Antinociceptive effects of thyrotrophin-releasing hormone and its analogues in the rat periaqueductal grey region

Webster, V.A.D.; Griffiths, E.C.; Slater, P.

doi:10.1016/0304-3940(83)90423-8

Cited by 33 publications

(6 citation statements)

References 6 publications

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“…The present finding that the antinociception produced by taltirelin is mediated by its action on the supraspinal structures is consistent with previous studies using TRH and its analogues ( Boschi et al ., 1983 ; Webster et al ., 1983 ; Zhukov et al ., 1988 ; Reny‐Palasse et al ., 1989 ). When administered systemically in rodents, taltirelin has about 30–100 times more potent CNS activity and 50 times weaker endocrine activity than TRH ( Suzuki et al ., 1990 ; Yamamura et al ., 1990 ).…”

Section: Discussionmentioning

confidence: 99%

“…The periaqueductal gray matter (PAG) has excitatory projections to the 5‐hydroxytryptaminergic nucleus raphe magnus and the noradrenergic locus coeruleus, A5 and A7 cell groups ( Basbaum and Fields, 1979 ; Willis et al ., 1984 ; Cameron et al ., 1995 ), which send descending 5‐hydroxytryptaminergic and noradrenergic projections to the spinal cord, respectively. Injection of TRH and its analogues to the PAG generates antinociception ( Webster et al ., 1983 ). Consistently, stimulation of the PAG inhibits nociceptive dorsal horn neurons concomitantly with the release of NA and 5‐HT ( Cui et al ., 1999 ).…”

Section: Discussionmentioning

confidence: 99%

“…Thyrotropin‐releasing hormone (TRH), a neuropeptide discovered originally as a pituitary hormone, has been shown to be distributed widely in the central nervous system (CNS), where it acts as a neurotransmitter or a neuromodulator ( Winokur and Utiger, 1974 ; Hökfelt et al ., 1975 ; Wu et al ., 1992 ) and exerts a variety of CNS effects that are not related to its endocrine activity in releasing thyroid‐stimulating hormone. When administered exogenously, TRH produces various behavioral changes including an increase in locomotor activity ( Andrews and Sahgal, 1983 ; Yamamura et al ., 1991 ), appearance of serotonin syndrome‐like activities ( Fone et al ., 1989 ; Funk et al ., 1997 ) and antinociceptive effects against noxious stimuli ( Boschi et al ., 1983 ; Webster et al ., 1983 ; Kawamura et al ., 1985 ; Reny‐Palasse et al ., 1989 ). In addition, clinical and preclinical studies have demonstrated a protective role of TRH against epilepsy ( Matsumoto et al ., 1987 ; Ujihara et al ., 1991 ; Broberger and McCormick, 2005 ) and neurodegeneration ( Pizzi et al ., 1999 ; Jaworska‐Feil et al ., 2001 , Urayama et al ., 2002 ).…”

Section: Introductionmentioning

confidence: 99%

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The synthetic TRH analogue taltirelin exerts modality‐specific antinociceptive effects via distinct descending monoaminergic systems

Tanabe

Tokuda

Takasu

et al. 2007

British J Pharmacology

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Background and purpose: Exogenously administered thyrotropin-releasing hormone (TRH) is known to exert potent but short-acting centrally-mediated antinociceptive effects. We sought to investigate the mechanisms underlying these effects using the synthetic TRH analogue taltirelin, focusing on the descending monoaminergic systems in mice. Experimental approach: The mice received systemic or local injections of taltirelin combined with either central noradrenaline (NA) or 5-hydroxytryptamine (5-HT) depletion by 6-hydroxydopamine (6-OHDA) or DL-p-chlorophenylalanine (PCPA), respectively, or blockade of their receptors. The degree of antinociception was determined using the tail flick and tail pressure tests. Key results: Subcutaneously (s.c.) administered taltirelin exhibited dose-dependent antinociceptive effects in the tail flick and tail pressure tests. These effects appeared to be primarily supraspinally mediated, since intracerebroventricularly (i.c.v.) but not intrathecally (i.t.) injected taltirelin generated similar effects. Depletion of central NA abolished only the analgesic effect of taltirelin (s.c. and i.c.v.) on mechanical nociception. By contrast, depletion of central 5-HT abolished only its analgesic effect on thermal nociception. Intraperitoneal (i.p.) and i.t. injection of the a 2 -adrenoceptor antagonist yohimbine respectively reduced the analgesic effect of taltirelin (s.c. and i.c.v.) on mechanical nociception. By contrast, the 5-HT 1A receptor antagonist WAY-100635 (i.p. and i.t.) reduced the effect of taltirelin (s.c. and i.c.v.) on thermal nociception. Neither the 5-HT 2 receptor antagonist ketanserin nor the opioid receptor antagonist naloxone altered the antinociceptive effect of taltirelin. Conclusions and Implications: These findings suggest that taltirelin activates the descending noradrenergic and serotonergic pain inhibitory systems, respectively, to exert its analgesic effects on mechanical and thermal nociception.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The synthetic TRH analogue taltirelin exerts modality‐specific antinociceptive effects via distinct descending monoaminergic systems

Tanabe

Tokuda

Takasu

et al. 2007

British J Pharmacology

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“…The response latency is the time interval from administration of the stimulus to withdrawal of the tail from the stimulus. Latency time is increased by TAL in WT mice (Webster et al, 1983). TAL increased the response latency by 65 and 70%, respectively, in WT and R2ko mice but had no effect in R1ko and R1/R2ko mice (Figure 4).…”

Section: Taltirelin and Trh Receptors Type 1 And 2 N Thirunarayanan Ementioning

confidence: 91%

Thyrotropin-Releasing Hormone Receptor Type 1 (TRH-R1), not TRH-R2, Primarily Mediates Taltirelin Actions in the CNS of Mice

Thirunarayanan

Nir

Raaka

et al. 2012

Neuropsychopharmacol

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Thyrotropin-releasing hormone receptor type 2 (TRH-R2), not TRH-R1, has been proposed to mediate the CNS effects of TRH and its more effective analog taltirelin (TAL). Consistent with this idea, TAL exhibited higher binding affinity and signaling potency at mouse TRH-R2 than TRH-R1 in a model cell system. We used TRH-R1 knockout (R1ko), R2ko and R1/R2ko mice to determine which receptor mediates the CNS effects of TAL. There was no TRH-R1 mRNA in R1ko and R1/R2ko mice and no TRH-R2 mRNA in R2ko and R1/R2ko mice. Specific [ 3 H]MeTRH binding to whole brain membranes was 5% of wild type (WT) for R1ko mice, 100% for R2ko mice and 0% for R1/R2ko mice, indicating TRH-R1 is the predominant receptor expressed in the brain. In arousal assays, TAL shortened sleep time with pentobarbital sedation in WT and R2ko mice by 44 and 49% and with ketamine/xylazine sedation by 66 and 55%, but had no effect in R1ko and R1/R2ko mice. In a tail flick assay of nociception, TAL increased response latency by 65 and 70% in WT and R2ko mice, but had no effect in R1ko and R1/R2ko mice. In a tail suspension test of depression-like behavior, TAL increased mobility time by 49 and 37% in WT and R2ko mice, but had no effect in R1ko and R1/R2ko mice. Thus, in contrast to the generally accepted view that the CNS effects of TAL are mediated by TRH-R2, these effects are mediated primarily if not exclusively by TRH-R1 in mice. Neuropsychopharmacology (2013) 38, 950-956;

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“…(for reviews, see Jackson, 1982;Griffiths and Bennett, 1983;Burt and Sharif, 1984;Griffiths, 1985;Sharif, 19851;Horita et al, 1986). Recently, TRH and its analogs have proved beneficial in reducing spasticity and muscle weakness associated with motoneuron disease (Engel et al, 1983) and in reversing hypovolemic shock (Holaday et al, 198 1;Amir et al, 1984), and TRH has exhibited antinociceptive activity (Boschi et al, 1983;Webster et al, 1983). These diverse actions of TRH appear to be mediated via high-affinity and pharmacologically distinct TRH receptors which also display a heterogeneous brain regional distribution (Ogawa et al, 198 1;Taylor and Burt, 1982;, 1984Pilotte et al, 1984;Manaker et al, 1985;Man-tyh and Hunt, 1985;Pazos et al, 1985), with high receptor density being associated with the retina and the limbic regions.…”

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confidence: 99%

Chemical and Surgical Lesions of Rat Olfactory Bulb: Changes in Thyrotropin‐Releasing Hormone and Other Systems

Sharif

1988

Journal of Neurochemistry

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Stereotaxic injection of kainic acid (15 micrograms) into rat olfactory bulbs was accompanied by a 53% (n = 4; p less than 0.02) depletion of endogenous thyrotropin-releasing hormone (TRH) as compared to sham-operated controls 2 weeks postlesion. TRH levels remained unaltered in three other caudal regions. Bulbar kainate lesions produced a 58% (n = 5; p less than 0.001) decrease in TRH receptor binding capacity without affecting the receptor affinity. Kainate lesions also reduced bulbar muscarinic and benzodiazepine receptors by 60% and 48%, respectively. Again, no changes in TRH receptors were apparent in six other brain areas after bulbar kainate treatment. Injection of the dopaminergic neurotoxin, 6-hydroxydopamine (8 micrograms), into rat bulbs decreased TRH receptors by 35% (n = 4; p less than 0.05) 1 week postlesion. One month after surgical bulbectomy, TRH and TRH receptor levels in a number of brain areas were unaltered compared to those of control animals. These studies suggest that TRH in the olfactory bulb originates intrinsically and may be produced predominantly for local use. Secondly, TRH receptors in the bulb appear to be postsynaptically localized on intrinsic neurons, although a small proportion are also associated with presynaptic elements of dopaminergic noradrenergic neurons. Bulbar TRH receptors exhibited nanomolar affinity and a pharmacological selectivity akin to that of the pituitary gland and other brain regions.

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Antinociceptive effects of thyrotrophin-releasing hormone and its analogues in the rat periaqueductal grey region

Cited by 33 publications

References 6 publications

The synthetic TRH analogue taltirelin exerts modality‐specific antinociceptive effects via distinct descending monoaminergic systems

The synthetic TRH analogue taltirelin exerts modality‐specific antinociceptive effects via distinct descending monoaminergic systems

Thyrotropin-Releasing Hormone Receptor Type 1 (TRH-R1), not TRH-R2, Primarily Mediates Taltirelin Actions in the CNS of Mice

Chemical and Surgical Lesions of Rat Olfactory Bulb: Changes in Thyrotropin‐Releasing Hormone and Other Systems

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