Assessment of Opioid Analgesia in New Zealand White Rabbits (Oryctolagus cuniculus) Using Thermal Threshold Testing
This study aimed to evaluate the effect of opioids on thermal threshold in rabbits. Eight healthy female New Zealand White rabbits randomly received each of 10 treatments at least 7 d apart. Treatments were morphine (1, 3, and 5 mg/kg), buprenorphine (0.05, 0.1, and 0.2 mg/kg), butorphanol (0.4, 0.8, and 1.6 mg/kg), and 0.9% saline all in equivalent volume of saline administered subcutaneously. Sedation scores and thermal threshold were evaluated prior to and at 30, 60, 120, 180, 240, and 300 min after treatment by a blinded observer. Sedation was assessed using a scoring system from 0 (unconscious) to 4 (normal) plus an additional category of 5 for excited behavior or increased activity. Morphine, at all 3 doses tested, increased thermal excursion (thermal threshold minus skin temperature) with effects from 3 to 5 mg/kg lasting to the 240-min evaluation. All morphine doses produced some degree of sedation. Buprenorphine (0.1 mg/kg) increased thermal excursion at 60 and 120 min and produced mild sedation. Two, 6, and 7 of the 8 rabbits took 12 to 18 h to urinate after administration of buprenorphine at 0.05, 0.1, and 0.2 mg/kg, respectively. Both saline and butorphanol had no effect on thermal threshold. Behavioral effects of butorphanol varied with some animals being sedated and some displaying heightened activity. Following butorphanol at 1.6 mg/kg, 5 of the 8 rabbits scored 5 at some time point. All rabbits had eaten and defecated within 12 h of all treatments.
(A) Effect of subcutaneous administration of saline (○) and morphine at 1 mg/kg (■), 3 mg/kg (▲), and 5 mg/kg (●) on thermal excursion (mean ± SEM) in unrestrained adult female New Zealand White rabbits (n = 8). Within treatment groups, * denotes significant difference from baseline. Between treatments at any given time point an ‘a’ denotes difference from saline control and a ‘b’ from morphine at 1 mg/kg. (B) Median sedation scores following drug administration as described above. Normal behavior is 4 on the scale, 0 represents unconsciousness, and 5 represents a state of arousal/hypervigilance.
(A) Effect of subcutaneous administration of saline (○) and buprenorphine at 0.05 mg/kg (■), 0.1 mg/kg (▲), and 0.2 mg/kg (●) on thermal excursion (mean ± SEM) in unrestrained adult female New Zealand White rabbits (n = 8). Within treatment groups, * denotes significant difference from baseline. (B) Median sedation scores following drug administration as described above. Normal behavior is 4 on the scale, 0 represents unconsciousness, and 5 represents a state of arousal/hypervigilance.
(A) Effect of subcutaneous administration of saline (○) and butorphanol at 0.4 mg/kg (■), 0.8 mg/kg (▲), and 1.6 mg/kg (●) on thermal excursion (mean ± SEM) in unrestrained adult female New Zealand White rabbits (n = 8). (B) Median sedation scores following drug administration as described above. Normal behavior is 4 on the scale, 0 represents unconsciousness, and 5 represents a state of arousal/hypervigilance.
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