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Mechanism of GABA involvement in post‐traumatic trigeminal neuropathic pain: Activation of neuronal circuitry composed of PKCγ interneurons and pERK 1/2 expressing neurons
Author(s) -
Dieb W.,
Hafidi A.
Publication year - 2015
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.525
Subject(s) - neuropathic pain , vigabatrin , nociception , glutamate receptor , ionotropic effect , pharmacology , glutamate decarboxylase , medicine , trigeminal ganglion , gabaa receptor , neuroscience , trigeminal neuralgia , chemistry , anesthesia , psychology , sensory system , anticonvulsant , epilepsy , receptor , biochemistry , enzyme
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 ( GAD 67), 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 PKC γ staining, i.e., of its phosphorylated active form and the number of pERK 1/2 positive cells within the MDH . These two markers were highly expressed in allodynic MDH . Conclusion The circuitry composed of PKC γ and pERK 1/2 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 .