Low doses of cannabinoids enhance the antinociceptive effects of intracisternally administered mGluRs groups II and III agonists in formalin-induced TMJ nociception in rats.
This study provides the first demonstration that central cannabinoids modulate the antinociceptive actions of metabotropic glutamate receptors (mGluRs) on formalin-induced temporomandibular joint (TMJ) nociception. Noxious scratching behavior induced by formalin injection in the TMJ was used as a model of pain. Intracisternal injection of 30mug of WIN 55,212-2, a non-subtype selective cannabinoid receptor agonist, attenuated the number of scratches by 75% as compared with the vehicle-treated group, whereas vehicle alone or 3 or 10 microg of WIN 55,212-2 had no effect. To explore the postulated interaction between central cannabinoid receptors and mGluRs, effects of combined administration of sub-analgesic doses of WIN 55,212-2 and group II or III mGluR agonists were tested. Group II or III mGluRs agonists were administered intracisternally 10 min after intracisternal administration of WIN 55,212-2. Neither 100 nmol APDC, a group II mGluRs agonist, nor L-AP4, a group III mGluR agonist, altered nociceptive behavior when given alone but significantly inhibited the formalin-induced nociceptive behavior in the presence of a sub-threshold dose ( 3microg) of WIN 55,212-2. The ED50 value of APDC or L-AP4 was significantly reduced upon co-treatment with WIN 55,212-2 than in the vehicle-treated group, highlighting the important therapeutic potential of the combined administration of group II or III mGluR agonists with cannabinoids to effectively treat inflammatory pain associated with the TMJ. Potentiating effects of group II or III mGluRs agonists will likely permit the administration of cannabinoids at doses that do not achieve significant accumulation to produce undesirable motor dysfunction.
Department of Oral Physiology, School of Dentistry, Kyungpook National University, 188-1 Sam Deok 2 ga, Chung-gu, Daegu 700-412, Republic of Korea Institution of BrainKorea21, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea Department of Orthodontics, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea Department of Neurobiology and Neurotoxicology, Meharry Medical College, 1005 D.B. Todd Boulevard, Nashville, TN 37208, USA.
Min K
MK
Lee
Byung Y
BY
Choi
Gwi Y
GY
Yang
Hye J
HJ
Jeon
Hee M
HM
Kyung
Oh W
OW
Kwon
Hyo S
HS
Park
Yong C
YC
Bae
Sukhbir S
SS
Mokha
Dong K
DK
Ahn
D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D018771:Arthralgia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D002186:Cannabinoids / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005557:Formaldehyde; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013705:Temporomandibular Joint Disorders / Q000188:drug therapy* / Q000503:physiopathology*
D000700:Analgesics; D002186:Cannabinoids; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D005557:Formaldehyde