Influence of NMDA and non-NMDA antagonists on acute and inflammatory pain in the trigeminal territory: a placebo control study.
NMDA and non-NMDA receptors are involved in spinal transmission of nociceptive information in physiological and pathological conditions. Our objective was to study the influence of NMDA and non-NMDA receptor antagonists on pain control in the trigeminal system using a formalin-induced orofacial pain model. Motor performance was also evaluated. Male Rattus norvegicus were pre-treated with topiramate (T) (n=8), memantine (M) (n=8), divalproex (D) (n=8) or isotonic saline solution (ISS) (n=10) intraperitoneally 30 minutes before the formalin test. Formalin 2.5% was injected into the right upper lip (V2 branch) and induced two phases: phase I (early or neurogenic) (0-3 min) and phase II (late or inflammatory) (12-30 min). For motor behavior performance we used the open-field test and measured latency to movement onset, locomotion and rearing frequencies, and immobility time. Pre-treatment of animals with M and D only attenuated nociceptive formalin behavior for phase II. T increased locomotion and rearing frequencies and reduced immobility time. Treatment with M increased immobility time and with D reduced locomotion frequency. Our results showed that the NMDA antagonist (M) is more potent than the non-NMDA antagonists (D and T) in the control of pain in the inflammatory phase. The non-NMDA topiramate improved motor performance more than did D and M, probably because T has more anxiolytic properties.
Piovesan
Elcio Juliato
EJ
Neurology Division, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba PR, Brazil. piovesan@avalon.sul.com.br
Randunz
Vitor
V
Utiumi
Marco
M
Lange
Marcos Cristiano
MC
Kowacs
Pedro André
PA
Mulinari
Rogério Andrade
RA
Oshinsky
Michael
M
Vital
Maria
M
Sereniki
Adriana
A
Fernandes
Artur Furlaneto
AF
e Silva
Lucas Leite
LL
Werneck
Lineu César
LC
D000818:Animals; D005106:Exploratory Behavior / Q000187:drug effects; D005157:Facial Pain / Q000188:drug therapy*; D005632:Fructose / Q000031:analogs & derivatives / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D008559:Memantine / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D010919:Placebos; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D000077236:Topiramate; D014277:Trigeminal Neuralgia / Q000188:drug therapy*; D014635:Valproic Acid / Q000627:therapeutic use
D010919:Placebos; D016194:Receptors, N-Methyl-D-Aspartate; D000077236:Topiramate; D005632:Fructose; D014635:Valproic Acid; D008559:Memantine