Management of Acute Pain at Home: Oral Analgesics for Dogs and Cats

When formulating an analgesic plan for the management of acute pain, practitioners must consider the type of pain their patient is experiencing, including potential chronic pain. The complex physiology of pain demands a multimodal analgesic plan targeting peripheral nociceptors, spinal pathways, and central nervous system (CNS) signaling to provide optimal pain management (Box 1).

It is worth noting that a major challenge in evaluating the evidence for oral analgesics is that they are often combined in efficacy studies. On one hand, this makes it difficult to interpret an individual drug’s usefulness, but on the other, it may highlight important synergism between analgesic classes.

Administration of oral analgesics at home presents challenges such as lack of owner compliance, diversion of controlled drugs, and failure of the owner to recognize adverse effects of the medications immediately.

Nociception and Pain Transmission

Acute pain management is challenging due to the complexity of the pain pathways. Nociception starts when peripheral nociceptors are activated in response to thermal, chemical, and/or mechanical stimuli. Pain signals are then transmitted to the central nervous system via nerve fibers: Aδ fibers for acute, sharp pain and C fibers for dull, aching pain. Additionally, the inflammatory cascade releases cytokines in response to these nociceptive stimuli and further activates peripheral nociceptors. This inflammatory activation of nociceptors highlights decreasing inflammation as a key component of acute pain management.

At the level of the spinal cord, pain transmission is modulated through either inhibition, which decreases the signal to the brain, or upregulation, which leads to increased signaling. Prolonged peripheral activation (inflammation) can lead to an increase in neuronal activation known as peripheral sensitization, while prolonged upregulation of neuron activity in the CNS can lead to central sensitization. Chronic pain states often lead to central sensitization and become maladaptive, making them especially challenging to treat.

NSAIDs

NSAIDs have been a mainstay of treating acute pain and inflammation in human and veterinary medicine for decades (Table 1).

Clinical Use

Clinically, NSAIDs provide potent analgesia for acute pain and inflammatory states (Box 2). They are also first-line analgesics for osteoarthritis pain and are often used for chronic pain.

Mechanism of Action

The primary mechanism of action of NSAIDs is inhibition of prostaglandin production throughout the body. Cyclooxygenase (COX) enzymes produce various prostaglandins (e.g., prostaglandin E₂, thromboxane, prostacyclin) from arachidonic acid, which is present in cell membranes, and prostaglandins are responsible for maintaining many homeostatic functions, including gastrointestinal (GI) and renal blood flow, water balance, and coagulation. However, uncontrolled upregulation of prostaglandin production in states of inflammation can contribute to the development of peripheral and central sensitization. Inhibition of COX enzymes by NSAIDs leads to decreased prostaglandin formation and, ideally, decreased inflammation and pain.

Generally, COX-1 enzymes are responsible for normal homeostasis, while COX-2 enzymes increase during times of inflammation. This has led to the development of drugs trying to target only COX-2 enzymes to mitigate adverse effects. However, COX-1 and COX-2 enzymes both have roles in homeostasis and inflammation. Therefore, despite various COX selectivity, all NSAIDs carry a risk of adverse effects if not administered at recommended doses.

Potential Adverse Effects

The main adverse effects of NSAIDs include GI signs such as vomiting, diarrhea, and decreased appetite. In severe cases, NSAIDs can cause GI ulceration, bleeding, and perforation. GI side effects occur via 2 mechanisms: (1) direct irritation of the mucosa and (2) a decrease in prostaglandin-mediated mucosal blood flow, cell turnover, and mucus production. Decreased prostaglandin synthesis hinders GI repair mechanisms, potentially leading to further damage.

Secondarily, NSAIDs can cause kidney injury due to inhibition of prostaglandin’s role in modulating renal blood flow and water balance. Studies investigating the renal effects of NSAIDs in dogs have shown no significant kidney injury if administered to healthy patients at recommended dosages.^1,2 In cases of decreased renal perfusion, such as from dehydration, hypovolemia, or hypotension, further reduction in renal blood flow caused by inhibition of prostaglandins can lead to or worsen acute kidney injury.

Many cats may have a mix of chronic pain and acute inflammation that could benefit from NSAID therapy. However, cats, especially those middle-aged or older, often have chronic kidney disease. Studies of cats with stable kidney disease did not show worsening of disease with meloxicam or robenacoxib administration at below-label and label dosing, respectively.³ In many cases, use of low-dose NSAIDs may be beneficial in cats with stable chronic kidney disease and concurrent chronic pain such as osteoarthritis without worsening kidney values. Guidelines for long-term use of NSAIDs for chronic pain conditions in cats were published in 2024 by the International Society of Feline Medicine and the American Association of Feline Practitioners.³ Having informed discussions with owners about the benefits (e.g., analgesia, improved quality of life) and risks (e.g., possible worsening renal values) of NSAID use in cats with chronic kidney disease is warranted.

Acetaminophen

Acetaminophen, also called paracetamol in Europe, often gets grouped with traditional NSAIDs despite noted differences.

Clinical Use

Unlike traditional NSAIDs, acetaminophen does not cause significant GI effects such as ulceration or renal injury. For this reason, it has increased in popularity in dogs for mild analgesia. Optimal dosing and timing are still debatable, as acetaminophen has a short half-life in dogs and may require dosing every 6 to 8 hours to maintain adequate plasma levels.⁴

Mechanism of Action

Acetaminophen’s mechanism of action is not on the COX-1 or COX-2 pathways and is still not fully understood. One possible mechanism behind acetaminophen’s fever-reducing and analgesic effects is COX-3 inhibition in the brain.

Supporting Evidence

Efficacy studies for acute pain management with acetaminophen in dogs are lacking, despite common use in Europe and the United States. In a noninferiority study comparing oral acetaminophen/codeine to oral meloxicam, both drug protocols provided adequate analgesia after soft tissue and orthopedic procedures when administered with buprenorphine for the first 24 hours postoperatively.⁵ Another study compared acetaminophen, carprofen, and meloxicam in dogs after elective ovariohysterectomy and found that each treatment was equally efficacious.⁶ However, in experimentally induced lameness in dogs, acetaminophen/codeine was less effective than carprofen in improving ground force assessments.⁷ In another study, acetaminophen at 20 mg/kg IV did not provide adequate analgesia after ovariohysterectomy in dogs premedicated with meperidine.⁸

When to Use

Currently, no veterinary-specific formulation of acetaminophen is approved in the United States. Over-the-counter (OTC) human formulations of acetaminophen and of acetaminophen with codeine (Tylenol 3 and Tylenol 4) are available.

Acetaminophen should never be administered to cats due to risk of severe toxicity, which can cause oxidative damage to the liver and red blood cells leading to methemoglobinemia and potentially death.

If prescribing acetaminophen, it is important to have careful, clear discussion with clients, including cautioning them about OTC human formulations, which can contain xylitol.

Opioids

After NSAIDs, opioids are the other major class of analgesics used perioperatively. While opioids provide excellent analgesia when administered parenterally, pharmacokinetic studies indicate that bioavailability after oral administration is poor in dogs and cats due to first-pass hepatic metabolism.

Opioid Derivatives

The oral opioid derivatives that have been studied in dogs and cats include tramadol, codeine, and hydrocodone.

Tramadol, a synthetic opioid agonist, acts as a serotonin and norepinephrine reuptake inhibitor. Its opioid agonism on the µ receptor is primarily mediated through its metabolite, O-desmethyltramadol, with far less activation from the parent drug. Unfortunately, dogs do not produce this metabolite in significant amounts necessary to provide adequate acute analgesia. An extensive systemic review on tramadol in dogs found that the efficacy of tramadol is low for treatment of postoperative pain compared to other analgesics.⁹ Cats produce higher concentrations of O-desmethyltramadol, and studies have shown analgesic effects after surgery.⁴ While this makes tramadol seem promising for use in cats, oral formulations are very unpalatable and cause hypersalivation, making administration challenging for owners.

Codeine and hydrocodone, both µ receptor agonists, have poor bioavailability in dogs and cats and do not provide adequate acute analgesia after oral administration.¹⁰

Transmucosal Buprenorphine

Transmucosal buprenorphine has shown some efficacy for postoperative pain management, especially in cats.^11,12

Clinical Use

While this route is distinctly different from oral administration, transmucosal buprenorphine is frequently prescribed for at-home administration for acute pain management.

Mechanism of Action

Buprenorphine, a partial µ receptor agonist, has a pKa, or dissociation constant, close to the feline oral pH, which keeps the drug in a nonionized state that is more readily absorbed.

Supporting Evidence

Several studies in cats have assessed the efficacy of transmucosal buprenorphine, with mixed results. Two different studies found that transmucosal buprenorphine did not provide reliable postoperative analgesia compared to intravenous or intramuscular routes, but the dose used could have been too low (0.01 mg/kg).¹¹ Pharmacokinetics studies show variable bioavailability, potentially due to factors such as individual variation, inadvertent swallowing of the drug, or differences in oral pH.

In dogs, oral transmucosal buprenorphine has shown efficacy at high doses (0.12 mg/kg) for dogs undergoing ovariohysterectomy.¹³ This high dose requires a large volume in larger dogs, which can be difficult to administer and more costly. A pharmacokinetics study assessed transmucosal administration of Simbadol (Zoetis), a more concentrated formulation, at a lower dose (0.03 mg/kg) and found a bioavailability of 41%.¹⁴ This bioavailability is potentially promising, and the smaller volume may be easier to administer; however, analgesic efficacy still needs to be explored.

When to Use

At this time, the current body of evidence does not support the use of oral opioids for the management of acute pain. The lack of efficacy studies, in conjunction with the high abuse potential, discourages prescription of these drugs. Oral transmucosal buprenorphine anecdotally provides postoperative analgesia in cats and may provide some benefit in dogs; however, volume, cost, and mixed results are discouraging. Despite the challenges with oral opioids, recent development of longer-acting buprenorphine formulations, both transdermal (Zorbium, Elanco) and injectable (Simbadol, Zoetis), may be effective alternatives for at-home analgesia.

Gabapentinoids

Gabapentin has grown in popularity in the last few years, with pregabalin less commonly used. Both drugs are structural analogs of γ-aminobutyric acid (GABA) but do not act on the GABA receptor. Their mechanism of action is mediated through the α₂δ subunit of voltage-gated calcium channels by inhibiting the release of excitatory neurotransmitters and decreasing cell signaling.

Gabapentin

In both dogs and cats, gabapentin has a short half-life, suggesting the need for frequent dosing (up to 3 times daily) and a wide dose range between 10 and 20 mg/kg. However, pharmacokinetics in cats with chronic kidney disease showed decreased elimination of gabapentin, suggesting the need to reduce the dose.¹⁵

Supporting Evidence

Used in human medicine as an anticonvulsant, gabapentin has been investigated in human and veterinary medicine for a role in treating acute, chronic, and neuropathic pain. Unfortunately, studies are still conflicted on the efficacy of gabapentin in acute pain management. For example, no significant reduction in pain score was seen with the addition of gabapentin to opioids in dogs after hemilaminectomy surgery.¹⁶ Another study that investigated gabapentin use in dogs after forelimb amputation did not see a difference in treatment groups.¹⁷ Limitations cited in that study include the small sample size and the concurrent use of other analgesics (e.g., opioids, locoregional block, NSAIDs) confounding the effects of gabapentin.

In cats, most research has focused on gabapentin’s anxiolytic and sedative effects. The literature on acute pain management is lacking, often with small sample sizes or in conjunction with other analgesic drugs, thus clouding the reliability of gabapentin as a solo agent. A recent systemic review found 56 articles on the use of gabapentin and pregabalin in cats, with only 7 assessing acute pain, 5 assessing chronic pain, and the remainder evaluating sedation effects.¹⁸ In 1 study, cats receiving buprenorphine in combination with either meloxicam or gabapentin showed no statistical difference in rescue analgesia requirements.¹² However, cats were only assessed for the first 8 hours postoperatively, which limits translation to analgesia at home, and more cats in the gabapentin group (25%) required rescue analgesia compared to meloxicam (13%). Thermal threshold testing of gabapentin at 3 escalating doses also did not show an antinociceptive effect of gabapentin in research cats.¹⁹

When to Use

In a 2021 survey of veterinary professionals, the most common reason to prescribe gabapentin was for analgesia when an NSAID was contraindicated.²⁰ Patients with concurrent GI, kidney, or liver disease may have contraindications to NSAID therapy. While gabapentin’s lack of significant adverse effects (primarily sedation and ataxia) makes it a desirable alternative, current research does not support its use as a solo oral analgesic. Evidence does support its use as an adjunctive analgesic to modulate pain signaling in conjunction with NSAIDs and/or opioids or for use in neuropathic conditions.

Pregabalin

Pregabalin also has limited research in veterinary species, with some supportive evidence for its use in neuropathic conditions but less benefit in acute pain conditions. Pregabalin’s site of action on calcium channels in the spinal cord and CNS could explain its documented benefit in neuropathic pain cases, while its lack of peripheral receptor activation could explain its limited benefit in acute inflammatory conditions.

Supporting Evidence

Pregabalin improved pain scores in dogs after hemilaminectomy compared with opioids alone, in contrast to the similar study using gabapentin.^16,21 This could be due to differences in pharmacokinetics between the drugs. Additionally, pregabalin decreased neuropathic pain behaviors in dogs with syringomyelia.^22,23 However, in dogs undergoing mastectomy, both pregabalin and gabapentin provided minimal or no additional analgesia when added to opioids and meloxicam.^24,25 These studies highlight the potential benefit pregabalin may have in modulating neuropathic pain but also its deficiency in acute pain management.

When to Use

While some studies suggest pregabalin could be more beneficial than gabapentin, prescribing pregabalin can be more challenging as it is a Schedule V controlled medication. Gabapentin is not federally controlled, but some states have passed laws defining it as a Schedule V medication as well, and other states are tracking prescriptions.

Amantadine

Amantadine acts as an N-methyl-d-aspartate (NMDA) antagonist and dopamine agonist and may help decrease central pain sensitization. Veterinary studies on the acute and chronic effects of amantadine are limited, with the few publications focusing on its use in osteoarthritis and neuropathic pain.

Supporting Evidence

In a population of research cats, amantadine did not significantly change thermal threshold response when administered in combination with oxymorphone.²⁶ However, in a study of owned cats, cats with osteoarthritis showed improved owner-reported quality of life and mobility when given amantadine alone.²⁷

In dogs, amantadine acted synergistically with meloxicam for osteoarthritis pain that failed NSAID therapy alone.²⁸ Amantadine, administered alone and in conjunction with meloxicam, improved force gait analysis in dogs with degenerative lumbosacral stenosis that was previously refractory to NSAID therapy.²⁹

When to Use

Repetitive activation of neurons in the dorsal horn of the spinal cord, as occurs in chronic pain conditions, leads to the activation and recruitment of NMDA receptors or central sensitization. Acute pain is typically short term and less likely to cause repetitive activation at the level of the spinal cord. This difference in acute and chronic pain pathway activation may explain amantadine’s conflicting clinical effect. Thus, similar to gabapentin, amantadine is not adequate as a solo analgesic agent for acute pain. It is best used in combination with NSAIDs or opioids when there may be a component of central sensitization.

Summary

Oral analgesic therapy in dogs and cats can greatly improve quality of life and is often essential for treatment of postoperative pain. Inflammation is often a major component of acute pain, requiring treatment with NSAIDs. Despite their potential adverse effects, NSAIDs remain the most effective oral analgesic option in dogs and cats. Acetaminophen may be an alternative mild analgesic in dogs with NSAID contraindications but lacks anti-inflammatory properties. Alternative drugs such as oral opioids, gabapentinoids, and amantadine show benefits as adjunctive analgesics targeting the CNS pain pathways, but their efficacy as solo agents may be lacking. Ultimately, when formulating an analgesic plan for dogs and cats, consider ways to target multiple areas of the pain pathway (peripheral and central) through combination drug therapy, use of locoregional techniques, or nonpharmaceutical therapies.