Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on inflammatory and neuropathic pain in mice.
In this study, the effect of (S)-3,4-dicarboxyphenylglycine (DCPG), a selective mGlu8 receptor agonist, has been investigated in inflammatory and neuropathic pain models in order to elucidate the role of mGlu8 receptor in modulating pain perception. Inflammatory pain was induced by the peripheral injection of formalin or carrageenan in awake mice. Systemic administration of (S)-3,4-DCPG, performed 15 min before formalin, decreased both early and delayed nociceptive responses of the formalin test. When this treatment was carried out 15 min after the peripheral injection of formalin it still reduced the late hyperalgesic phase. Similarly, systemic (S)-3,4-DCPG reduced carrageenan-induced thermal hyperalgesia and mechanical allodynia when administered 15 min before carrageenan, but no effect on pain behaviour was observed when (S)-3,4-DCPG was given after the development of carrageenan-induced inflammatory pain. When microinjected into the lateral PAG (RS)-alpha-methylserine-O-phoshate (MSOP), a group III receptor antagonist, antagonised the analgesic effect induced by systemic administration of (S)-3,4-DCPG in both of the inflammatory pain models. Intra-lateral PAG (S)-3,4-DCPG reduced pain behaviour when administered 10 min before formalin or carrageenan; both the effects were blocked by intra-lateral PAG MSOP. (S)-3,4-DCPG was ineffective in alleviating thermal hyperalgesia and mechanical allodynia 7 days after the chronic constriction injury of the sciatic nerve, whereas it proved effective 3 days after surgery. Taken together these results suggest that stimulation of mGlu8 receptors relieve formalin and carrageenan-induced hyperalgesia in inflammatory pain, whereas it would seem less effective in established inflammatory or neuropathic pain.
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Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Faculty of Medicine and Surgery-Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
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D000704:Analysis of Variance; D000818:Animals; D001559:Benzhydryl Compounds / Q000627:therapeutic use; D001565:Benzoates / Q000627:therapeutic use*; D002351:Carrageenan; D015226:Dinucleoside Phosphates; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005557:Formaldehyde; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010768:Phosphoserine / Q000008:administration & dosage; D011930:Reaction Time / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*
C110733:3,4-dicarboxyphenylglycine; D001559:Benzhydryl Compounds; D001565:Benzoates; D015226:Dinucleoside Phosphates; D018691:Excitatory Amino Acid Antagonists; C507346:N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride; D018094:Receptors, Metabotropic Glutamate; C111435:metabotropic glutamate receptor 8; C120877:methylserine phosphate; C072639:N-(deoxycytidylyl-(3'-5')-guanosin-8-yl)aniline; D010768:Phosphoserine; D005557:Formaldehyde; D002351:Carrageenan; D005998:Glycine