Chronic pain: Decreased activity starts vicious cycle of problems

Chronic pain: Decreased activity starts vicious cycle of problems

Dec 01, 2003

QPlease provide educational material about canine chronic pain management for the client that is not commercially prepared.

AAt the recent Southwest Veterinary Symposium of 2003 in Fort Worth, Texas, Dr. Darryl L. Millis from University of Tennessee presented an excellent talk on chronic pain management that would be appropriate for the client and is not commercially based. Selected aspects from his presentation follow.

Chronic pain is frequently associated with orthopedic conditions, such as osteoarthritis. Other conditions resulting in chronic pain include neoplasia, neurologic conditions, myopathies and chronic inflammatory conditions.

Animals with chronic painful conditions generally do not display many of the dramatic painful behaviors associated with acute pain. For example, dogs with osteoarthritis may have restricted activity, limited ability to perform, muscle atrophy, pain and discomfort, decreased range of motion and decreased quality of life. Other signs of chronic pain include reduced appetite, licking the area and laying quietly in an area free of other activity.

As animals reduce their activity level because of chronic pain, a vicious cycle of decreased flexibility, joint stiffness, loss of strength and decreased cardiovascular fitness occurs.

Management of dogs with chronic pain should include medication and physical modalities. Medication for chronic painful conditions should reduce pain and discomfort, decrease the severity of clinical signs, maintain an acceptable quality of life, improve strength and fitness, slow the progression of the underlying disease if possible and promote the repair of damaged tissue. Surgical treatment may focus on correcting the underlying condition, or performing a salvage procedure such as a total hip replacement for hip dysplasia or amputation for osteosarcoma.

Managing painManagement of dogs with chronic pain due to osteoarthritis includes anti-inflammatory and analgesic medications, disease-modifying osteoarthritis agents, weight reduction, low-impact exercise programs and physical modalities, alteration of the environment. The management of chronic osteoarthritis is a lifelong commitment and requires diligent effort and regular follow-up assessments.

Many inflammatory mediators may be involved in chronic painful conditions, including prostaglandins, leukotrienes, interleukins and metalloproteinases. It is possible that nonsteroidal anti-inflammatory agents (NSAIDs) provide benefits to arthritic dogs in several ways. One of the primary modes of action is the reduction of inflammatory mediators, especially prostaglandins, in the peripheral tissues and in the central nervous system. The inflammatory cascade is initiated when cell membrane phospholipids are acted on by phospholipase to produce arachidonic acid. Cyclooxygenase (COX) and lipoxygenase then act on arachidonic acid to produce eicosanoids, such as prostaglandins and leukotrienes.

NSAIDs inhibit the COX enzyme, thereby decreasing the production of inflammatory mediators and reducing pain associated with osteoarthritis. Recently, two forms of the COX enzyme have been identified, COX-1 and COX-2. COX-1 is a constitutive enzyme and is normally produced in relatively constant amounts and has "house-keeping" functions, such as protection of the gastric mucosa, maintaining renal perfusion and production of platelet thromboxane A2. The COX-2 enzyme is inducible and its production increases in response to inflammation.

In addition to the induction of COX-2 in peripheral tissues with inflammation, COX-2 is also induced in the central nervous system. The inhibition of the COX-1 enzyme by NSAIDs is believed to be responsible for adverse side effects, including gastric ulceration, platelet dysfunction and decreased renal perfusion.

Non-selective COX inhibitors inhibit both COX-1 and COX-2 enzymes. The identification of the two COX isoforms has resulted in the development of products that preferentially or selectively inhibit the inducible "bad" COX-2 enzyme while sparing the COX-1 enzyme. Selective inhibition of COX-2 with preservation of COX-1 should reduce the adverse effects associated with the GI tract, kidneys and platelets. The concept of COX-1:COX-2 ratios helps in the understanding of the relative ability to inhibit the various forms of cyclooxygenase. A ratio >1 indicates that the drug inhibits more COX-1 activity than COX-2 activity, while a ratio <1 indicates that the drug inhibits more COX-2 activity than COX-1 activity. Theoretically, fewer side effects should occur with a COX-1:COX-2 ratio >1.

Unfortunately, there are no standard ways of measuring this ratio, and ratios may be significantly affected by the type of in vitro or in vivo test system, the substrates used, and the incubation times and conditions of the test system.

The best guidelines are the clinical efficacy of a particular drug, while maintaining an acceptable level and degree of side effects. NSAIDs that are frequently used include deracoxib, carprofen, etodolac, and aspirin. Phenylbutazone, meclofenamic acid, meloxicam, and piroxicam have also been used, and ketoprofen is approved for use in other countries and has been used in the USA. Acetaminophen with or without codeine is occasionally used in dogs but should not be used in cats.

Deracoxib is a COX-2 specific inhibitor, as defined by the World Health Organization, while carprofen, etodolac, and meloxicam have some preferential selectivity to inhibit COX-2. While no NSAID has been shown to clearly be more efficacious than others in the relief of chronic pain, some dogs apparently have a better response to some drugs as compared with others. Veterinarians should not be reluctant to perform therapeutic trials to evaluate the efficacy of various NSAIDs in a particular animal to determine which will provide the best clinical improvement without side effects. Two-week trials of various NSAIDs with adequate animal evaluation should be performed to determine which medication provides the best response. Before prescribing any medication, the animal's health status, especially liver and kidney function, should be assessed. It is important to educate owners regarding potential side effects.

Slow-acting disease-modifying osteoarthritic agents are substances which are thought to alter the course of osteoarthritis by improving the health of articular cartilage or synovial fluid. Nutraceuticals are nutritional supplements believed to have a positive influence on cartilage health by providing precursors necessary for repair and maintenance. Glucosamine and chondroitin sulfate are routinely combined as disease-modifying agents.