Skip to Main content Skip to Navigation
Theses

Modulation de la transmission nociceptive par les récepteurs métabotropiques du glutamate de groupe I et les canaux calciques de type L dans la moelle épinière : approche électrophysiologique in vivo

Abstract : Pain is an unpleasant experience which is part of our lives. When it does not last long time, it is often a warning sign for our organism. However unfortunately, in some pathological cases, it can last a long time, and become chronic, intolerable, and requires a treatment that is not always enough to relieve the patient, a treatment that has limited efficacy with significant undesirable side effects. It is important now to ameliorate our knowledge about the mechanisms implicated in pain transmission to develop new therapeutic tools. In this context, many studies conducted in recent years in our laboratory have indicated that the neurons in the dorsal horn of the spinal cord express intrinsic amplification properties of afferents input rely on calcium currents via the L type calcium channels. For that, the role of L type calcium channels and especially the role exact of each canal: Cav1.2 and Cav1.3, the two only iso-forms of L channels expressed in the dorsal horn of the spinal cord, in the painful sensitization has been studied in the first part of this present work. We studied in rat, in vivo, and by using a computational approach to simulate neuronal activity, the impact of these currents Cav1.2 and Cav1.3, both on the phenomenon of Wind-up, a form of short term sensitization, and in the model of a peripheral neuropathy model (SNL) characterized by a form of long-term sensitization. We showed that the presence of Cav1.3 (but not the Cav1.2) is important for Wind-up’s expression regardless of the physio-pathological context (control / neuropathy), whereas the removal of Cav1.2 (but not Cav1.3) decreases significantly the expression of the pain behavior in the context of neuropathy. In another side, it has been shown in our laboratory that group I metabotropic glutamatergic receptors (mGluRs I), receptors of Glutamate, the main excitatory neurotransmitter in nociceptive transmission, interact with L channels by modulating their activity. In pathological condition such in the condition of inflammatory pain the role of these channels L is controversial, and if the interaction between mGluRs I and L channels is always present in these inflammatory conditions is poorly known. We decided then to study in the second part of this work the role of these channels, and their interaction with mGluRs I in the condition of inflammatory pain. By using electrophysiological extracellular recording, pharmacology, behavior, intrathecal injections, and molecular biology, we showed that pharmacological activation of mGluRs I increase the nociceptive transmission and that this effect requires the activation of L type calcium channels in control conditions. Unexpectedly, in the context of the inflammation, our results show that activation of mGluRs I induce an anti-nociceptive effect and this effect is independent of L channels. Moreover, we confirmed that the blockade of L calcium channels is without effect in case of the inflammation. Furthermore, we showed that the contradictory effect due to the activation of mGluRs I pass through a strengthening of inhibitory transmission. In conclusion, our results show the interest to target L type calcium channels and more specifically the Cav1.2 channel in case of neuropathic chronic pain. We also show that mGluRs I could be good therapeutic candidates in the inflammatory context.
Document type :
Theses
Complete list of metadatas

Cited literature [310 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-01965320
Contributor : Abes Star :  Contact
Submitted on : Wednesday, December 26, 2018 - 1:01:23 AM
Last modification on : Wednesday, September 23, 2020 - 3:53:14 AM
Long-term archiving on: : Wednesday, March 27, 2019 - 12:13:04 PM

File

RADWANI_HOUDA_2016.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01965320, version 1

Collections

Citation

Houda Radwani. Modulation de la transmission nociceptive par les récepteurs métabotropiques du glutamate de groupe I et les canaux calciques de type L dans la moelle épinière : approche électrophysiologique in vivo. Neurosciences [q-bio.NC]. Université de Bordeaux; Université Abdelmalek Essaâdi (Tétouan), 2016. Français. ⟨NNT : 2016BORD0383⟩. ⟨tel-01965320⟩

Share

Metrics

Record views

120

Files downloads

59