Introduction: Nerve excitability study in experimental animals can directly test a hypothesis at a molecular level by a specific pharmacological agent or a genetic model. Unlike human subjects, animal study is often performed under anesthesia, however, the anesthetic effects on peripheral nerve excitability has not been fully investigated.

Methods: We performed nerve excitability testing under two commonly used anesthetic agents in normal male mice: (1) 1.5% isoflurane inhalation (N=6) and (2) the triple agents - medetomidine (0.3 mg/kg), midazoram (4 mg/kg) and btorphanol (5 mg/kg) - intraperitoneal injection (N=5). Sensory nerve at the tail was orthodromically recorded, immediately after the animal was under control for maximal duration of 2 hours to assess the time course of the excitability changes. QtracS software (Digitimer, UK) was used.

Result: Threshold changes by long hyperpolarizing stimulation (i.e., threshold electrotonus and current-threshold relationship) increased approximately 30 minutes after induction of anesthesia that sustained thereafter. By contrast, recovery cycle, strength-duration time constant and depolarizing threshold electrotonus showed no remarkable change during the recording.

Conclusion: The results suggest anesthetic blockade of HCN channels which are activated by long hyperpolarizing current. When we assess the nerve excitability in experimental animals, the influence of anesthesia on nerve excitability should be taken into account.