Un nocicepteur (ou récepteur nociceptif) est un récepteur sensoriel de la douleur qui fait naître un message nerveux lorsqu’il est stimulé. Le message passe d'abord par le bulbe ou la moelle épinière, où se déclenche un réflexe de sauvegarde de l'intégrité physique (réflexe défensif, réflexe court), avant d'être relayé jusqu’au cerveau où il sera interprété (intégration, modulation, habituation). Le nocicepteur peut être cutané. Dans ce cas, on distinguera trois types de nocicepteurs :

Mécanorécepteurs, (fibre Aδ) sensibles à la déformation mécanique de la peau, à une pression intense (par exemple lorsque l'on frappe violemment un mur de la main) ;

Thermorécepteurs, (fibre Aδ) sensibles aux températures extrêmes : supérieures à 45 °C ou inférieures à 10 °C ;

Récepteur polymodal, (fibre C) sensibles à la fois aux effets mécaniques et à la température, ce sont les récepteurs les plus nombreux.

Le nocicepteur peut être également musculaire et articulaire. Définition

Acetylated tubulin is essential for touch sensation in mice

Antonino Asaro, Kai Johnsson, Luc Reymond

At its most fundamental level, touch sensation requires the translation of mechanical energy into mechanosensitive ion channel opening, thereby generating electro-chemical signals. Our understanding of this process, especially how the cytoskeleton influences it, remains unknown. Here we demonstrate that mice lacking the α-tubulin acetyltransferase Atat1 in sensory neurons display profound deficits in their ability to detect mechanical stimuli. We show that all cutaneous afferent subtypes, including nociceptors have strongly reduced mechanosensitivity upon Atat1 deletion, and that consequently, mice are largely insensitive to mechanical touch and pain. We establish that this broad loss of mechanosensitivity is dependent upon the acetyltransferase activity of Atat1, which when absent leads to a decrease in cellular elasticity. By mimicking α-tubulin acetylation genetically, we show both cellular rigidity and mechanosensitivity can be restored in Atat1 deficient sensory neurons. Hence, our results indicate that by influencing cellular stiffness, α-tubulin acetylation sets the force required for touch.

Elife Sciences Publications Ltd2016

Recombinant adeno-associated virus serotype 6 (rAAV2/6)-mediated gene transfer to nociceptive neurons through different routes of delivery

Patrick Aebischer, Christopher Towne

BACKGROUND: Gene transfer to nociceptive neurons of the dorsal root ganglia (DRG) is a promising approach to dissect mechanisms of pain in rodents and is a potential therapeutic strategy for the treatment of persistent pain disorders such as neuropathic pain. A number of studies have demonstrated transduction of DRG neurons using herpes simplex virus, adenovirus and more recently, adeno-associated virus (AAV). Recombinant AAV are currently the gene transfer vehicles of choice for the nervous system and have several advantages over other vectors, including stable and safe gene expression. We have explored the capacity of recombinant AAV serotype 6 (rAAV2/6) to deliver genes to DRG neurons and characterized the transduction of nociceptors through five different routes of administration in mice. RESULTS: Direct injection of rAAV2/6 expressing green fluorescent protein (eGFP) into the sciatic nerve resulted in transduction of up to 30% eGFP-positive cells of L4 DRG neurons in a dose dependent manner. More than 90% of transduced cells were small and medium sized neurons (< 700 microm 2), predominantly colocalized with markers of nociceptive neurons, and had eGFP-positive central terminal fibers in the superficial lamina of the spinal cord dorsal horn. The efficiency and profile of transduction was independent of mouse genetic background. Intrathecal administration of rAAV2/6 gave the highest level of transduction (approximately 60%) and had a similar size profile and colocalization with nociceptive neurons. Intrathecal administration also transduced DRG neurons at cervical and thoracic levels and resulted in comparable levels of transduction in a mouse model for neuropathic pain. Subcutaneous and intramuscular delivery resulted in low levels of transduction in the L4 DRG. Likewise, delivery via tail vein injection resulted in relatively few eGFP-positive cells within the DRG, however, this transduction was observed at all vertebral levels and corresponded to large non-nociceptive cell types. CONCLUSION: We have found that rAAV2/6 is an efficient vector to deliver transgenes to nociceptive neurons in mice. Furthermore, the characterization of the transduction profile may facilitate gene transfer studies to dissect mechanisms behind neuropathic pain

2009

Recombinant adeno-associated virus serotype 6 (rAAV2/6)-mediated gene transfer to nociceptive neurons through different routes of delivery

Patrick Aebischer, Christopher Towne

2009

Nocicepteur

Mécanorécepteurs, (fibre Aδ) sensibles à la déformation mécanique de la peau, à une pression intense (par exemple lorsque l'on frappe violemment un mur de la main) ;

Thermorécepteurs, (fibre Aδ) sensibles aux températures extrêmes : supérieures à 45 °C ou inférieures à 10 °C ;

Récepteur polymodal, (fibre C) sensibles à la fois aux effets mécaniques et à la température, ce sont les récepteurs les plus nombreux.

Acetylated tubulin is essential for touch sensation in mice

Recombinant adeno-associated virus serotype 6 (rAAV2/6)-mediated gene transfer to nociceptive neurons through different routes of delivery

Recombinant adeno-associated virus serotype 6 (rAAV2/6)-mediated gene transfer to nociceptive neurons through different routes of delivery

Acetylated tubulin is essential for touch sensation in mice