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especially in case of any gastrointestinal sign in dogs and cats with diminished appetites. 5. Perform laboratory monitoring. The frequency will depend on the risk factor of the patient. Ideally within first month of initiating therapy then q 6 mo thereafter in low-risk patients. For at-risk patients, monitor q 2–4 mo depending on risk-factor assessment. 6. Utilize a balanced, integrated analgesic approach as part of NSAID-sparing strategies. 7. Consider washout periods. Clinically relevant washout periods remain controversial and largely undefined. Based on pharmacokinetics, practitioners who wish to err on the side of caution may want to withhold meloxicam for 5 days and other NSAIDs or short-acting corticosteroids for 7 days prior to initiating treatment with another NSAID. In the case of long-acting corticosteroids, a longer washout period needs to be considered. Aspirin should not be administered because there are safer alternatives. If a course of treatment with aspirin has been started in a dog, the recommended washout period before starting an approved veterinary NSAID is up to 10 days. 8. Use gastroprotectants to either treat suspected gastropathy or prevent its occurrence, especially if no washout period occurs. Proton pump inhibitors, H2 antagonists, misoprostol (the drug of choice in humans), and sucralfate can be helpful. 9. Dose optimization. Base dosage on lean body weight. Although there is no definitive evidence that NSAID dose reduction lowers the risk of adverse events, some clinicians recommend titrating to the lowest effective dose. JAAHA.ORG 73 Pain Management Guidelines for Dogs and Cats Ketamine Ketamine exerts a pain-modifying effect via its N-methyl-Daspartate receptor antagonist actions. Subanesthetic ketamine constant rate infusion (CRI) in humans prevents pain and has antihyperalgesic, and antiallodynic effects.36,37 Studies appear to support a similar clinical effect in dogs, although ketamine’s analgesic effect has not yet been studied in a feline surgical model.38–40 The International Veterinary Academy of Pain Management has adopted a position that the pain-modifying effects and safety profile of subanesthetic doses of ketamine warrant its use as part of a multimodal approach to transoperative pain management, especially in patients with risk factors that may predispose them to either exaggerated or maladaptive pain states. Systemic Lidocaine There is strong evidence of the safety and beneficial effects of IV lidocaine on pain after abdominal surgery (although not for other surgeries eliciting somatic pain) in humans and possibly in horses, including both analgesia and return of bowel function.41 IV lidocaine is anesthetic-sparing in dogs and cats, but current evidence for a pain-modifying effect in those species remains inconclusive.42 Some investigators discourage the use of IV lidocaine in cats due to negative cardiovascular effects, but successful use in clinical practice has been anecdotally reported.43 Various formulations for a combination of morphine, lidocaine, and ketamine CRIs have been described in dogs.44 Tramadol In contrast to humans, tramadol in dogs has a very short half-life (1.7 hr) and negligible amounts of the opioid M1 metabolite are produced.45–48 Pharmacodynamic studies demonstrate the anesthesia-sparing and pain-modifying effect of parenteral tramadol in dogs.49–53 Convincing evidence for a pain-modifying effect of oral tramadol, however, remains elusive, and already low plasma levels quickly diminish with sequential administration.54–57 One small study of oral tramadol did report a statistically significant increase of mechanical threshold levels in dogs, but only at the 5 and 6 hr time points.48 In contrast to dogs, cats do produce the l-agonist M1 metabolite. A pain-modifying effect has been demonstrated in both a thermal threshold and clinical surgical model.58,59 One case series involving the use of oral tramadol in a flavored compounded form (the drug is otherwise quite bitter), and dose-titration, toxicity, and safety data are currently lacking in both dogs and cats.60 Gabapentin Gabapentin is an anticonvulsant with analgesic properties that may be primarily derived by down-regulating calcium channels.61 Because of its efficacy and tolerability, gabapentin is widely used in humans with neuropathic and other maladaptive pain conditions.62 Along with published clinical case reports in animals, the data suggest a strong rationale for using gabapentin in dogs and cats with similar conditions.63,64 One canine study suggested a disease-modifying effect in experimental DJD, but clinical studies are lacking.65 In cats, one unpublished study demonstrated a benefit of gabapentin in naturally-occurring DJD (E. Troncy, personal communication 2013), and one case series of chronic musculoskeletal pain has also been published.66 The evidence for gabapentin in human postsurgical pain is encouraging, but not yet in dogs and cats.67–72 An 8–12 hr dosing interval has been suggested based on one publication.73 The primary adverse effect in dogs appears to be somnolence (also the case in humans), which usually resolves with patient acclimation over several days, allowing for a tapering-up schedule. Amantadine Amantadine exerts a pain-modifying effect as an N-methyl-Daspartate receptor antagonist and remains a drug of interest for chronic pain (but not specifically for DJD) in humans.74 One study demonstrated utility as an adjunct to NSAIDs in dogs with refractory DJD, and there is one case report utilizing amantadine to treat neuropathic pain in a dog.75,76 Toxicity and pharmacokinetic studies have been performed in humans and cats but not in dogs.77,78 Tricyclic Antidepressants (TCAs) As a class, TCAs are the most effective medications for selective neuropathic pain conditions in humans.79 In dogs, there exists only a single case report where amitriptyline was used for neuropathic musculoskeletal pain.80 Selective Serotonin (Norepinephrine) Reuptake Inhibitors [SS(N)RIs] These compounds exert their effect by increasing serotonin with or without norepinephrine in the synaptic cleft. At least one SS(N)RI, duloxetine, has a chronic pain label indication