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Protéine kinase C γ et hypersensibilité mécanique trigéminale chez le rat

Abstract : Inflammatory and neuropathic chronic pain syndromes are characterized by pain hypersensitivy, manifest as spontaneous pain, allodynia and hyperalgesia. The γ isoform of protein kinase C (PKCγ), which is concentrated in a specific class of interneurons within inner lamina II (IIi) of the spinal (SDH) and medullary (MDH) dorsal horns, has been implicated in the central mechanisms underlying mechanical allodynia, a condition wherein touch produces pain. We used behavioral and immunohistochemical techniques in the trigeminal system.Whereas there is clear evidence for the involvement of PKCγ in neuropathic mechanical allodynia, that for the involvement of PKCγ in inflammatory mechanical allodynia is still controversial. We investigated the involvement of PKCγ into the persistent mechanical allodynia induced by complete Freund’s adjuvant (CFA) inflammation. Subcutaneous injection of CFA into the vibrissa pad of rats induced a persistent selectively static mechanical allodynia. Monitoring neuronal activity within medullary dorsal horn (MDH) with phospho-ERK1/2 immunoreactivity showed that activation of both laminae I-IIo and IIi-IIIo neurons, including lamina IIi PKCγ-expressing interneurons, was associated with the expression of static mechanical allodynia. Intracisternal injection of the selective PKCγ antagonist, KIG31-1, prevented CFA-induced static mechanical allodynia only when it was injected before, but not 3 days after, CFA injection. These results show that, as for neuropathic mechanical allodynias, PKCγ activation is necessary for inflammatory mechanical allodynia.We also examined whether PKCγ activation in naïve animals is sufficient for the establishment of mechanical allodynia. Intracisternal injection of the phorbol ester, 12,13-dibutyrate (PDBu), concomitantly induced static and dynamic facial mechanical allodynias Monitoring neuronal activity within MDH with phospho-ERK1/2 immunoreactivity revealed that the same activation of both laminae I-IIo and IIi-IIIo neurons, including lamina IIi PKCγ-expressing interneurons, was associated with the manifestation of both mechanical allodynias. PDBu-induced mechanical allodynias and associated neuronal activations were all prevented by intracisternal KIG31-1.Our findings reveal that PKCγ activation is sufficient for the development of static and dynamic mechanical allodynias. Lamina IIi PKCγ interneurons have been shown to be directly activated by low-threshold mechanical inputs carried by myelinated afferents. The level of PKCγ activation might thus gate the transmission of innocuous mechanical inputs to lamina I, nociceptive output neurons, thus turning touch into pain.
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Nathalie Pham Dang. Protéine kinase C γ et hypersensibilité mécanique trigéminale chez le rat. Médecine humaine et pathologie. Université d'Auvergne - Clermont-Ferrand I, 2014. Français. ⟨NNT : 2014CLF1MM27⟩. ⟨tel-02062594⟩

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