Introduction
Effective control of pain for the avian patient is a tremendous challenge to the veterinarian. It is easily accepted that birds are able to feel pain, but very little research has been conducted to objectively determine methods to relieve pain in birds. No set of objective criteria has been established to assess pain or the effectiveness of an analgesic agent. Perhaps this accounts for the lack of published information which in turn may account for the infrequent use of analgesic agents in clinical care of birds.
Conditions that cause pain to people can be assumed to be painful to birds. A perplexing component of this approach is that not all people respond to pain in the. same manner. Two people can have the same surgical procedure and their individual analgesic requirements can vary greatly. This seems to be true for individual birds as well as variations between species of birds. Prey species may not respond in the same manner as predatory species. Social species may exhibit different behaviors than solitary species. Many birds do not respond to procedures that would be painful to humans with easily interpreted, overt painful behaviors. Some would assume that if the bird does not show painful behaviors such as crying or whining then perhaps their experience of pain is less severe. My concern is that our ability to recognize pain is inadequate and that we continually underestimate our avian patients. Avian behavior changes are subtle such as a slight alteration in posture, a slight restlessness or change in perching position, a decrease in appetite or being quieter than usual. Birds may guard a painful area and decrease their social interactions with the owner or other birds. Rather than looking for obvious changes in behavior we should key in on the absence of normal behavior.
Opioids
Limited studies in chickens suggest that pain perception is mediated by neural pathways and neurotransmitters that are similar to mammals.11,12 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.1,8,9,11-13,20 Studies performed in pigeons and chickens suggest that opiate receptors are present in birds.13,17 Early avian opioid studies described the effects of morphine administered to chickens and it was determined that dosages greater than 10–30 times a mammalian dose were needed to produce analgesia.1,20 Subsequent studies using different strains and ages of chickens yielded conflicting information. Testing methods varied using several different forms of noxious stimuli. The diversity of testing methods permit only one conclusion: opioid effects are variable depending on the species, strain and route of administration.16 Drug discrimination trials have been used to investigate the stimulus properties of opiates and pigeons were a common animal used in these studies. Pigeons can identify several opioid drugs such as buprenorphine, oxymorphone and fentanyl as being more like morphine than saline.10 Other pigeon studies 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.14 A recent study with chickens tested both a mu agonist and a kappa agonist and found that both drugs similarly decreased isoflurane anesthetic concentrations in a dose-dependent manner when administered to chickens.7
Buprenorphine is a partial agonist that avidly binds to mu opioid receptors but activates them less than morphine does which results in a long duration of analgesia in mammals. Pigeons can discriminate buprenorphine for up to 120 hours, yet pharmacokinetic studies in the African gray parrot show a rapid metabolism and excretion of the drug within 8 hours (Paul-Murphy, unpublished data). Current studies evaluating buprenorphine in African gray parrots indicate that even at extremely high IM dosages (0.2 mg/kg ) the analgesic effect is minimal.19
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. In the pigeon forebrain, 76% of the total opioid receptors are kappa.17 If other species of birds are like the pigeon, then these kappa agonist drugs may be more effective than mu opioid agonists. Butorphanol is a mixed agonist-antagonist drug. The use of butorphanol as an analgesic was recently studied in psittacines by determining its isoflurane-sparing effect. After administration of 1 mg/kg butorphanol tartrate intramuscularly (IM), the effective dose 50 (ED50) of isoflurane was decreased in cockatoos and African gray parrots but was not significantly changed in blue-fronted Amazon parrots. Current studies evaluating butorphanol in awake African gray parrots at 1.0 mg/kg determined that 50% of the birds showed an analgesic response.19 Mixed agonist-antagonist have a low therapeutic ceiling in mammals such that the analgesic effect is maximum at a specific dosage and higher dosing will not improve efficacy. The therapeutic dosage of butorphanol for many species of bird is not yet determined, but empirical dosages recommended for psittacines range from 1–4 mg/kg. In my experience, this dosage level will cause recumbence and respiratory depression in buteos.
Nonsteroidal Antiinflammatory Agents
NSAIDs act by inhibiting cyclooxygenase and the production of prostaglandins. There are several categories of NSAIDs, but few have been investigated in birds. A study of analgesic agents using pigeons tested 5 mM solutions of naproxen, ibuprofen, ketoprofen, piroxicam and acetaminophen and found that only naproxen was significantly effective against ingestion of chemical irritants.3 High levels of aspirin were fed to chickens to assess effects on fertility and embryo health.18 Phenylbutazone and indomethacin were tested in chickens to assess the inhibitory effects on anaphylactic responses. A few drugs have published dosages based on empirical use such as acetylsalicylic acid (aspirin) at 5.0 mg/kg PO TID or 325 mg per 250 ml drinking water, flunixin meglumine at 1.0–10.0 mg/kg IM SID, ketoprofen at 2 mg/kg IM, and meclofenamic acid at 2.2 mg/kg PO SID. Phenylbutazone has been used in raptors at 20 mg/kg PO and 3.5–7.0 mg/kg q 8 h in psittacines.4,21
A common side effect of NSAIDs is gastrointestinal ulceration caused by direct mucosal irritation and inhibition of prostaglandin synthesis. High dosages of flunixin meglumine (10 mg/kg) have been reported to cause regurgitation and tenesmus in budgerigars.2 Prolonged used of flunixin meglumine has caused frank blood in the feces of birds which cleared after cessation of the treatment.4
Renal ischemia and tissue damage is a serious complication of flunixin meglumine in birds. Test groups of bobwhite quail were given 0.1 and 32.0 mg/kg daily IM for 7 days, and all birds had histologic evidence of renal damage. Lesions consisted of acute necrotizing glomerulitis, gout tophi in the renal tubules and visceral gout. The severity of the lesions was directly correlated to the dosage of flunixin meglumide.15
Local Anesthetics
Local anesthetics block ion channels, which interrupts the transmission of pain impulses. Local anesthetic blocks can prevent central sensitization when used preoperatively. Lidocaine can be used safely in birds at dosages below 4 mg/kg. Overdosage has been reported to cause seizures in small birds.
Literature Cited
1. Bardo, M.T. and R.A Hughes. 1978. Shock-elicited flight response in chickens as an index of morphine analgesia. Pharmacol Biochem Behav. 9:147–149.
2. Bauk, L. 1990. Analgesics in avian medicine. Proc Assoc Avian Vet. 239–244.
3. Clark, L. 1995. Modulation of avian responsiveness to chemical irritants: effects of prostaglandin El and analgesics. J. Exp Zool. 271: 432–440.
4. Clyde, V.L. 1994. Avian Analgesia. Proc. Am Assoc Zoo Vet. 125–127.
5. Curro, T.G., Brunson D., Paul-Murphy, J., 1994. Determination of the ED50 of isoflurane and evaluation of the analgesic properties of butorphanol in cockatoos (Cacatua spp.) Vet Surg. 23:429–433.
6. Curro, T.G. 1993. Evaluation of the isoflurane-sparing effects of butorphanol and flunixin in Psittaciformes. Proc Assoc Avian Vet. 17–19.
7. Concannon, K.T., Dodam, J.R., Hellyer, P.W. 1996. Influence of a mu and kappa opioid agonist on isoflurane minimal anesthetic concentration in chickens. Am J Vet Res. 56: 806–812.
8. Duncan I.J., Beattye, R., Hocking P.M., et al. 1991. Assessment of pain associated with degenerative hip disorders in adult male turkeys. Res Vet Sci. 50:200–203.
9. Duncan, I.J., Slee. G.S., Seawright, E., et al. 1989. Behavioral consequences of partial beak amputation (beak trimming) in poultry. Br Poult Sci. 30(3):479–488.
10. France, C.P., Jacobson, A.E., Woods, J.H. 1983. Irreversible and reversible narcotic agonists: Discriminative and analgesic effects of buprenorphine, oxymorphanozone, and morphine. 45th Annual Scientific Meeting of the Committee on Problems of Drug Dependence, Inc: Chemistry and Pharmacology.
11. Gentle, M. 1990. Behavioural and physiological responses to pain in the chicken. Acta XX Congressus Internationalis Ornithologici. 111:1915–1919.
12. Gentle M.J. Hunter L.N. 1991. Physiological and behavioral responses associated with feather removal in Gallus gallus var domesticus. Res Vet Sci. 50(l):950101.
13. Gentle, M.J., Hunter, L.N. Waddington, D. 1991. The onset of pain-related behaviors following partial beak amputation in the chicken. Neurosci Lett. 28:113–116.
14. Herling, S., Coale, E.H., Valentino, R.J., et al. 1980. Narcotic discrimination in pigeons. J Pharmacol Exp Ther. 214:139–146.
15. Klein, P.N., Charmatz, Langenberg, J. 1994. The effect of flunixin meglumide on the renal function in northern bobwhite quail. Proc Amer Assoc Zoo Vet:128–131.
16. Ludders, J.W., Matthew, N. 1996. Birds In: Lumb and Jones’ Veterinary Anesthesia. Thurmon, J.C., Tranquilli, W.J., Benson GJ, eds. Lea and Febiger: 645–669.
17. Mansour, A., Khachaturian, H., Lewis M.E. et al. 1988. Anatomy of CNS opioid receptors. TINS. 11:308–314.
18. McDaniel, C.D., Balog, J.M., Elkin, R.G. et al. 1993. Poultry Sci. 72:1100–1108.
19. Paul-Murphy, J., 1997. Evaluation of analgesic properties of butorphanol and buprenorphine for the psittacine bird. Proc Assoc Avian Vet. 125–128.
20. Rager, D.R., and Gallup, Jr., G.G. 1986. Apparent analgesic effects of morphine in chickens may be confounded by motor deficits. Physiol Behav. 37:269–270.
21. Tully, T.N. 1997. Formulary. In: Avian Medicine and Surgery. Altman, R.B., Clubb, S.L., Dorrestein, G.M., Quesenberry, K, eds. W.B. Saunders: 671–688.