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Mechanism of GABA involvement in post-traumatic trigeminal neuropathic pain: Activation of neuronal circuitry composed of PKCgamma interneurons and pERK1/2 expressing neurons.

Authors: Dieb, W  Hafidi, A 
Citation: Dieb W and Hafidi A, Eur J Pain. 2014 May 28. doi: 10.1002/ejp.525.
Pubmed: (View Article at PubMed) PMID:24890317
DOI: Full-text: DOI:10.1002/ejp.525

BACKGROUND: GABA disinhibition within the spinal dorsal horn has been implicated in pain hypersensitivity on injury in different neuropathic models. However, GABA alteration has been explored in only one study on trigeminal neuropathic pain. METHODS: The present study investigated the implication of GABA in trigeminal dynamic mechanical allodynia (DMA) obtained after chronic constriction of the infraorbital nerve (CCI-IoN), and explored the cellular and molecular mechanisms by which GABA dysfunction induced DMA. RESULTS: Our data demonstrated a significant decrease in labelling in two GABA cell markers, glutamate acid decarboxylase (GAD67), and parvalbumin, in the medullary dorsal horn (MDH) of allodynic rats in comparison to sham rats. Increasing GABA by intracisternal injections of vigabatrin (VGB), a blocker of the catabolic enzyme GABA transaminase, alleviated pain behaviour and restored normal GABA cell marker expression in allodynic MDH. Interestingly, intracisternal VGB administration also significantly decreased PKCgamma staining, i.e., of its phosphorylated active form and the number of pERK1/2 positive cells within the MDH. These two markers were highly expressed in allodynic MDH. CONCLUSION: The circuitry composed of PKCgamma and pERK1/2 cells is silent under physiological conditions but is activated after CCI-IoN, therefore, switching touch stimuli to pain sensation. The decrease of GABA transmission constituted a key factor in the activation of this neuronal circuitry, which opens the gate for non-noxious stimuli to reach nociceptive projection neurons in lamina I.

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RGD Object Information
RGD ID: 9588557
Created: 2014-10-30
Species: All species
Last Modified: 2014-10-30
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.