Optical control of pain <i>in vivo</i> with a photoactive mGlu<sub>5</sub> receptor negative allosteric modulator.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28395733.
- Also identified by DOI 10.7554/eLife.23545 and PMC identifier 5388536.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative of the metabotropic glutamate type 5 (mGlu<sub>5</sub>) receptor negative allosteric modulator raseglurant. Violet light illumination of JF-NP-26 induces a photochemical reaction prompting the active-drug's release, which effectively controls mGlu<sub>5</sub> receptor activity both in ectopic expressing systems and in striatal primary neurons. Systemic administration in mice followed by local light-emitting diode (LED)-based illumination, either of the thalamus or the peripheral tissues, induced JF-NP-26-mediated light-dependent analgesia both in neuropathic and in acute/tonic inflammatory pain models. These data offer the first example of optical control of analgesia <i>in vivo</i> using a photocaged mGlu<sub>5</sub> receptor negative allosteric modulator. This approach shows potential for precisely targeting, in time and space, endogenous receptors, which may allow a better management of difficult-to-treat disorders.
Medical subject headings
- Allosteric Regulation
- Analgesics
- Light
- Neurons
- Pain
- Photosensitizing Agents
- Receptor, Metabotropic Glutamate 5