)90279-3

Cited by 25 publications

(7 citation statements)

References 30 publications

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“…Baclofen exerts an antinociceptive effect which is not reduced by GABAA (Bartolini et al, 1981;Sawynok & La Bella, 1982), opioid (Levy & Proudfit, 1979;Bartolini et al, 1981) or muscarinic receptor antagonists (Bartolini et al, 1981). It has been suggested that baclofen antinociception has both supraspinal and spinal components (reviewed by Sawynok, 1987) and catecholamines and substance P may play some role in the antinociceptive effect (Sawynok 1983;Sawynok et al, 1984;Sawynok & Dickson, 1985b;Hwang & Wilcox, 1989). Although some compounds, namely (+ )-baclofen, 6-aminovaleric acid and phaclofen have been reported to prevent (±)-baclofen-induced antinociception, their lack of brain penetration and low potency have hampered in vivo studies (Bowery, 1989).…”

Section: Introduction Methodsmentioning

confidence: 99%

CGP 35348, a new GABA_B antagonist, prevents antinociception and muscle‐relaxant effect induced by baclofen

Malcangio

Ghelardini

Giotti

et al. 1991

British J Pharmacology

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Section: Introduction Methodsmentioning

confidence: 99%

CGP 35348, a new GABA_B antagonist, prevents antinociception and muscle‐relaxant effect induced by baclofen

Malcangio

Ghelardini

Giotti

et al. 1991

British J Pharmacology

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“…The i.t. administration of the non-selective 5-HT antagonists methysergide and metergoline has been reported to produce hyperalgesia in the tail flick and hot plate thermal threshold tests (PROUDFIT and HAMMOND 1981;BERGE et al 1983;SAWYNOK and DICKSON 1985), and these observations are consistent with tonic activity. Hyperalgesia induced by systemic administration of 5-HT antagonists has been attributed to changes in skin temperature (TJ0LSEN et al 1989), but the contribution of temperature changes to determining nociceptive thresholds subsequently has been questioned (LICHTMAN et al 1993).…”

Section: Tonic Regulation Of Nociceptive Transmissionmentioning

confidence: 71%

“…administration of the serotoninergic neurotoxins 5,6-and 5,7-DHT produces hyperalgesia in the tail flick test 2-5 days following administration but this is no longer observed at 10-14 days FASMER et al 1983). The detection of hyperalgesia is intensity dependent, as it is more readily observed when a milder stimulus intensity is used (SAWYNOK and DICKSON 1985). Some studies suggest that hyperalgesia is an apparent effect due to changes in skin temperature rather than reflecting tonic activity (TJ0LSEN et al 1988;EIDE et al 1988).…”

Section: Tonic Regulation Of Nociceptive Transmissionmentioning

confidence: 99%

Modulation of Nociception by Descending Serotoninergic Projections

Sawynok¹

2000

Serotoninergic Neurons and 5-Ht Receptors in the CNS

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A. Introduction5-Hydroxytryptamine (5-HT) plays a multifaceted role in the regulation of nociceptive transmission. Complexity arises from actions at multiple sites within the pain transmission system (periphery, spinal cord, supraspinal sites), actions at multiple 5-HT receptor subtypes with the potential for opposing or interactive influences, and interactions with a number of endogenous mediators at all levels. At sensory nerve terminals in the periphery, 5-HT plays a role in the inflammatory response and mediates pronociceptive effects by activation of 5-HT1A' 5-HT2 and 5-HT, receptors (RICHARDSON et a1. 1985; MELLER et a1. 1991; T AIWO and LEVINE] 992). Within the spinal cord. 5-HT can modulate sensory neurotransmission in a complex manner. as there is evidence for both pain facilitatory (5-HTIA and 5-HT2 receptors) and pain inhibitory actions (5-HT lB • 5-HT2 and 5-HT, receptors) (Sect. E). The spinal 5-HT system constitutes the area of termination of a descending system that originates in the brainstem and projects to the dorsal horn of the spinal cord. and is a significant substrate for antinociception by systemicany administered morphine as well as for analgesia mediated by stimulation of midbrain and brainstem sites (reviewed by BASBAUM and FIELDS 1984; BESSON and CHAOUCH 1987). At supraspinal sites, forehrain projections of 5-HT also can contribute to analgesia by morphine, as wen as providing a supraspinal circuitry that modifies pain transmission in ascending pain projection pathways (reviewed by LEBARS 1988;WANG and NAKAI 1994). In the present chapter. the focus is on the spinal regulation of nociception by the various 5-HT receptors which subserve the descending serotoninergic projection from the brainstem. and on the interactions of 5-HT receptors with endogenous systems within the spinal cord. B. Raphe-Spinal Serotoninergic Projections5-HT immunoreactive neurons within the dorsal horn of the spinal cord originate primarily within the rostroventral medulla, which includes the nucleus raphe magnus and adjacent reticular formation. with additional inputs from the caudal pons (BOWKER et a1. 1982;SKAGERBERG and BJORKLUND 1985; KWIAT and BASBAUM 1992). Descending 5-HT fibres project to the dorsal horn primarily via the ipsilateral dorsolateral funiculus. while those in more ventral areas

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“…I.t. administration of 6 OHDA reduced the NA levels in the spinal cord (17). On the other hand, 5,7-DHT has a neurotoxic mode of action on 5-HT neurons, and it also has this mode of action, to a lesser extent, on NA neurons in the CNS (18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Studies on Lappaconitine: Possible Interaction with Endogenous Noradrenergic and Serotonergic Pathways to Induce Antinociception.

Ono¹,

Satoh

1992

Jpn.J.Pharmacol

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Systemic and intracerebroventricular (i.c.v.) injections of lappaconitine (LA) produced a dose-dependent inhibition of the response to thermal stimulation in sham-operated mice as assayed by the tail-immersion test. After spinal transection, the antinociceptive potencies of s.c. or i.c.v.-administered LA were markedly re duced. Antinociception induced by systemically administered LA was clearly reduced by pretreatment with 6-hydroxydopamine or 5,7-dihydroxytryptamine through the i.c.v. and intrathecal (i.t.) routes. When LA was administered by 1. c.v. -injection, the LA-induced antinociception was reduced by pretreatment with timolol, a Q-adrenergic antagonist, and ketanserin, a 5-HT2 antagonist. Administration of LA by the i.t. route resulted in a significant antinociceptive activity, which was also reduced by pretreat ment with phenoxybenzamine, an a-adrenergic antagonist, and mianserin, a 5-HT1 antagonist. The results of these studies suggest that the central noradrenergic and serotonergic systems may be involved in the antinociception of systemically adminis tered LA, and these pathways are mediated by /9-adrenoceptors and 5-HT2 receptors in the brain and a-adrenoceptors and 5-HT, receptors in the spinal cord.In a previous paper, we demonstrated that lappaconitine (LA) had naloxone-resistant analgesic effects (1). Furthermore, we re ported that a supraspinal-spinal interaction was important for the production of the anti nociceptive action of systemically administered LA (2) and that LA acted at the supraspinal level to inhibit nociceptive transmission or to block the spinal action of nociceptive neuro transmitters via the descending pathways (3).It is well-known that the descending inhibi tory systems play an important role in pain modulation and analgesia, and central norad renergic and serotonergic pathways, particular ly bulbospinal pathways, may modulate the transmission in these systems (4, 5).The purpose of the present study was to ex amine the role of central noradrenergic and serotonergic systems in the antinociceptive ac tion of LA. MATERIALS AND METHODS AnimalsMale mice of the Std:ddY strain, weighing 20 to 30 g, were used. Mice were maintained in a temperature and humidity-controlled room (22-23T, 50-60%) and allowed free access to food and water.

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Evidence for the involvement of descending noradrenergic pathways in the antinociceptive effect of baclofen

Cited by 25 publications

References 30 publications

CGP 35348, a new GABA_B antagonist, prevents antinociception and muscle‐relaxant effect induced by baclofen

CGP 35348, a new GABA_B antagonist, prevents antinociception and muscle‐relaxant effect induced by baclofen

Modulation of Nociception by Descending Serotoninergic Projections

Pharmacological Studies on Lappaconitine: Possible Interaction with Endogenous Noradrenergic and Serotonergic Pathways to Induce Antinociception.

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Evidence for the involvement of descending noradrenergic pathways in the antinociceptive effect of baclofen

Cited by 25 publications

References 30 publications

CGP 35348, a new GABAB antagonist, prevents antinociception and muscle‐relaxant effect induced by baclofen

CGP 35348, a new GABAB antagonist, prevents antinociception and muscle‐relaxant effect induced by baclofen

Modulation of Nociception by Descending Serotoninergic Projections

Pharmacological Studies on Lappaconitine: Possible Interaction with Endogenous Noradrenergic and Serotonergic Pathways to Induce Antinociception.

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CGP 35348, a new GABA_B antagonist, prevents antinociception and muscle‐relaxant effect induced by baclofen

CGP 35348, a new GABA_B antagonist, prevents antinociception and muscle‐relaxant effect induced by baclofen