Neuropathic pain - page 12 Scientific Publications

Latest publication 08/08/2010

Disrupting 5-HT2A Receptor and PDZ Protein Interactions Reduces Hyperalgesia and

Antidepressants are one of the first-line treatments for neuropathic pain. Despite the influence of serotonin (5-hydroxytryptamine, 5-HT) in pain...

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    [title] => Disrupting 5-HT2A Receptor and PDZ Protein Interactions Reduces Hyperalgesia and
    [paragraph] => Disrupting 5-HT2A Receptor/PDZ Protein Interactions Reduces Hyperalgesia and Enhances SSRI Efficacy in Neuropathic Pain. 
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Authors
X. Pichon, A. Wattiez, C. Becamel, I. Ehrlich, J. Bockaert, et al. 

 Lab
Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la Douleur, Clermont-Ferrand, France.
Journal
Molecular Therapy
Abstract
Antidepressants are one of the first-line treatments for neuropathic pain. Despite the influence of serotonin (5-hydroxytryptamine, 5-HT) in pain modulation, selective serotonin reuptake inhibitors (SSRIs) are less effective than tricyclic antidepressants. Here, we show, in diabetic neuropathic rats, an alteration of the antihyperalgesic effect induced by stimulation of 5-HT(2A) receptors, which are known to mediate SSRI-induced analgesia. 5-HT(2A) receptor density was not changed in the spinal cord of diabetic rats, whereas postsynaptic density protein-95 (PSD-95), one of the PSD-95/disc large suppressor/zonula occludens-1 (PDZ) domain containing proteins interacting with these receptors, was upregulated. Intrathecal injection of a cell-penetrating peptidyl mimetic of the 5-HT(2A) receptor C-terminus, which disrupts 5-HT(2A) receptor-PDZ protein interactions, induced an antihyperalgesic effect in diabetic rats, which results from activation of 5-HT(2A) receptors by endogenous 5-HT. The peptide also enhanced antihyperalgesia induced by the SSRI fluoxetine. Its effects likely resulted from an increase in receptor responsiveness, because it revealed functional 5-HT(2A) receptor-operated Ca(2+) responses in neurons, an effect mimicked by knockdown of PSD-95. Hence, 5-HT(2A) receptor/PDZ protein interactions might contribute to the resistance to SSRI-induced analgesia in painful diabetic neuropathy. Disruption of these interactions might be a valuable strategy to design novel treatments for neuropathic pain and to increase the effectiveness of SSRIs.
BIOSEB Instruments Used
Grip strength test (BIO-GS3)

Keywords/Topics
Neuropathic pain; Mechanical allodynia & Hyperlagesia; Pain
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An easy way to objectively quantify the muscular strength of mice and rats, and to assess the effect of drugs, toxins, muscular (i.e. myopathy) and neurodegenerative diseases on muscular degeneration. It is widely used in conjunction with the ROTAROD motor coordination test: a normally coordinated rodent will show a decreased latency to fall off the rotating rod if its muscular strength is low. The Grip Strength Test is a must for your research on activity, motor control & coordination, and is particularly well suited for studies on Parkinson's & Huntington's disease.
New features GS4 - 2023: Color display with permanent backlight screen for easier reading, reset by footswitch, Improved battery time, Larger data memory of 500 values, Animal counter, USB port (charging/data transfer)

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