"The most promising canine studies indicate the use of amantidine not as a sole agent, but rather as an adjunctive treatment in combination with an NSAID, as it seems to potentiate the analgesic effect of the NSAID."
"Tramadol, while not a true narcotic, provides analgesia by binding to mu-opioid receptors as well as by inhibiting reuptake of norepinephrine and serotonin."
"Gabapentin is one of my personal favorite medications for chronic pain. Originally designed as a treatment for neuropathic pain and seizure control, gabapentin may help patients with chronic and nerve-based pain, as well as aid in preventing or treating wind-up."
Take a moment, if you will, to reflect upon your last work week. How many of your patients came to see you because their owners perceived some degree of discomfort? What percentage of the aging dogs needed assistance exiting the car before stiffly walking through your door? Did the guardians of your geriatric feline patients note that their cats were sleeping more or jumping onto furniture less often? As our patients live longer and encounter the discomforts of aging bodies, a greater demand is rising for us to provide pain-free quality of life in the final years. Arthritis and cancer pain top the lists of frequently-seen chronic pain conditions both in human and veterinary medicine. Our younger patients can certainly also benefit from comprehensive analgesia when suffering from the marked pain of conditions such as IVDD, cystitis, or orthopedic surgery. Chronic pain presents a particularly difficult challenge, as it is often accompanied by the phenomenon of “wind-up”, “hyperalgesia”, or “sensitization”. In the case of wind-up, there is increased neuron membrane sensitivity in the dorsal horn of the spinal cord, allowing normally non-painful stimuli to elicit pain. These sensory changes occur not just at the original site of injury, but in surrounding tissues and even in the CNS. Furthermore, due to a change in the neuronal firing threshold, these changes may last many days after the initial stimulus has passed and may spread to adjacent neurons.
If you are like most veterinary practitioners facing a painful patient, you have your favorite arsenal of NSAIDs and steroids close at hand. These wonderful drugs have their rightful place on our shelves. Inflammation is a key component of the pain pathway in many diseases through the production of chemical mediators such as prostaglandin, bradykinin, and nerve growth factor; no other class of medications addresses this specific aspect. NSAIDs function to inhibit inflammation peripherally, decrease sensitization at the spinal level, and provide some central analgesia within the brain. Thus, for mild-moderate discomfort, anti-inflammatory analgesics may be sufficient. In many cases, though, our patients are still limping, stiff, reluctant to exercise, or withdrawn from social interaction, suffering from persistent pain despite the medication. What can we do when NSAIDs or steroids are not enough? How can we offer relief to our patients when steroids or NSAIDs are not an option at all? Fortunately, recent advances in pharmaceutical research have provided us with a much deeper shelf of analgesic options. To our benefit, these additional drugs can be used together, often with a synergistic effect! (Please note that dosages listed are compiled from a variety of sources: drug formularies, conference proceedings, journal articles, and pain management listserves.)
First, let me note that acetaminophen does not act as a true NSAID, as it does not provide specific anti-inflammatory effects (nor does it effect platelet aggregation). Acetaminophen primarily acts at the level of the spinal cord to decrease sensitization. With this in mind, dogs may receive acetaminophen in addition to an NSAID (dosage is up to 10 mg/kg BID long term).
Amantidine, originally developed as an antiviral drug, functions as an NMDA receptor antagonist, blocking the pain signal within the dorsal horn of the spinal cord. There is good evidence for relief of neuropathic pain in human medical literature. Amantidine works particularly well to eliminate wind-up in chronic pain. The most promising canine studies indicate the use of amantidine not as a sole agent, but rather as an adjunctive treatment in combination with an NSAID, as it seems to potentiate the analgesic effect of the NSAID. Side effects, when seen, appear to be mild, including diarrhea or agitation. Dosage is 3-5 mg/kg PO SID. Up to two weeks may be needed to see positive effects. Amantidine is not well-studied in cats.
Tramadol, while not a true narcotic, provides analgesia by binding to mu-opioid receptors as well as by inhibiting reuptake of norepinephrine and serotonin. Canine sensitivity to this medication seems to vary from patient to patient, with some dogs requiring more frequent dosing than others. Dosage recommendations generally range from 2-6 mg/kg up to QID. The most common side effect seen is lethargy; ataxia, dry mouth, or vomiting appear much less frequently. Tramadol can interact with tricyclic antidepressants and additionally should not be administered with SSRI medications. Despite its pharmacodynamics, this is not a controlled substance.
Gabapentin is one of my personal favorite medications for chronic pain. Originally designed as a treatment for neuropathic pain and seizure control, gabapentin may help patients with chronic and nerve-based pain, as well as aid in preventing or treating wind-up. Analgesia is obtained by blockage of presynaptic glutamate release in the dorsal horn and nucleus caudalis of the spinal cord, thus preventing hypersensitization of NMDA receptors. It appears to be equally effective for both dogs and cats. While pain relief is often seen within 24-48 hours of starting the medication, up to two weeks may be required for the full effect to be apparent. The most common side effects are sedation or hind end ataxia. If these effects are mild, no dosage adjustment is necessary, as they will subside as the patient accommodates to the medication, usually within 1-2 weeks. If the side effects are marked, then lowering the dosage temporarily and titrating upwards is usually successful. While no specific nephrotoxic effects have been described, the renal excretion of gabapentin warrants dosage adjustment in patients with kidney disease. Most sources cite a starting dose of 3-5 mg/kg PO BID, working upward to as high as 15-20 mg/kg TID. Several studies using 35-50 mg/kg/day divided BID-TID in dogs have shown no adverse effects. Cessation of gabapentin should be accomplished via gradual weaning. One special word of caution: a liquid formulation is widely available through human pharmacies; however, this formulation contains xylitol at a concentration that risks hypoglycemia and hepatotoxic effects in veterinary patients. Compounding may be required for smaller patients.
Disease Modifying Agents, such as Adequan, glucosamine, chondroitin sulfate, and omega 3 fatty acids may provide mild anti-inflammatory properties as well as address underlying joint pathology in arthritic patients. While strong evidence-based-medicine support of these agents is lacking, a seemingly large volume of subjective reports suggest a reduction in pain with their use. Side effects are negligible, making these treatments a safe option in both dogs and cats.
Our pharmaceutical attacks on the neurochemical pain pathway will undoubtedly make for much more comfortable patients. However, we cannot underestimate the importance of addressing the physical needs of our patients as well. When a quadruped patient chronically favors a limb, ambulates asymmetrically, or tensely guards a body part, secondary physical impairments arise. Muscle spasticity rapidly develops in both the favored and over-used limbs, leading to local ischemia, lactic acid accumulation, and further pain. These tense muscles, lacking normal elasticity, are more susceptible to injury. For example, in OA of the hips, we often find that the hind limb adductors, the quadriceps, and the lower lumbar epaxials suffer marked spasticity and sensitivity. When muscle tension exerts consistent force on the vertebrae or pelvis, these bones can in turn rotate or tilt, creating a secondary (or tertiary) malalignment and further discomfort. With articular dysfunction, chronic compensatory muscle overloading may lead to the formation of myofascial pain and trigger points (identified as taut bands within the muscle associated with focal regions of intense pain). When a patient guards a limb over a period of time, keeping a joint relatively stationary, the joint capsule contracts, effectively immobilizing that joint. Attempts to subsequently begin moving the joint through a more normal range will then yield pain. Physical rehabilitation modalities are critical in affected patients to address these musculoskeletal sources of discomfort.
Manual therapies, such as joint mobilizations, various massage techniques, passive stretching, and joint PROM (passive range of motion) exercises can bring immense relief. These techniques help to increase flexibility, mobility, tissue elasticity, and blood flow to affected tissues. Manual therapies also provide relief from the pain-spasm-ischemia-pain cycle of chronic muscle tension.
Cryotherapy consists of cold compresses or ice massage applied to appropriate tissues, particularly after periods of increased activity. This modality assists in analgesia both by reducing inflammation and by inducing direct numbness to the treated site.
Thermotherapy increases blood flow to target tissues and greatly aids in increasing tissue extensibility and relieving muscle spasticity. Many patients appear to receive direct analgesia with warm compresses applied to painful tissues. A simple warm compress or hot pack can effectively heat tissues to a depth of roughly 1cm. This may work well for small limbs or superficial tissues, but deeper structures will remain relatively unaffected; deeper heating modalities are needed in these cases.
Therapeutic ultrasound provides tissue heating up to a depth of ~ 5 cm. Benefits of this modality include direct pain relief, reduction of muscle spasm, increased collagen extensibility (to increase ROM and decrease stiffness), increased blood flow, and increased tissue metabolic rate. Indications for therapeutic ultrasound include deep muscle spasticity, myofascial trigger points, tendon contracture, and joint capsule fibrosis/contracture. When used with different settings (higher frequency, lower intensity, pulsed mode), ultrasound can induce mechanical (vs. thermal) effects on target tissues, leading to a regional elevation in cell diffusion and membrane permeability, increased calcium ion transport, increased GAG synthesis, elevated growth factor production, and increased fibroblast proliferation, among other effects…in short, ultrasound can speed tissue healing!
Hydrotherapy allows a patient to move more freely in a partial weight-bearing state, relieving stress on painful joints. For the painful patient, this modality is often employed when greater active ROM is desired, when muscle strengthening is needed, or when cardiovascular fitness or obesity management goals must be met. Movement in a warm water environment provides added thermal benefits, as mentioned above.
Transcutaneous electrical nerve stimulation (E-Stim, or TENS) provides analgesia by transmitting a small electrical current through target tissue. Several theories have been proposed for how this analgesia is specifically achieved. The first is the “gate control” theory of pain (proposed by Melzack and Wall in 1965): severity of pain sensation is determined by the balance of excitatory and inhibitory inputs to the T (transmission) cells in the spinal cord. E-Stim leads to increased activity of the A-Beta sensory afferents, causing pre-synaptic inhibition of the T cells, thus “closing the gate” to the cerebral cortex and decreasing the sensation of pain. E-Stim has also been shown to induce release of endogenous opiates (endorphins and enkephalins). Finally, a counter-irritant theory has been proposed, arguing that a continuous non-painful sensation (a tingling, of sorts) induced at an otherwise painful tissue will compete with the pain signal for transmission through the afferent nerve pathway en route to the spinal cord. Regardless of which theory/theories are correct, E-Stim clearly provides relief for acute and chronic pain conditions alike.
As veterinarians all know, each patient (and client) is an individual and not every analgesic tool discussed will be appropriate for all cases. Even so, it is gratifying to be able to offer many options in our mission to relieve animal suffering and extend quality of life in the face of chronic conditions. I would be happy to provide specific pain management consultations for any of your complicated cases. We also are excited to offer the above-mentioned physical rehabilitation therapies at our BEVS facility. Please feel free to call or email with any questions.