Table 1.
Drugsacting on mGluR2/3 tested in pain models.
| Compounds | Selectivity | Route of application | Pain model | Effect | Behaviors tests | Neural activity | |
|---|---|---|---|---|---|---|---|
| Orthosteric agonists | DCG-IV | mGluR2/3, NMDA | i.th. | Spinal nerve ligation | Inhibition | Allodynia, mechanical hyperalgesia | |
| L-CCG-I | Potent but not selective for mGluR2/3 | Intra-PAG | Formalin | Inhibition | Paw-licking, lifting, shaking, flicking | ||
| Facilitation | Hot plate | ||||||
| Intra-spinal | Capsaicin | Inhibition | Spinothalamic tract – neuronal activity | ||||
| (1S,3S)-ACPD | mGluR2/3 | i.th. | Carrageenan | Inhibition | Spinal dorsal horn – neuronal activity | ||
| (2R,4R)-APDC | mGluR2/3 | s.c. | PGE2-sensitization, carrageenan, formalin | Inhibition | Thermal hyperalgesia, allodynia | ||
| i.th. | Capsaicin | Inhibition | Allodynia | ||||
| Capsaicin, Complete Freund’s adjuvant | No effect | Thermal hyperalgesia, allodynia | |||||
| Ex vivo (skin nerve preparation and cultured DRG) | Capsaicin, PGE2-sensitization | Inhibition | Neuronal activity and calcium signals | ||||
| LY379268 | mGluR2/3 | i.p. | Formalin | Inhibition | Paw-licking | ||
| Spinal nerve ligation | Inhibition | Allodynia | |||||
| Ex vivo (mPFC slice) | Kaolin-carrageenan-induced monoarthritis | mPFC – pyramidal output, excitatory transmission | |||||
| SLx-3095-1 | mGluR2/3 | Ex vivo (amygdala slice) | Formalin | Inhibition | Amygdala – neuronal activity, excitatory transmission | ||
| LY354740 | mGluR2/3 | i.p. | Formalin | Inhibition | Paw-licking | ||
| Intra-amygdala and ex vivo (amygdala slice) | Kaolin-carrageenan-induced monoarthritis | Amygdala – neuronal activity, excitatory transmission | |||||
| LY389795 | mGluR2/3 | i.p. | Formalin | Inhibition | Paw- licking | ||
| LY2934747 | mGluR2/3 | Oral | Formalin, capsaicin, complete Freund’s adjuvant, plantar incision postsurgical, visceral (colorectal distension) | Inhibition | Allodynia, thermal and mechanical hyperalgesia | ||
| i.v. | Spinal nerve ligation | Inhibition | Allodynia | Spinal dorsal horn – neuronal activity | |||
| Orthosteric antagonists | EGLU | mGluR2/3 | Intra-PAG | Formalin | No effect | Hotplate | |
| Intra-reticular thalamic nucleus | Complete Freund’s adjuvant | Inhibition | Ankle-bend score | ||||
| Intra-amygdala | Kaolin-carrageenan-induced monoarthritis | Facilitation | Amygdala – neuronal activity, excitatory transmission | ||||
| APICA | mGluR2/3 | s.c. | PGE2-sensitization, carrageenan, capsaicin | Facilitation | Allodynia, paw-licking, flinching | ||
| Ex vivo (skin nerve preparation and cultured DRG) | Capsaicin | Nociceptive fiber activity; calcium signals | |||||
| LY341495 | mGluR2/3 | s.c. | PGE2-sensitization, carrageenan, capsaicin | Facilitation | Allodynia, paw-licking, flinching | ||
| i.th. | Complete Freund’s adjuvant | Inhibition | Allodynia | ||||
| No effect | Thermal hyperalgesia | ||||||
| Ex vivo (skin nerve preparation and cultured DRG) | Capsaicin | Facilitation | Nociceptive fiber activity; calcium signals | ||||
| Ex vivo (mPFC slice) | Kaolin-carrageenan-induced monoarthritis | mPFC – pyramidal output, excitatory transmission | |||||
See the sections “Pharmacological Manipulation of mGluR2/3 in Pain: Behavioral Studies” and “Pharmacological Manipulation of mGluR2/3 in Pain: Electrophysiological Studies” for references.