Top 5 Pain Medications in Clinical Practice

Acute pain is a needed process, alerting the body to possible injury. The process starts with the activation of terminal pain receptors, stops once tissue has healed, and usually responds to classic analgesics. Chronic pain, meanwhile, is a prolonged response that is complex and often inappropriate. It does not need the activation of pain receptors to propagate pain; it persists long past the time tissue has healed and can be unresponsive to long-term use of classical analgesics. Injectable medications can be used to manage pain; however, oral medications are a mainstay of chronic pain management for at-home patients. Pain has been traditionally defined as acute or chronic, but more specific terms, including adaptive or maladaptive, are suggested.

1. NSAIDs

NSAIDs act by blocking the cyclooxygenase (COX) enzyme, which drives production of prostaglandins. The COX enzyme has several forms: COX-1, which is responsible for normal body functions; COX-2, which increases in response to inflammation; and, in dogs, COX-3, a third isoenzyme whose action is inhibited by acetaminophen.1 Specific COX-2–blocking drugs have been developed (deracoxib [Deramaxx], firocoxib [Previcox]) to decrease adverse effects; however, the role of the various COX forms is more complicated, as COX-2 also contributes to normal body functions.¹ Prostaglandins from both COX-1 and COX-2 have important protective and reparative roles in the GI tract, and prostaglandins from COX-2 regulate renal blood flow. COX-1 can be proinflammatory, whereas the role of COX-3 remains unclear.¹

Related Article: Pain Management in Cats

Analgesic response varies between individuals; if needed, an alternate NSAID may be helpful after a washout period (dogs, 5–7 days²; cats, 2 weeks^3,4). Adverse effects include GI, renal, and hepatic damage; bleeding; and dermatologic issues.^5-7 The primary cause of adverse effects from NSAIDs is incorrect dosing (eg, concurrent use with corticosteroids or another NSAID, changing NSAID without a suitable washout).8 Dosing at the lowest effective level (in response to client assessment of pain), maintaining adequate hydration through client education, and drawing blood for frequent tests (ie, chemistry panel 3–4 weeks from initial dose, then q3–6mo depending on risk) can help diminish the incidence of these effects.

The American Association of Feline Practitioners (AAFP) has published guidelines for the chronic use of NSAIDs in cats, reporting that little data are available about feline COX isoenzymes and drug metabolism; these guidelines suggest using a COX-2 selective NSAID, titrating to lowest effective dose and frequency, and dosing based on lean body weight in addition to general guidelines for all species.⁹ NSAIDs are highly protein bound and persist in tissue longer than in the bloodstream, so dosing can be less frequent than recommended.⁸ NSAID response can improve for up to 12 weeks,⁵ partly because of binding in tissue and time needed to decrease nervous system sensitization.¹⁰

Acetaminophen is a COX-3 inhibitor with a weak effect on COX-1¹¹ and can be used in dogs (not cats) at 10 mg/kg q12h,^12,13 although its use is not FDA approved. The only NSAID licensed for use in cats in the United States is robenacoxib (Onsior), which is FDA approved for 6-day use q24h in oral form; an IV injection can precede this.^9,14 As robenacoxib is in tablet form, compliance may be more challenging than with liquid administration. Meloxicam is used in cats in Canada, and 3–5 day PO administration q24h revealed no significant adverse effects over a 5-day period in adult cats undergoing onychectomy and sterilization.¹⁵ A retrospective analysis of long-term use (>6 months) showed no significant difference in age of mortality between treated and untreated cats with or without chronic kidney disease.¹⁶

2. Opioids

The analgesic effect of opioids is a result of binding of opioid receptors in the central and peripheral nervous system and GI tract. They decrease perception of and reaction to pain and are effective analgesics. Opioids often have a short half-life in dogs and cats, requiring relatively frequent administration. Also, these medications are FDA controlled, potentially presenting challenges with long-term use. Oral administration of opioids suffers from the first-pass effect of liver metabolism after GI absorption, which can significantly reduce blood levels of the opioid.

Tramadol is an atypical opioid; it has weak μ-opioid action and also acts on the noradrenergic and serotonergic systems.¹⁷ It has been used in both dogs and cats (not FDA approved). In the dog, tramadol is not converted to the active opioid metabolite O-desmethyltramadol in significant amounts, and levels are 10 times lower than those in humans after oral administration.^17,18 In dogs, tramadol is metabolized as N,O-didesmethyltramadol which may have some weak opioid effects; however, repeated doses of tramadol either decreased drug absorption or enhanced presystemic metabolism of tramadol in a previous study.¹⁷

Related Article: Tramadol

Parenteral administration of tramadol has analgesic effects in dogs,^19,20 likely caused by noradrenergic and serotonergic mechanisms.²¹ Oral tramadol has a short half-life resulting in low plasma levels; it should be dosed q6–8h^17,22 and has poor analgesic effect.^17,18,23 In cats, tramadol is converted to the active opioid-binding metabolite and has a longer half-life.²⁴

When administered in cats, oral buprenorphine is absorbed transmucosally,²⁰ provides good analgesia, and is dosed q6h.²⁵

3. Anticonvulsants

Gabapentin has analgesic properties and works by inhibiting calcium flow to halt release of excitatory neurotransmitters, although the mechanism of analgesia is not completely understood.^26,27 Whereas gabapentin is frequently used for chronic pain in dogs and cats,^28,29 such use is off label. Studies evaluating the efficacy of gabapentin have focused on short-term (or acute) pain management and have shown little positive effect.<sup17, 29-31sup> A case study of neuropathic pain in a dog showed clinical improvement with gabapentin,³² and long-term use for chronic pain in cats has been reported.^33,34 In dogs, the drug is rapidly absorbed and eliminated; dosing is recommended q8h.³⁵ The drug is used for seizure management in both the dog and cat. The author starts at an initial lower dose and increases to an adequate established analgesic dose; it is given 2–3 times daily, depending on client compliance. Dogs show some liver metabolism of gabapentin, but the drug is excreted mainly through the kidneys.^36,37 Side effects reported in humans include weakness, drowsiness, blurred vision, and tremor (rarely ataxia).³⁸ Anecdotal adverse effects include loose stools, weakness, and ataxia. Weakness is usually transient and is the reason the initial dose is low; the author then increases the dose every 2–3 days as the patient adapts. Gabapentin has been combined with opioids and NSAIDs.^28,29

Related Article: Alternative Anticonvulsants for Dogs & Cats

4. NMDA-receptor antagonists

N-methyl-d-aspartate (NMDA) receptors play an important role in CNS sensitization to pain. Antagonist medications reduce sensitization. Oral administration of amantadine (an NMDA-receptor antagonist) with meloxicam (an NSAID) has been shown to improve pain in dogs.³⁹ Clients should be advised that, because amantadine needs to reduce CNS sensitivity, it may take several weeks for maximum effect. Safety studies have not been reported; however, daily dosing of dogs with 50 mg/kg for 30 days showed no mortality.¹⁷ Side effects in humans are minor GI disturbances, dizziness, and drowsiness.¹³ Use of amantadine in dogs is off label.

5. Antidepressants

Tricyclic antidepressants, mainly amitriptyline, are used to treat chronic pain.⁴⁰ Amitriptyline has been used as an adjunctive analgesic in dogs¹⁷ and for interstitial cystitis in cats.⁴¹ Amitriptyline blocks NMDA-receptor antagonists, interacts with opioid receptors, and blocks sodium channels.³⁸ Side effects of amitriptyline in humans include elevated heart rate, constipation, and sedation.⁴² Clomipramine is another tricyclic antidepressant¹³ that may be applicable for pain management, but it can be more costly. Amitriptyline has been combined with opioids and NSAIDs for management of chronic pain.<sup42 sup> 

Selective serotonin reuptake inhibitors (SSRIs) are generally considered less effective in managing pain than tricyclic antidepressants, and although SSRIs have fewer reported adverse effects, they can still cause decreased appetite, nausea, drowsiness, and increased heart rate.⁴³ Use with tramadol should be avoided, as both boost serotonin levels. Fluoxetine is commonly used in human pain management and has been shown to block nerve sodium channels in addition to increasing serotonin.⁴² The author has used it successfully for pain in chronically disabled dogs with a reduced quality of life, and it is useful in cats as well.

COX = cyclooxygenase, NMDA = N-methyl-d-aspartate

See the WSAVA Guidelines for Recognition, Assessment, & Treatment of Pain by the WSAVA Global Pain Council Members.

JULIA TOMLINSON, BVSc, MS, PhD, DACVS, DACVSMR, is a certified veterinary spinal manipulative therapist and member of the International Veterinary Academy of Pain Management. Dr. Tomlinson has a PhD in physiology from North Carolina State University, where she studied pain medications. Dr. Tomlinson lectures nationally and is a consultant in musculoskeletal wellness for the pet food industry. She founded the American Association of Rehabilitation Veterinarians, for which she is past president. Dr. Tomlinson earned her BVSc  from University of Liverpool, England.