The alpha₂ agonists bind to alpha₂ receptors in the dorsal horn of the spinal cord and modulate the release of various neurotransmitters involved in processing pain. This class of drugs is analgesic in cats, but the strong sedative effects of alpha₂ agonists will mask obvious pain behaviors. So do not assume that an animal sedated with an alpha₂ agonist is completely pain-free. Alpha₂ agonists can be used quite effectively as adjuncts to the mildly analgesic opioids, such as butorphanol, in healthy patients with no cardiovascular or respiratory compromise. For example, in a healthy cat, 0.2 mg/kg of butorphanol could be combined with 2 to 10 µg/kg of medetomidine as an intramuscular premedication for preemptive analgesia for surgical procedures such as ovariohysterectomy and dentistry. These combinations, however, are likely not adequate for major orthopedic surgery.

Ketamine is another drug commonly found in private practice that can be used for its analgesic effects. Again, not a traditional analgesic, ketamine acts by antagonistic effects at the N-methyl-D-aspartate (NMDA) receptor. Like the alpha₂ agonists, ketamine (e.g. 5 to 10 mg/kg intramuscularly) is most effective when used in combination with an opioid for analgesia. When ketamine is administered without opioids, its primary analgesic effect is to prevent spinal cord dorsal horn wind-up, where neurocellular processes change quickly with a painful event to amplify the sensation of pain. Ketamine is also a dissociative and hallucinogenic drug, which, although not specifically analgesic, may prevent memory of a painful event. So adding ketamine to the anesthetic protocol may help decrease the amount of pain perceived, prevent the wind-up of that pain, and provide the patient with dissociative anesthesia perioperatively.

The opioid-like drug tramadol may be useful in treating chronic pain in cats. Tramadol may exert mild opioid effects within the spinal cord, but it also works by inhibiting reuptake of norepinephrine. Anecdotally, doses of 1 to 4 mg/kg given orally every eight hours have been effective in cats with chronic pain, such as arthritis.

Little scientific, well-controlled research has been done on the long-term use of NSAIDs in cats. Many studies have documented the utility of NSAIDs (e.g. ketoprofen, carprofen, meloxicam) for short-term use in cats.^14-19 The use of NSAIDs in cats is considered extralabel, except for the use of meloxicam (Metacam—Boehringer Ingelheim). The injectable form of meloxicam is now FDA-approved for one-time-only use in cats. This does not preclude the use of NSAIDs in cats but does imply that there is much to learn about their physiologic effects and side effects in cats. There are many possible drug interactions between commonly used medications and NSAIDs in people. Such interactions have not been widely studied in cats and other animals, but it is safe to assume that the risk of drug interaction exists in veterinary patients as it exists in people.

Of the many NSAIDs available, the three most commonly used in cats are ketoprofen, carprofen, and meloxicam. The recommended preoperative or postoperative doses (one time only) are

• Ketoprofen, 2 mg/kg subcutaneously or 1 mg/kg orally;
• Carprofen, 4 mg/kg orally;
• Meloxicam, 0.3 mg/kg subcutaneously or orally.

Ketoprofen administration has been associated with decreases in platelet adhesion and increased incidence of bleeding, probably because of its inhibitory effects on the constitutive platelet COX-1 isoenzyme.¹⁵ Carprofen and meloxicam are relatively selective for blocking the inducible COX-2 isoenzyme responsible for a component of the inflammatory response. This does not mean that they are completely safe under all circumstances. We can assume that carprofen and meloxicam have some inhibitory effect on COX-1 systems. For example, in an in vitro system, carprofen in feline whole blood was more selective for inhibiting COX-2 than COX-1, but it did have some COX-1 inhibitory effects.²⁰ The same results have been reported for meloxicam.²⁰