The effects of pyrilamine and cimetidine on mRNA C-fos expression and nociceptive flinching behavior in rats.
C-fos and Fos expression, frequently used as a neural nociceptive marker, is altered by many drugs. The effects of histamine receptor antagonists on c-fos messenger (m)RNA expression are unknown. We examined the effect of local and systemic administration of pyrilamine (H(1) receptor antagonist) and cimetidine (H(2) receptor antagonist) on the nociceptive flinching behavior elicited by injection of 50 micro L of 1% formalin into the dorsal region of the hind paw of rats. Nociceptive flinching behavior was observed for 45 min, and the rats were then killed and lumbar spinal cord obtained for c-fos mRNA expression, measured using the Northern blot hybridization technique. Systemic administration of pyrilamine and cimetidine did not elicit response in nociceptive behavior or in c-fos mRNA expression. When the drugs were locally administered, they affected behavior and c-fos mRNA expression in different patterns. Pyrilamine decreased the number of flinches in a dose dependent manner in both phases, whereas cimetidine did not affect Phase I and decreased the number of flinches in Phase II, but only partially. Pyrilamine 5 and 20 mM decreased c-fos mRNA expression, and cimetidine decreased the expression only at 100 mM. The systemic use of the drugs had no effect on c-fos mRNA expression.


CONCLUSIONS
Histamine receptor antagonists present antinociceptive effects when administered peripherally. These effects are observed through a nociceptive flinching behavior test and mRNA c-fos expression. Pyrilamine (H(1) receptor antagonist) has a greater antinociceptive effect than cimetidine (H(2) receptor antagonist).
Ashmawi
Hazem Adel
HA
*Anesthesiology Branch Department of Surgery and †Biochemistry, University of São Paulo School of Medicine; and ‡Department of Anesthesiology, Hospital Pérola Byington, São Paulo, Brazil.
Chambergo
Felipe S
FS
Araújo Palmeira
Cláudia C
CC
Posso
Irimar de Paula
IP
D000818:Animals; D001522:Behavior, Animal; D015152:Blotting, Northern; D002927:Cimetidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000008:administration & dosage; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D011738:Pyrilamine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism*
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D005557:Formaldehyde; D002927:Cimetidine; D011738:Pyrilamine