Spotlight on acute pain in cats: Improving your assessment, treatment, and prevention of pain in feline patients (Sponsored by Abbott Animal Health)

Pet cats outnumber pet dogs in the United States, yet cats receive far less veterinary care than their canine counterparts.1 Many factors have contributed to this divide, which greatly affects cats' quality of life. Nowhere is this more apparent than in the area of pain identification and control.

Worldwide, there is an unmet need for effective pain control in cats. Shockingly, several studies comparing postoperative pain management in dogs and in cats have highlighted the disparity. Following laparotomy - an invasive and painful procedure - performed by British veterinary surgeons, 71% of dogs received analgesia, but only 56% of cats did, despite equal pain scores between the two species.2  In another study in New Zealand, as few as 50% of cats undergoing castration received analgesia.3 And in a Brazilian study, demonstrating that pain is often underestimated in postoperative feline patients, cats received lower pain scores than dogs for common procedures such as laparotomy, orchiectomy, and dental procedures.4 The direness of the situation has been summed up by leading feline experts, “Cats are popular pets but until recently their perioperative and traumatic pain was seriously underestimated and undertreated.5

Why are cats undertreated for pain?

Cats are undertreated for pain for a number of reasons.5 Perhaps the most challenging are the difficulties in detecting pain in feline patients and the small number of FDA-approved analgesic drugs for use in cats. Other obstacles include the fear of potential adverse effects from some drug classes (nonsteroidal anti-inflammatory drug toxicity and opioid-induced mania) and the possibility of adverse effects or analgesic ineffectiveness related to cat-specific metabolic deficiencies (i.e. deficiency in the glucuronidation pathway). The difficulty of administering frequent treatments is another deterrent (cats can be difficult to medicate).

Difficulty detecting pain in cats

In human medicine, pain is called the 5th vital sign (in addition to heart rate, respiratory rate, arterial blood pressure, and body temperature). In veterinary medicine, pain is often called the 4th vital sign (because we don't often measure blood pressure in a routine physical examination). Why is pain considered a vital sign? Because pain is the main reason that people seek medical care and because of the importance of untreated pain:

• Pain is a stressor that can cause adverse effects throughout the entire body through physiologic responses to stress. Examples include tachycardia, hypertension, and gastrointestinal ulceration.

• Inadequately treated pain can lead to delayed healing through release of cortisol and activation of catabolism. Pain can also lead to anorexia and insomnia, and both have a negative impact on healing.

• Unrelieved acute pain can predispose the patient to the development of chronic pain.

What does this mean for veterinarians?

Our patients feel pain too. The pain pathway is neuroanatomically similar in all mammals (Figure 1), so if a noxious stimulus causes pain in a human, it also causes pain in an animal. Pain is not the main reason that pet owners seek veterinary care for their animals, but the importance of unrecognized pain is the same in veterinary patients as it is in people. One reason that owners don't seek pain relief for their pets is that pain is hard to recognize in animals. Animals try to hide pain since the survival instinct for concealing weakness still exists in pets. We must actively look for pain in our patients.

Of course, pain prevention is preferred and is best achieved with appropriate perioperative and post-trauma analgesia. As a leading veterinary pain management advocate has stated, “Veterinarians should no longer force patients to prove that they are in pain when common sense indicates that they might be.6 But we must also follow up our treatment with pain assessment since pain management is not a one-size-fits-all treatment, and there is individual sensitivity to both pain and analgesics.

Looking for pain

Since animals do not “tell” us about their pain level, we must “look for” pain (Table 1). We can use the other vital signs to aid in pain assessment. Since pain is a stressor, veterinarians can look for physiologic signs of stress: tachycardia, tachypnea, and hypertension. Also, changes in feline posture and gait can often be quite specific for pain. A tucked abdomen or hunched back usually indicates pain. Head down, neck stretched, ears back or flat, whiskers drooped, and tail down are all signs that could indicate pain in cats.

Body posture while recumbent is also important. For instance, cats generally sleep curled up, and cats that are lying stretched out may be experiencing pain. However, assessment of postural changes should be linked to a potential painful condition or event. A happy cat stretched out in the sun has no obvious reason to be experiencing pain. Animals that do not exhibit normal sleep behavior, especially those that do not want to lie down and sleep after surgery, may also be experiencing pain. Vocalization (meowing, growling, hissing) can be useful too but may be due to dysphoria. Cats in pain may even purr; so don't conclude that a purring cat is necessarily a pain-free cat.

Facial expression changes

Changes in facial expressions due to pain were not attributed to animals until recently. However, with the publication of the “rat grimace scales,”7 the ability to identify changes in facial expressions in animals has been validated, and expressions related to pain have been described in other species. Although there is no validated scale for cats, many of the components of the rat scale can be applied to recognition of pain in cats (Figure 2).

Behavior changes

One of the most useful indicators of pain is a change in behavior. Of course, a change in behavior does not necessarily mean that the cat is experiencing pain, but a change in behavior that coincides with a painful event (e.g. surgery or trauma) should be investigated. Animals that were friendly may become aggressive or defensive, and those that were solitary may seek human companionship and comfort. The animal's behavior may even seem normal until the painful area is approached or touched, and then fear or aggression may be exhibited. The most useful way to determine whether or not an animal is in pain is to administer an analgesic drug and evaluate the response. For acute pain, administering an opioid is often the best option because of their rapid onset and high potency. If the patient's behavior returns to normal after treatment, then the diagnosis has been made - pain. Then the next step is to develop a treatment plan that will provide the patient with continued pain relief.

Pain scoring systems

The best way to use all of the observations and clinical findings is to put them together in a pain score using one of the available scoring systems. In human medicine, pain scoring of patients is required by law in some countries, including in the United States.8 With human patients, pain level can be verbalized, whereas with veterinary patients, veterinarians and their trained staff have to rely on their perception of what the animal is either feeling or trying to hide. Thus, pain scoring is more difficult. However, if all of the categories on the score sheet are diligently assessed, pain - and especially the relief of pain after treatment - can be recognized in most patients. The consistency and accuracy of the scoring system can be improved with the implementation of some simple practices (Table 2).

There are many scoring systems, so each clinic can choose the one that works best for them. The two most commonly used systems in cats are the Colorado State University Feline Acute Pain Scale 9 and the UNESP-Botucatu Multidimensional Scale.10 Both scales allow variables to be compiled and assigned a number. A simple numeric scale from 0 to 10 (e.g. 0 = no pain and 10 = worst pain) can also be used, but may be less robust than the other systems because there are no descriptors to help the assessor know what to evaluate.

Drugs available to treat pain in cats

Addressing the small number of FDA-approved analgesic drugs for use in cats is important since FDA approval requires rigorous safety and efficacy studies in the target species. Compounded drugs do not undergo FDA review, and drugs that are FDA-approved for other species (e.g. people, dogs) do not have to undergo safety and efficacy studies in a species in which the drug may be used in an extra-label fashion. FDA-approved products provide assurance that a drug is safe and efficacious in the majority of animals in the target species, which assures veterinarians (and owners) that the most appropriate therapies are being used.

The number of FDA-approved drugs is important in pain management because multimodal analgesia (i.e. the use of drugs from different classes) generally improves both the analgesic potency and duration of pain relief. Multimodal therapy is superior to single agent therapy in part because different classes of analgesic drugs exert their effect at different locations in the pain pathway (Figure 3), thereby allowing their effects to be additive or even synergistic. Without adequate choices for multimodal analgesia, pain relief may not be optimized.

Six FDA-approved drugs are currently available to control acute postoperative pain in cats - two nonsteroidal anti-inflammatory drugs (NSAIDs), two alpha-2 adrenergic agonists, and two opioids. No drugs are FDA-approved to treat chronic pain in cats.

Dr. Sheilah A. Robertson

Don't miss this free CE webcast!

Managing Acute Pain in Cats through Recognition, Prevention, and Treatment

Presented by Sheilah A. Robertson, BVMS, PHD, DACVAA, DECVAA, DACAW, DEBAWBM (WSEL)

Sponsored by Abbott Animal Health and Powered by dvm360.com

NSAIDs

The main advantage of the NSAID class of drugs is that the NSAIDs control not only the sensation of pain but also the source of pain (i.e. inflammation). This makes the NSAIDs a powerful and effective class of drugs. NSAID-induced analgesia is fairly long lasting, decreasing the need for frequent dosing.

The main disadvantage of the NSAID class is that the drugs can cause gastrointestinal, hepatic, and renal damage.11 Cats may be more susceptible to NSAID-induced toxicity since the species has a deficiency in the glucuronidation pathway, which results in slowed metabolism of multiple drugs, including some NSAIDs.5,12  Slowed metabolism could lead to accumulation - and increased likelihood of toxicity - of inappropriately dosed NSAIDs.12 This does not mean that NSAIDs should be avoided in all cats, but it does tend to limit their use to healthy cats and also makes it critical to adhere to the correct dose. However, NSAIDs should be a part of multimodal analgesic therapy whenever appropriate.

Alpha-2 adrenergic agonists

The alpha-2 adrenergic agonists are commonly thought of as potent sedatives, but they are FDA-approved as sedative analgesics. The provision of both sedation and analgesia is useful when the patient requires preoperative sedation or sedation for painful diagnostic procedures or medical treatment. The effects of alpha-2 agonists are reversible, adding to the safety of the drug class. However, the reversal drugs for this class are not FDA-approved in cats. The main disadvantage is alpha-2-mediated vasoconstriction, which can cause decreased cardiac output, increased cardiac work, and a reflex bradycardia. This has minimal clinical impact in patients with healthy hearts but may exacerbate pre-existing disease in patients with cardiovascular dysfunction. The other clinically relevant disadvantage is that the duration of analgesia is fairly short. The alpha-2 agonists are an excellent component of perioperative multimodal analgesia.

Opioids

Opioids are the most widely used drugs for treatment of acute pain in many species. Opioids have many advantages:

• They are the most potent class of systemically administered analgesic drugs.

• They have a high safety margin.

• Their effects are reversible (although the reversal agent is not FDA-approved in cats).

The main disadvantages of opioids are generally of minimal clinical significance. Opioids may cause excitement in cats; however, the profound opioid-induced dysphoria (“morphine mania”) does not occur at clinically appropriate dosages. Opioids may also cause sedation, but this is usually minor and is actually a desired effect when the drugs are administered before anesthesia. Opioids have been implicated in anorexia, slowed gastrointestinal motility, respiratory depression, and hyperthermia. All of these effects can occur sporadically but are generally mild, self-limiting, and of minimal clinical importance in most healthy cats. The drugs with FDA approval for analgesia in cats (an opioid agonist-antagonist and a mu opioid partial agonist) are less likely to cause these effects than the full opioid agonists, which are not FDA-approved for use in cats. Of the two FDA-approved opioids for cats, one (butorphanol; a partial opiate agonist/antagonist) has a duration of antinociceptive action of only 90 minutes (range 15 minutes to 8 hours),13 while the other (buprenorphine; a partial mu opiate agonist) has a duration of 24 hours (see the Simbadol® Brief Summary and Simbadol® Important Safety Information below). The other buprenorphine products approved for use in people and used extra-label in cats have a duration of action of 4 to 8 hours.14 Choosing drugs with a longer duration of action requires less frequent dosing, which may improve analgesic therapy in patients that are difficult to medicate.

INDICATION: For the control of postoperative pain associated with surgical procedures in cats

IMPORTANT SIMBADOL (buprenorphine injection) SAFETY INFORMATION

WARNINGS, PRECAUTIONS and CONTRAINDICATIONS: Due to serious human safety and abuse concerns, including physical or psychological dependence, life-threatening respiratory depression and additive CNS depressant effects, read the full prescribing information before using this drug, including the complete Boxed Warning. Not for use in humans. Hospital staff should be trained in the handling of potent opioids and should avoid accidental exposure. For subcutaneous (SQ) injectable use in cats. Opioid excitation has been observed up to 8 hours after anesthetic recovery. Use with caution in cats with impaired hepatic function. SIMBADOL has not been evaluated in breeding, pregnant, or lactating cats, in cats younger than 4 months of age or moribund cats. Do not use in cats with known hypersensitivity to buprenorphine hydrochloride or any of the components of SIMBADOL, or known intolerance to opioids.

ADVERSE REACTIONS: In two controlled field studies, the most frequent adverse reactions with SIMBADOL were hypotension, tachycardia, hypothermia, hyperthermia, hypertension, anorexia, and hyperactivity. Less frequent but serious adverse reactions included two deaths following apnea and two reports of presumptive post-anesthetic cortical blindness. See the full prescribing information for a complete list and additional details of adverse reactions for each field study.

Opioids are also versatile and can be administered by many routes. In general, intravenous or intramuscular dosing is preferred over subcutaneous dosing since opioids, including buprenorphine, delivered by the subcutaneous route are poorly absorbed.15  However, FDA-approved opioids for cats are labeled for subcutaneous injection only. The FDA-approved buprenorphine (Simbadol® - Abbott Laboratories) for cats is designed for subcutaneous delivery and the pharmacokinetics support the efficacy of this particular opioid by this route (see Simbadol® Brief Summary). The dose (0.24 mg/ml) and concentration (1.8 mg/ml) of this product are vastly different from the buprenorphine products approved for use in people and used extra-label in cats. It is the novel combination of formulation, dose, and concentration that allows subcutaneous dosing once every 24 hours to provide effective pain relief in cats.

Key points

Cats feel pain and pain can add to morbidity. However, since cats are masters at hiding pain, it is necessary to look for and assess pain in feline patients. Evaluating physiologic, physical, and behavioral signs of pain, especially when assessed by using a pain scoring system, can help veterinarians identify patients that need analgesic therapy. Often, the best way to identify pain is to administer an analgesic drug and monitor the patient's response to treatment. Ideally, all practices should utilize a pain scoring system and a team approach to pain management. Optimizing the care of feline patients requires that every person in the clinic be part of the pain management team and be trained to identify and score pain level in cats, and that the clinic establishes a pain prevention and treatment protocol for all surgical patients.

The FDA-approved analgesic drugs available are best used in multimodal protocols to maximize their effectiveness for pain relief in cats. FDA-approved drugs go through rigorous safety and efficacy trials in the target species, and these drugs should be the first choice for treating patients. Drugs such as the FDA-approved buprenorphine (Simbadol® - Abbott Laboratories) are specifically designed for cats, with the necessary safety and efficacy data to ensure that appropriate care is provided for cats experiencing pain.

SUGGESTED READING

1. AAHA/AAFP Task Force. The American Animal Hospital Association and the American Association of Feline Practitioners AAHA/AAFP Pain Management Guidelines. J Am Anim Hosp Assoc 2007;43:235-248. Available at http://www.aahanet.org/PublicDocuments/PainManagementGuidelines.pdf.

2. WSAVA Global Pain Council. Guidelines for the recognition, assessment and treatment of pain. Available at http://www.wsava.org/sites/default/files/jsap_0.pdf.

REFERENCES

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3. Williams VM, Lascelles BD, Robson MC. Current attitudes to, and use of, peri-operative analgesia in dogs and cats by veterinarians in New Zealand. NZ VetJ 2005;53(3):193-202.

4. Lorena SE, Luna SP, Lascelles BD, et al. Current attitudes regarding the use of perioperative analgesics in dogs and cats by Brazilian veterinarians. Vet Anaesth Analg 2014;41(1):82-89.

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A partially automated method for quantifying pain in the laboratory rat via facial expressions. Molecular Pain 2011(7):55-65. Available at http://www.molecularpain.com/content/7/1/55.

8. The Joint Commission. Facts about pain management. Available at http://www.jointcommission.org/pain_management/. Accessed Sept. 26, 2014.

9. Hellyer PW, Uhrig SR, Robinson NG Colorado State University Veterinary Medical Center Feline Acute Pain Scale. 2006. Available at http://www.csuanimalcancercenter.org/assets/files/csu_acute_pain_scale_feline.pdf. Accessed Sept. 26, 2014.

10. Brondani JT, Mama KR, Luna SP, et al. Validation of the English version of the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats. BMC Vet Res 2013;17;9:143-158.

11. Khan SA, McLean MK. Toxicology of frequently encountered nonsteroidal anti-Inflammatory drugs in dogs and cats. Vet Clin North Am Small Anim Pract 2012;42(2):289-306.

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13. Lascelles BD, Robertson SA. Use of thermal threshold response to evaluate the antinociceptive effects of butorphanol in cats. Am J Vet Res 2004;65(8):1085-1089.

14. Steagall PVM, Monteiro-Steagall BP, Taylor PM. A review of the studies using buprenorphine in cats. J Vet Intern Med 2014;28:762- 770.

15. Giordano T, Steagall PV, Ferreira TH, et al. Postoperative analgesic effects of intravenous, intramuscular, subcutaneous or oral transmucosal buprenorphine administered to cats undergoing ovariohysterectomy. Vet Anaesth Analg 2010;37(4):357-366.