Tailoring acute pain therapy to the type of pain (Proceedings)

(Thanks to Dr. Peter Hellyer in the preparation of these notes)

When planning for the recognition, prevention, and treatment of pain in animal patients it is useful first to decide whether we are dealing acute pain or chronic pain. These two categories of pain patients have some needs that overlap, but our approach to them needs to be different as we articulate our middle-term and long-term plans.

Acute pain in animals comes from several predictable sources. Trauma, accidents, and injuries bring unexpected pain. Step one for these patients is to do a thorough physical examination, assessing for pain and mobility, but also examining them for any problems that are not immediately obvious. Obviously, triage must be done in order to establish the treatment priorities for any individual. Once those priorities are established, treatment of pain can begin. For trauma patients it is important that our drug choices for pain management do not create more problems than the animals already has — creating respiratory depression, for instance. Ongoing monitoring of these animals is absolutely essential. Also, naloxone should be a part of every practitioner's "crash cart" in the event of an unexpected response to opioids.

A second, and often more common, source of acute pain in pets is surgery.

Surgical pain is one area where we have the greatest opportunity to make a difference for our patients. By starting our pain management protocols BEFORE surgery begins, we not only decrease the animal's pain experience during the procedure, we decrease the animal's need for inhalant anaesthesia, as well as modifying the pain experience in the post-operative procedure. This leads to greater comfort for the pet both immediately after surgery as well as during the initial healing period.

Articulating all the various peri-operative pain protocols currently in use is beyond the scope of this manuscript — particularly because this is one of the most rapidly changing areas of pain management as different combinations are tried, "tweaked", and tried again. That said, multimodal, balanced per-operative analgesia is clearly the gold standard, however that is achieved. Opioids remain the mainstay of pre-emptive analgesia. Typically opioids are combined with other agents like midazolam, dexmedetomidine, or acepromazine. Another systemic option for pre-emptive analgesia is to provide constant-rate-infusion (CRI) delivery of an opioid with or without CRI low-dose ketamine with or without CRI lidocaine. These CRI protocols prevent central sensitization and dramatically reduce the amount of inhalant anaesthesia these patients require. Finally, it is important to remember the effects of epidural delivery of local anaesthesia or opioids. Epidural is another effective way to prevent pain prior to surgery, to lower anaesthetic requirements, and provide effective pain management post-operatively. Non-steroidal anti-inflammatory drugs (NSAIDs) also play an important role in the management of pain in the peri-operative period. There is still some controversy about the timing of administration as well as the appropriateness of NSAIDs in renal failure patients. A conservative approach is not to administer the drug until the anaesthetic event has come to a close, and to reserve administration of NSAIDs in certain older or compromised patients until the morning following their surgical event, relying on other agents in the immediate post-operative period.

A multimodal approach to pain management relies on the use of two or more analgesic drugs with differing mechanisms of action. The goal of a multimodal approach is to provide additive or synergistic analgesic effects while reducing the doses and potential side effects of any individual drug. Importantly, multimodal analgesia can provide superior analgesia to a single analgesic, even if that single analgesic is administered at very high doses. For example, the combination of morphine and a NSAID provides much better analgesia than simply administering morphine to the point that the patient is obtunded. Many of our patients are painful and anxious, and there is no one right way to manage the painful and distressed animal. Pain and anxiety often have similar clinical signs; therefore it may be difficult to determine what approach should be taken with an individual patient. In regards to acute postoperative pain management, there are several points worth considering:

1. Give the patient the benefit of the doubt and treat for if there is the possibility it is present.

2. Pain is easier to prevent than treat once it is established.

3. As needed dosing schedules are less effective than scheduled analgesic dosing to treat pain.

4. Traditional NSAIDS are often ineffective as the sole agent for acute postoperative pain; however they are very effective agents used in combination with opioids.

5. The therapeutic and side-effects of opioid analgesics are dose-dependent.

6. The agonist-antagonist opioids have a "ceiling" effect on analgesia. (In other words, there is a limit to the efficacy of butorphanol, at least in mammals.)

7. Many animals benefit from the management of anxiety.

8. Don't be afraid to let patients sleep, provided they have stable vital signs.

9. Do not stop analgesic therapy abruptly

10. Many animals benefit from combined or multi-modal therapy (i.e., combining an opioid, local anesthetic, and a NSAID).

Therapeutic Strategy

1. Administer analgesic before the onset of surgical trauma. This is an attempt to prevent the "wind-up" of the pain pathways that result in a facilitation of pain signals in the CNS.

2. Therapeutic agents:

• opioids

• alpha-2 agonists

• NSAIDS

• local and regional anesthetic techniques

• ketamine

• gabapentin (relatively new application of this drug)

Although all analgesics, tranquilizers, and local anesthetics possess some undesirable properties, deleterious side effects can be minimized by the selection of the appropriate drug and dose for a given individual. The combination of analgesic drugs from different classes may greatly enhance the analgesic effects while allowing for reduced dosages and minimizing adverse effects.

It is appropriate to think about the various targets in the nervous system that we can pursue, and then to choose agents that reach those destinations. Here are some options to consider:

1. NSAIDs — act at the nociceptors, reduce inflammation, act centrally

2. Local anaesthetics — block nociceptive input from peripheral afferents, act on the spinal cord when used epidurally

3. Ketamine (as a CRI) — NMDA receptor antagonist – dorsal horn of the spinal cord

4. Opioids — (e.g. morphine, fentanyl, hydromorphone) — enhance descending pain inhibitory pathways, alter perception of pain, obtund pain sensation peripherally

5. Alpha-2 agonist — dexmedetomadine — enhances descending pain inhibitory pathways, alter central pain perception

6. Tranquilizers/sedatives — acepromazine, midazolam — decrease anxiety when used WITH opioids, enhance effects of opioids, decrease the emotional/suffering aspect of pain

7. Non-pharmacology — massage, cryotherapy, keeping the patient warm, acupuncture — dorsal horn of the spinal cord