Clinical evaluation of pre-emptive use of oral Amantadin on intraoperative pain during ovariohysterectomy in NZ White Rabbit

 Background When painful stimulations are constantly perceived by the pain sensation system, pain management becomes more difficult and pain will turn from acute to chronic. Therefore, prevention and management of acute pain will ultimately reduce both acute and chronic pain in patients and the development of appropriate analgesia during surgery and subsequent pain control can be important in  healing process. (5,6)    appropriate analgesia during painful stimulations surgery and reducing postoprative pain is one of the constant challenges of anesthesia(7) and every year many researches are conducted on anesthetic compounds with the aim of achieving the best compounds for the most effective effects in different animals. Amantadine is an antiviral medicine, it is used to prevent or treatment of type A influenza infection (1,2,3) and a non-competitive antagonist of NMDA receptor(4), which increases dopamine releae and prevents dopamine reuptake, which also acts as an antiparkinson agent.   Because of its NMDA receptor antagonist characteristics, amantadine may  improve analgesia when administered with meloxicam preemptively. This study aimed to evaluate the pre-emptive analgesic effect of amantadine in female rabbits, underwent ovariohysterectomy. Methods Twenty female rabbits were randomly divided to four groups of five. The first group (KXD) received Ketamine-Xylazine-Diazepam at the time of surgery, without any additional analgesic drug. Second group (M-KXD) received  0.5 mg/kg subcutaneous Meloxicam, one hour before surgery and then Ketamine-Xylazine-Diazepam at the time of surgery. Third group (A-KXD) received 5 mg/kg oral amantadine once in a day, during five days before surgery and Ketamine-Xylazine-Diazepam at the time of surgery. Fourth group (AM-KXD) received 0.5 mg/kg subcutaneous meloxicam, one hour before surgery and 5 mg/kg oral amantadine once in a day, five days before surgery and then Ketamine-Xylazine-Diazepam at the time of surgery. Heart rate, respiration rate and, SpO2 were recorded and intraoperative pain was evaluated in chronographic assign such as skin incision, white line incision, ovarian pedicle ligature and cervix ligature. Results There was significant difference in the heart rate in moments of white line incision and ovarian pedicle ligature between the groups, as first group (KSD) had significantly higher heart rate than the other groups. Third (A-KXD) and forth groups (AM-KXD) had slower heart rate in moment of cervix ligature than first (KXD) and second (M-KXD) groups. Respiration rate was significantly higher in first group (KSD) than other groups in moments of white line incision and ovarian pedicle ligature. There were no significant differences in Spo2 measurement between groups. conclusion Results of this animal study showed the preemptive visceral analgesic effects of amantadine as an adjuvant to meloxicam administration, compared to meloxicam alone and suggesting the use of multiple daily oral Amantadine before a single dose of Meloxicam prior to ovariohysterectomy operation.