HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Secondary mechanical allodynia and hyperalgesia depend on descending facilitation mediated by spinal 5-HT₄, 5-HT₆ and 5-HT₇ receptors.

Abstract
In the present study we determined the role of spinal 5-hydroxytriptamine (5-HT) and 5-HT(4/6/7) receptors in the long-term secondary mechanical allodynia and hyperalgesia induced by formalin in the rat. Formalin produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-term secondary mechanical allodynia and hyperalgesia in both paws. In addition, formalin increased the tissue content of 5-HT in the ipsilateral, but not contralateral, dorsal part of the spinal cord compared to control animals. Intrathecal (i.t.) administration of 5,7-dihydroxytriptamine (5,7-DHT), a serotonergic neurotoxin, diminished tissue 5-HT content in the ipsilateral and contralateral dorsal parts of the spinal cord. Accordingly, i.t. 5,7-DHT prevented formalin-induced secondary allodynia and hyperalgesia in both paws. I.t. pre-treatment (-10 min) with ML-10302 (5-HT(4) agonist), EMD-386088 (5-HT(6) agonist) and LP-12 (5-HT(7) agonist) significantly increased secondary mechanical allodynia and hyperalgesia in both paws. In contrast, i.t. pre-treatment (-20 min) with GR-125487 (5-HT(4) antagonist), SB-258585 (5-HT(6) antagonist) and SB-269970 (5-HT(7) antagonist) significantly prevented formalin-induced long-term effects in both paws. In addition, these antagonists prevented the pro-nociceptive effect of ML-10302, EMD-386088 and LP-12, respectively. The i.t. post-treatment (6 days after formalin injection) with GR-125487, SB-258585 and SB-269970 reversed formalin-induced secondary allodynia and hyperalgesia in both paws. These results suggest that spinal 5-HT, released from the serotonergic projections in response to formalin injection, activates pre- or post-synaptic 5-HT(4/6/7) receptors at the dorsal root ganglion/spinal cord promoting the development and maintenance of secondary allodynia and hyperalgesia.
AuthorsB Godínez-Chaparro, F J López-Santillán, P Orduña, V Granados-Soto
JournalNeuroscience (Neuroscience) Vol. 222 Pg. 379-91 (Oct 11 2012) ISSN: 1873-7544 [Electronic] United States
PMID22796074 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
Chemical References
  • 2-piperidinoethyl 4-amino-5-chloro-2-methoxybenzoate
  • 5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole
  • Indoles
  • Phenols
  • Piperazines
  • Piperidines
  • Pyridines
  • Receptors, Serotonin
  • SB 258585
  • SB 269970
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Sulfonamides
  • para-Aminobenzoates
  • serotonin 6 receptor
  • serotonin 7 receptor
  • Receptors, Serotonin, 5-HT4
  • Formaldehyde
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • GR 113808
Topics
  • 5,7-Dihydroxytryptamine (pharmacology)
  • Animals
  • Female
  • Formaldehyde
  • Hyperalgesia (chemically induced, physiopathology)
  • Indoles (pharmacology)
  • Injections, Spinal
  • Phenols (pharmacology)
  • Piperazines (pharmacology)
  • Piperidines (pharmacology)
  • Pyridines (pharmacology)
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin (drug effects, physiology)
  • Receptors, Serotonin, 5-HT4 (drug effects, physiology)
  • Serotonin (metabolism)
  • Serotonin Antagonists (pharmacology)
  • Serotonin Receptor Agonists (pharmacology)
  • Spinal Cord (drug effects, metabolism, physiopathology)
  • Sulfonamides (pharmacology)
  • para-Aminobenzoates (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: