PEER REVIEWED MANAGING CHRONIC PAIN IN DOGS & CATS Part 3: Management of Nonosteoarthritic Pain Conditions Mark E. Epstein, DVM, Diplomate ABVP (Canine/Feline), CVPP Carolinas Animal Pain Management & TotalBond Animal Hospitals (Forestbrook), Gastonia, North Carolina Parts 1 and 2—The Two Most hile osteoarthritis (OA) may be the most commonly Important Tools in the Management recognized cause of chronic pain in dogs and cats, Wother pain syndromes exist. The following scenarios, of Osteoarthritis and The Best of when evaluated together, may have a prevalence approaching the Rest in the Management of that of OA: Osteoarthritis (November/December 1. Chronic or chronic–active inflammatory pain 2. Maladaptive chronic pain 2013 and September/October 2014, 3. Cancer pain. respectively; available at tvpjournal Treatment of these pain phenomena has not been inves- .com)—of this 3-part series discussed tigated in depth, so therapeutic rationale must be inferred from disease pathophysiology and existing evidence regard- therapeutic options for its most common ing individual treatment modalities. manifestation in companion animals: osteoarthritis. CHRONIC OR CHRONIC–ACTIVE INFLAMMATORY PAIN A growing body of evidence suggests that peripheral and central sensitization not only exists in chronic inflammatory disease states (Table 1) but may actually advance pathologic abnormali- TABLE 1. Examples of Chronic & ties through proinflammatory neurogenic mechanisms. Chronic–Active Inflammatory Pain Few studies have assessed the management of nonOA chronic inflammatory conditions, and such studies may be Chronic periodontal disease difficult to perform. However, a treatment sequence for this Feline lymphocytic–plasmacytic stomatitis category of chronic pain can be inferred, in the following Idiopathic feline lower urinary tract disease* approximate order: Inflammatory bowel disease 1. Anti-inflammatory medications: nonsteroidal anti-inflam- Meningoencephalitides matory drug (NSAID) or corticosteroid Otitis externa 2. Treatment of underlying disease or aggravating comor- Pancreatitis bidities 3. Neuromodulatory analgesic drugs, such as gabapentin, * Feline interstitial cystitis is increasingly being consid- tramadol, and amitriptyline ered a somatic pain syndrome.1 4. Weight optimization. 40 Today’s Veterinary Practice November/December 2014 tvpjournal.com MANAGEMENT OF NONOSTEOARTHRITIC PAIN CONDITIONS | mend the following drugs: tricyclic antidepressants, gaba- TABLE 2. Examples of Potential or Existing pentin, and opioids.3 While these papers are drawn mainly Maladaptive Chronic Pain2 from trials involving diabetic neuropathy and postherpetic neuralgia—clinical conditions not identified in animals— Central nervous system lesions, including post- these drugs commonly play a more prominent role in trauma or vascular accidents, intracranial masses, managing maladaptive pain than NSAIDs. and congenital defects (eg, syringomyelia) • Gabapentin can be considered a relatively well-tolerat- Chronic intervertebral disk disease ed, inexpensive, easy-to-administer, and effective pain Diabetic neuropathy medication in dogs and cats, with efficacy supported by Feline hyperesthesia syndrome numerous case reports.4–7 Feline orofacial pain syndrome • Use of the tricyclic antidepressant amitriptyline for Postperipheral nerve injury (eg, trauma, amputation) pain has been described in canine and feline case Postsurgical conditions (eg, fractures, hernia repair) 7,8 9 Others reports and for feline interstitial cystitis. • Oral opioids may also have a role in treating these syn- dromes. MALADAPTIVE CHRONIC PAIN Additional medications that have been used in humans Maladaptive pain occurs through the process of peripheral for maladaptive pain states include: and central sensitization. Its features include pain that is • Other anticonvulsants (pregabalin, lamotrigine) protracted in duration, exaggerated in severity (hyperal- • Ion channel blockers (mexiletine, infusions of sys- gesia, allodynia), and expanded in field, and can occur in temic lidocaine, ketamine) the absence of obvious tissue pathology. These types of • Selective serotonin-norepinephrine reuptake inhib- disease states (Table 2) include many poorly understood itors (duloxetine, venlafaxine). pain syndromes. However, lack of experience with, and data on, these agents for pain in animals limits their use at this time. NSAIDs To the degree that inflammation is considered a compo- Additional Therapies nent of the underlying pathologic abnormality activating As adipose tissue is the body’s largest endocrine organ nociceptive pathways, NSAIDs can be considered a first- and secretes a witches brew of degradative enzymes and line drug. However, many maladaptive chronic pain states pro-inflammatory cytokines, weight optimization may have progressed to, or are intrinsically, a neuropathic have the same important role to play in managing nonOA state. In these cases, NSAIDs may contribute a less robust chronic pain as it does in OA. In elderly humans, central analgesic effect. obesity (abdominal fat) doubles the risk for chronic pain from any cause.10 Other Analgesic Therapies Table 3 outlines therapeutic options for maladaptive In humans, systematic reviews of neuropathic pain recom- chronic pain. TABLE 3. Management of Maladaptive Pain: Therapies to Consider MODALITY COMMENTS 1. Neuromodulatory Agents Gabapentin • Anticonvulsants Pregabalin • Gabapentin preferred in dogs • Possible role for pregabalin Amitriptyline • Tricyclic antidepressant Tramadol • Pharmacokinetics of oral tramadol do not favor its use for pain in dogs11-15 • It may have better results in cats16 Amantadine • NMDA receptor antagonist Venlafaxine • Selective serotonin-norepinephrine reuptake inhibitor • Oral venlafaxine has approximately 50% bioavailability in dogs, with half-life of 3 H17 • Duloxetine has poor oral bioavailability in dogs18 Acetaminophen + • Consider judicious use, especially for breakthrough pain in dogs hydrocodone or codeine • The dog does not appear to demonstrate a special proclivity toward hepatotoxicity, but methemoglobinemia and anemia are reported with overdosage and long-term use. Complete blood count monitoring is recommended. • Pharmacokinetic, but not clinical, data support the utility of codeine and hydrocodone in the dog (Table continued on page 42) tvpjournal.com November/December 2014 Today’s Veterinary Practice 41 | MANAGEMENT OF NONOSTEOARTHRITIC PAIN CONDITIONS TABLE 3. Management of Maladaptive Pain: Therapies to Consider (continued) MODALITY COMMENTS 1. Neuromodulatory Agents (continued) IV CRI of ketamine • Have been used with success to treat refractory neuropathic pain states in 19,20 IV CRI of lidocaine humans • Have not yet been investigated for canine and feline neuropathic pain 2. Weight Optimization 3. NSAIDs (may play a role in managing maladaptive pain) 4. Physical Modalities (limited data-based studies available) • Acupuncture • Myofascial trigger point therapy • Physical therapy (prescribed therapeutic exercises, hydrotherapy) • Energy-based modalities (therapeutic laser, extracorporeal shock wave therapy) CANCER PAIN tin, pregabalin, and strong opioids as the most effective Any primary neoplasm or cancer metastasis to bone, and best-tolerated drugs, while amitriptyline, tramadol, including osteosarcoma (OSA), causes a chronic pain con- and NSAIDs elicited less effect or had a more unfavorable dition in dogs and cats; pain is due to many unique factors safety profile.21 to this disease (Table 4). See Medications for Cancer Pain in Dogs & Cats for further information. TABLE 4. Factors That Cause CONCLUSION Chronic Cancer Pain The treatment of chronic pain in dogs and cats remains a vast and largely unexplored frontier, but provides enor- Action of osteoclasts mous opportunities for positive outcomes for patients, pet Local necrosis owners, veterinary teams, and practices themselves. With Lymphatic obstruction focus, continued learning, and leadership, this arena of Neurochemical blend of bi-active, proinflammatory cytokines, which distinctly sustain and enhance veterinary medicine is a means for personal and profes- nociceptive pathways sional growth and, ultimately, compassionate care of com- Upregulation of cyclooxygenase (COX) enzymes panion animal populations. n COX = cyclooxygenase; CRI = constant rate infusion; NMDA = N-methyl-D-aspartate; NSAID = nonsteroidal Palliative Care anti-inflammatory drug; OA = osteoarthritis; OSA = For patients whose owners have opted for palliative care— osteosarcoma pain management and disease control versus amputation or References chemotherapy—inadequate pain control, rather than the 1. Buffington CAT. Idiopathic cystitis in domestic cats—beyond the lower disease itself, will probably be the terminal event leading to urinary tract. J Vet Intern Med 2011; 25(4):784-796. euthanasia. Once a collaborative decision is made between 2. Mathews KA. Neuropathic pain in dogs and cats: If only they could tell us if they hurt. Vet Clin North Am Small Anim Pract 2008; 38(6):1365-1414. the veterinarian and pet owner that pain can no longer be 3. Finnerup NB, Otto M, McQuay HJ, et al. Algorithm for neuropathic pain sufficiently managed, humane euthanasia should quickly treatment: An evidence based proposal. Pain 2005; 118:289-305. follow. 4. Rusbridge C, Heath S, Gunn-Moore DA, et al. Feline orofacial pain syndrome (FOPS): A retrospective study of 113 cases. J Feline Med Surg In these difficult cases, it is important to access the entire 2010; 12(6):498-508. pain