Your browser is out-of-date!

Update your browser to view this website correctly. Update my browser now

×

InFocus

Evidence-based analgesia in exotic pet medicine

Options for analgesia in our exotic species are numerous, although not always well known

The use of analgesia in exotic pet medicine remains in its infancy, due to minimal pharmacokinetic studies and a lack of understanding in identifying signs of pain. The majority of analgesia administered to exotic pets in the UK is done so through off-licence use of medications through the prescribing cascade. Veterinary surgeons must provide analgesia to any species showing signs of pain but many may be unsure of the options available to them.

Mammals

FIGURE (1) Pain will trigger defensive or guarding behaviours in small mammals, such as hedgehogs rolling up

Many of our small mammals are prey species and therefore mask signs of pain in order to avoid predation. Recent research has developed a number of “grimace scales” for rabbits (Keating et al., 2012), mice (Langford et al., 2010) and rats (Sotocinal et al., 2011) in order to identify signs of pain. Whilst these are currently unavailable for other species, signs of pain are presumed to be similar, generally including hunched posture, abdominal pressing, vocalisation and reluctance to move (Allweiler, 2016) and defensive or guarding behaviours (Figure 1). Some patients are reluctant to show these behaviours when observed, with guinea pigs more demonstrative of pain when observed remotely rather than directly (Ellen et al., 2016).

Meloxicam and carprofen seem to be the most studied of all NSAIDs (Flecknell, 2018); however, vast differences in dose rates do occur. Higher dose rates of meloxicam have been reported as beneficial in mice (Wright-Williams et al., 2007) compared to rats (Ogino et al., 1997). Meloxicam is widely used in practice, as injectable and oral forms are easily sourced and titrated based on species, and currently meloxicam for cats is licensed for use in guinea pigs in the UK. It is important to consider the gastrointestinal comparative anatomy between different small mammal species, as hindgut fermenters such as rabbits and guinea pigs vastly differ in drug absorption compared with omnivorous rodents or carnivorous mustelids. Dosing of NSAIDs should always be based on the most up-to-date scientific data for the species in question.

Buprenorphine is the most commonly used opioid analgesic in rodents (Stokes et al., 2009). It is a partial mu agonist and is widely thought of as sufficient for normal levels of post-operative pain (Flecknell, 2018). Pure mu agonists such as morphine and methadone can be considered in situations where increased intra- and post-operative pain is expected; however, their duration of action is shorter than that of buprenorphine (Gades et al., 2000). Some concern has surrounded the use of opioids and their tendency to cause ileus in hindgut fermenters, but in clinical practice this is rare (Flecknell, 2018) and it is more likely that the lack of provision of adequate analgesia is responsible for any post-operative ileus observed.

Tramadol is a weak opioid with good oral bioavailability (Flecknell, 2018). Pharmacokinetics of tramadol have been studied in rabbits (Souza et al., 2008), rats (Taylor et al., 2016) and mice (Wolfe et al., 2015) with varying levels of efficacy and so more proven analgesics should be considered prior to, or in combination with, tramadol.

Local anaesthetics are an excellent component of multimodal analgesia, especially when used for peri- and post-operative pain. They are often overlooked due to the relatively small doses required; however, dose rates and toxic doses are similar to those of our other companion species (Flecknell, 2018). Volumes can be diluted with water for injection and administered either by infiltration, splash blocks, topical cream formulations, nerve blocks or epidural injections.

Birds

FIGURE (2) Feather destructive behaviour can be indicative of chronic pain. The fluffed-up appearance of this African grey parrot can also be an indicator of pain

Pain in birds can be difficult to identify, but as knowledge of bird behaviour increases, so does our understanding of their response to pain. Both reductions and severe increases in preening behaviours to the point of feather destructive behaviours (Figure 2) can be indications of pain (Hawking and Paul-Murphy, 2011), as can isolation from a flock, lethargy, hyporexia and aggression (Lierz and Korbel, 2012).

A study of intramuscular and oral administration of meloxicam following orthopaedic procedures in pigeons showed doses of 0.5mg/kg provided ineffective analgesia, but doses of 2mg/kg resulted in greater degrees of weightbearing on the affected limb (Desmarchelier et al., 2012). Evidence of pain following experimentally induced arthritis in Hispaniolan parrots was greatly reduced by administration of intramuscular meloxicam at 1mg/kg, compared to doses of 0.5mg/kg and below (Cole et al., 2009). Both these studies indicate that avian patients require far higher doses of meloxicam compared to their mammalian counterparts.

Opioids are useful for moderate to severe pain in birds. There are considerable species differences in distribution of opioid receptors, and due to an early study in pigeons showing 76 percent of receptors in the forebrain were kappa receptors (Reiner et al., 1989), it was assumed that butorphanol was the opioid of choice for avian patients. Recently, studies in American kestrels have shown an increased thermal withdrawal threshold (TWT) after administration of intramuscular buprenorphine (Ceulemans et al., 2014; Guzman et al., 2018), indicating its efficacy in falcons. However, a similar study failed to show any change in TWT after intramuscular administration of buprenorphine in cockatiels (Guzman et al., 2018). A study comparing intramuscular buprenorphine and butorphanol in African grey parrots showed that buprenorphine had no significant effect on withdrawal from a noxious stimulus, but butorphanol did increase TWT. This indicates buprenorphine is not useful for psittacine species, whereas butorphanol remains an appropriate analgesic. Similar studies evaluating the efficacy of intramuscular hydromorphone in orange-winged Amazon parrots (Guzman et al., 2017) and cockatiels (Houck et al., 2018) showed an increased TWT in orange-winged Amazons, however no change in TWT in cockatiels.

Local anaesthetics in birds appear to require much higher dose rates (Hocking et al., 1997). Given the lack of research and the concern for toxicities, they are seldom used (Lierz and Korbel, 2012).

Reptiles

FIGURE (3) Severe injuries in chelonians, such as this traumatic amputation in a Hermann’s tortoise, will usually cause the patient to withdraw into their shell

There is a misconception that reptiles do not feel as much pain as their mammalian and avian counterparts, as their signs of pain are far more subtle. Debate centres around whether reptiles feel pain or merely react to noxious stimuli (Perry and Nevarez, 2018); however, we should assume an animal can feel pain until proven otherwise and treat as such. Pain assessment should be carried out at a distance if possible, as green iguanas have been shown to reveal a greater response to painful stimuli when the observer is not visible (Fleming and Robertson, 2012). Signs of pain should be considered similar to those of mammalian patients, such as hunched posture, guarding of the affected area, excessive scratching, foot or tail flicking, exaggerated flight response or poor appetite (Mosley, 2011), as well as specific behaviours such as withdrawing into their shell in chelonians (Figure 3).

The body temperature of a reptile plays an important role in drug absorption, as does anatomic variations between species (Mosley, 2011). Reptiles should always be at their preferred optimum temperature zone when drugs are administered to ensure maximal absorption. It is recommended that drug administration into the caudal body of reptiles is avoided, as concerns have been raised due to renal first-pass effects and potential nephrotoxicity. Whilst this is not consistent between species (Holz et al., 1997), it is best to avoid administration of potentially nephrotoxic drugs, such as NSAIDs, into the tail and hindlimbs of reptiles.

Pharmacokinetic data for NSAIDs in reptiles is poor and their efficacy has not been proven despite multiple studies (Perry and Nevarez, 2018). Non-selective COX inhibitors have been advocated as a study of eastern box turtles demonstrated COX-1 and COX-2 proteins are expressed within the turtle tissues (Royal et al., 2012).

Butorphanol has been shown to have little or no effect in red-eared sliders (Sladky et al., 2007), bearded dragons and corn snakes (Sladky et al., 2008), but these same studies demonstrated antinociceptive effects of morphine in red-eared sliders and bearded dragons. Buprenorphine has been shown to not be efficacious in green iguanas (Greenacre et al., 2006) and red-eared sliders (Mans et al., 2012). However, the study by Mans et al. showed that hydromorphone was efficacious, indicating that pure mu receptor agonists should be used for analgesia in reptiles.

Tramadol has been shown to increase TWT when administered orally and subcutaneously in red-eared sliders (Baker et al., 2011) and intramuscularly in yellow-bellied sliders (Giorgi et al., 2015), indicating it is useful for analgesia and likely a good choice for outpatient analgesia for long-term patients such as those suffering thermal burns.

Use of local anaesthesia is in its early stages in reptile medicine but is being used in clinical practice with success. Intrathecal lignocaine, bupivacaine and morphine have been shown to successfully block motor function of the cloacal sphincter and hindlimbs as well as provide analgesia to the hindlimbs for up to 48 hours (Mans et al., 2011). Toxicity can be avoided by following the known toxic doses of local anaesthetics in mammals (Mosley, 2011).

References

Allweiler, S.I.

2016

How to improve anaesthesia and analgesia in small mammals. Veterinary Clinics of North America: Exotic Animal Practice, 19, pp. 361-377

Keating, S., Thomas, A., Flecknell, P. and Leach, M.

2012

Evaluation of EMLA cream for preventing pain during tattooing of rabbits: changes in physiological, behavioural and facial expression responses. PLoS ONE, 7, p.e44437

Baker, B., Sladky, K. and Johnson, S.

2011

Evaluation of the analgesic effects of oral and subcutaneous tramadol administration in red-eared slider turtles. Journal of the American Veterinary Medical Association, 238, pp. 220-227

Ceulemans, S., Guzman, D., Olsen, G., Beaufrère, H. and Paul-Murphy, J.

2014

Evaluation of thermal antinociceptive effects after intramuscular administration of buprenorphine hydrochloride to American kestrels (Falco sparverius). American Journal of Veterinary Research, 75, pp. 705-710

Cole, G., Paul-Murphy, J., Krugner-Higby, L., Klauer, J., Medlin, S., Keuler, N. and Sladky, K.

2009

Analgesic effects of intramuscular administration of meloxicam in Hispaniolan parrots (Amazona ventralis) with experimentally induced arthritis. American Journal of Veterinary Research, 70, pp. 1471-1476

Desmarchelier, M., Troncy, E., Fitzgerald, G. and Lair, S.

2012

Analgesic effects of meloxicam administration on postoperative orthopedic pain in domestic pigeons (Columba livia). American Journal of Veterinary Research, 73, pp. 361-367

Ellen, Y., Flecknell, P. and Leach, M.

2016

Evaluation of using behavioural changes to assess post-operative pain in the guinea pig (Cavia porcellus). PLoS ONE, 11

Fleming, G.J. and Robertson, S.A.

2012

Assessments of thermal antinociceptive effects of butorphanol and human observer effect on quantitative evaluation of analgesia in green iguanas (Iguana iguana). American Journal of Veterinary Research, 73, pp. 1507-1511

Giorgi, M., Salvadori, M., De Vito, V., Owen, H., Demontis, M. and Varoni, M.

2015

Pharmacokinetic/pharmacodynamic assessments of 10 mg/kg tramadol intramuscular injection in yellow-bellied slider turtles (Trachemys scripta scripta). Journal of Veterinary Pharmacology and Therapeutics, 38, pp. 488-496

Greenacre, C., Takle, G., Schumacher, J., Klaphake, E. and Harvey, R.

2006

Comparative antinociception of morphine, butorphanol, and buprenorphine versus saline in the green iguana, iguana iguana, using electrostimulation. Journal of Herpetological Medicine and Surgery, 16, pp. 88-92

Guzman, D., Ceulemans, S., Beaufrère, H., Olsen, G. and Paul-Murphy, J.

2018

Evaluation of the thermal antinociceptive effects of a sustained-release buprenorphine formulation after intramuscular administration to American kestrels (Falco sparverius). Journal of Avian Medicine and Surgery, 32, pp. 1-7

Guzman, D., Houck, E., Knych, H., Beaufrère, H. and Paul-Murphy, J.

2018

Evaluation of the thermal antinociceptive effects and pharmacokinetics after intramuscular administration of buprenorphine hydrochloride to cockatiels (Nymphicus hollandicus). American Journal of Veterinary Research, 79, pp. 1239-1245

Hawkins, M. and Paul-Murphy, J.

2011

Avian Analgesia. Veterinary Clinics of North America: Exotic Animal Practice, 14, pp. 61-80

Hocking, P., Gentle, M., Bernard, R. and Dunn, L.

1997

Evaluation of a protocol for determining the effectiveness of pre-treatment with local analgesics for reducing experimentally induced articular pain in domestic fowl. Research in Veterinary Science, 63, pp. 263-267

Holz, P., Barker, I.K., Burger, J.P., Crawshaw, G.J. and Conlon, P.D.

1997

The effect of the renal portal system on pharmacokinetic parameters in the red-eared slider (Trachemys scripta elegans). Journal of Zoo and Wildlife Medicine, 28, pp. 386-393

Houck, E., Guzman, D., Beaufrère, H., Knych, H. and Paul-Murphy, J.

2018

Evaluation of the thermal antinociceptive effects and pharmacokinetics of hydromorphone hydrochloride after intramuscular administration to cockatiels (Nymphicus hollandicus). American Journal of Veterinary Research, 79, pp. 820-827

Langford, D.J., Bailey, A.L., Chanda, M.L., Clarke, S.E., Drummond, T.E., Echols, S., Glick, S., Ingrao, J., Klassen-Ross, T., Lacroix-Fralish, M.L., Matsumiya, L, Sorge, R.E., Sotocinal, S.G., Tabaka, J.M., Wong, D. Van Den Maagdenberg, A.M.J.M., Ferrari, M.D., Craig, K.D. and Mogil, J.S.

2010

Coding of facial expressions of pain in the laboratory mouse. Nature Methods, 7, pp. 447-449

Lierz, M. and Korbel, R.

2012

Anaesthesia and Analgesia in Birds. Journal of Exotic pet Medicine, 21, pp. 44-58

Mans, C., Steagall, P., Lahner, L., Stephen, J. and Sladky, K.

2011

Efficacy of intrathecal lidocaine, bupivacaine, and morphine for spinal anesthesia and analgesia in red-eared slider turtles (Trachemys scripta elegans). In: American Association of Zoo Veterinarians Annual Conference. Kansas City: American Association of Zoo Veterinarians, p. 135

Mans, C., Lahner, L., Baker, B., Johnson, S. and Sladky, K.

2012

Antinociceptive efficacy of buprenorphine and hydromorphone in red-eared slider turtles (Trachemys scripta elegans). Journal of Zoo and Wildlife Medicine, 43, pp. 662-665

Mosley, C.

2011

Pain and nociception in reptiles. Veterinary Clinics of North America: Exotic Animal Practice, 14, pp. 45-60

Ogino, K., Hatanaka, K., Kawamura, M., Katori, M. and Harada, Y.

1997

Evaluation of pharmacological profile of meloxicam as an anti-inflammatory agent, with particular reference to its relative selectivity for cyclooxygenase-2 over cyclooxygenase-1. Pharmacology, 55, pp. 44-53

Perry, S.M. and Nevarez, J.G.

2018

Pain and Its Control in Reptiles. Veterinary Clinics of North America: Exotic Animal Practice, 21, pp. 1-16

Reiner, A., Brauth, S., Kitt, C. and Quirion, R.

1989

Distribution of mu, delta, and kappa opiate receptor types in the forebrain and midbrain of pigeons. The Journal of Comparative Neurology, 280, pp. 359-382

Royal, L., Lascelles, B., Lewbart, G., Correa, M. and Jones, S.

2012

Evaluation of cyclooxygenase protein expression in traumatised versus normal tissues from Eastern Box Turtles (Terrapene carolina carolina). Journal of Zoo and Wildlife Medicine, 43, pp. 289-295

Sanchez-Migallon Guzman, D., Douglas, J., Beaufrère, H. and Paul-Murphy, J.

2017

Thermal antinociceptive and agitation-sedation effects after intramuscular administration of hydromorphone hydrochloride in orange-winged Amazon parrots (Amazona amazonica). Veterinary Anaesthesia and Analgesia, 44, pp. 1262.e13-1262.e14

Sladky, K., Miletic, V., Paul-Murphy, J., Kinney, M., Dallwig, R. and Johnson, S.

2007

Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles. Journal of the American Veterinary Medical Association, 230, pp. 1356-1362

Sladky, K., Kinney, M. and Johnson, S.

2008

Analgesic efficacy of butorphanol and morphine in bearded dragons and corn snakes. Journal of the American Veterinary Medical Association, 233, pp. 267-273

Sotocina, S.G., Sorge, R.E., Zaloum, A., Tuttle, A.H., Martin, L.J., Weiskopf, J.S., Mapplebeck, J.C.S., Wei, P., Zhan, S., Zhang, S. Mcdougall, J.J., King, O.D., Mogil, J.S.

2011

The rat grimace scale: a partially automated method for quantifying pain in the laboratory rat via facial expressions. Molecular Pain, 7, pp.1744-8069-7-55

Souza, M., Greenacre, C. and Cox, S.

2008

Pharmacokinetics of orally administered tramadol in domestic rabbits (Oryctolagus cuniculus). American Journal of Veterinary Research, 69, pp. 979-982

Stokes, E., Flecknell, P. and Richardson, C.

2009

Reported analgesic and anaesthetic administration to rodents undergoing experimental surgical procedures. Laboratory Animals, 43, pp. 149-154

Taylor, B.F., Ramirez, H.E., Battles, A.H., Andrutis, K.A. and Neubert, J.K.

2016

Analgesic activity of tramadol and buprenorphine after voluntary ingestion by rats (Rattus norvegicus). Journal of the American Association for Laboratory Animal Science, 55, pp. 74-82

Wolfe, A.M., Kennedy, L.H., Na, J.J. and Nemzek-Hamlin, J.A.

2015

Efficacy of tramadol as a sole analgesic for postoperative pain in male and female mice, Journal of the American Association for Laboratory Animal Science, 54, pp. 411-419

Wright-Williams, S., Courade, J., Richardson, C., Roughan, J. and Flecknell, P.

2007

Effects of vasectomy surgery and meloxicam treatment on faecal corticosterone levels and behaviour in two strains of laboratory mouse. Pain, 130, pp. 108-118

Ashton Hollwarth

Ashton Hollwarth, BSc, BVMS, CertAVP (Zoo Med), MRCVS, studied in Western Australia and moved to England following graduation. She is currently enrolled in an ECZM residency in Avian Medicine and Surgery at Great Western Exotics. Ashton gained her Certificate of Advanced Veterinary Practice in Zoological Medicine in 2020 and became an Advanced Practitioner in Zoological Medicine in 2021.


More from this author

Looking for a range of resources, insights and CPD all in one place?

Join the ALL-NEW Veterinary Practice community; the online platform with nugget-sized, CPD-accredited veterinary training and resources!

Everything you need for your professional development, delivered by experts.

One place. One login. It’s online. All the time.

Annual subscription: £299 for Vets and £199 for Vet Nurses

Subscribe Now