Abstract
Very little research has been conducted to objectively determine relief of pain for birds. Synthetic opioids are frequently used in veterinary medicine, including companion avian medicine, in an attempt to control pain and provide analgesia. We have developed a model to study the effects of opioids in awake psittacines. Response to a noxious electrical stimuli was compared before and after intramuscular administration of butorphanol or saline. Based on preliminary data, using African grey parrots, butorphanol is effective at 1.0 mg/kg in 50% of the birds.
Introduction
It is easily accepted that birds are able to feel pain, but very little research has been conducted to objectively determine ways to relieve pain in birds.1,2,6,12 In addition to the humane reasons to relieve pain, pain has many secondary physiological consequences which may impede patient recovery.22 Reliable information on analgesia for psittacines is needed by veterinarians, bird owners, and research scientists who are concerned with the palliation of painful conditions in these companion animals.2,3,15 Early studies with birds have primarily used chickens or pigeons and were not intended to correlate with clinical application. The lack of information detailing dose-response characteristics and dosing intervals for analgesic agents has forced veterinarians to extrapolate information obtained from studies performed in dogs, cats, and humans.
Opioids are a diverse group of natural and synthetic drugs with morphine-like actions. These drugs combine reversibly with specific receptors in the brain and spinal cord, modifying the transmission and recognition of pain. The analgesic effect of opioids varies widely among animal species. This may be due to the distribution, number and type of opioid receptors within the brain. Opioid receptors are classified into 5 major types and drugs that affect the specific receptors, mu and kappa, are the most common analgesics used. In general, distribution of opioid receptor types is conserved across species in brainstem and spinal cord areas but varies significantly in the forebrain.16 In mammalian species such as the guinea pig, monkey, and human, kappa opioid receptors represent only a third of the total opioid receptor population of the forebrain while in the pigeon forebrain 76% of the total opioid receptors are kappa.16
Butorphanol is a mixed agonist-antagonist opioid drug. Mixed agonist-antagonist opioids are the most common drugs used in veterinary medicine for prolonged pain relief. Mixed agonist-antagonists are characterized by agonist activity at opioid kappa receptors and minimal or antagonist effects at opioid mu receptors. If other species of birds are like the pigeon, having a high percentage of kappa opioid receptors, then these drugs may be more effective than mu opioid agonists.15
Limited studies in chickens suggest that pain perception is mediated by neural pathways and neurotransmitters that are similar to mammals.9 Studies to evaluate pain in birds (primarily gallinaceous birds) have been based upon changes in heart rate, increases in blood pressure, vocalizations, attempts to escape, and behavioral changes.1,7-11,19,21 Studies performed in pigeons and chickens suggest that opiate receptors are present in birds.13,16 Early behavioral studies with pigeons concluded that birds could not discriminate between mu and kappa agonists and, therefore, both opioid receptors were thought to have a similar mechanism of action.13 Psittacine physiological parameters such as heart rate, mean arterial pressure, arterial pCO2 and pO2, tidal volume, inspiratory, and expiratory time are easiest to measure while the bird is anesthetized. If an opioid is administered concurrently with an inhalation anesthetic such as isoflurane, and the concentration of inhalant anesthetic can be reduced, this indicates the opioid may be providing analgesia to the animal. This method to assess analgesic effects of opioids by reduction of inhalant anesthetic concentration has been studied and accepted in mammalian species,14,17,18 turkeys,20 and chickens6. A recent study tested both a mu and kappa opioid agonist and found that both drugs effectively decreased isoflurane anesthetic concentrations in a dose-dependent manner when administered to chickens.6
Results and Discussion
The first studies of analgesic agents in psittacines were done at the University of Wisconsin using butorphanol in anesthetized parrots. Our laboratory studied the effects of butorphanol in cockatoos4 African grey parrots and blue-fronted Amazon parrots.5 Studies with African grey parrots showed a significant 11% reduction in the effective dose for 50% of the birds in a population (ED50) of isoflurane following administration of butorphanol 1 mg/kg IM. In the cockatoo and African gray parrot, butorphanol did not cause any significant changes in physiological parameters. To validate the technique of isoflurane reduction as a reliable method to evaluate avian analgesia, preliminary studies in awake psittacines have been completed.
The effects of electrical current on nociception thresholds and tolerance were evaluated in non-anesthetized parrots. A perch was designed to deliver an electrical stimulus to the foot of the bird. Response to the noxious stimuli was compared before and after administration of butorphanol or saline. In the African gray parrot, butorphanol significantly decreased the response to a noxious electrical stimulus. Seven of 14 parrots given butorphanol 1.0 mg/kg IM required a higher electrical stimulus to generate an aversion response.
Conclusions
These results from the awake parrot studies suggest 1.0 mg/kg is the ED50. This dosage is found in most avian medicine textbooks and formularies and is the same dosage tested in the study using anesthetized birds to evaluate butorphanol’s analgesic properties. Further studies are in progress to evaluate butorphanol at higher dosages and to find a clinically effective dosage greater than 1 mg/kg, to recommend for psittacines.
Literature Cited
1. Bardo MT, Hughes RA. Shock-elicited flight response in chickens as an index of morphine analgesia. Pharmacol Biochem Behav. 1978;9:147–149.
2. Bauk L. Analgesics in avian medicine. In: Proceedings of the Association of Avian Veterinarians. 1990:239–244.
3. Clyde VL. Avian analgesia. In: Proceedings of the American Association of Zoo Veterinarians. 1994:125–127.
4. Curro TG, Brunson D, Paul-Murphy J. Determination of the ED50 of isoflurane and evaluation of the analgesic properties of butorphanol in cockatoos (Cacatua spp.). Vet Surg. 1994;23:429–433.
5. Curro TG. Evaluation of the isoflurane-sparing effects of butorphanol and flunixin in psittaciformes. In: Proceedings of the Association of Avian Veterinarians. 1993:17–19.
6. Concannon KT, Dodam JR, Hellyer PW. Influence of a mu- and kappa-opioid agonist on isoflurane minimal anesthetic concentration in chickens. Am J Vet Res. 1996;56:806–812.
7. Duncan IJH, Beatty ER, Hocking PM, Duff SRI. Assessment of pain associated with degenerative hip disorders in adult male turkeys. Res Vet Sci. 1991;50:200–203.
8. Duncan IJ, Slee GS, Seawright E, Breward J. Behavioral consequences of partial beak amputation (beak trimming) in poultry. Br Poult Sci. 1989;30(3):479–488.
9. Gentle M. Behavioural and physiological responses to pain in the chicken. Acta XX Cong. Internl. Ornith. 1990;III:1915–1919.
10. Gentle MJ, Hunter LN. Physiological and behavioral responses associated with feather removal in Gallus gallus var domesticus. Res Vet Sci. 1991;50(1):950101.
11. Gentle MJ, Hunter LN, Waddington D. The onset of pain-related behaviors following partial beak amputation in the chicken. Neurosci Lett. 1991;128:113–116.
12. Glatz PC, et al. Analgesia therapy of beak-trimmed chickens. Aust Vet J. 1992;69:18.
13. Herling S, Coale EH, Valentino RJ, Hein DW, Woods JH. Narcotic discrimination in pigeons. J Pharmacol Exp Ther. 1980;214:139–146.
14. Lake CL, et al. Reduction in halothane MAC: comparison of morphine and alfentanil. Anesth Analgesia. 1985;64:807–810.
15. Ludders JW, Matthew N. Birds. In: Thurmon JC, Tranquilli WJ, Benson GJ, eds. Lumb and Jones’ Veterinary Anesthesia. Philadelphia, PA: Lea and Febiger; 1996:645–669.
16. Mansour A, Khachaturian H, Lewis M, Akil H, Watson SJ. Anatomy of CNS opioid receptors. Trends Neutosci. 1988;11:308–314.
17. Matthews NS, Lindsay SL. Effect of low-dose butorphanol on halothane minimum alveolar concentration in ponies. Eq Vet J. 1990;22:325–327.
18. Murphy MR, Hug Jr. CC. The anesthetic potency of fentanyl in terms of reduction of enflurane MAC. Anesth. 1982;57:485–488.
19. Rager DR, Gallup Jr. GG. Apparent analgesic effects of morphine in chickens may be confounded by motor deficits. Physiol Behav. 1986;37:269–272.
20. Reim DA, Middleton CC. Use of butorphanol as an anesthetic adjunct in turkeys. Lab Anim Sci. 1995;45:696–698.
21. Szolcsanyi J, Sann H, Pierau FK. Nociception in pigeons is not impaired by capsaicin. Pain. 1986;27:247–260.
22. Tanelian DL, Brunson DB. Anatomy and physiology of pain with special reference to ophthalmology. Invest Ophthal Vis Sci. 1994;35:759–763.