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Pain Medications 101

Pain Medications for pets, 101

Pain management is a field of medicine that is changing very rapidly. If a veterinarian hasn’t been to any lectures on pain management in the past two years he or she is likely out of date already. Here at Best Friends we work very hard to stay current in this area because one of the basic principles we live by is “Pets should not have to be in pain.” The following is our attempt to make sense of a confusing array of medications that our clients are mostly unfamiliar with.

First, some basic principles about pain management:

  • Multimodal therapy is the norm in pain management today. Pain is very complicated, with multiple pathways, neurotransmitters and receptors. No single pain medication works on all of these pathways. The more severe or chronic the pain, the more likely it will require two or more medications given together to control it. We are trying to interrupt pain pathways to the brain in as many places as we can.
  • It is easier to prevent pain than to control it once it is there. It also takes higher dosages to bring pain back down once it is present. The best pain management preempts the pain, cutting it off before it has a chance to start. This is why we usually have you start your pet’s pain medication prior to surgery, and why we might use high doses of medication immediately following a painful injury or procedure and then taper down gradually.
  • Pet owners get worried when their pet is groggy and “drugged up” but that’s normal when a dog or cat is on strong pain medication, just as it is for a human on morphine. Animals can’t push the button on the morphine pump so we have to guess at how much medication they need. It is always better to have a groggy pet who is comfortable than one who is painful.
  • Chronic pain tends to worsen with time, not only because the cause, especially arthritis, is often progressive but also because pain reinforces itself. The more pain transmitters are used up, the harder the body works to replace them, and the more become available to trigger yet more pain. With severe pain, even gentle touches can trigger pain because the whole nervous system has been over-sensitized. This is called “ramp up.”
  • Drugs are not the only way to address pain. Cold laser, acupuncture, cold packs and massage are examples of alternative therapies for pain. The best pain control for arthritis is weight loss. Patients usually require far less pain medication if they are of normal weight.

NSAIDs

Non-steroidal anti-inflammatory Drugs, or NSAIDs, have been the mainstay of pain management for decades. Not only are they effective at reducing pain but they also reduce inflammation. For many diseases, we must address the inflammation or it will continue to damage tissue, such as joint cartilage, and cause more pain. Inflammation causes swelling, bruising and redness, so any injury or infection with these signs is likely to be treated with an NSAID. See our separate handout on this class of drugs, or our video on the subject, for more information.

NSAID SAFETY

Pet owners may be very leery of NSAID drugs, as there is a lot of negative, false and misleading information about them on the internet. We have been accused more than once of trying to kill someone’s pet by prescribing “dangerous” medications. The facts are that dogs taking NSAID drugs such as carprofen (Rimadyl®), deracoxib (Deramaxx®) and meloxicam (Metacam®) actually have two year longer life expectancies. The risk of liver failure from carprofen is only 1.5 out of every 10,000 dogs. It’s untreated pain from arthritis that shortens dogs’ lives by the millions, not the drugs we use to treat the disease. Once a dog can’t get up anymore, it is usually euthanized.

A newer arthritis drug for dogs called grapiprant (Galliprant®) has very little risk to the kidneys or liver. Grapiprant works similarly to an NSAID but it targets just one specific pain receptor. Other NSAIDs also affect other similar receptors that are important to kidney health and the maintenance of the lining of the stomach, so those drugs have a higher risk for side effects to those organs. Grapiprant is a great choice for treating chronic pain in dogs who don’t tolerate other NSAIDs such as carprofen and deracoxib. The downside of it is that it’s a weaker pain medication.

For cats, we love a different type of NSAID called Onsior®. Onsior® (robenacoxib) binds to areas where there is pain and inflammation, while staying at a lower level in the bloodstream. This is another way toxicity from the medication is reduced, making Onsior safer than older NSAIDs such as carprofen and meloxicam. It comes in a small, chewable tablet. Onsior is also available for dogs now.

Meloxicam is usually our first line drug for acute pain in cats because it comes in an oral liquid that is easy to administer or hide in food, but we are reaching for Onsior more and more because of its safety factor.

Opioids

Another important category of pain medications is opioids. This class was originally derived from the opium poppy and includes opium, codeine and hydrocodone, morphine and its derivatives (hydromorphone, oxymorphone), and newer forms such as fentanyl and oxycodone (Oxycontin®). The drugs in this class most commonly used in dogs and cats are hydromorphone and hydrocodone for dogs, and butorphanol and buprenorphine for cats. Methadone is being used more in animals as well. Most people know of methadone only in its role in helping with heroin addiction but it is an opioid pain reliever in its own right.

The latest advance in this class of medications is a topical form of Buprenorphine for cats, called Zorbium™. The contents of one little tube, applied to the skin on the back of the neck, begin working in about 45 minutes and lasts for 72 hours. We’ve been using this for surgeries and dental extractions for a couple of years and we’ve been very happy with the results. Most cats are comfortable without being too drowsy.

Tramadol is an opioid as well. It blocks Mu opioid receptors in humans and cats. It also has mild effects on the serotonin and norepinephrine nerve pathways. Tramadol is absorbed poorly in most dogs and is rapidly eliminated from the body, meaning there is little of it circulating in the bloodstream to bind to or block those Mu receptors. The serotonin and norepinephrine effects can make dogs sleepy but provide very little pain control.

Research has shown tramadol doesn’t work nearly as well in dogs as it does in people, because dogs do not absorb it well and they metabolize it too quickly. It works well in cats, however.

We relied on tramadol heavily in years past. We have phased tramadol out for dogs but many veterinary hospitals have not yet caught up with us. If your dog has been taking tramadol, we will be talking to you about switching to something that works better.

Since we are not using tramadol very much for dogs now, we are relying more on other oral opioids such as codeine and hydromorphone. Unfortunately, these are not absorbed consistently from dog to dog, so they work well in some dogs but not so well in others.

Cats do well on tramadol. It tastes very bitter, so we hide the piece of pill in a gel capsule or a Pill Pocket treat. If your cat won’t eat Pill Pockets you would need to be able to administer a pill in order to use it. We can also use oral methadone for pain in cats.

Opioids can cause a variety of side effects, but these are rarely serious and almost never fatal except in the case of a massive overdose or long term use. Drowsiness, vocalizing and lethargy are common.

Some cats and dogs experience what is called “dysphoria,” sort of the opposite of euphoria. Instead of being blissed out they become restless, tending to pace and pant, which can drive pet owners crazy. Nausea and constipation are occasional problems. Fentanyl can increase appetite, which is a blessing for us when addressing severe pain in cats. Cats on fentanyl tend to be happy and hungry.

Multimodal Therapy

For severe and acute pain we will likely be reaching for an NSAID and an opioid to use in combination. More and more we are also using gabapentin, a drug that affects many types of nerve transmission, making it useful for treating seizures and anxiety as well as pain (see below).

For post-surgical pain, preemptive pain management is extremely important. In dogs, we start an NSAID drug the day prior to surgery. Gabapentin needs to be started 7-10 days prior to surgery to be an effective drug for immediate postoperative pain.

Chronic pain is different from acute pain and in fact is an entire disease process in and of itself. Even when the original source of pain is removed, the chronic pain may not resolve. 15-47% of human patients who undergo hip or knee replacement surgery continue to feel pain in the operated-on joint. Pain can be disabling, to people or pets, even after a technically successful, uncomplicated procedure.

Other Commonly Used Pain Medications

Gabapentin is used at a low dose to control seizures, at a moderate dose for pain prevention and antianxiety effects, and at high doses for severe or chronic pain, especially neurological pain and tissue damage. It frequently causes drowsiness. The higher the dosage, the more likely this will happen. However, the drowsiness usually diminishes over the first week as a pet gets used to it. For severe or chronic pain, we usually start with a lower dose and gradually increase it, especially for dogs. Another similar option for large dogs that is sometimes less expensive than gabapentin is pregabalin.

This means it takes a few weeks to gradually raise the dose until it’s working effectively. While we are doing this, we will be using other medications to tide us over until the gabapentin is working. As pets age, their efficiency at metabolizing gabapentin can wane and side effects may reappear again, especially hind leg weakness. If this happens, we reduce the dosage.

Cats are very tolerant of gabapentin and it has less risk of side effects than many NSAIDs do in felines. Gabapentin is our first choice drug for arthritis in cats. Many cats will take it mixed in canned food. It is available as a flavored oral liquid, a plain tablet or a generic, inexpensive capsule.
We are making a change to our pain protocol for arthritis in dogs. For years, our protocol has been to start with supplements for Stage 1 arthritis, add an NSAID drug for stage 2, and then add gabapentin at stage 3. That recommendation has changed. Gabapentin has not been proven to be effective for this particular use in dogs.

Instead of gabapentin, we will be switching to amantadine for our second line arthritis drug. We have been using amantadine as a third tier drug for arthritis and a first tier one for neurologic pain, but it is moving up the ranks for arthritis treatment. Amantadine is fairly inexpensive and it only needs to be administered twice a day, whereas gabapentin should be given every 8 hours in dogs for best effect.

Amantadine takes a long time to start working, 4-6 weeks, so it’s not a good drug for acute pain conditions. Arthritis is chronic, though, so we have time to let it take effect. While we are waiting for it to kick in, we can experiment with a ketamine injection, CBD or additional supplements. We can also use therapy laser and Assisi Loop treatment.

Amantadine is also very effective for nerve pain, and for “ramping down” severe, chronic pain. For slipped discs, spinal injuries, amputations, diabetic neuropathy or burns, it can be a wonder drug. For severe arthritis, it is sometimes used just for 3-4 weeks to break the pain cycle and ratchet it back a few notches, so that we can then keep the pain under control with our other therapies. We may or may not decide to continue it long term.

Acetaminophen (Tylenol®) is being used more frequently in dogs, either as an adjunctive to other arthritis medications or in combination with codeine. Acetaminophen can be toxic to the liver in people, and is deadly to cats, but it is very safe in dogs as long as it’s not overdosed.

Monoclonal Antibody Therapy

For many pets with arthritis pain, it may make more sense to switch from oral arthritis medication to monthly injections. NV-01 (for dogs) & NV-02 (for cats) consist of antibodies that bind with a chemical messenger called nerve growth factor or NGF, which is important in osteoarthritis.

The feline NV-02 drug, frunevetmab, has been developed by Zoetis and is sold under the name Solensia™. A 3-month study showed that 77% of cat owners noticed signs of improvement in their cat’s pain, improving their mobility, comfort and well-being. Some cats show improvement in as little as a few days, though some don’t respond until after the second monthly injection.

The most common side effects of Solensia were vomiting and injection site pain. Solensia is not for use in pregnant or lactating cats. It also can affect human women who are trying to conceive, or are pregnant or breastfeeding, if they inject any Solensia into themselves.

The dog version, betinvetmab, also made by Zoetis, is called Librela™. This, too, is a monthly injection. Librela just became available in the fall of 2023.

Solensia and Librela have some big advantages over the drugs we’ve been using, especially as far as safety. They don’t cause drowsiness and hind leg weakness like gabapentin can. They don’t cause the liver, kidney and GI side effects that NSAIDs can, and we don’t need to do blood testing twice a year to monitor for those side effects. In the long run, this probably also makes them less expensive, especially if your dog or cat is also taking supplements. We may be able to discontinue those as well.

Solensia is also safe for use in cats with stage 1 and 2 chronic kidney disease, CKD, which is reassuring. Most older cats with arthritis also are in some stage of CKD. If your pet has been taking an NSAID or other medications already, we will continue those drugs for a couple of weeks, and taper off of them once the injections start working.

The disadvantage of these injections is that you have to come in every month. This can be a problem for fearful pets.

What About CBD?

CBD is another treatment for arthritis and other types of pain. We have a separate handout about CBD if this is an option appropriate for your pet. The main things to realize with CBD are first, it’s totally unregulated by the FDA, so you have to be very careful not to spend money on worthless products; and second, the effective dose for pain is much higher than is practical to give using commonly available products. Ask us before choosing this option on your own.

Summary

Our goal in pain management is always to enable your pet to regain normal “activities of daily life” (ADLs). We want your dog or cat to be able to do what they love to do. Let’s get started!

Pain management for surgical or dental procedures

Below is information on how we address pain during surgical and dental procedures to keep your pet comfortable. Preventing pain before it starts is the goal.

Before Surgery
Most of our patients coming in for painful procedures have already been started on oral medication prior to surgery, typically an NSAID. This will usually be Carprofen for dogs or Onsior™ for cats. Gabapentin may be used for cats both before and after procedures, not just for pain but for anxiety as well.

Gabapentin is also used for dogs when there is tissue damage or a neurologic component to their surgery or pain. Ideally, we would start gabapentin 7-10 days prior to surgery, as it is slower to kick in than an NSAID drug.

The exception to this rule about starting medication ahead of time is the use of some NSAID drugs in cats. Cats are most likely to have kidney damage from NSAIDs when their blood pressure or temperature drops below normal. Since anesthesia commonly causes these effects, we may wait until after surgery or dentistry to administer meloxicam or carprofen. We rely on local anesthetics to provide pain control initially. Onsior, however, is an NSAID that doesn’t stay in the bloodstream but rather targets areas of inflammation. Onsior is safe to start ahead of time.

We will usually have a discussion with the owner to decide which NSAID drug will work best for cats. Meloxicam is inexpensive and consists of a small amount of liquid medication. Onsior is a chewable tablet that is safer but more expensive and not as easy to administer.

At the hospital
Your pet will very likely receive an opioid injection as part of his pre-medication before surgery. Hydromorphone is our most common choice for dogs before surgery or dentistry. It provides good pain control for about 4-5 hours. It can be used in combination with other drugs for greater sedation or as part of a general anesthesia protocol.

In cats, we are more likely to use a milder, short-duration opioid called butorphanol.

Another drug we use for both anesthesia and pain control is Dexdomitor® (medetomidine). It is used for short procedures where both pain control and sedation are needed; in combination with opioids and ketamine for general anesthesia; and in small amounts for pain control or to relieve anxiety. One of the nicest things about Dexdomitor is we can reverse its effects, so we can wake a pet up when a procedure is over or if the pet has unwanted side effects.

Local anesthetics are underused in both human and veterinary medicine. Lidocaine and its sister drug bupivacaine are actually the most effective pain medications we have, because they prevent pain from ever getting started in the first place. These are given via injection in a specific area to block pain, such as under the skin before a lump removal or in the mouth before a tooth extraction.

Ketamine has been used in veterinary medicine as an anesthetic drug for at least forty years. We add ketamine to every liter of fluids we administer IV during procedures, because studies have shown it can reduce pain, not only during the procedure but for hours afterwards. We also use ketamine as part of the initial anesthetic injection that anesthetizes patients, which helps the ketamine fluid drip be more effective.

After Surgery
Your pet will continue on the oral medications started prior to surgery, and we may also add in an opioid depending on the procedure and expected level of pain. There is a lot of variation from pet to pet as to how much pain medication is needed and for how long.

Buprenorphine (Buprenex®) can be given as a single injection, administered orally or via a 72 hour long-acting topical solution called Zorbium™. Most cats do very well on buprenorphine.

Oral buprenorphine works well for small dogs too, but it is expensive for large ones. Dogs are more likely to go home on oral hydromorphone, hydrocodone or codeine.

Fentanyl is another opioid we use frequently. It is given intravenously for short duration pain control during surgery. Post-operatively, it is applied in a patch form to provide pain control for 3-5 days. We use Fentanyl patches occasionally in both cats and dogs.

After surgery or dental work, you are in the best position to look for subtle changes in behavior that indicate your pet may be in pain – but pain doesn’t always look like what owners expect. Plus, animals are very good at hiding pain. Please see our handout titled “How to Tell if Your Dog/Cat is in Pain” for more information on what to watch for.

We have carefully chosen the most appropriate pain medication and the duration of treatment based on the level of pain expected for the procedure your pet had done. Pets should not be in pain!

Please administer pain medication as prescribed. We don’t want you to see any pain symptoms – if we have managed post-operative pain properly you should not see signs of pain at all!

Other Adjunctive Pain Medications

We all would like chronic pain to be something easily corrected. Unfortunately, it’s not, and what works well for one patient may not work well for another. Most patients, human or animal, do best when several medications are combined. It may take weeks or a few months to nail down the combination that works best for your individual pet.

For any type of pain expected to be long lasting we recommend omega 3 fatty acids (fish oil). Glucosamine is almost always added in for arthritis, though the purpose is more to slow the deterioration of the joint than to alleviate pain. For more information on supplements, see our separate handout.

Rehabilitation is also used for many types of pain, both acute and chronic. Therapy laser treatments, Assisi Loop treatment, acupuncture, dry needling and underwater treadmill therapy are all frequently recommended. We also have separate handouts on these therapies.

There are many drugs and supplements that are used less commonly for severe or chronic pain. When we are frustrated and not controlling pain well enough with our regular cocktails of drugs we will start adding in some of these. Many of them were used first for other purposes but have been found to decrease pain as well. Some are used for specific types of pain, e.g. osteoarthritis, neck and back pain or cancer pain. Several are used in humans as antidepressants. Medications that affect brain chemicals can work for both depression and pain. The following is a not-so-brief list of some of the things we are beginning to use more of.

  • Probiotics: Keeping the gut balanced and healthy with probiotic bacteria improves immune system function and helps to relieve chronic pain as well.
  • Antidepressants: Tricyclic antidepressants (TCAs) such as amitriptyline, as well as serotonin-norepinephrine reuptake inhibitors such as Cymbalta™ and Effexor™, can be effective as pain medications. Generics are available, which makes the price pretty reasonable to try. They are especially useful for treating cancer pain.
  • Apoquel: This is our primary anti-itch drug used for allergies in dogs. The Janus-kinase receptors it targets are involved in pain sensation as well as itch. 
  • Cerenia™ (miropitant): This is our primary antinausea drug and it also reduces abdominal pain with efficacy similar to morphine.
  • Doxycycline/minocycline: These drugs are antibiotics that also have anti-inflammatory effects, especially inside joints and muscle tissue. They can also be quite helpful for osteosarcoma (bone cancer).
  • Melatonin: Melatonin is a hormone produced in the brain that regulates sleep/wake and seasonal cycles. It is used for jet lag in humans, for disruption of hair growth in dogs and ferrets, as well as for anxiety and pain relief. It is especially helpful for cancer pain. It is very inexpensive.
  • Mexiletine: This is a drug primarily used for certain types of heart disease. It’s like an oral version of lidocaine, which is a sodium channel blocker. Sodium channels are important in conducting signals between cells – pain signals as well as electrical signals in the heart muscle. 
  • Piroxicam: Piroxicam is an older NSAID drug that works particularly well for bone cancer and bladder cancer. It does not have the high safety profile of newer NSAIDs, so it has higher risk of causing gastric ulcers. If your dog is taking piroxicam we may need to stop giving it for a time periodically, just to give the stomach lining a break to repair itself.
  • Prednisone/prednisolone: These steroid drugs can reduce pain and inflammation from many different types of cancer. 
  • PEMF: Pulsed electromagnetic fields therapy is safe and effective in improving arthritis pain. It is also used to speed bone healing after fracture repair and to induce faster healing after nerve damage. 

It works by stimulating calcium (Ca) to transform into a molecule called calmodulin (CaM). This transformation is a voltage-dependent process, which is why an electromagnetic field can stimulate it. CaM then triggers a natural anti-inflammatory cascade within cells. 

You would rent our Assisi Loop device, which your dog would wear for 10 minutes per joint or other painful area, beginning with 3-4 treatments per day. Velcro wrap vests are available to hold the device in place for use on shoulder or hip joints. It also comes in a mat, called an Assisi Lounge, that can be placed under a cat’s or small dog’s bed.

  • Pamidronate™, Zolidronate (bisphosphonates): For bone cancer pain, bisphosphonates are our best tools to use in addition to oral pain medication. These are drugs that were developed for treating osteoporosis in humans. They provide long-lasting bone pain relief. They stimulate fracture healing, too, so even a cancer-affected broken leg will heal with treatment. Bisphosphonate is administered intravenously here in the hospital, once a month or so.
  • Intra-articular injections: It is very common to inject steroids in the joints of humans with arthritis. We also can do this with dogs. We usually use a combination of triamcinolone (the steroid part) and hyaluronic acid (which is a component of joint fluid and cartilage). Steroid injections degrade cartilage so they are rarely used unless the cartilage is already eroded away. The hyaluronic acid helps to counteract the degradation of cartilage from the steroid injection.
  • Another product you may be surprised to hear can be injected into a painful joint is Botulinum toxin, or Botox™. Botulinum toxin injections into the joints have shown a long-lasting benefit in human end-stage osteoarthritis patients. Consistent pain reductions and improvements in function have been sustained for 6 to 12 months or more after injection and we can repeat the treatment again as the effects wear off. A single (expensive) vial of Botox will treat two joints.
  • Synovetin OA is the brand name and 117mSn is the scientific notation for a particular radioactive tin isotope. A new and interesting treatment for arthritis in dogs involves injecting this tin into an arthritic joint. It is taken up by the cells inside the joint that cause inflammation. The radiation then kills these cells so they can’t continue to release pain signals or cause inflammation. A single injection is supposed to last a year. The radiation is very low-level so it doesn’t affect the rest of the body and it doesn’t make your dog radioactive. It is being used primarily in the elbow joints. Elbows are a difficult joint to inject so we would refer you to an orthopedic surgeon to do the injection.
  • Platelet-Rich Plasma (PRP): Harvesting blood, separating the plasma and platelets out and then injecting them into the affected joint(s) is being done more and more often. Hyaluronic acid, mentioned above, is most effective when injected along with PRP. This combination can have beneficial effects for a full year, and leads to better cartilage regeneration.
  • Stem cell therapy: Stem cells can be harvested from fat and then injected back into the dog, either into the affected joints themselves or into the bloodstream, where they tend to target damaged tissue and end up back in the joints that way. The idea is that the stem cells will transform into cartilage-producing cells that will rebuild the inside of the joint. 

Two anesthetic procedures are needed for a stem cell transplant, one to harvest the fat and the second to inject the stem cells collected from the fat into the joints. Fat can be harvested and banked for later, so we could acquire fat tissue during a spay, neuter or other routine procedure and save it until it’s needed. Injections can be repeated later (usually 1-2 years later) using the same stem cell bank created previously. Stem cell therapy is very expensive to do and doesn’t work any better than PRP, so it’s falling out of favor. We would consider it a salvage procedure when nothing else has worked.

Osteosarcoma treatment facts:
OSA is one of the most painful forms of cancer. We will attack that pain very aggressively in order to provide decent quality of life. Amputation without chemo-therapy leads to faster growth of metastatic tumors in the lungs. Leg amputation should always be followed by chemo. Median survival after amputation and chemo is 8-12 months, with 20% of patients living two years. Adding the new cancer vaccine Her-2/neu extends survival to an average of 956 days!