Drugs and supplements: Working together to manage veterinary pain

Today, appropriate pain management in veterinary patients extends beyond the use of pure mu opioids or nonsteroidal anti-inflammatory drugs (NSAIDs). A variety of analgesics and supplements provide the veterinary team with a myriad of options for relieving both acute and chronic pain. This article outlines some of the analgesics and supplements commonly used for pain management in companion animals.

Pain is a function of the nervous system. It is unique to each patient and can present as a cognitive or emotional response to nociception that occurs in the higher centers of the central nervous system. Attempting to manage pain in the same way for every patient can result in inadequate analgesia for some.

One of the negative effects of untreated pain is windup.¹ Left untreated, pain causes neurophysiologic changes in the brain by disrupting normal pain pathways.² This central sensitization, or windup, occurs after neurons in the brain and spinal cord become hyperexcitable, leading to changes in synaptic neurotransmitter levels and resulting in heightened or exaggerated pain states. Often, these exaggerated pain states do not respond well to conventional analgesic therapy.

Pharmaceutical options

When evaluating pain management options, the first step is to rethink predetermined protocols. Because pain is a unique experience for every patient, treatment should be tailored to each patient’s needs. Identifying the appropriate interventions begins with a thorough physical exam and assessment. Once the pain protocol has been determined and implemented, repeated exams are recommended for ongoing assessment and to guarantee that the correct drugs and doses are being used.

Ketamine

Ketamine can prevent sustained and excruciating states of pain. It is associated with the treatment of windup pain through blockade of the N-methyl-D-aspartate (NMDA) receptor. Ketamine can be a key component in the treatment or prevention of chronic pain, and can have analgesic effects even at subanesthetic doses.³ When used in an anesthetic protocol, ketamine reduces minimum alveolar concentration requirements, promotes a synergistic effect with other anesthetics, and improves cardiovascular and respiratory parameters.³ Ketamine also is an ideal rescue analgesic in opioid-tolerant and/or opioid-hyperalgesic patients.

This 8-year-old dog was treated surgically for a large mass on the right lateral thorax that was impeding movement. Pain related to the mass had not been managed adequately prior to surgery. Postoperatively, a fentanyl constant-rate infusion plus an additional bolus of fentanyl were administered but proved unsuccessful in managing the windup pain (video above). Following a one-time intravenous administration of ketamine (1 mg/kg), pain was relieved and the dog was able to sleep comfortably (video below).

Amantadine

Similar to ketamine, amantadine mitigates the effects of windup. It antagonizes the NMDA receptor as well but is not recommended as a solitary analgesic; rather, it enhances the effects of other drugs in the cocktail. It is most effective when used with an opioid or NSAID, but is also effective when used with gabapentin. Because of its use in chronic pain management, amantadine is ideal when introduced during the weaning of ketamine in a postoperative setting.¹

Gabapentin

The primary use of gabapentin is as an anticonvulsant, but it also works as an anti-nociceptive and anti-hyperalgesic agent to offer relief for chronic and neuropathic pain.⁴ Gabapentin is ideal for patients that are experiencing severe pain and need adjunctive analgesic drugs. The addition of gabapentin can reduce the required dose of opioids or other drugs in a pain management cocktail. Preoperative administration of gabapentin reduces the potential for hyper-excitability of secondary nociceptive neurons in the dorsal horn,¹ preventing windup.

Amitriptyline

The selective serotonin reuptake inhibitor amitriptyline produces analgesia at supraspinal, spinal, and peripheral sites.¹ By blocking the re-uptake of norepinephrine and serotonin, amitriptyline enhances the descending inhibitory actions in the spinal cord to allow relief of neuropathic pain.¹

Supplement options

Veterinary supplements are becoming increasingly common as part of a multimodal approach to pain management as well as overall veterinary medical care. Despite their wide availability, however, the American Veterinary Medical Association advises practitioners to be aware of possible concerns about the “safety, efficacy, and quality control of supplements” because, unlike drugs, most supplements are not regulated by the Food and Drug Administration (FDA).⁵ Therefore, care should be taken when choosing and administering any supplement to veterinary patients.

Glucosamine/chondroitin

Osteoarthritis can cause chronic and severe pain. The chondroprotective combination supplement glucosamine/chondroitin works to boost repair of damaged cartilage between the joints through the induction of biosynthetic activity in the cartilage.¹ It also provides a protective effect when used prior to an acute joint injury.¹ Keep in mind that excess weight can potentiate pain related to osteoarthritis. Therefore, helping patients to obtain and maintain an optimal body condition score will also assist in managing this pain.

Polysulfated glycosaminoglycan

Supplements with polysulfated glycosaminoglycan (PSGAG) can aid the management of joint disease as well. PSGAG promotes synovial fluid viscosity through enzymatic degradation of cartilage in osteoarthritic joints, in turn improving joint lubrication.¹ PSGAG injections also assist in the repair of cartilage and the production of new cartilage (Sanchez J, personal communication, Veterinary Cancer and Surgery Specialists, 2020).

PSGAG is administered via injection under the skin. During the initial loading period, twice-weekly injections are administered for 1 month. Thereafter, injections are given once or twice monthly for life. The only FDA-approved PSGAG is Adequan (Luitpold Animal Health).

Omega-3 fatty acids

Omega-3 fatty acid supplements reduce joint discomfort though anti-inflammatory properties. Dogs and cats do not produce essential fatty acids naturally, so their only source is through diet or supplementation. The two most important omega-3 fatty acids are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are found most commonly in fish (Sanchez J, personal communication). Care should be taken to choose a source of EPA and DHA that is bioavailable and produced in accordance with pharmaceutical standards.¹

Cannabidiol

The use of cannabidiol (CBD) to manage pain in animals has been gaining steadily in popularity. This has resulted in a large and growing market of unregulated supplements, thus allowing for wide variation in quality and CBD concentration within individual products. Commercial CBD is hemp based and can be costly due to the low amount of cannabinoids found in the hemp plant.

Because CBD is typically used in conjunction with other supplements and analgesics, it can be difficult to determine its exact therapeutic benefits. Only a handful of randomized controlled studies of CBD use in animals have been published (although research is increasing steadily), but it seems to have some merit as an adjunct agent for managing pain. There is evidence that supports its benefits in combating chronic neuropathic pain in people (Weaver C, personal communication, Bush Veterinary Neurology Service, 2020).

Table. Dosing for some pain management pharmaceuticals and supplements

Conclusion

Recognizing and quantifying pain are integral to patient care. By treating the patient, not the disease, the practitioner can tailor drugs, doses, and supplements to a patient’s individual needs, and thus more effectively manage their pain.

Heather Carter is manager of operational excellence at Bush Veterinary Neurology Service in Frederick, Maryland.

References

1. Gaynor J, Muir W. Handbook of Veterinary Pain Management, ed 3. Elsevier; 2013.
2. Joshi J. Getting to know—and treat—central sensitization. YouTube page. Accessed August 20, 2020. https://www.youtube.com/watch?v=CJsuZFteWHI
3. Epstein ME. Ketamine: To use or not to use for pain management. Today’s Veterinary Practice.Published July 2011. Accessed August 20, 2020. https://todaysveterinarypractice.com/ketamine-use-for-pain-management/
4. Grubb T. Gabapentin and amantadine for chronic pain: is your dose right? Today’s Veterinary Practice. Accessed August 20, 2020. https://todaysveterinarypractice.com/gabapentin-and-amantadine-for-chronic-pain-is-your-dose-right/
5. Burns K. Assessing pet supplements. American Veterinary Medical Association. Published January 4, 2017. Accessed August 20, 2020. https://www.avma.org/javma-news/2017-01-15/assessing-pet-supplements