The delayed phase of cisplatin-induced emesis is mediated by the area postrema and not the abdominal visceral innervation in the ferret.
The anti-cancer chemotherapeutic agent cisplatin induces an acute (approximately 24 h) and delayed (approximately 24-72 h+) emetic response in humans; whereas the mechanism mediating the acute phase has been characterised, the delayed phase is relatively poorly understood. We have used nerve lesions (abdominal vagus, VX; greater splanchnic nerve, GSNX) and area postrema ablation (APX) in the ferret model of cisplatin (5 mg/kg, i.p.) delayed emesis and demonstrated that VX and VX+GSNX did not significantly modify the delayed emetic response (24-72 h), which consisted of 276.0+/-62.8 retches+vomits (R+V) in sham-operated ferrets and 167.2+/-34.0R+V and 214.8+/-40.2R+V, in the VX and VX+GSNX groups, respectively. APX virtually abolished the delayed phase of emesis and sham-operated ferrets had 93.0+/-22.9R+V whilst only 6.0+/-3.6R+V (p=0.009) were observed in APX animals. These data suggest that, in contrast to the acute emetic response triggered by cisplatin, the delayed phase does not rely on abdominal visceral afferents but is mediated via the area postrema.
Percie du Sert
Nathalie
N
Division of Basic Medical Sciences, St. George's University of London, Cranmer Terrace, London, SW17 0RE, UK. npercied@sgul.ac.uk
Rudd
John A
JA
Moss
Raymond
R
Andrews
Paul L R
PL
D000005:Abdomen / Q000294:innervation / Q000503:physiopathology; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D001058:Apomorphine / Q000009:adverse effects / Q000494:pharmacology; D031608:Area Postrema / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D002369:Castration; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005289:Ferrets; D008139:Loperamide / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D013153:Splanchnic Nerves / Q000187:drug effects / Q000503:physiopathology; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology; D014781:Viscera / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D014839:Vomiting / Q000139:chemically induced* / Q000503:physiopathology
D000970:Antineoplastic Agents; D008139:Loperamide; D001058:Apomorphine; D002945:Cisplatin