Weaker opioids, such as codeine and tramadol, can be useful for moderate cancer pain. Tramadol has been around for over 15 years and has received attention in recent years regarding its use for chronic pain, both in people and companion animals. Tramadol is considered a good analgesic for moderate cancer pain in people and is better tolerated than equianalgesic true opioids.^2,3,7,54,55 Recent pharmacokinetic and pharmacodynamic studies in dogs, in addition to the growing body of anecdotal evidence of analgesic efficacy by various investigators, suggest that tramadol may be safely and effectively used for various pain conditions in dogs.^56-59 Still, few reports exist on the efficacy of tramadol for treating pain in dogs or cats, though studies are ongoing. Tramadol is a mu-receptor agonist and also has serotonin and norepinephrine reuptake inhibition effects.² Combining it with other analgesics, including NSAIDs, provides better analgesia.

Alpha₂ agonists

The main alpha₂ agonists are medetomidine and xylazine, which are useful in the context of multimodal and preemptive analgesia. Their analgesic effects are especially pronounced when combined with other agents such as opioids and ketamine.^9,14 Medetomidine is often used in combination with opioids to provide adequate analgesia for moderately to severely painful procedures and is known to have an opioid-sparing effect. Alpha₂ agonists may cause bradycardia secondary to increased vagal tone and are contraindicated in patients negatively affected by a decreased cardiac output and increased afterload.^9,14 They may also cause transient hypertension.

Adjuvant drugs

Table 3. Adjuvant Analgesic Drugs Used to Treat Cancer Pain in Dogs and Cats

Local anesthetics

Local anesthetics are valuable in many situations, and, being often used for local or regional blocks, their intravenous, oral, or transdermal application can also be helpful in certain conditions.^4,7,9,14 A good local or regional block may help provide adequate pain control and permit much lower doses of systemic drugs. The systemic administration of certain sodium channel blockers, such as intravenous lidocaine and oral mexiletine, to potentiate analgesia from other drugs, is becoming more common in treating cancer pain in people.^2,4,7,14 The systemic administration of local anesthetics for analgesia in dogs and cats is relatively recent and may increase in the near future.

NMDA antagonists

This class of analgesics includes drugs such as ketamine, tiletamine, amantadine, and dextromethorphan. Ketamine has been in use for many years as a dissociative agent, but its NMDA-receptor antagonistic effect is now considered an important part of its central analgesic effect.⁹ It is especially useful when combined with other agents and permits adequate analgesia with lower doses of opioids (sparing effect) and lower side effects. It can be effective for intraoperative and postoperative analgesia when used at a microdose in a continuous-rate infusion combined with fentanyl or morphine. Amantadine was initially developed and used as an antiviral agent against influenza in people and is available as an oral preparation. It also has NMDA-receptor antagonistic activity, and its use in people as an analgesic for chronic cancer pain has recently increased.^2-4 No studies have evaluated the use of amantadine for pain treatment in dogs and cats, but investigations are ongoing.^9,11,14