Musk shrews selectively bred for motion sickness display increased anesthesia-induced vomiting

Abstract

Susceptibility to motion sickness is a predictor of postoperative nausea and vomiting, and studies in humans suggest that genetic factors determine sensitivity to motion sickness. The aim of the current study was to determine if a preclinical model could be selectively bred for motion-induced emesis and to assess a potential relationship to anesthesia-induced emesis. Musk shrews were tested for motion-induced emesis using a shaker plate (10 min, 1 Hz, and 4 cm of lateral displacement). Animals were rank ordered for motion-induced emesis and selectively bred to produce high and low response strains. Shrews were also tested with nicotine (5 mg/kg, sc), copper sulfate (CuSO4; 120 mg/kg, ig), and isoflurane anesthesia (10 min; 3%) to determine responses to a panel of emetic stimuli. High response strain shrews demonstrated significantly more emetic responses to motion exposure compared to low response strain animals in the F1 and F2 generations. In F2 animals, there were no significant differences in total emetic responses or emetic latency between strains after nicotine or CuSO4 injection. However, isoflurane exposure stimulated more emesis in F1 and F2 high versus low strain animals, which suggests a relationship between vestibular- and inhalational anesthesia-induced emesis. Overall, these results indicate genetic determinants of motion sickness in a preclinical model and a potential common mechanism for motion sickness and inhalational anesthesia-induced emesis. Future work may include genetic mapping of potential “emetic sensitivity genes” to develop novel therapies or diagnostics for patients with high risk of nausea and vomiting.

Impact of electrical stimulation of the stomach on gastric distension‐induced emesis in the musk shrew

“…Excessive gastric distension can also provide nociceptive input to the spinal cord; and thus, is not a purely vagal stimulus. Furthermore, the number of emetic episodes following gastric stretch is less than with other emetic stimuli, such as subcutaneous nicotine or intra‐gastric CuSO 4 , and our unpublished data (CCH and DMR) indicate that gastric stretch is a rapidly adapting emetic stimulus; these observations suggest that gastric distension could be relatively insensitive to small antiemetic effects. Finally, the experiments were of short duration.…”

An assay of drug‐induced emesis in the squirrel monkey (Saimiri sciureus)

“…71 Indeed, shrews selectively bred for motion sickness do not display a higher sensitivity to nicotine-induced emesis than wild-type shrews. 72 Arecoline did produce hypersalivation in a dose-dependent manner, despite failing to produce emesis. High doses of arecoline also produce salivation in several other laboratory species, including rodents 73 and rhesus macaques.…”

“…However, the vestibular system is implicated in motion‐induced emesis, but not necessarily in drug‐induced emesis . Indeed, shrews selectively bred for motion sickness do not display a higher sensitivity to nicotine‐induced emesis than wild‐type shrews . Arecoline did produce hypersalivation in a dose‐dependent manner, despite failing to produce emesis.…”

The HCN Channel Blocker ZD7288 Induces Emesis in the Least Shrew (Cryptotis parva)

“…Thus, our findings not only demonstrate that HCN1 may be involved in vomiting induced by ZD7288, but also shows efficacy differences in the capacity of HCN blockers in evoking emesis. Of further interest, there are several well-known proemetic drugs with additional HCN channel-blocking activities: (1) Nicotine is a cholinergic agonist with proemetic effects in animals when given subcutaneously ( Beleslin et al, 1981 ; Ueno et al, 1987 ; Yamamoto et al, 2004 ; Parker et al, 2009 ; Horn et al, 2014 ). Moreover, neuronal excitability induced by nicotine has been shown to be mediated via binding and inhibiting the HCN channels ( Griguoli et al, 2010 ; Kodirov et al, 2014 ).…”