Sex differences in the effects of amiloride on formalin test nociception in mice.
Amiloride is a nonspecific blocker of acid-sensing ion channels (ASICs) that have been recently implicated in the mediation of mechanical and chemical/inflammatory nociception. Preliminary data using a transgenic model are suggestive of sex differences in the role of ASICs. We report here that systemic administration of amiloride (10-70 mg/kg ip) produces a robust, dose-dependent blockade of late/tonic phase nociceptive behavior on the mouse formalin test (5%; 20 microl) in female but not male mice, completely abolishing the known sex difference in formalin test response. Adult gonadectomy produced a "switching" of sex differences in amiloride efficacy, with castrated males displaying an amiloride blockade and ovariectomized females rendered less sensitive to amiloride. Gonadectomized mice could be switched back to their intact status using chronic estrogen benzoate or testosterone propionate replacement via osmotic minipump (6 microg/day or 250 microg/day, respectively). It is unclear whether this striking sex difference is due to sex-specific involvement of ASICs in pain processing, but the present data represent one of the first demonstrations of pain-related sex differences with no obvious opioid involvement.
Chanda
Mona Lisa
ML
Department of Psychology nd Centre for Research on Pain, McGill University 1205 Dr. Penfield Ave., Montreal, QC H3A 1B1, Canada.
Mogil
Jeffrey S
JS
D000584:Amiloride / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005557:Formaldehyde; D006066:Gonads; D020249:Hormone Replacement Therapy; D008297:Male; D051379:Mice; D010146:Pain; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D012727:Sex Characteristics; D026941:Sodium Channel Blockers / Q000494:pharmacology
D004967:Estrogens; D026941:Sodium Channel Blockers; D005557:Formaldehyde; D000584:Amiloride