Vet Times The website for the veterinary profession https://www.vettimes.co.uk

APPROACHES TO MANAGEMENT OF CHRONIC OA PAIN IN DOGS AND CATS

Author : GEORGINA L HERBERT, MATTHEW GURNEY

Categories : Vets

Date : October 7, 2013

GEORGINA L HERBERT and MATTHEW GURNEY consider the challenges in providing pain relief and good quality of life in pets with the most common form of degenerative joint disease

OSTEOARTHRITIS (OA) is a progressive disease of synovial joints, characterised by cartilaginous degeneration and osteophyte formation. It is presumed to be the most prevalent cause of degenerative joint disease (DJD) in dogs and cats1 and is a common 4 cause of chronic pain in both dogs and cats, the incidence of which increases with age2- .

In dogs, the radiographic incidence of OA is 20 per cent across the general adult population and 80 per cent in older dogs (more than eight years old)3. In cats, the radiographic incidence of OA is 16.5 per cent in the general adult population and 82 per cent to 91 per cent in older cats (more than 12 years old)2,4,5. It is likely the true incidence of OA in both species is underestimated, as joints affected with cartilaginous changes alone will not be radiographically abnormal.

The onset of OA-associated chronic pain in dogs and cats is insidious and the signs are often subtle and very different from those associated with acute pain. Pain is mediated by release, but over time, other nociceptive mediators may become involved.

Lameness is the most common presenting sign in dogs with OA (with or without crepitus, synovial effusion and reduced range of motion). Cats rarely become lame, presenting instead with a history 8 of reduced activity and reluctance to jump2,6- .

1 / 18 In both species behavioural changes are used to identify chronic pain. These changes may manifest as either a loss of normal behaviour or the development of abnormal behaviour, as -10. While chronic pain-related behaviours have been validated in dogs8, 7 thedescribed published in the behaviours literature associated with chronic pain have yet to be validated in cats11. Because of the subtle and insidious signs of chronic pain, owner assessment-based quality of life (QoL) questionnaires appear to be the best tools for its diagnosis in dogs and cats, just as they are in humans8,11,12.

Treatment of the chronic pain associated with osteoarthritis in dogs and cats is a clinical challenge due to:

• the difficulty and, therefore, potential delay in diagnosis;

• the presence of allodynia and hyperaesthesia;

• ongoing progression of the disease process;

• concurrent medical conditions, particularly in the ageing population (obesity, heart disease, metabolic/endocrinological disease); and

• the dynamic change, both increasing and decreasing intensity, of the pain experience that occur over time.

These challenges, in particular the need to work with a progressive disease process and variable pain experience within individuals, necessitate the use of a multimodal approach to pain management13:

• pharmacological interventions using the “treatment ladder” concept;

• multimodal environmental modification (MEMo);

• exercise modification;

• weight control;

• acupuncture; and

• physical and adjunctive therapies.

Treatment of OA is palliative. The goal is a comfortable animal that can express as many of its normal behaviours as is physically possible.

2 / 18 Getting the most out of NSAIDs

As NSAIDs form the cornerstone of treatment for OA pain, it is important to understand how to optimise their use; the class has well known gastrointestinal and renal adverse side effects (ASEs) and the consequences of misuse may be dire.

For most animals, gastrointestinal (GI) irritation is self-limiting and clinical signs (inappetence, vomiting and diarrhoea) resolve within two days, but in severe cases it may lead to fatal gastric perforation. Severe GI ASEs are more likely following coadministration of NSAIDs and corticosteroids, in the face of pre-existing compromise of the GI tract or in individuals intolerant to a particular NSAID14,15. Individual intolerance of an NSAID cannot be predicted and, in these cases, an alternate NSAID should be selected.

Renotoxicity is unlikely to occur when the clinical dose rates are used in systemically well animals with ad libitum access to water14. However, in the face of arterial hypotension or hypovolaemia, NSAIDs incapacitate the normal renoprotective effect of in maintaining renal perfusion and glomerular filtration, leading to medullary hypoperfusion and renal papillary necrosis and, in severe cases, acute renal failure may follow15.

Dehydration should be corrected prior to NSAID administration. If blood pressure is not monitored and hypotension corrected accordingly during general anaesthesia, an NSAID should not be administered until the recovery period.

In cases with pre-existing renal insufficiency NSAIDs should be used with caution, but renal insufficiency may not be a contraindication per se. In 2011, Gowan et al16 found cats on long-term administration of with osteoarthritis and renal insufficiency had a slower progression of their renal insufficiency than case-controlled cats not administered meloxicam. One hypothesis was the cats given meloxicam were more comfortable and so ate and drank more normally, resulting in better and more consistent hydration than those cats not administered an NSAID16.

Owners of animals on longterm NSAID therapy should always be counselled to cease NSAID administration until further veterinary advice is sought if their animal stops eating or drinking, is systemically unwell, has severe or bloodstained vomiting/diarrhoea or less severe vomiting/diarrhoea if signs persist for more than two days.

Other, less common, potential ASEs of NSAIDs tend to be drug-specific and include blood dyscrasias, respiratory distress in asthmatics (non-selective NSAIDs only), reduced ovulation, foetotoxicity and hepatotoxicity. Reports on the effects of NSAIDs on bone and soft tissue healing are conflicting, but it is the authors’ view and experience that any effect is not clinically significant and is far outweighed by the benefits of alleviating pain in the convalescent period.

Dose reduction has been suggested as one means of reducing the likelihood of ASEs in dogs and

3 / 18 -19. Unfortunately, “dose reduction is a less effective means of pain control compared with 16 maintainedcats dosing. However, NSAID dose reduction with maintained efficacy is possible, but success appears to be individual dog dependent”17 and doses of less than 40 per cent the licensed maintenance dose in cats are generally ineffective16,17,19.

Another important consideration regarding NSAID administration is the timing of the dose. If an animal is more active later in the day or overnight, morning administration will avoid low plasma drug concentration during high activity levels. For those animals more active during the day, and particularly in the morning, then evening administration is most appropriate.

Choosing the right NSAID

The ideal NSAID for treatment of OA pain is:

• licensed for long-term administration in the target species;

• easy to administer by owners; and

• well tolerated by animals, with few ASEs.

In the UK, six NSAID molecules are licensed to treat musculoskeletal pain long term in dogs (, , mavacoxib, meloxicam, and ), one licensed for osteoarthritis in dogs for up to three days at a time (tolfenamic acid), one licensed for indefinite use in cats (meloxicam) and one licensed to treat acute musculoskeletal pain for up to six days in cats (robenacoxib) that have acceptable ASE profiles in the target species (Table 1).

When choosing which NSAID to use it is important to remember no NSAID has been shown to be a superior analgesic than any other in dogs, it is just the ASE profile that differs.

Until recently, this was the case in cats too, but in 2012 results from a clinical trial in Japan indicated robenacoxib may provide superior pain relief in the first 24 hours after surgery compared to meloxicam20. This study investigated the effects of a single dose only and had several flaws that may have biased the results, so it should be interpreted with caution; however, if these findings are repeatable it will be the first study to show analgesic superiority of one NSAID over another in any species.

As there is so little evidence for analgesic superiority between NSAIDs, it is more likely the ease of administration, both for owner compliance and animal tolerance, is more important when choosing between them. In a study commissioned by Abbott, 29 per cent of dog owners were concerned their dog was not getting its and previous research shows many owners find cats difficult to tablet. If an animal will eat a chewable tablet but avoid a liquid preparation, or vice versa, then the formulation that can be more easily administered is the better option. Similarly, if an

4 / 18 animal is intolerant (develops an ASE) to NSAID X administration but not NSAID Y, then NSAID Y is the better choice irrespective of whether NSAID X was easier for the owner to administer.

The treatment ladder

The chronic pain caused by OA in dogs and cats is not an all or nothing phenomenon. There will invariably be periods of more or less intense pain over the course of the disease. As such, the treatment should be varied according to the needs of the animal at that time.

The concept of a “treatment ladder” helps us to visualise these variations in pain intensity and, therefore, treatment required. Figure 1 shows what the WHO treatment ladder would look like if we extrapolated from man to dogs and cats, but does not fully take into account the role other analgesic adjuvants (Table 2) may play in chronic pain management. As pain intensity and/or duration increases, so too does the aggressiveness of analgesic therapy, and vice versa.

On the first tier we have mild chronic pain, treated with a non-opioid analgesic, that is, NSAID or (dogs only); on the second tier there is moderate or persisting chronic pain for which a “mild” opioid (tramadol) is required in addition to a non-opioid analgesic; on the third tier severe and/or persisting chronic pain requires treatment with a “strong” opioid (buprenorphine, morphine, methadone or fentanyl) in addition to a non-opioid analgesic and hospitalisation during therapy may be required.

Drug options and dose rates are in Table 1. Analgesic adjuvants (Table 2) may be incorporated into the treatment ladder at any stage according to the response to non-opioid or combined non-opioid- opioid treatment.

Pharmacologic analgesic adjuvants

In one study “using dogs with OA pain that was refractory to NSAID treatment, the ability to perform everyday activities in subjects with mobility impairment was improved by the addition of amantadine to the NSAID therapy”21. This improvement in mobility was not apparent until after three to six weeks of treatment; owners should be informed the treatment must be continued for six weeks before we can assess the efficacy of amantadine.

There is also encouraging evidence in humans that gabapentin provides effective acute and chronic pain relief22,23. While there are no clinical trials evaluating the efficacy of gabapentin in dogs and cats, its use has been recommended for treatment of chronic pain in both species6,24,25.

Both amantadine and gabapentin are neuromodulating agents that may also cause apparently dose-dependent sedation24. A reduced dose rate or increased dosing interval may be required to avoid unacceptable sedation and analgesic efficacy, reassessed after four to six weeks to ensure the dosing regime with acceptable side effects is also effective.

5 / 18 Addition of amantadine or gabapentin to the analgesic treatment regime should be considered when pain becomes refractory to NSAIDs or a neuropathic pain component is suspected (when allodynia is observed). As such it is the authors’ opinion they are most commonly required for those animals that are either intermittently or continually in Tier 2.

Antidepressants, particularly amitriptyline, have also been suggested as adjunctive analgesics for chronic pain treatment6,13,24. Unfortunately, the ASEs of tricyclic antidepressants may be dominant to the analgesic effects and it is the authors’ opinion they should only be used if the animal was intolerant, or the pain refractory, to amantadine or gabapentin therapy. Tricyclic antidepressants should not be used in conjunction with tramadol as the combination may cause serotonin syndrome, which is potentially fatal.

Local anaesthetic drugs may be used topically26,27 or infiltrated as a part of a regional anaesthetic technique to provide temporary pain relief and may be particularly useful when managing animals that have progressed to Tier 328.

Which opioid, when?

When an NSAID ceases to provide adequate pain relief, we have three options:

• try an alternative NSAID;

• begin concomitant treatment with an analgesic adjuvant; or

• move to Tier 2 and start concomitant opioid administration.

By combining analgesic drugs from two different classes we hope to achieve better overall pain relief, with fewer ASEs, by treating pain along different points in the nociceptive pathway. This is called multimodal analgesia.

Tramadol has been shown to provide analgesia in both dogs and cats but is unlikely to be effective in every animal, probably due to differences in metabolism25,29. An alternative to tramadol is codeine, but evidence of an analgesic effect is limited in dogs and non-existent in cats; most studies focus on the antitussive effects.

We do know that in humans the analgesic effect of orally administered codeine is attributed to the metabolism of 10 per cent of the parent compound to morphine. In dogs and cats only 1.5 per cent of the parent compound is metabolised to morphine24.

There is little evidence at the present time either for or against the use of codeine in dogs or cats, making tramadol the better first-line choice. For moderate-severe pain, a period of hospitalisation may be required for parenteral administration of more efficacious µ-agonist opioid analgesics, such

6 / 18 as when an arthritic dog develops a septic arthritis. Depending on the severity of clinical signs, buprenorphine, methadone or fentanyl infusion titrated to effect may be required. Fentanyl may cumulate over time so prolonged infusion (longer than two days) is undesirable and lower infusion rates may be needed.

For longer-term treatment at Tier 3, off-licence transdermal fentanyl can be considered. In cats, a fentanyl patch can be used to provide analgesia for up to three days, but absorption and efficacy is variable30. In dogs, a transdermal fentanyl solution lasting four days is now licensed for perioperative use in orthopaedic conditions. This preparation must not be used in cats. In the interest of public safety, dogs weighing more than 20kg must remain hospitalised for 48 hours after administration and small children or other pets must not come into contact with the animal until 72 hours after administration. If the pain of OA has become so severe that long-term administration of fentanyl is required in Tier 3, then, unless there was a clear and reversible exacerbating cause (trauma or septic arthritis), palliative treatment has been exhausted and euthanasia may be the only humane treatment option.

Are there any new developments?

No revolutionary new drugs or techniques have been discovered, but there is at least some veterinary evidence available to support the use of tramadol and amantadine in dogs and cats, as previously discussed.

While no scientific papers assess the therapeutic use of paracetamol in dogs, its use, either as the sole agent or in combination with an NSAID (for Pardale-V this is against the labelled advice), has made a resurgence over the past few years13,24,29,31. It is the authors’ experience that paracetamol is a useful analgesic in dogs, but it does not appear to be equivalent to the pain relief afforded by other NSAIDs. It cannot be stated strongly enough that paracetamol should never be administered to a cat.

More evidence is emerging to support the use of omega-3 supplemented joint diets, and supplementation with and (GCS) and green lipped mussel extract -36. The analgesia (GLME)afforded nutraceuticalsis superior to thatprovide of a analgesiacontrol diet to and, both where dogs andthey cats have with been OA compared6,32 to an NSAID, have a longer onset (six to 10 weeks) and duration of action with lesser analgesic effect.

Polysulfated glycosaminoglycans (PSGAGs) and pentosan polysulfate (PPS) are both disease- modifying agents of osteoarthritis, theoretically improving the quality and reducing destruction of cartilage13,35. There is some evidence PSGAGs and PPS are of benefit in treating OA in dogs, but there is little evidence for their use in cats. Unfortunately, both PSGAGs and PPS have anti- coagulant effect and coadministration with an NSAID is contraindicated. This significantly compromises the usefulness of these agents in dogs already showing signs of OA where NSAIDs form the cornerstone of treatment.

7 / 18 A more appropriate use of PSGAGs and PPS may be in delaying the progression of joint degeneration in high risk animals for OA (elbow/hip dysplasia) that don’t yet require treatment with an NSAID. Unfortunately, at the present time, dose rates for nutraceuticals vary widely, if present in the literature at all.

Multimodal environmental modification

Multimodal environmental modification is a key part of managing OA pain and, while there is more discussion of its use in managing feline OA6,37, the authors feel it is valuable in managing dogs and cats alike.

The aim is to provide an environment in which the animal can express normal behaviour by providing places to hide, sleep, play, groom, interact with the owner, eat, drink and toilet in security and comfort. Access to favourite places and the outdoors (including access to outdoor toileting areas) can be improved with ramps or series of small steps and obstacles removed or bypassed where possible.

For cats, litter trays should be large enough to posture in and at least one edge low enough to comfortably walk over. Modified food and water bowls may be useful and should always be located in an easy to access location; larger dogs may be more comfortable with bowls at chest height, either placed on a surface or in a cradle, while cats prefer shallow water bowls separated from food bowls.

Bedding should be adequately cushioned without being spongy and difficult to move on. Regular interaction and play with the owner, including grooming and gentle physiotherapy/ massage, reinforces the pet-owner bond, while also providing mental stimulation and gentle exercise. In cats, grooming also leads to the release of neurotransmitters that improve mood and ability to cope with pain6.

Acupuncture uses application of a needle, pressure, heat and/or an electric current to specific anatomic loca- tions stimulating the release of endorphins, dynorphins and enkephalins and, with some techniques (high frequency electric stimulation), serotonin, adrenaline and noradrenaline in the cerebrospinal fluid38,39. The release of endorphins, dynorphins and enkephalins causes cumulative analgesia over time.

Acupuncture can also be applied directly to trigger points, decreasing muscle spasm to relieve pain. The exact mechanism by which acupuncture induces these changes is poorly understood, but 40 the technique is widely accepted and useful in the treatment of most dogs and many cats6,31,38- .

Physical rehabilitation with massage, hydrotherapy (dogs and cats), active exercise, passive range of motion, stretching, balance and proprioception exercises, cryotherapy, moist heat and transcutaneous electrical nerve stimulation (TENS) can all help to improve blood and lymph flow,

8 / 18 loosen and stretch exciting musculature and further develop the supportive musculature around joints, reduce the risk of osteopenia developing and improve the animal: owner bond39.

The combined effect of these therapies is reduced inflammation, improved range of motion, prevention of abnormal joint loading and improved patient comfort and mobility6,13,39.

In some animals, arthrodesis or replacement of affected joint(s) may be appropriate and necessary for pain management, particularly for end-stage hips, elbows, carpi and tarsis3.

Weight management

43 Obesity in animals has been shown to reduce QoL and increase the severity of OA41- .

Weight control may reduce obesity-related inflammation44 as well as reducing abnormal joint loading and improving the ability to exercise. As well as directly improving the musculoskeletal system, weight loss aids in the control and management of other diseases that may contribute to the chronic pain experience42.

Monitoring therapy – tools for owners

Serial “client specified outcome measures” QoL questionnaires appear to be the most appropriate means of monitoring chronic pain6,9,45,46. Serial documentation of the QoL of animals with OA is of vital importance in assessing the response to therapy and owners should be educated in their use. The Canine Brief Pain Inventory can be downloaded at: http://research.vet.upenn.edu/PennChart/AvailableTools/ tabid/1969/Default.aspx

Conclusion

Chronic pain caused by OA in dogs and cats can be treated palliatively using a multimodal approach with analgesic drugs (non-opioid and opioid) and adjuvants (pharmacological, nutraceutical and physical) including MEMo and weight loss. The treatment ladder helps the clinician to visualise the dynamic nature of chronic OA pain, while QoL questionnaires provide the best means of documenting and assessing the response to treatment.

References

1. Bennett D (2010). Canine and feline osteoarthritis. In Ettinger S J and Fieldman E C (eds), Textbook of Veterinary Internal Medicine (7th edn), Vol 1, Saunders Elsevier, St Louis, Missouri: 750-761. 2. Lascelles B D X (2010). Feline degenerative joint disease, Veterinary Surgery 39: 2-13. 3. Johnston S A (1997). Osteoarthritis. Joint anatomy, physiology, and pathobiology, Veterinary Clinics of North America: Small Animal Practice 27: 699-723. 4. Clarke S P, Mellor D, Clements D

9 / 18 N et al (2005). Prevalence of radiographic signs of degenerative joint disease in a hospital population of cats, Veterinary Record 157: 793-799. 5. Slingerland L I, Hazewinkel H A W, Meij B P et al (2011). Crosssectional study of the prevalence and clinical features of osteoarthritis in 100 cats, Veterinary Journal 187: 304-309. 6. Bennett D, Zainal Ariffin S Mb and Johnston P (2012). Osteoarthritis in the cat: 2. How should it be managed and treated? Journal of Feline Medicine and Surgery 14: 76-84. 7. Hielm-Bjorkman A K, Kuusela E, Liman A et al (2003). Evaluation of methods for assessment of pain associated with chronic osteoarthritis in dogs, Journal of the American Veterinary Medical Association 222: 1,552-1,558. 8. Wiseman-Orr M L, Scott E M, Reid J et al (2006). Validation of a structured questionnaire as an instrument to measure chronic pain in dogs on the basis of effects on health-related quality of life, American Journal of Veterinary Research 67: 1,826-1,836. 9. Lascelles B D X, Hansen B D, Roe S et al (2007). Evaluation of client-specific outcome measures and activity monitoring to measure pain relief in cats with osteoarthritis, Journal of Veterinary Internal Medicine 21: 410-416. 10. Bennett D, Zainal Ariffin S Mb, Johnston P (2012). Osteoarthritis in the cat: 1. How common is it and how easy to recognise? Journal of Feline Medicine and Surgery 14: 65-75. 11. Zamprogno H, Hansen B D, Bondell H D et al (2010). Item generation and design testing of a questionnaire to assess degenerative joint disease-associated pain in cats, American Journal of Veterinary Research 71: 1,417-1,424. 12. Skevington S M, Carse M S and Williams A C (2001). Validation of the WHOQOL-100: pain management improves quality of life for chronic pain patients, Clinical Journal of Pain 17: 264-275. 13. Johnston S A, McLaughlin R M and Budsberg S C (2008). Nonsurgical management of osteoarthritis in dogs, Veterinary Clinics of North America: Small Animal Practice 38: 1,449-1,470. 14. Papich M G (2008). An update on nonsteroidal anti-inflammatory drugs (NSAIDs) in small animals, Veterinary Clinics of North America: Small Animal Practice 38: 1,243-1,266. 15. Monteiro-Steagall B P, Steagall P V M and Lascelles B D X (2013). Systematic review of nonsteroidal anti-inflammatory drug-induced adverse effects in dogs, Journal of Veterinary Internal Medicine 27 (5): 1,011-1,019. 16. Gowan R A, Lingard A E, Johnston L et al (2001). Retrospective case-control study of the effects of long-term dosing with meloxicam on renal function in aged cats with degenerative joint disease, Journal of Feline Medicine and Surgery 13: 752-761. 17. Wernham B G J, Trumpatori B, Hash J et al (2011). Dose reduction of meloxicam in dogs with osteoarthritis- associated pain and impaired mobility, Journal of Veterinary Internal Medicine 25: 1,298-1,305. 18. Sparkes A H, Heiene R, Lascelles B D X et al (2010). ISFM and AAFP consensus guidelines: long-term use of NSAIDs in cats, Journal of Feline Medicine and Surgery 12: 521-538. 19. Gunew M, Menrath V and Marshall R (2008). Long- term safety, efficacy and palatability of oral meloxicam at 0.010.03mg/kg for treatment of osteoarthritic pain in cats, Journal of Feline Medicine and Surgery 10: 235-241. 20. Kamata M, King J N, Seewald W et al (2012). Comparison of injectable robenacoxib versus meloxicam for peri- operative use in cats: results of a randomised clinical trial, Veterinary Journal 193: 114-118. 21. Lascelles B D X, Gaynor J S, Smith E S et al (2008). Amantadine in a multimodal analgesic regimen for alleviation of refractory osteoarthritis pain in dogs, Journal of Veterinary Internal Medicine 22: 53-59. 22. Sen H, Sizlan A, Yanarates O et al (2009). A comparison of gabapentin and ketamine in acute and chronic pain after hysterectomy, Anesthesia and Analgesia 109: 1,645-1,650. 23. Turan A, White P F, Karamanlio lu B et al (2007). Premedication with gabapentin: the effect on tourniquet pain and quality of intravenous regional anesthesia, Anesthesia and

10 / 18 Analgesia 104: 97-101. 24. Grubb T (2010). What do we really know about the drugs we use to treat chronic pain? Topics in Companion Animal Medicine 25: 10-19. 25. KuKanich B (2013). Outpatient oral analgesics in dogs and cats beyond nonsteroidal anti-inflammatory drugs: an evidence-based approach, Veterinary Clinics of North America: Small Animal Practice 43 (5): 1,109-1,125. 26. Weiland L, Croubels S, Baert K et al (2006). Pharmacokinetics of a lidocaine patch 5 per cent in dogs, Journal of Veterinary Medicine, A, Physiology, Pathology, Clinical Medicine 53: 34-39. 27. Ko J C, Maxwell L K, Abbo L A et al (2008). Pharmacokinetics of lidocaine following the application of 5 per cent lidocaine patches to cats, Journal Veterinary Pharmacology and Therapeutics 31: 359-367. 28. Robertson S A and Taylor P M (2004). Pain management in cats – past, present and future. Part 2. Treatment of pain-clinical pharmacology, Journal of Feline Medicine and Surgery 6: 321-333. 29. Malek S, Sample S J, Schwartz Z et al (2012). Effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis, BMC Veterinary Research 8: 185. 30. Egger C M, Glerum L E, Allen S W et al (2003). Plasma fentanyl concentrations in awake cats and cats undergoing anesthesia and ovariohysterectomy using transdermal administration, Veterinary Anesthesia and Analgesia 30: 229-236. 31. Gaynor J S (2008). Control of cancer pain in veterinary patients, Veterinary Clinics of North America: Small Animal Practice 38: 1,429-1,448. 32. Roush J K, Dodd C E, Fritsch D A et al (2010). Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs, Journal American Veterinary Medical Association 236: 59-66. 33. Lascelles B D X, DePuy V, Thomson A et al (2010). Evaluan tion of a therapeutic diet for feline degenerative joint disease, Journal of Veterinary Internal Medicine 24: 487-495. 34. McCarthy G, O’Donovan J, Jones B et al (2007). Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/ chondroitin sulfate for the treatment of dogs with osteoarthritis, Veterinary Journal 174: 54-61. 35. Vandeweerd J M, Coisnon C, Clegg P et al (2012). Systematic review of efficacy of nutraceuticals to alleviate clinical signs of osteoarthritis, Journal of Veterinary Internal Medicine 26: 448-456. 36. Hielm-Bjorkman A, Tulamo R M, Salonen H et al (2009). Evaluating complementary therapies for canine osteoarthritis part I: greenlipped mussel (Perna canaliculus), Evidence Based Complement Alternative Medicine 6: 365-373. 37. Ellis S L H, Rodan I, Carney H C et al (2013). AAFP and ISFM feline environmental needs guidelines, Journal of Feline Medicine and Surgery 15: 219-230. 38. Gaynor J S (2000). Acupuncture for management of pain, Veterinary Clinics of North America: Small Animal Practice 30: 875-884. 39. Downing R (2011). The role of physical medicine and rehabilitation for patients in palliative and hospice care, Veterinary Clinics of North America: Small Animal Practice 41: 591-608. 40. Grubb T (2010). Chronic neuropathic pain in veterinary patients, Topics in Companion Animal Medicine 25: 45-52. 41. German A J, Holden S L, Wiseman- Orr M L et al (2012). Quality of life is reduced in obese dogs but improves after successful weight loss, Veterinary Journal 192: 428-434. 42. German A J (2006). The growing problem of obesity in dogs and cats, Journal of Nutrition 136: 1,940S-1,946S. 43. Impellizeri J A, Tetrick M A and Muir P (2000). Effect of weight reduction on clinical signs of lameness in dogs with hip osteoarthritis, Journal American Veterinary Medical Association 216: 1,089-1,091. 44. Tvarijonaviciute A, Tecles F, Martínez-Subiela S et al (2012). Effect of weight loss on inflammatory biomarkers in obese dogs, Veterinary Journal 193: 570-572. 45. Hielm-Bjorkman A K, Rita H and Tulamo R-M (2009). Psychometric testing of the Helsinki chronic pain index by completion of a questionnaire in Finnish

11 / 18 by owners of dogs with chronic signs of pain caused by osteoarthritis, American Journal of Veterinary Research 70: 727-734. 46. Brown D C, Boston R C, Coyne J C et al (2008). Ability of the canine brief pain inventory to detect response to treatment in dogs with osteoarthritis, Journal American Veterinary Medical Association 233: 1,278-1,283

Figure 1. The treatment ladder for chronic OA pain in dogs and cats. ‡The use of paracetamol is restricted to dogs only. *Drug is unlicensed in dogs or cats but use in the treatment of OA pain has been reported in both species. †A transdermal fentanyl solution is licensed for perioperative use in dogs only, that provides up to four days of analgesia. Modified from: The WHO palliative care: symptom management and end of life care interim

12 / 18 guidelines 2004 (http://whqlibdoc. who.int/hq/2004/WHO_CDS_IMAI_2004.4.pdf)

13 / 18

14 / 18 An example of multimodal environmental modification for cats. The use of ramps and staged shelving allows step-wise access to the window.

15 / 18

TABLE 1. Analgesic non-opioid and opioid drugs for use in dogs and cats, according to the treatment ladder

16 / 18 17 / 18

TABLE 2. Analgesic adjuvants that may be included in a multimodal pain management plan for OA in cats and dogs

18 / 18

Powered by TCPDF (www.tcpdf.org)