Metabotropic glutamate receptor 5 and dorsal raphe serotonin release in inflammatory pain in rat.
In this study, we evaluated the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective antagonist of metabotropic glutamate subtype 5 receptors (mGlu(5)), delivered through different paths on dorsal raphe serotonin (5-HT) and on thermoceptive responses in rats with inflammatory pain. Intraplantar formalin and carrageenan increased 5-HT (137+/-11% and 212+/-6% of pre-injection baseline, respectively) and reduced nociceptive threshold (23+/-7% and 19+/-3% of pre-injection baseline, respectively). MPEP (2 mg/kg i.p.) further enhanced formalin and carrageenan-induced 5-HT increases (180+/-11% and 260+/-12% of pre-injection baseline, respectively) and reduced thermal hyperalgesia (71+/-8% and 80+/-10% of pre-injection baseline, respectively). MPEP (1 mM) through microdialytic probe into the dorsal raphe did not change formalin- or carrageenan-induced 5-HT increases (147+/-10% and 189+/-10% of pre-injection baseline, respectively) and thermal hyperalgesia (35+/-8% and 25+/-9% of pre-injection baseline, respectively). Finally, MPEP (30 nmol/rat) into the hind paw reduced the formalin- and carrageenan-induced 5-HT increase (108+/-3% and 126+/-7% of pre-injection baseline, respectively) and thermal hyperalgesia (77+/-6% and 117+/-7% of pre-injection baseline, respectively). Dorsal raphe serotonergic neurons activity increased following a peripherally induced inflammatory injury. In these conditions, peripheral but not dorsal raphe mGlu(5) receptors blockade prevented over activation of dorsal raphe serotonergic neurons and reversed thermal hyperalgesia.
Palazzo
Enza
E
Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Faculty of Medicine and Surgery, II University of Naples, via Costantinopoli 16, 80138 Naples, Italy. enza.palazzo@unina2.it
Genovese
Rita
R
Mariani
Loredana
L
Siniscalco
Dario
D
Marabese
Ida
I
De Novellis
Vito
V
Rossi
Francesco
F
Maione
Sabatino
S
D000818:Animals; D002351:Carrageenan; D005557:Formaldehyde; D006614:Hindlimb; D007249:Inflammation / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D010147:Pain Measurement; D011725:Pyridines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012701:Serotonin / Q000096:biosynthesis*
D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D005557:Formaldehyde; D012701:Serotonin; C121465:6-methyl-2-(phenylethynyl)pyridine; D002351:Carrageenan