The science of veterinary pain management

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Providing relief for animal suffering is an important component of the Veterinarian’s Oath and a common aspect of practicing veterinary medicine. At the inaugural Fetch dvm360® virtual conference, veterinary pain management expert Robin Downing, DVM, MS, DAAPM, DACVSMR, CVPP, CCRP, presented a multimodal approach to both acute and chronic pain management in dogs and cats.

According to the International Association for the Study of Pain (IASP), pain is defined as an unpleasant and emotional experience associated with actual or potential tissue damage.¹ The IASP further explains that the inability to communicate in no way negates the possibility that an individual is experiencing pain and is in need of appropriate pain-relieving treatment. This is particularly applicable for veterinary patients, which lack the ability to communicate in a traditional way yet still experience pain. Downing reminded attendees of the old Buddhist proverb “Pain is inevitable. Suffering is optional.” It is our duty to prevent suffering in our patients.

Components and categorization of pain

Downing described pain as a complex and 3-dimensional experience. The first dimension is the sensory component, which is the traditional informational component of pain. The second is the emotional dimension that occurs with suffering. The third is the cognitive component, in which past experiences of pain can influence both future perceptions of pain and assessment of perceived threats.

Pain is categorized as either adaptive or maladaptive. According to Downing, adaptive pain is the pain that protects us, and the same holds true with our pets. The types of pain that fall into this category are transient nociceptive pain in response to a noxious stimulus (such as what occurs as a warning sign to avoid further injury) and inflammatory pain. By contrast, maladaptive pain has no such beneficial effect, and pain in this category is considered pathological. Neuropathic pain, functional pain, and windup pain are all types of maladaptive pain. In the case of windup pain, the area of perceived pain expands beyond the original site of pathology due to sensitization of nociceptors in the peripheral and central pain pathways, in response to a barrage of afferent nociceptive impulses. Any of these types of maladaptive pain may become chronic.

Studies have shown the beneficial results of administering intraoperative local analgesia to prevent chronic pain. Intraoperative local analgesia can lessen the occurrence of chronic pain postoperatively, lower the doses of postoperative analgesics needed to control pain, and improve patient outcomes.²

Identifying pain

Identifying pain in our patients can be clinically challenging, and pain is easily overlooked. Using a systematic approach, Downing starts her assessment with a thorough physical examination. Patients exhibiting the third dimension of pain—in which their past pain experience is triggering fear, anxiety, or stress (eg, the perception of threats)—may require alterations to your diagnostic plan. This is a cyclic when anxiety exacerbates pain, and pain exacerbates anxiety. Previously complacent pets may now exhibit fear in these situations due to the presence of pain.

Give any pet that is reluctant to be handled the benefit of the doubt that they may be in pain and may require analgesic treatment before continuing with diagnostic tests. In these situations, consider which components of your plan for that visit are truly necessary at that time. Postpone any procedures or diagnostic tests that are not deemed necessary until pain control has improved, and the patient is more tolerant and less stressed.

A diagnostic plan should be determined as appropriate for the patient, in order to reach a diagnosis. As Downing noted, the reason for this is to ensure proper treatment of the appropriate underlying condition. For example, suppose you forgo diagnostic radiographs in a dog experiencing lameness. In that case, you may miss osteosarcoma and head down an inappropriate treatment path that could result in treating the patient for osteoarthritis, missing the true problem, and whittling away at a prognosis that was already limited. Once you have determined the location of the pain, the underlying cause, and whether the pain is acute or chronic, you can develop a plan to address the pain directly.

Addressing chronic pain

Chronic pain is best addressed using a multimodal management plan. Patients with chronic pain are typically less active and often overweight. This cycle can resemble the chicken and egg dilemma. In general, overweight patients put more stress on their joints, are more prone to injuries, and may develop chronic pain. Likewise, patients with chronic pain will be less active and thus prone to weight gain. Regardless, normalizing body condition is crucial. In dogs, also ensure the patient is not hypothyroid and treat as appropriate. (Don’t be fooled by euthyroid sick syndrome, which can occur when patients are painful).

Pharmacotherapy

Ultimately, with chronic pain, there is a need to break the pain cycle pharmacologically. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of pain management, for both chronic and acute pain. NSAIDs decrease inflammation and modulate pain at various levels of the central and peripheral nervous system. Some patients may have experienced a previous failure or sensitivity to an NSAID. This does not mean they will have a similar failure or reaction with another NSAID. In these cases, Downing feels it is worth attempting therapy with a different class of NSAID; however, if a sensitivity occurs again, eliminate NSAIDs as a viable option.

Another target for maladaptive and chronic pain is the dorsal horn of the spinal cord. Targeted therapy would include such medications as gabapentin and amantadine. According to a study Downing conducted, the appropriate gabapentin dosage for maladaptive pain is 5 to 10 mg/kg orally every 8 to 12 hours, titrated up to effect.³ Beneficial effects may be noted within 24 to 48 hours but reach steady state with peak activity in 10 to 14 days. Gabapentin is safe for long-term use, but do not discontinue the drug abruptly or rebound pain may occur. Sedation is the primary side effect and is typically transient. Persistent sedation can be addressed by dose reductions. Amantadine is an N-methyl-D-aspartate antagonist and may be used in combination with NSAIDs and gabapentin. Amantadine is also well tolerated for long-term use and is typically dosed at 2 to 5 mg/kg per day orally. Downing noted that, in a study of dogs with osteoarthritis of the stifle and elbow, tramadol was shown to have no effect on pain management and is not recommended.⁴

Polysulfated glycosaminoglycan (Adequan; American Regent Animal Health) is also useful in dogs and cats. Polysulfated glycosaminoglycans are the building blocks of cartilage. Although they do not replace lost cartilage, they can heal microfractures and have indirect anti-inflammatory effects. Downing uses an extralabel dosing scheme of 2 mg/lb subcutaneously twice weekly for 4 weeks, then once weekly for 4 weeks, then every 10 to 15 days as maintenance. She prefers to dose Adequan subcutaneously rather than intramuscularly. As an injectable option, this may be of particular value in cats that do not tolerate oral medication administration.

Nutraceuticals

Evidence varies for the value of nutraceuticals in chronic pain. Among the discussion points in her talk, Downing cautioned attendees in using the triglyceride formulation of omega-3 fatty acids because the esterized formulation is not bioavailable. There is some evidence that undenatured collagen type II (UC-II) may slow deterioration of articular cartilage in rodent models by promoting anti-inflammatory cytokines.⁵ UC-II may be used in dogs and cats.

Microlactin is a milk protein for hyperimmunized cows that has immunomodulatory effects that decrease destructive chronic inflammation. As this is a different pathway and mechanism of action than NSAIDs and corticosteroids, it can be used in conjunction with either of these. The initial effect is seen within 5 to 7 days, with peak effects within 10 to 14 days. Side effects are typically minimal and limited to sporadic gastrointestinal signs. Green-lipped mussel contains the essential fatty acid eicosapentaenoic acid and can be used with hyaluronic acid of the appropriate molecular weight.

Downing emphasized that it is the formulation and manufacturing process, not just the ingredient, that is important when considering nutraceuticals for pain management. All of these products must be manufactured in a way that does not denature the compounds or interfere with their efficacy. For this reason, efficacy tests should ideally be conducted for each formulation used.

Physiotherapy

Downing acknowledged that, as part of the multimodal approach to managing pain, physiotherapy also has a role and should be incorporated into pain protocols. A plethora of modalities and tools can be used to manage pain. Assistive devices such as wheelchairs, slings, supportive vests, rolling carts, and wagons also play a role in managing patients with chronic pain that require mobility assistance. Modifications to the home environment play a role as well. Pet owners should be encouraged to videotape their home environment, so that you can assess for items that should be modified (eg, raise food and water dishes, cover slick floors, secure access to stairs, use ramps, modify play with other pets in the household).

Conclusion

The most important aspect of pain management is breaking the pain cycle by first capturing and controlling the pain. Once pain is controlled, medications can be titrated to the lowest effective dose. This is typically only possible after employing multimodal pain management protocols.

References

1. IASP announces revised definition of pain. International Association for the Study of Pain. July 16, 2020. Accessed November 10, 2020. https://www.iasp-pain.org/PublicationsNews/NewsDetail.aspx?ItemNumber=10475#:~:text=The%20definition%20is%3A%20%E2%80%9CAn%20unpleasant,pain%20for%20further%20valuable%20context.&text=Pain%20and%20nociception%20are%20different%20phenomena
2. Andreae MH, Andreae DA. Local anaesthetics and regional anaesthesia for preventing chronic pain after surgery. Cochrane Database Syst Rev. 2012;10:CD007105. doi:10.1002/14651858.CD007105.pub2
3. Davis LV, Hellyer PW, Downing RA, Kogan LR. Retrospective study of 240 dogs receiving gabapentin for chronic pain relief. J Vet Med Res. 2020;7(4):1194.
4. Budsberg SC, Torres BT, Kleine SA, Sandberg GS, Berjeski AK. Lack of effectiveness of tramadol hydrochloride for the treatment of pain and joint dysfunction in dogs with chronic osteoarthritis. J Am Vet Med Assoc. 2018;252(4):427-432. doi:10.2460/javma.252.4.427
5. Bagi CM, Berryman ER, Teo S, Lane NE. Oral administration of undenatured native chicken type II collagen (UC-II) diminished deterioration of articular cartilage in a rat model of osteoarthritis (OA). Osteoarthritis Cartilage. 2017;25(12):2080-2090. doi:10.1016/j.joca.2017.08.013

Rebecca A. Packer, DVM, MS, DACVIM (Neurology/Neurosurgery), is an associate professor of Colorado State University College of Veterinary Medicine and Biomedical Sciences in Fort Collins. She is active in clinical and didactic training of veterinary students and residents and has developed a comparative neuro-oncology research program at Colorado State University.