Reversible Induction of Pain Hypersensitivity following Optogenetic Stimulation of Spinal Astrocytes

Abstract

While glial activation is an integral part of pain pathogenesis, the existence of a causal relationship between glia and pain processing has yet to be demonstrated in vivo. Here, we have investigated whether the activation of spinal astrocytes could directly evoke pain hypersensitivity in vivo via the use of optogenetic techniques. Optogenetic stimulation of channelrhopdopsin-2 (ChR)-expressing spinal astrocytes induced pain hypersensitivity in a reversible and time-dependent manner, which was accompanied by glial activation, NR1 phosphorylation, ATP release, and the production of proalgesic mediators. Photostimulation of ChR2-expressing astrocytes in culture and spinal slices recapitulated in vivo findings, demonstrating the release of proalgesic mediators and electrophysiological disinhibition of spinal projection neurons. These findings deepen our understanding of the role of astrocytes in pain pathogenesis and provide the scientific basis for an astrocyte-oriented pain treatment.

Phenotypic change in trigeminal ganglion neurons associated with satellite cell activation via extracellular signal‐regulated kinase phosphorylation is involved in lingual neuropathic pain

“…and heat stimulation (1 h after iv.). Previously, it has been reported that alteration in GABAergic and glycinergic inhibitory systems involving in the development of mechanical allodynia, but not thermal hyperalgesia (Polgar et al ., ; Nam et al ., ). Together with these results, our data suggest that inhibitory systems may not affect thermal hyperalgesia rather than mechanical allodynia in LNC rats.…”

Granulocyte-colony–stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis

“…This persistent postinflammatory sensitization mirrors what is seen in patients with inflammatory diseases (4,(7)(8)(9)(10). While a number of mechanisms of peripheral sensitization have been characterized (5,11,12), there is a growing appreciation that, as observed at the periphery, neuro-immune interactions occurring in the spinal cord regulate pain sensitivity caused by tissue damage (8,(12)(13)(14)(15)(16). Microglia, the tissue-resident macrophages of the central nervous system, have been directly implicated in the initiation of mechanical hypersensitivity following peripheral nerve injury (17)(18)(19).…”

The Impact of Optogenetics on Regenerative Medicine

“…In recent years, many studies have investigated the usefulness of optogenetics in pain therapy [44]. Chronic pain is often related to neuronal damage, immunological impairment, and inflammatory conditions: it is characterized by the production of molecules correlated with specific ion channels [45]. The connection between the modulation of ionic channels activating the nociceptors was observed.…”

“…The connection between the modulation of ionic channels activating the nociceptors was observed. In the priming of immune cells, the receptors that couple to the G proteins (GPCR) are very important [45]. Light-mediated manipulation of G protein subunits of ChR2 and NpHR proteins can activate or inhibit the receptors of injured neurons.…”