A ‘double-edged’ role for type-5 metabotropic glutamate receptors in pain disclosed by light-sensitive drugs
- Mediterranean Neurological Institute, IRCCS Neuromed, Italy
- Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, United States
- MCS - Medicinal Chemistry & Synthesis, Institute for Advanced Chemistry of Catalonia, Spain
- Department of Experimental Medicine, Division of Pharmacology, University of Campania “Luigi Vanvitelli”, Italy
- Institute of Functional Genomics IGF, National Centre for Scientific Research CNRS, INSERM, University of Montpellier, France
- Department of Physiology and Pharmacology, Sapienza University of Rome, Italy
- Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, United States
- Garrison Institute on Aging, Texas Tech University Health Sciences Center, United States
Figures
Figure 1 with 1 supplement
Neuropathic pain model and mGlu5 receptor signaling in different brain regions.
(a) Experimental protocol. (b) Mechanical (hyper-)sensitivity on the left hind paw measured with von Frey filaments was reduced in chronic constriction injury (CCI) mice (n=10) versus sham-operated …
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Figure 1—source data 1
Neuropathic pain model and mGlu5 receptor signaling in different brain regions.
- https://cdn.elifesciences.org/articles/94931/elife-94931-fig1-data1-v1.zip
Figure 1—figure supplement 1
mGlu5 receptor protein levels in different brain regions in sham and chronic constriction injury (CCI) mice.
(a–e) mGlu5 receptor protein levels in the contralateral (to the side of injury) infralimbic cortex (a), prelimbic cortex (b), anterior cingulate cortex (c), amygdala (d), and thalamus (e). …
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Figure 1—figure supplement 1—source data 1
mGlu5 receptor protein levels in different brain regions in sham and CCI mice.
- https://cdn.elifesciences.org/articles/94931/elife-94931-fig1-figsupp1-data1-v1.zip
Figure 2 with 3 supplements
Behavioral effects of light-induced manipulations of mGlu5 receptors in different brain regions in chronic constriction injury (CCI) mice.
Schematic representation of sites of stereotaxic implantation of LED optical fibers in different brain regions. (b) Experimental protocol for optical modulation. (c) Optical activation (blue-violet …
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Figure 2—source data 1
Behavioral effects of light-induced manipulations of mGlu5 receptors in different brain regions in CCI mice.
- https://cdn.elifesciences.org/articles/94931/elife-94931-fig2-data1-v1.zip
Figure 2—figure supplement 1
Effects of light-induced blockade of mGlu5 receptors in different brain regions on mechanical pain thresholds in the unlesioned paw of chronic constriction injury (CCI) mice.
Mechanical thresholds were measured in the right paw (contralateral to the injury) of CCI mice before and after light-induced activation of systemic JF-NP-26 (10 mg/kg, i.p.) in the contralateral …
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Figure 2—figure supplement 1—source data 1
Effects of light-induced blockade of mGlu5 receptors in different brain regions on mechanical pain thresholds in the unlesioned paw of CCI mice.
- https://cdn.elifesciences.org/articles/94931/elife-94931-fig2-figsupp1-data1-v1.zip
Figure 2—figure supplement 2
Effects of light-induced blockade of mGlu5 receptors in different brain regions on mechanical pain thresholds in the left paw of sham mice.
Mechanical thresholds were measured in the left paw of sham mice before and after light-induced activation of systemic JF-NP-26 (10 mg/kg, i.p.) in the contralateral infralimbic cortex (a), …
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Figure 2—figure supplement 2—source data 1
Effects of light-induced blockade of mGlu5 receptors in different brain regions on mechanical pain thresholds in the left paw of sham mice.
- https://cdn.elifesciences.org/articles/94931/elife-94931-fig2-figsupp2-data1-v1.zip
Figure 2—figure supplement 3
Effects of light-induced blockade of mGlu5 receptors in the right basolateral amygdala (BLA) on anxiety-like (risk-taking) and depressive-like behaviors of sham and chronic constriction injury (CCI) mice.
For the evaluation of risk-taking behavior in the light-dark box test the following groups were used: (i) sham-operated mice treated with vehicle; (ii) CCI mice treated with vehicle; (iii) CCI mice …
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Figure 2—figure supplement 3—source data 1
Effects on risk-taking and depressive-like behavior of sham and CCI mice.
- https://cdn.elifesciences.org/articles/94931/elife-94931-fig2-figsupp3-data1-v1.zip
Figure 3 with 1 supplement
Electrophysiological effects of light-induced manipulations of mGlu5 on prelimbic pyramidal neurons and on amygdala feed-forward inhibition in neuropathic pain.
(a) Prelimbic circuitry to explain mGlu5 receptor action. Basolateral amygdala (BLA) input (E) activates (I) interneuron projects onto excitatory (E) inputs to pyramidal output neurons (O). (b, c) …
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Figure 3—source data 1
Electrophysiological effects of light-induced manipulations of mGlu5 on prelimbic pyramidal neurons and on amygdala feed-forward inhibition in neuropathic pain.
- https://cdn.elifesciences.org/articles/94931/elife-94931-fig3-data1-v1.zip
Figure 3—figure supplement 1
Effects of light-induced blockade of mGlu5 receptors in the prelimbic cortex on descending pain control (rostroventromedial medulla, RVM) and in the basolateral amygdala (BLA)-prelimbic circuitry in chronic constriction injury (CCI) mice.
(a) Single-unit recordings were performed from RVM ON-cells in anesthetized CCI mice 16 days after injury. An LED optic fiber was implanted into the contralateral (to the side of injury) prelimbic …
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Figure 3—figure supplement 1—source data 1
Effects of light-induced blockade of mGlu5 receptors in prelimbic cortex on descending pain control (RVM) and on BLA-prelimbic circuitry in CCI mice.
- https://cdn.elifesciences.org/articles/94931/elife-94931-fig3-figsupp1-data1-v1.zip
Figure 4
Putative circuitry of brain region-specific functions of mGlu5 receptors in pain modulation.
Hypothesized neural circuitry based on in vivo and ex vivo electrophysiology and behavioral data. mGlu5 receptor blockade decreases feedforward inhibition from BLA to CeA to increase amygdala output …
Additional files
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MDAR checklist
- https://cdn.elifesciences.org/articles/94931/elife-94931-mdarchecklist1-v1.pdf
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Supplementary file 1
Effect size of optical modulation in prelimbic cortex on RVM activity, according to Cohen’s d calculation from t-tests.
- https://cdn.elifesciences.org/articles/94931/elife-94931-supp1-v1.docx
