Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator
- Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Spain
- Universitat Autònoma de Barcelona, Spain
- Facultat de Medicina i Ciències de la Salut, IDIBELL, Universitat de Barcelona, Spain
- Universitat de Barcelona, Spain
- I.R.C.C.S. Neuromed, Italy
- Universitat Ramon Llull, Spain
- CNRS, INSERM, Univ. Montpellier, France
- Instituto de Salud Carlos III, Spain
- University Sapienza, Italy
Figures
Figure 1 with 2 supplements
Design and synthesis of JF-NP-26.
The synthesis of JF-NP-26 from raseglurant involves a one-pot procedure using raseglurant and 4-hydroxymethyl-7-diethylaminocoumarin (DEACM). In brief, a first reaction with triphosgene, NEt3 and …
Figure 1—figure supplement 1
Supporting spectra for the synthesis of raseglurant.
https://doi.org/10.7554/eLife.23545.003
Figure 1—figure supplement 2
Supporting spectra for the synthesis of JF-NP-26.
https://doi.org/10.7554/eLife.23545.004
Figure 2
Photochemical properties of JF-NP-26.
(A) UV-visible absorption spectra of raseglurant (Ras), the coumarine DEACM, and JF-NP-26 (JF) in PBS. The sum of the free Ras and DEACM spectra shows important differences relative to that of their …
Figure 3
Optical modulation of mGlu5 receptor activity in cultured cells and in primary striatal neurons.
(A) Determination of mGlu5 receptor-mediated inositol phosphate accumulation in transiently transfected HEK-293T cells. Normalized dose-response of raseglurant (Ras)- and JF-NP-26 (JF)-mediated …
Figure 4
In vivo assessment of JF-NP-26 light-dependent analgesic efficacy in neuropathic pain.
(A) Scheme showing the different LED-mediated irradiation points within the pain neuraxis (i.e. hind paw and thalamus) and pain triggering (i.e. hind paw formalin administration and chronic …
Figure 5
Peripheral and central light-dependent JF-NP-26-mediated antinociception in mice.
In the upper panel a scheme of the irradiation regime at 405 nm light (violet rectangles) and liking recordings (green rectangles - Phase I and Phase II) in the formalin animal model of pain is …
Figure 6
Effect of systemic administration and in vivo photoactivation of JF-NP-26 in liver toxicity and memory in mouse.
(A) Effect of Raseglurant and JF-NP-26 on serum transaminases. Mice were treated with vehicle (veh), acetaminophen treatment (APAP; 300 mg/kg, ip), raseglurant (Ras; 50 mg/kg, ip) or JF-NP-26 (JF; …
Videos
Video 1
Video showing formalin-induced hind paw licking in a JF-NP-26 -treated mouse upon dark conditions from Figure 5.
Mouse, in a glass beaker (15 cm ø x 20 cm height), was administered with JF-NP-26 (10 mg/kg, i.p.). After 20 min, the LED-based irradiation system was attached to the thalamic implanted optic fiber …
Video 2
Video showing formalin-induced hind paw licking in a JF-NP-26-treated mouse upon 405 nm irradiation from Figure 5.
Mouse, in a glass beaker (15 cm ø x 20 cm height), was administered with JF-NP-26 (10 mg/kg, i.p.). After 20 min, the LED-based irradiation system was attached to the thalamic implanted optic fiber …
