Nonsteroidal anti-inflammatory drugs (NSAIDs) provide analgesia by modifying the inflammatory response. Since NSAIDs approved for use in dogs were introduced into the market (Rimadyl 1997), they have been universally accepted as the treatment of choice for osteoarthritis. NSAIDs remain the most widely used analgesics in the treatment of chronic pain. However, they are also extremely effective in reducing acute pain in the peri-operative period. Recent changes in our understanding of animal pain and the best ways to manage it, as well as new FDA drug approvals, have led to NSAIDs becoming one of the most widely used classes of veterinary analgesics in a variety of situations. There is a great deal of information flooding the veterinarians and technicians as new NSAIDs come to market.
All research in human and veterinary medicine shows that preventing pain is unquestionably the best approach to treatment. Imagine that tomorrow at 5:00 PM you were going to have an excruciating headache. What would you want do at 4:30? Probably you would want to take an analgesic like ibuprofen or another NSAID. A looming headache is an example of a planned painful event. Knowing the pain is coming allows you the opportunity to try to stop the pain before it starts. Elective surgery is also a planned painful event. It makes sense to preempt the pain that is associated with all surgical procedures whenever possible. It is an easy concept to grasp but not so easy to remember to implement. That is because we have become used to treating animal pain on "request," that is, when we see overt signs of pain even though we rationally know that once we see the signs it is already too late. We have already missed the opportunity to effectively manage pain in that patient.
Research shows that pretreatment with NSAIDs greatly reduces intraoperative and postoperative pain. Also, NSAIDs have been shown to have synergistic effect when combined with other classes of drugs such as opioids. Patients with severe acute pain can be weaned to NSAIDs alone as their pain diminishes.
How NSAIDs Work
NSAIDs have been referred to in the past as anti-prostaglandins. Prostaglandin's role in the body is to protect renal, platelet, and gastrointestinal function. Prostaglandins also serve as inflammatory mediators, meaning they are a main cause of inflammation resulting from tissue trauma. In the 1990s, it was discovered that NSAIDs do not actually inhibit prostaglandin directly, but rather inhibit cyclooxygenase (COX), an enzyme that synthesizes prostaglandin. Two isoforms of COX were identified: type 1 (COX-1) giving rise to the group of prostaglandins that maintain renal function, platelet function and gastrointestinal mucosal integrity, and type 2 (COX-2) giving rise to the group of prostaglandins that mediate the inflammatory response associated with pain. COX-2 inhibition reduces inflammation, the desired effect of treatment with NSAIDs. However, COX-1 inhibition can result in mucosal sloughing, GI ulceration and bleeding. This explains the unpleasant side effects, particularly GI bleeding that have been associated with the older NSAIDs like aspirin. Ideally, NSAID therapy is directed at inhibiting COX-2, thereby reducing inflammation while sparing COX-1, thereby reducing the negative effects. New NSAIDs have emerged over the recent past, such as carprofen (Rimadyl®), that have been targeted towards selective COX-2 inhibition. There has been much recent debate as to the optimum ratio of COX-1 to COX-2 inhibition. While it is clear that some COX-2 selectivity/COX-1 sparing is important for safety, the precise ratio is yet undetermined.
Pharmacologic actions of NSAIDs include analgesia, antipyresis (fever reduction), and control of inflammation. These analgesics have an onset of action of 30 to 60 minutes, duration of action from 8 to 96 hours, and are best suited for mild to moderate pain, whether acute or chronic in nature.
Who Needs NSAIDs?
Patients with expected postoperative pain, orthopedic or soft tissue, benefit from NSAID administration, especially when given preemptively. Patients should be normotensive, with normal renal function, without hemostatic abnormalities, without evidence or concern for gastric ulceration and not receiving corticosteroids or aspirin. In addition to controlling postsurgical pain, NSAIDs are extremely effective in controlling inflammatory pain associated with traumatic soft-tissue injury, ophthalmic conditions, otitis, gingivitis and some cancer pain. They are most effective when given prior to initiation of the inflammatory process; however, care must be taken to ensure adequate blood pressure is maintained throughout anesthetic procedures for optimal patient health. This is especially true when preemptive NSAIDs are administered, since the COX-2 enzyme plays an important role in regulating fluid balance in hypotensive patients.
The availability of NSAIDs has greatly improved outpatient pain management. These relatively inexpensive analgesics provide long-lasting postoperative pain relief in convenient oral formulations. NSAIDS are ideal for managing mild-moderate postoperative pain as a take-home medication. They have the advantages of being convenient to administer (SID, chewable), relatively inexpensive and providing long-lasting pain relief compared to other analgesics. The current anecdotal recommendation from pain management experts is that elective soft-tissue procedures, such as spay or castration, require 3-4 days of postoperative treatment with NSAIDs. Orthopedic procedures may require treatment for a week or more. Of course, each individual animal must be evaluated for presence of pain that persists beyond the expected time or that is of significant intensity as to require additional analgesics. Other take-home medications, such as tramadol and gabapentin, can be safely used as adjuncts with NSAIDs.
NSAIDs and Cats
Meloxicam, carprofen and robenacoxib are labeled in various countries for use in cats. Even in countries where NSAIDs are approved in cats, it is only for short-term or one-time use. This is owing to the extreme variation in metabolic rate of this drug class among individual cats. NSAIDs have been shown to provide excellent control of perioperative pain and inflammation in the cat, but must be used with caution to avoid complications, particularly renal failure.