Intrathecal galanin potentiates the spinal analgesic effect of morphine: Electrophysiological and behavioural studies

Wiesenfeld‐Hallin, Zsuzsanna; Xu, Xiao‐Jun; Mj, Villar; Hökfelt, Tomas

doi:10.1016/0304-3940(90)90566-r

Cited by 96 publications

(20 citation statements)

References 19 publications

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“…Therefore, it does seem unlikely that the proconflict/anxiogenic-like effect observed in the present study was attributable to a suppression of thirst or other appetitive motivation by galanin. Furthermore, although antinociceptive effects of central galanin have been reported after intrathecal administration (Wiesenfeld-Hallin et al 1990), it is unlikely that the suppression of punished drinking observed in the present study was related to this type of galanin action, because shock thresholds were unaffected by intra-amygdala galanin treatment. Moreover, no effects of intra-amygdala galanin were seen on locomotor activity, or over-all activity on the plus-maze.…”

Section: Discussioncontrasting

confidence: 50%

“…Numerous studies have pointed out possible effects of galanin; a role for the peptide has been proposed in memory function (Ögren et al 1992), food intake (Kyrkouli et al 1990) and endocrine control . Galanin receptor agonists are thought to relieve pain (Wiesenfeld-Hallin et al 1990) and prevent ischaemic damage (Ari and Lazdunski, 1989), and galanin receptor antagonists are being tried in the treatment of depression (Seutin et al 1989), feeding disorders, and Alzheimers disease (Chan-Palay, 1988).…”

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confidence: 99%

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Anxiogenic-Like Action of Galanin after Intra-Amygdala Administration in the Rat

Möller

1999

Neuropsychopharmacology

104

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Section: Discussioncontrasting

confidence: 50%

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confidence: 99%

Anxiogenic-Like Action of Galanin after Intra-Amygdala Administration in the Rat

Möller

1999

Neuropsychopharmacology

104

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“…In this context, it should be also recalled that galanin antagonizes substance P-evoked hyperalgesia (23,70; see Ref. 69 also for further references) and that its antinociceptive effects involve opioid receptors and display positive interactions with NMDA receptor antagonists (22,25,62,66; see Ref. 69 also for further references).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory control of the cough reflex by galanin receptors in the caudal nucleus tractus solitarii of the rabbit

Mutolo

Cinelli

Bongianni

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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The caudal nucleus tractus solitarii (NTS) is the main central station of cough-related afferents and a strategic site for the modulation of the cough reflex. The similarities between the characteristics of central processing of nociceptive and cough-related inputs led us to hypothesize that galanin, a neuropeptide implicated in the control of pain, could also be involved in the regulation of the cough reflex at the level of the NTS, where galanin receptors have been found. We investigated the effects of galanin and galnon, a nonpeptide agonist at galanin receptors, on cough responses to mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. Drugs were microinjected (30 -50 nl) into the caudal NTS of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Galnon antitussive effects on cough responses to the mechanical stimulation of the airway mucosa via a custom-built device were also investigated. Bilateral microinjections of 1 mM galanin markedly decreased cough number, peak abdominal activity, and increased cough-related total cycle duration. Bilateral microinjections of 1 mM galnon induced mild depressant effects on cough, whereas bilateral microinjections of 10 mM galnon caused marked antitussive effects consistent with those produced by galanin. Galnon effects were confirmed by using the cough-inducing device. The results indicate that galanin receptors play a role in the inhibitory control of the cough reflex at the level of the caudal NTS and provide hints for the development of novel antitussive strategies. airway defensive reflexes; galanin; galanin receptors; galnon; nucleus tractus solitarii COUGH IS A VERY IMPORTANT airway protective reflex and is one of the most common reason why patients seek medical attention. Cough is purposeful and useful under many circumstances, but in case of persistent or chronic cough (e.g., 15) is without an apparent aim and benefit and can results in a wide range of physical and psychological complications including urinary incontinence, insomnia, depression, and anxiety. The efficacy of antitussive drugs is far from clear from the available evidence and, in addition, limited by important side effects. Therefore, further research to find better antitussive approaches is necessary (for reviews see Refs. 4 and 15). Studies undertaken to provide insights into the neural mechanisms subserving the cough reflex may also provide useful suggestions for novel antitussive therapeutic strategies. The cough reflex involves several brain stem structures that also underlie respiratory rhythm generation (e.g., 7,9,10,19,24,27,[47][48][49]55).In particular, the nucleus tractus solitarii (NTS), especially in its caudal aspects, is the main central terminus of cough-related afferents (14, 39 -41, 43, 53 also for further references) and, in addition, a possible strategic site of synaptic plasticity, where cough-related sensory inputs can be modulated (e.g., 10,14,34,39,40,43).In recent years, we and other researchers have focused our attention on the s...

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“…A number of studies have suggested that galanin agonists could have pharmacological value as analgesics because intrathecal galanin administration potentiates morphine analgesia (predominantly in models of chronic pain), and thus, lower morphine doses could be coadministered with galanin to produce an analgesic effect (41)(42)(43)(44)(45). In addition, galanin antagonizes morphine place preference (2).…”

Section: Discussionmentioning

confidence: 99%

The neuropeptide galanin modulates behavioral and neurochemical signs of opiate withdrawal

Zachariou

Brunzell

Hawes

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Much research has focused on pathways leading to opiate addiction. Pathways opposing addiction are more difficult to study but may be critical in developing interventions to combat drug dependence and withdrawal. Galanin decreases firing of locus coeruleus neurons, an effect hypothesized to decrease signs of opiate withdrawal. The current study addresses whether galanin affects morphine withdrawal signs by using a galanin agonist, galnon, that crosses the blood-brain barrier, and mice genetically engineered to under-or overexpress galanin peptide. Galnon significantly decreased morphine withdrawal signs in C57BL͞6 mice. Further, knockout mice lacking galanin showed exacerbated morphine withdrawal signs, suggesting that endogenous galanin normally counteracts opiate withdrawal. Transgenic mice overexpressing galanin in noradrenergic neurons also showed decreased morphine withdrawal signs, suggesting a possible neuroanatomical locus for these effects of galanin. Both c-fos immunoreactivity, a marker of neuronal activity, and phosphorylation of tyrosine hydroxylase at Ser-40, a marker of cAMP levels, are decreased in the locus coeruleus by galnon treatment after morphine withdrawal, suggesting a possible molecular mechanism for the behavioral effects of galanin. These studies suggest that galanin normally acts to counteract opiate withdrawal and that small molecule galanin agonists could be effective in diminishing the physical signs of withdrawal.

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Intrathecal galanin potentiates the spinal analgesic effect of morphine: Electrophysiological and behavioural studies

Cited by 96 publications

References 19 publications

Anxiogenic-Like Action of Galanin after Intra-Amygdala Administration in the Rat

Anxiogenic-Like Action of Galanin after Intra-Amygdala Administration in the Rat

Inhibitory control of the cough reflex by galanin receptors in the caudal nucleus tractus solitarii of the rabbit

The neuropeptide galanin modulates behavioral and neurochemical signs of opiate withdrawal

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