PMID- 17220907
OWN - NLM
STAT- MEDLINE
DCOM- 20070417
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Linking)
VI  - 150
IP  - 4
DP  - 2007 Feb
TI  - The synthetic TRH analogue taltirelin exerts modality-specific antinociceptive 
      effects via distinct descending monoaminergic systems.
PG  - 403-14
AB  - 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 
      alpha2-adrenoceptor antagonist yohimbine respectively reduced the analgesic 
      effect of taltirelin (s.c. and i.c.v.) on mechanical nociception. By contrast, 
      the 5-HT1A 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-HT2 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.
FAU - Tanabe, M
AU  - Tanabe M
AD  - Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, 
      Nagoya City University, Nagoya, Japan. mitana@phar.nagoya-cu.ac.jp
FAU - Tokuda, Y
AU  - Tokuda Y
FAU - Takasu, K
AU  - Takasu K
FAU - Ono, K
AU  - Ono K
FAU - Honda, M
AU  - Honda M
FAU - Ono, H
AU  - Ono H
LA  - eng
PT  - Journal Article
DEP - 20070115
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Adrenergic alpha-Antagonists)
RN  - 0 (Analgesics)
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Serotonin Agents)
RN  - 0 (Sympatholytics)
RN  - 103300-74-9 (TA 0910)
RN  - 2Y49VWD90Q (Yohimbine)
RN  - 333DO1RDJY (Serotonin)
RN  - 36B82AMQ7N (Naloxone)
RN  - 5Y5F15120W (Thyrotropin-Releasing Hormone)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - 9002-71-5 (Thyrotropin)
RN  - 97F9DE4CT4 (Ketanserin)
RN  - R5J7E3L9SP (Fenclonine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Adrenergic alpha-Antagonists/pharmacology
MH  - *Analgesics
MH  - Animals
MH  - Biogenic Monoamines/*physiology
MH  - Dose-Response Relationship, Drug
MH  - Fenclonine/pharmacology
MH  - Hot Temperature
MH  - Injections, Intraventricular
MH  - Injections, Spinal
MH  - Injections, Subcutaneous
MH  - Ketanserin/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Naloxone/pharmacology
MH  - Narcotic Antagonists/pharmacology
MH  - Neural Pathways/drug effects
MH  - Norepinephrine/physiology
MH  - Oxidopamine/pharmacology
MH  - Pain Measurement/drug effects
MH  - Physical Stimulation
MH  - Reaction Time/drug effects
MH  - Serotonin/physiology
MH  - Serotonin Agents/pharmacology
MH  - Sympatholytics/pharmacology
MH  - Thyrotropin/*analogs & derivatives
MH  - Thyrotropin-Releasing Hormone/*analogs & derivatives/pharmacology
MH  - Yohimbine/pharmacology
PMC - PMC2189720
EDAT- 2007/01/16 09:00
MHDA- 2007/04/18 09:00
PMCR- 2008/02/01
CRDT- 2007/01/16 09:00
PHST- 2007/01/16 09:00 [pubmed]
PHST- 2007/04/18 09:00 [medline]
PHST- 2007/01/16 09:00 [entrez]
PHST- 2008/02/01 00:00 [pmc-release]
AID - 0707125 [pii]
AID - 10.1038/sj.bjp.0707125 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2007 Feb;150(4):403-14. doi: 10.1038/sj.bjp.0707125. Epub 2007 
      Jan 15.