Felipedia

Pain management in cats

Behaviours suggestive of pain are routinely used to diagnose injuries and diseases, guide therapy, and provide prognostic information. Obvious signs of pain alert owners and veterinarians to the fact that something is wrong with the animal. Thus, there is nothing novel about considering pain to be important clinically in the overall evaluation of an animal. What is relatively new is the understanding of the complexity of pain and the recent emphasis on the ethical and medical obligations to treat pain in animals. Although there is some limited survey data and anecdotal evidence to suggest that the management of pain is receiving more attention in veterinary medicine than before, the assessment, prevention, and treatment of pain has yet to become an integral part of every physical examination and treatment plan. In order to address pain management, let us first consider the various types of pain which exist (in terms of origin rather than intensity).

Visceral Pain - is a dull, deep, constantly aching pain. It is also poorly defined and often responds best to narcotic analgesics when pain is significant. Inflammatory and somatic pain. Inflammatory and somatic pain is frequently described in humans as well localized, constant, and aching. Common sources of this type of pain include bone metastases, tissue damage, and musculoskeletal, dental, and integument pain. In humans, this type of discomfort responds well to analgesics such as aspirin, acetaminophen, or the non-steroidal anti-inflammatory drugs (NSAIDs).
Neuritic Pain - involves inflammation of nerves or nerve roots, which can be a paraneoplastic syndrome or a direct effect of cancer compression, causes neuritic pain. Humans describe this as a constant dull aching pain that may have periods of burning "shock-like" sensations.
Neuropathic Pain - is the result of a damaged segment of the nervous system that normally transmits pain stimuli. This is due to metabolic, immunologic, or direct physical effects on the nervous system. It is difficult to control with standard analgesics.

Pain perception¹

Pain serves a protective role to alert an individual to injury from the environment or from within the individual. Based on what is known to date, all vertebrates, and some invertebrates, experience pain in response to actual or potential tissue damage. Many different types of pain are encountered, with the most common being acute, chronic, cancer, and neuropathic pain. Acute pain is the normal predicted physiologic response to an adverse chemical, thermal, or mechanical stimulus. It may also be the initiation phase of an extensive, persistent nociceptive and behavioural cascade triggered by tissue injury. Acute pain generally improves within the first 3 days following an event such as surgery, but may persist for weeks or months. Chronic pain may be defined as pain that persists for longer than the expected time frame for healing or pain associated with progressive non-malignant disease (such as osteoarthritis). Cancer pain refers to pain that is the result of primary tumour growth, metastatic disease, or the toxic effects of chemotherapy and radiation. Neuropathic pain refers to a persistent pain syndrome resulting from damage to a peripheral nerve, dorsal root ganglion or dorsal root, or the CNS. Neuropathic pain is recognized in veterinary medicine much less often than in human medicine.

For an animal to experience pain, nociceptive information must be sent to the higher centres in the CNS to be integrated and interpreted into the sensory experience of pain. Noxious stimuli (heat, cold, mechanical, chemical) activate free sensory nerve endings known as nociceptors. A-δ and C-fibres transmit sensory information from the nociceptors to the dorsal horn of the spinal cord, which directs and modulates the input from sensory neurons. Nociceptive information arriving in the dorsal horn of the spinal cord may activate motor neurons responsible for the reflex responses to noxious stimuli (such as withdrawing a limb). Importantly, the nociceptive sensory input may be amplified or inhibited by spinal interneurons. Sensory information is relayed to higher centres in the CNS along a variety of pathways that differ according to species. In general, nociceptive information ascends the spinal cord along superficial and deep pathways to the brain stem with connections to the thalamus, reticular formation (responsible for level of arousal), and limbus (responsible for emotions). From these areas of the brain, nociceptive information is relayed to the cortex where it is recognized as pain. Activity in spinal nociceptive pathways is strongly influenced by descending antinociceptive systems that originate in the brain stem. Endogenous antinociceptive neurotransmitters (eg, endorphin, encephalin, and dynorphin) inhibit the transmission of nociceptive information in the spinal cord and brain.

The neuroanatomic components of the nociceptive/pain pathways and pain-suppressing systems can change in response to sustained sensory input. Peripheral sensitization of nociceptors and central sensitization of nociceptive neurons and pathways in the spinal cord and brain can develop as a result of extensive tissue trauma or nerve injury. The process of peripheral and central sensitization has been termed ‘‘wind-up” and refers to the neuroanatomical changes that result in heightened or exaggerated pain states. Additionally, chronic pain sometimes does not respond to conventional analgesic therapy due to changes in the CNS processing of nociceptive input. Thus, changes in the CNS in response to repeated and sustained nociceptive input (ie, pain) complicate the clinical management of pain.

Recognition and assessment of pain in animals

The assessment of pain in animals can be challenging. Recognizing pain in animals is not intuitive, particularly by individuals unfamiliar with normal behaviour for a species or individual. In recent years, there has been an increased focus on determining and measuring species-specific pain behaviours, which should improve recognition and treatment of pain in animals. Nevertheless, the assessment of pain in animals remains a subjective and inaccurate undertaking. Numerous factors complicate the evaluation of pain in animals. Any pain scale should consider the following characteristics: species, breed, environment and rearing conditions, age, gender, cause of pain (eg, trauma, surgery, pathology), body region affected (eg, abdominal pain, musculoskeletal pain), character of pain state (eg, acute, chronic), and pain intensity. Any pain scale or methodology employed to assess pain should be able to recognize individual sensitivities. Differences in pain tolerance have been demonstrated experimentally in people and animals, and play an important role in the clinical management of pain.

No “gold standard” exists to measure pain in animals or to compare one type of scale or measurement instrument with another. All of the pain scales used in animals rely on the recognition and/or interpretation of some behaviour and are subject to some degree of variability among observers. Pain scales that are based on the determination of the presence or absence of species-specific behaviours, and that minimize the interpretation of those behaviours, are likely to be more accurate than generic scales that rely heavily on subjective assessment and interpretation. All current methods used to measure pain in animals are prone to errors of under- or overestimation. Even if the amount of pain is correctly estimated, determining how well the individual animal is coping with the pain may be difficult. This is particularly true if the animal is removed from its normal environment. Finally, all current methods assess the effects of physical pain; none has been designed to evaluate mental or psychological dimensions of pain that an animal may experience.

Physiologic parameters (eg, changes in heart rate, respiratory rate, arterial blood pressure, pupil dilation) may be used to assess responses to an acute noxious (painful) stimulus, particularly during anaesthesia, and to assess pain in some clinical situations (eg, horses with acute colic pain). However, physiologic measurements often do not differentiate between animals that have undergone surgery and are experiencing pain and those that did not undergo surgery. Likewise, animals experiencing chronic pain may have normal physiologic parameters. Lack of change in physiologic responses should not be construed to mean there is no pain if other clinical signs suggest otherwise. Physiologic parameters are not specific enough to differentiate pain from other stressors such as anxiety, fear, or physiologic responses to metabolic conditions (eg, anaemia).

Unfamiliarity with normal behaviours typical of a particular species or breed makes recognition of pain-induced behaviours difficult or impossible. Behavioural changes indicative of pain may be too subtle or take too long to recognize under routine clinical situations in both large and small animals. Sporadic observation of animal behaviour may not reveal signs of pain. Except in the most severe circumstances, signs of pain may be “masked” by behaviour that is stereotypical of the species being observed. For instance, dogs may wag their tails and greet observers in spite of being in pain. Flock animals, such as sheep, may be startled when an observer approaches and attempt to conceal any signs of pain by staying bunched up with the rest of the flock. Behavioural changes indicating pain may not be what we expect. A cat sitting quietly in the back of the cage after surgery may be painful; however, pain would not be recognized if the caregiver expects to see more active signs of pain such as pacing, agitation, or vocalization.

In general, responses to acute surgical and traumatic pain are likely to be more marked and readily recognizable than clinical signs associated with chronic pain. Clinical criteria used to assess chronic pain, eg, lack of activity, lack of grooming, decreased appetite, weight loss, are not specific signs of pain and point only to an underlying problem in need of further diagnosis. Evaluating the degree of lameness of affected limb(s) is often used to assess chronic orthopaedic pain. For socialized animals, observations of owners are essential to detect more subtle signs of chronic pain such as changes in attitude or interaction with family members. Response to therapy, such as increased activity after administering an NSAID, may provide important information regarding the role that pain has played in behavioural changes.

Cancer pain may have components of acute pain (eg, expansion of a tumour or secondary responses to surgical, radiation, or chemotherapy treatment) and components of chronic pain. Thus, assessment of cancer pain requires the caregiver to use methods that can detect behavioural changes associated with both acute and chronic pain.

Pain alleviation

Acute peri-operative, traumatic, and disease-related (eg, cancer, pancreatitis, pleuritis) pain is generally treated pharmacologically with one or more analgesics. The optimal drug or drug combinations are determined principally by the anticipated severity of pain, health status, and available drugs for the given species. The more extensive the tissue trauma or disease-induced tissue damage is, the greater the need to use analgesics from more than one drug class (multimodal or balanced analgesia). Multimodal analgesia maximizes the beneficial analgesic effects of multiple drugs through additive or synergistic interactions while minimizing adverse drug effects by lowering the dose of any individual drug. A peri-operative approach to managing surgically induced pain should be used, beginning with the administration of an analgesic before surgery (pre-emptive analgesia) and continuing with appropriate analgesia throughout the intraoperative periods. Three days is a useful guideline for the duration of analgesic therapy following acute surgical pain. Depending on multiple factors (eg, procedure performed, species, breed) some animals require a shorter duration of therapy, whereas other animals require analgesia for longer periods. Aggressive prevention and management of acute pain often prevents wind-up of the nociceptive pathways and hastens a return to normal function.

Minimizing stress and ensuring that overall care and husbandry are in accordance with the needs of the animal improve pain management. Proper housing conditions, nutritional support, and interaction with other animals and/or people should be optimal for the given species and breed. For example, separating a sheep from the flock for pain management may be quite stressful, whereas separating a house pet from other animals may not be stressful provided there is sufficient interaction with human caregivers. Managing painful and distressed animals requires a combination of good nursing care, non-pharmacologic methods (eg, bandaging, ice packs or heat, physical therapy), and pharmacologic methods. Pharmacologic methods available for the treatment of pain generally involve opioids, NSAID, corticosteroids, local anaesthetics, a₂-agonists, and ketamine.

In the management of acute postoperative and traumatic pain, the following should be considered:

Pain is easier to prevent than treat once it is established. Peri-operative analgesia should cover the entire operative period, beginning before the start of surgery and continuing for hours to days into the postoperative period.
As-needed dosing schedules are less effective than scheduled analgesic dosing to treat pain. As-needed dosing schedules require the animal to demonstrate overt pain behaviours to the extent that they are recognized by the veterinarian and/or owner.
Traditional NSAID may be ineffective as the sole agent for treatment of acute postoperative pain, whereas NSAID in combination with other analgesic drugs (i.e., multimodal analgesia) may be very effective.
The therapeutic and side effects of analgesics are dose-dependent. Combining analgesic drugs allows for reduction in the dose of any one analgesic.
Agonist-antagonist opioids (eg, butorphanol) have a “ceiling” effect on analgesia.
Many animals benefit from the management of anxiety. Acepromazine is an effective anxiolytic in small animals, but should only be used after appropriate analgesics have been administered. Acepromazine does not have analgesic properties.
If in doubt about the role of pain in an animal, treat for pain and observe the results.
Appropriate analgesia following surgery or trauma will allow animals to rest. Dogs and cats often sleep, but should be arousable following surgery if their pain is controlled.
Aggressive analgesic therapy of several days’ duration should be tapered rather than stopped abruptly.
Many animals benefit from combined or multimodal therapy (eg, combining an α₂-agonist and an opioid, also administering an NSAID).

Local and regional pain control

Local and regional anaesthetic techniques are extensively used in large animals for a variety of minor and major surgical procedures. Local anaesthetics are used in small animals much less frequently and primarily to facilitate suturing of minor lacerations. Due to the relative ease and safety of inducing general anaesthesia in small animals, local and regional anaesthetic techniques are often overlooked. Nevertheless, local anaesthetic techniques provide an excellent alternative to general anaesthesia for select cases, and are increasingly being used in conjunction with general anaesthesia to improve postoperative analgesia. Local anaesthetics used prior to surgery may decrease the requirement for potent injectable and/or inhalant general anaesthetics.

Conduction blockade of nerve fibres by local anaesthetics is related to the size of the nerve, amount of myelination, and frequency of activity. Small sensory and autonomic fibres tend to be anesthetized before larger motor and proprioceptive fibres. Nerves that are repetitively stimulated are more sensitive to local anaesthetics than resting nerves. The most commonly used agents are lidocaine, mepivacaine, and bupivacaine. Bupivacaine is the preferred drug for postoperative analgesia because of a relatively long duration of action (~3-8 hr). Bupivacaine (0.25-0.75%), with or without epinephrine, is administered in a dose not to exceed 3 mg/kg (dogs) for line or ring blocks of an incision, ring blocks prior to declaw in cats (epinephrine-containing solutions should not be used for distal extremity ring blocks), intercostal nerve blocks and intrapleural local anaesthesia (diluted to twice the volume) following a thoracotomy, proximal nerve infiltration during limb amputations, tissue infiltration for lateral ear resections, and local blocks of facial nerves (maxillary, infraorbital, mental and mandibular nerves). Bupivacaine is frequently administered into the epidural space at the lumbosacral space for pelvic limb and perianal procedures.

Chronic pain

The treatment of chronic pain relies on pharmacologic and non-pharmacologic methods. Some chronic pain responds to drugs used to treat acute pain, such as opioids and NSAID; however, other types of chronic pain require the addition of novel drugs such as an anticonvulsant (eg, gabapentin). The non-pharmacologic treatment of chronic pain depends on the underlying cause and the species. Therapy should be tailored to the individual animal.

The non-pharmacologic goals for managing osteoarthritis pain in dogs include increasing mobility, limiting disease progression, and possibly facilitating tissue repair within the joint. Weight control or reduction and mild to moderate amounts of exercise may be beneficial. Excessive and strenuous exercise should be avoided as it may further strain the joints. Providing warmth during cold and damp weather and extra bedding or padding may also improve comfort. Surgically removing loose fragments of bone, joint mice, and osteochondrosis lesions, and restoring joint stability is often necessary to slow the progression of disease and reduce pain. Joint replacement or arthrodesis may be indicated in severe cases. Chondroprotective agents such as glycosaminoglycans, chondroitin sulphates, and glucosamine may help heal cartilage, stimulate cartilage matrix synthesis, and inhibit enzymatic degradation of cartilage. However, the efficacy of these agents may vary with specific product used, route of administration, and underlying musculoskeletal problems. Acupuncture and physical therapy have been used to treat chronic osteoarthritis pain in animals with promising results.

Analgesic pharmacology

Control of pain in lame or operative animals involves broad classes of compounds such as NSAID and opioids. Delivery of analgesia can be via oral, parenteral, epidural, local, or transdermal routes. Non-pharmacologic pain management strategies include acupuncture therapy, massage, and diet. Commonly used NSAID include firocoxib (5 mg/kg, PO, sid), meloxicam (0.1 mg/kg, IV, SC, PO, sid), carprofen (2.2 mg/kg, PO, bid), ketoprofen (1.0 mg/kg, PO, IV, SC, IM, sid), etodolac (12.5 mg/kg, PO, sid), and aspirin (22 mg/kg, PO, bid in dogs; 10 mg/kg, PO, every 48 hr in cats). The use of NSAID is contraindicated in animals with hepatic or renal insufficiency, gastroenteritis, coagulopathy, or in animals receiving concurrent corticosteroid therapy. Opioid analgesics bind to m, k, and d receptors in the CNS to provide pain relief. Commonly used opioids include morphine (0.1 mg/kg, IV, SC, IM, every 3-4 hr), oxymorphone (0.05 mg/kg, IV, IM, SC, every 3-4 hr), hydromorphone (0.1 mg/kg, IV, IM, SC, every 2-4 hr), butorphanol (0.1 mg/kg, IV, IM, SC, every 3-4 hr), and buprenorphine (10 mg/kg, IV, IM, SC, tid). Opioid narcotics can be given with sedatives such as acepromazine (0.5 mg/kg, IV, IM, SC, every 4-6 hr) for enhanced efficacy of analgesia and sedation. Oxymorphone, hydromorphone, and butorphanol are more potent than morphine. Buprenorphine has the longest duration of action. Another opioid, fentanyl, is most frequently administered via transdermal patches applied for 3 days on shaved areas. Oral opioids used for pain relief include butorphanol (1.0 mg/kg, tid), hydromorphone (0.5 mg/kg, tid), and oxycodone (0.3 mg/kg, tid). Local administration of analgesics involves joint injections with morphine (1 mg diluted in 5 mL of saline) or bupivicaine (1 mL/20 kg body wt) before joint surgery as a pre-emptive block of intracapsular pain receptors. Epidural morphine (0.1 mg/kg) in the lumbosacral space is also a useful adjunct for postoperative pain relief in the hindlimbs and for reduced anaesthetic requirements. Corticosteroids are considered weak analgesic adjuncts because they indirectly reduce pain by their primary action as local anti-inflammatory agents at the site of injury. Drugs used include prednisone or prednisolone (1-2 mg/kg, PO, sid) or dexamethasone (1-2 mg/kg, IV, sid). Their use is contraindicated during concurrent treatment with NSAID.

1) Opioids

The opioids are a diverse group of naturally occurring and synthetic drugs used primarily for their analgesic activity. Despite some well-known side-effects and disadvantages, opioids are the most effective analgesics available for the systemic treatment of acute pain in many species, particularly dogs and cats. Opioids combine reversibly with specific receptors in the brain, spinal cord, and periphery, altering the transmission and perception of pain. In addition to analgesia, opioids can induce other CNS effects that include sedation, euphoria, dysphoria, and excitement. The clinical effects of opioids vary between the µ opioid receptor agonists (eg, morphine, hydromorphone), partial mu agonists (i.e., Buprenorphine), and agonist-antagonists (eg, butorphanol). Species and individual differences in the response to opioids are marked, necessitating the adjustment of doses for different species. For example, a 30-kg dog may receive a preoperative dose of morphine (15-30 mg) that is similar to that of a 300-kg horse. The clinical effect of an opioid depends on additional patient factors, including the presence or absence of pain, health status of the animal, concurrent drugs administered (eg, tranquilizers), and individual sensitivity to opioid effects.

2) Non-steroidal Anti-inflammatory Drugs and Corticosteroids

NSAID are useful adjuncts in the treatment of post-surgical pain in a variety of species. Decreasing inflammation following surgery or trauma can greatly improve analgesia. A significant advantage of NSAID over other analgesics is that an owner can easily administer them for several days after the animal has been discharged from the hospital. NSAID are also readily available, have a relatively long duration of action, and are generally inexpensive. NSAID have long been used to decrease inflammation and provide analgesia and should be considered as part of the analgesic plan provided the animal does not have pre-existing renal, hepatic, coagulation, or GI problems. NSAID should be administered only to well hydrated animals. Corticosteroids also reduce inflammation and provide analgesia. Corticosteroids are used less frequently in the postoperative period due to the potential for decreasing immune function and due to other well-known side effects (eg, immune suppression, polyphagia, polydipsia, polyuria) following repeated dosing. Corticosteroids and NSAID should not be administered concurrently.

3) α ₂ - agonists

Xylazine, medetomidine, detomidine, and romifidine are potent analgesics. α₂-Agonists are used in large animals for standing restraint that includes analgesia and sedation, although there is evidence to suggest that the sedation lasts longer than the analgesia. Combination therapy of α₂ -agonists and opioids induces profound analgesia and sedation that is additive or synergistic as compared with the effects of either drug alone. α₂-Agonists are used as part of multimodal analgesia in the peri-operative period in many species. Notwithstanding the beneficial analgesic properties, many practitioners are uncomfortable with the use of these drugs for maintenance of analgesia following surgery or trauma due to the deep sedation that accompanies analgesic doses of the α₂ -agonists in small animals and the potential for excessive sedation and ataxia in large animals. Xylazine and medetomidine may be reversed in small animals following surgery to hasten recovery and minimize cardiopulmonary depression. Once reversed, however, these drugs provide no analgesia. α₂ -Receptors play an important role in the modulation of pain by the CNS. They may be used to induce analgesia when administered as anaesthetic premedications (pre-emptive analgesia) and may be used to supplement postoperative analgesia. Postoperatively, much lower doses of α₂-agonists are generally used than would be required preoperatively.

4) Ketamine

Ketamine has long been known to provide excellent superficial analgesia but rather poor visceral analgesia. Recently, interest in ketamine has increased because of its potential role in preventing wind-up (sensitization) of central nociceptive pathways. Ketamine is an antagonist of the excitatory neurotransmitter glutamate at the N-methyl-D-aspartate (NMDA) receptors in the spinal cord and brain. Inhibition of the NMDA receptors prevents or decreases exaggerated pain states in laboratory animals and people. Thus, ketamine may be incorporated into the anaesthetic protocol to prevent the development of exaggerated or chronic pain states.