Pain in animals is what we (humans) say it is. There is tremendous variability among both patients and observers. Pet pain is complex and scientifically intriguing, clinically challenging, and easy to overlook. Studies reveal that approximately 20 percent of dogs across all ages suffer from the chronic maladaptive pain associated with osteoarthritis (OA). The disease causes debilitation and interferes with the activities of daily living. Unfortunately, it is easy for dog owners to overlook OA pain, as they often misinterpret behavior changes as “just getting old,” rather than recognizing a chronic pathological condition that can and should be treated. Managing chronic maladaptive pain in dogs with OA has been a priority in veterinary medicine in recent years, resulting in rapid expansion of the evidence-based components of multimodal pain management strategies. Slowing the disease progression Fundamentals of chronic pain management include understanding that treating pain is good medicine, and a multimodal pain management plan is the strategy of choice. Multimodal chronic pain management utilizes multiple actions on the central nervous system (CNS) and other tissue targets to treat and slow OA’s progression. We need to reach for pharmaceuticals, nutrition, physical medicine, and nutraceuticals—all the tools in the pain management toolbox—to manage painful canine patients appropriately. We also need to be sure to start with a comprehensive, hands-on physical examination alongside a metabolic profile to ensure we do not overlook any comorbidities, such as renal disease or hypothyroidism. For OA patients, inflammation is an important element of their disease. Obesity and being overweight contribute to systemic inflammation, so normalization of body composition is a critical component of reducing inflammation. From a medication perspective, nonsteroidal anti-inflammatory drugs (NSAIDs) remain a cornerstone of multimodal chronic pain management, at least initially. NSAIDs decrease inflammation rapidly, providing immediate relief during the time needed for nutraceuticals to exert their effects. While OA patients derive some benefit from NSAIDs, these drugs alone cannot maximize comfort for patients experiencing chronic maladaptive pain. For that, we need to reach for adjunctive agents. Gabapentin addresses the maladaptive component of chronic OA pain by targeting the dorsal horn of the spinal cord, where pain signals are modulated on their way to pain perception in the brain. The key to success in using gabapentin for chronic maladaptive OA pain is to use it to effect—that is, escalating the dose to achieve comfort for the dog without inducing sedation. Amantadine is another pharmaceutical affecting the spinal cord that may have a place in a particular patient’s chronic pain plan. Finally, injectable polysulfated glycosaminoglycans (PSGAGs) exert a disease-modifying effect in the body by supporting cartilage structure and joint function. Dosing guidelines for gabapentin, amantadine, and PSGAGs can be found elsewhere. Physical medicine modalities also work adjunctively to help maximize comfort in dogs with OA. Nutrition and nutraceuticals play a critical role in managing OA pain in dogs. Our canine patients need to eat something each and every day, and that provides a unique way to influence overall health. Good, science-based nutrient profiles allow us to tailor what our patients eat to best meet their individual needs. For painful patients, the most important nutritional step is normalizing body composition. All other pain management strategies work more effectively once body composition is normalized. Likewise, this important step helps to relieve pain and slow OA progression because of a lessened impact on joints. This means using an established nutrient profile in specific portions to achieve the weight target, at which time a proven joint-support formulation may be chosen. Pain relief through nutraceuticals Once daily nutrition is in place, canine patients with OA can receive additional pain relief from nutraceuticals, which are nutritional supplements that provide therapeutic benefits yet are not drugs. There is clear evidence high levels of the omega-3 fatty acid, eicosapentaenoic acid (EPA), in triglyceride form accomplish two major functions in the joint with OA: 1) Decreases inflammation in and around the joint 2) Downregulates the genes responsible for the degradation enzymes that lead to cartilage damage It is important to understand that flax seed is not an effective source of EPA for dogs. Also, the EPA dose must be high enough to “bottom load” the omega-3/omega-6 ratio and thus reduce inflammatory mediators. While the esterized form of omega-3 fatty acids is less expensive to manufacture, and thus sells for a lower price than the triglyceride form, it is the triglyceride form that is bioavailable. Microlactin is a milk protein extracted from the milk of hyper-immunized cows. It acts by a very selective mechanism to block cytokines, which contribute to the perpetuation of inflammation. It modifies the biological response to inflammation and changes the signals that “call” neutrophils to sites of inflammation. Thus, neutrophils cannot then release the destructive enzymes that perpetuate the inflammatory process. While it exhibits much the same efficacy as NSAIDs, it employs a different mechanism, so it does not share the same adverse event profile. Undenatured collagen type II (UC-II) has demonstrated cartilage support effects via immune system modulation. This unique mechanism of action targets Peyer’s patches in the small intestine to stimulate the immune system, generating compounds that block the enzymes responsible for cartilage degradation. In the U.S., attention is increasingly turning to green-lipped mussel (GLM) extracts, which have demonstrated decreased inflammation and pain associated with OA via multiple tissue targets. While the unique combination of omega-3 fatty acids (EPA, eicosatetraenoic acid [ETA], and docosahexaenoic acid [DHA]) are likely to be a major contributing factor to the anti-inflammatory action, GLM contains a host of furan fatty acids (F-acids), sphingolipids, phytosterols, diacylglycerols, diterpenes, sesquiterpenes, and saponins, alongside antioxidants such as carotenoids, xanthophylls, and anthocyanins. Identifying the overall mechanisms relating to each of these active compounds is the subject of ongoing research. It is certainly possible this combination of ingredients is working synergistically to be chondroprotective, gastroprotective, and anti-inflammatory. Research suggests GLM may have chondroprotective properties. Studies reveal GLM extracts suppress the same inflammatory pathways affected by NSAIDs, but without their side effect profile. Like many other nutraceuticals providing anti-inflammatory pain relief, GLM is safe to administer long-term, making it well suited for chronic conditions such as OA. There appears to be additional benefit to using GLM, as it has a washout period longer than NSAIDs, still demonstrating effect after four weeks of withdrawal, which is useful in a condition where veterinarians regard owner compliance as the primary barrier in the treatment of chronic pain. Which is best? While understanding the individual ingredients in nutraceuticals is important, there are some details we must consider: The most important factor in choosing a nutraceutical is a specific product’s performance in clinical studies in the target species. What matters is how the ingredients work together in a particular formulation in the patients we will treat. This means clinical studies in the target species with the condition we intend to treat (in this case OA in dogs) that demonstrate efficacy and safety in that patient population. Quality assurance is critical. We must understand how nutraceuticals are manufactured, how individual ingredients are sourced or formulated, and what quality control strategies are in place. It is appropriate to seek independent analyses affirming consistency. Ingredient sourcing is also important. For instance, in the case of green-lipped mussels, there is huge variability among populations depending on where and how they are farmed. Understanding that variability, as one example, offers the opportunity to hold manufacturers accountable to provide information about such details. Managing osteoarthritis in dogs is an evolving discipline. Not many years ago, veterinarians reached for NSAIDs and that was the only thing offered. Within a relatively short time, treatment options for OA expanded dramatically. Nutraceuticals have become an important component of a multimodal pain management strategy for dogs with OA. That said, it is important for veterinarians and their health-care teams to maintain open minds coupled with healthy skepticism, as they evaluate the nutraceuticals they will add to their treatment plans. There is no doubt our canine patients will reap additional benefits as the science continues to advance and new treatment choices are developed. This bodes well for pets and the people who love them. Robin Downing, DVM, MS, DAAPM DACVSMR, CVPP, CCRP, is hospital director of The Downing Center for Animal Pain Management. She’s received many regional, national, and international awards, including the American Veterinary Medical Association’s (AVMA’s) Leo K. Bustad Companion Veterinarian of the Year in 2020 and the Excellence in Veterinary Medicine Award in 2001 from the World Small Animal Veterinary Association (WSAVA). Dr. Downing is an internationally sought-after speaker on topics such as pain management, physical rehabilitation, physical medicine, hospice/end-of-life care, and overcoming compliance obstacles/issues in veterinary medicine. She is also a member of the YuMOVE ADVANCE 360 Veterinary Advisory Board, a hip and joint supplement for dogs. In 2016, she completed her masters of science in clinical bioethics, and is now working on her doctorate in clinical bioethics. MAY IN SEPTEMBER: A TALE IN CALCIUM DEPLETION IN NURSING DOGS By Jennifer W. Harris, DVM It was a Wednesday, two days after Labor Day in a rural small animal practice at the entryway into the North Georgia mountains. The weather was still steamy, but a glimpse of the approaching fall was evident each day as a few more olive, copper, and golden leaves peacefully touched the ground. It was a busy Wednesday afternoon at the clinic, but when the receptionist walked back to the treatment area and said, “There’s an emergency on the way. They said their dog is having seizures,” I was not surprised. There seemed to be a lot of emergencies lately for some reason. We began the usual preparations: ensuring a full oxygen tank was ready, retrieving the diazepam and blood glucose meter, and bringing the crash cart nearby. A short time later, our technician, Debbie, carried a miniature schnauzer in her arms toward us. The tremors of the dog’s body and legs were immediately obvious, but in the split second while we were placing her on the treatment table, I looked into her eyes: two ebony marbles filled with gentleness and a silent plea for help. Instead of fear, I saw trust. The tremors were strong, but she was alert and responsive. Her mammary region was well-developed, and as they told me she was nursing a litter of five two-week-old puppies, the diagnosis was instantly made: tetany due to periparturient hypocalcemia. Her body did not have enough available calcium due to the high demand required to nourish her nursing puppies. We placed an IV catheter in the cephalic vein of her front leg, and began administering 10 percent calcium gluconate intravenously in small, slow increments. Many dogs with hypocalcemia also have hypoglycemia (low blood glucose or sugar). In this case, the blood glucose was normal. However, low blood calcium was confirmed with a blood calcium level of 4.5 (normal reference range on our blood machine is 7.9 to 12). As the calcium infusion began and continued slowly, we connected the ECG leads to her body to be sure the calcium did not incite cardiac arrhythmias or bradycardia. This potentially life-threatening condition is referred to by several names. It is sometimes called puerperal tetany, postpartum hypocalcemia, or eclampsia. Pregnant and nursing dogs may both be affected by hypocalcemia. Nursing dams during peak lactation (two to five weeks after giving birth) are at greatest risk and may require four times the dietary energy they would normally need. Unfortunately, owners sometimes are unaware of this fact or of the risk of dangerously low blood calcium. Such was the case with this sweet schnauzer. This is the rest of her story. As the calcium administration continued, the tremors subsided and resolved completely. She was stable and able to be transported to our overnight emergency hospital for continuation of treatment, IV fluids, and initiation of a puppy growth diet, which she was delighted to eat. She was discharged from the hospital the following day, bright and alert with oral calcium supplementation. There are several recommendations that can help prevent periparturient hypocalcemia: 1) A dog’s gestation lasts approximately nine weeks. The last third of gestation is the time during which unborn puppies are growing rapidly. After birth, lactation to nurse the puppies places an even greater demand on the dam’s nutrient stores. Although it cannot totally prevent hypocalcemia, feeding the dam a high-quality diet formulated for growth and development (i.e. a puppy diet) during pregnancy and lactation helps supply the additional nutrients and energy needed for the latter part of pregnancy and throughout lactation. 2) When lactation (or less commonly, growth of unborn puppies shortly before parturition) begins depleting blood calcium in the dam, her body’s natural response is to trigger hormones to cause release of calcium from bone and better absorption of calcium through her intestines. If a dam has been given calcium supplementation throughout her pregnancy, those hormones have been downregulated, prohibiting them from prompting the body to respond. This could actually increase the dam’s risk for eclampsia. Therefore, adding supplemental calcium to the diet of dogs throughout pregnancy is not generally recommended. 3) There is often an increased incidence of hypocalcemia in small breed dogs, dams with large litters, and dams with large puppies, but all pregnant and nursing dams (at any stage of lactation) can be at risk. 4) Dogs who have experienced periparturient hypocalcemia in the past will be at high risk for developing it with subsequent pregnancies. In this case, oral calcium supplementation during the time of high milk production may be helpful. Supplementing the puppies with milk replacer during the first few weeks of life and with solid food at three to four weeks and beyond could help ease the nutritional burden on a higher-risk dam. Hopefully this true story provides information to help another dog in some way. September has arrived, and I believe I will always remember the gentle schnauzer with the trusting eyes and five puppies. Her name was May. Jennifer W. Harris, DVM, is a Georgia-based small animal veterinarian.
