Inhibitory effects of clonidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by α-adrenergic receptor antagonists

Ono, Hideki; Mishima, Asuka; Ono, Shunsuke; Fukuda, Hideomi; Vasko, Michael R.

doi:10.1016/0028-3908(91)90077-o

Cited by 103 publications

(40 citation statements)

References 20 publications

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“…Identification of a role for the ␣ 2C AR in analgesia is consistent with its localization and with physiological responses to adrenergic agonists. Adrenergic agonists inhibit release of peptides from spinal cord slices (Ono et al, 1991) and inhibit dorsal horn nociceptive neurons (Fleetwood-Walker et al, 1985). These actions suggest both presynaptic localization on primary afferent terminals in dorsal horn and postsynaptic localization on spinal neurons.…”

Section: Discussionmentioning

confidence: 95%

α_2C-Adrenergic Receptors Mediate Spinal Analgesia and Adrenergic-Opioid Synergy

Fairbanks

Stone²,

Kitto³

et al. 2002

J Pharmacol Exp Ther

166

124

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The ␣ 2A -adrenergic receptor (AR) subtype mediates antinociception induced by the ␣ 2 AR agonists clonidine, dexmedetomidine, norepinephrine, and 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK-14,304) as well as antinociceptive synergy of UK-14,304 with opioid agonists [D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]-enkephalin and deltorphin II. Differential localization of ␣ 2 -adrenergic (␣ 2A -, ␣ 2B -, ␣ 2C -) and opioid (-, ␦-, -) subtypes suggests differential involvement of subtype pairs in opioid-adrenergic analgesic synergy. The present study applies a novel imidazoline 1 /␣ 2 -adrenergic receptor analgesic, moxonidine, to test for involvement of ␣ 2B -and ␣ 2C ARs in antinociception and antinociceptive synergy, because spinal antinociceptive activity of moxonidine shows minimal dependence on ␣ 2A AR. Intrathecal administration of moxonidine produced similar (2-3-fold) decreases in both mutant mice with a functional knockout of ␣ 2A AR (D79N-␣ 2A AR) and ␣ 2C AR knockout (KO) mice. The potency of moxonidine was not altered in ␣ 2B KO mice, indicating that this subtype does not participate in moxonidine-induced spinal antinociception. Moxonidine-mediated antinociception was dose dependently inhibited by the selective ␣ 2 -receptor antagonist SK&F 86466 in both D79N-␣ 2A mice and ␣ 2C KO mice, indicating that ␣ 2 AR activation is required in the absence of either ␣ 2A -or ␣ 2C AR. Spinal administration of antisense oligodeoxynucleotides directed against the ␣ 2C AR decreased both ␣ 2C AR immunoreactivity and the antinociceptive potency of moxonidine. Isobolographic analysis demonstrates that moxonidine-deltorphin antinociceptive synergy is present in the D79N-␣ 2A mice but not in the ␣ 2C AR-KO mice. These results confirm that the ␣ 2C AR subtype contributes to spinal antinociception and synergy with opioids.

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Section: Discussionmentioning

confidence: 95%

α_2C-Adrenergic Receptors Mediate Spinal Analgesia and Adrenergic-Opioid Synergy

Fairbanks

Stone²,

Kitto³

et al. 2002

J Pharmacol Exp Ther

166

124

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“…On the other hand, α 2 -adrenergic receptor agonists may have other functions in the nervous system through the regulation of the release of other neurotransmitters or by the activation of postsynaptic α 2 -adrenergic receptors (e.g. Ono et al, 1991 andCinelli et al, 2013 for further Refs.). Another study (Mutolo et al, 2014) investigated the regulation of the cough reflex by galanin (a neuropeptide implicated in pain control) at the level of the NTS, where galanin receptors are known to be present (Endoh et al, 2008).…”

Section: Cough Downregulation By Drugs Relevant To Chronic Pain Treatmentioning

confidence: 99%

Brainstem mechanisms underlying the cough reflex and its regulation

Mutolo

2017

Respiratory Physiology & Neurobiology

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A B S T R A C TCough is a very important airway protective reflex. Cough-related inputs are conveyed to the caudal nucleus tractus solitarii (cNTS) that projects to the brainstem respiratory network. The latter is reconfigured to generate the cough motor pattern. A high degree of modulation is exerted on second-order neurons and the brainstem respiratory network by sensory inputs and higher brain areas. Two medullary structures proved to have key functions in cough production and to be strategic sites of action for centrally active drugs: the cNTS and the caudal ventral respiratory group (cVRG). Drugs microinjected into these medullary structures caused downregulation or upregulation of the cough reflex. The results suggest that inhibition and disinhibition are prominent regulatory mechanisms of this reflex and that both the cNTS and the cVRG are essential in the generation of the entire cough motor pattern. Studies on the basic neural mechanisms subserving the cough reflex may provide hints for novel therapeutic approaches. Different proposals for further investigations are advanced.

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“…administration, antinociception activity increased. These findings are difficult to explain, but previous works have demonstrated that Pra had no effect (Solomon et al, 1989), antagonized (Ono et al, 1991;Danzebrink & Gebhart, 1990) or increased (Brenner et al, 1994) Howe et al, 1983;Murata et al, 1989;Ossipov et al, 1988;Danzebrink & Gebhart, 1990;Kumar et al, 1993;Naguib & Yaksh, 1994. The results obtained with Pra and Yoh in the chemical acetic acid nociceptive test, independent of their pharmacological profile, suggest that a,-and a2-adrenoceptors, either located at pre-and/or post-synaptic level, are involved in the control of spinal antinociception.…”

Section: Analysis Of Resultsmentioning

confidence: 40%

α‐Adrenoceptor and opioid receptor modulation of clonidine‐induced antinociception

Sierralta

Naquira

Pinardi

et al. 1996

British J Pharmacology

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1The antinociceptive action of clonidine (Clon) and the interactions with a,, a2 adrenoceptor and opioid receptor antagonists was evaluated in mice by use of chemical algesiometric test (acetic acid writhing test).2 Clon produced a dose-dependent antinociceptive action and the ED50 for intracerebroventricular (i.c.v.) was lower than for intraperitoneal (i.p.) administration (1 ng kg-' vs 300 ng kg-'). The parallelism of the dose-response curves indicates activation of a common receptor subtype. 3 Systemic administration of prazosin and terazosin displayed antinociceptive activity. Pretreatment with prazosin produced a dual action: i.c.v. Clon effect did not change, and i.p. Clon effect was enhanced. Yohimbine i.c.v. or i.p. did not induce antinonciception, but antagonized Clon-induced activity. These results suggest that al-and a2-adrenoceptors, either located at the pre-and/or postsynaptic level, are involved in the control of spinal antinociception.4 Naloxone (NX) and naltrexone (NTX) induced antinociceptive effects at low doses (pg kg-' range) and a lower antinociceptive effect at higher doses (mg kg-' range). Low doses of NX or NTX antagonized Clon antinociception, possibly in relation to a preferential p opioid receptor antagonism. In contrast, high doses of NX or NTX increased the antinociceptive activity of Clon, which could be due to an enhanced inhibition of the release of substance P. 5 The results obtained in the present work suggest the involvement of al-, x2-adrenoceptor and opioid receptors in the modulation of the antinociceptive activity of clonidine, which seems to be exerted either at spinal and/or supraspinal level.

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Inhibitory effects of clonidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by α-adrenergic receptor antagonists

Cited by 103 publications

References 20 publications

α_2C-Adrenergic Receptors Mediate Spinal Analgesia and Adrenergic-Opioid Synergy

α_2C-Adrenergic Receptors Mediate Spinal Analgesia and Adrenergic-Opioid Synergy

Brainstem mechanisms underlying the cough reflex and its regulation

α‐Adrenoceptor and opioid receptor modulation of clonidine‐induced antinociception

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Inhibitory effects of clonidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by α-adrenergic receptor antagonists

Cited by 103 publications

References 20 publications

α2C-Adrenergic Receptors Mediate Spinal Analgesia and Adrenergic-Opioid Synergy

α2C-Adrenergic Receptors Mediate Spinal Analgesia and Adrenergic-Opioid Synergy

Brainstem mechanisms underlying the cough reflex and its regulation

α‐Adrenoceptor and opioid receptor modulation of clonidine‐induced antinociception

Contact Info

Product

Resources

About

α_2C-Adrenergic Receptors Mediate Spinal Analgesia and Adrenergic-Opioid Synergy

α_2C-Adrenergic Receptors Mediate Spinal Analgesia and Adrenergic-Opioid Synergy