Pain has been defined by the International Association for the Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage.” It may occur alone or in combination with inflammation. Pain sensation arises in the terminal ends of sensory nerve fibers called nociceptors, which are located in every tissue of the body. Nociceptors may be activated through mechanical, thermal, and chemical stimulation to create a nerve impulse. Chemical stimulation may be derived from an exogenous source or from endogenous chemicals such as eicosanoids (prostaglandins), bradykinin, serotonin, and others released in response to tissue damage. These substances may create a “sensitizing soup,” which may create a lower threshold for nociceptors, amplifying the pain response (Muir, 2009)

Physiologic pain can be beneficial in that it can allow the animal to avoid damaging stimuli. Pathologic pain results from tissue or nerve damage and may be further classified according to its origin, severity, or duration. Visceral pain arises from hollow abdominal organs, peritoneum, heart, liver, and lungs while somatic pain arises from the musculoskeletal system. Somatic pain may be further described as superficial (arising from the skin) or deep (arising from periosteum, tendon, or joint tissues). Neuropathic pain can arise due to injury to the peripheral or central nervous system and is described in humans as “burning” or “shooting” (Gaynor, 2009). Pain can have varying degrees of severity (none, mild, moderate, or severe) and may be acute or chronic.

Severe or chronic pain may have an emotional content that activates sympathetic stimulation. It can be harmful because it can lead to stress and related problems such as gastrointestinal lesions, immunosuppression, delayed healing, hypertension, fatigue, abnormal behavior, and potential dysrhythmias. The ethical treatment of animals includes the “five freedoms”: freedom from pain, freedom from hunger and malnutrition, freedom from discomfort, freedom from disease and injury, and freedom to express normal behavior.

Assessment of pain in animals can be very difficult because of the dependence on nonverbal communication in veterinary medicine. Furthermore, animals differ from people in their pain response. It is important for wild animals to control the expression of pain to avoid predation or abandonment. Response to pain varies among individuals and may include increased heart rate, increased respiratory rate, mydriasis, salivation, vocalization, changes in facial expression, aggressive behavior, guarding of the painful site, restlessness, unresponsiveness, failure to groom, abnormal gait, and abnormal stance. A patient that is pain-free will be quiet and calm (Paddleford, 1999). Consult the Handbook of Veterinary Pain Management for pictures and descriptions of pain behaviors in animals. Pain scales and evaluation instruments (Figure 14-1) have been developed to make pain evaluation more objective.

The production of pain sensation arises through a four step process: transduction, transmission, modulation, and perception (Figure 14-2). The first step called transduction occurs in nociceptors, which are terminal sensory nerve endings found in almost every tissue of the body. The nociceptor creates action potentials (electric impulses) in peripheral sensory nerves when activated by noxious stimuli. The second step is the transmission of the impulses to the central nervous system (CNS) by two fiber systems: type C unmyelinated fibers are responsible for dull, poorly localized pain (in humans), and type A delta fibers are responsible for sharp, localized pain (Ganong, 2003). Type A and type C fibers carry impulses to the dorsal horn of the spinal cord (Figure 14-3). This information then, in the third step, undergoes modulation (suppression or amplification) and is transmitted up the cord via the spinothalamic tract through the thalamus to the cerebral cortex, where processing occurs and recognition results in pain perception. If any part of this neuronal chain or the cortical interpretive area is nonfunctional, pain sensation does not occur. Multimodal therapy takes advantage of this concept to intervene at different sites within the pathways. Because an active cortex is required, the perception of pain can occur only in a conscious animal. It should be remembered that reflexive activity (e.g., withdrawal reflex) without pain recognition can occur as a result of nociceptor stimulation (see Chapter 4).

The perception of pain can be enhanced by phenomena called hyperalgesia and central sensitization (Boothe, 2012). Hyperalgesia occurs when the area of tissue injury becomes more sensitive and the threshold for subsequent stimuli decreases. This sensitivity can spread to surrounding uninjured tissue (secondary hyperalgesia). When the neurons of the spinothalamic tract of the spinal cord are stimulated repeatedly, they apparently become sensitized and discharge at a much lower threshold. This activity is called central sensitization, or “wind-up,” and is the rationale for the idea that pain control is enhanced if an analgesic is given before pain is generated.

When spinal cord lesions occur, superficial pain is inhibited before deep pain or lesion severity worsens. The absence of deep pain is often a poor prognostic sign.

As mentioned previously, pharmacologic intervention for pain control may target a single or multiple points of intervention in the pain process. Transduction can be inhibited by local anesthetics, opioids, NSAIDs, and other substances. Transmission of nerve impulses can be inhibited by local anesthetics and alpha-2 agonists. Modulation of pain impulses can occur in the spinal cord through the effects of local anesthetics, opioids, alpha-2 agonists, tricyclic antidepressants, NSAIDs, anticonvulsants, and other drugs. Pain perception in the cortex can be inhibited by the use of anesthetics, opioids, benzodiazepines, and alpha-2 agonists.

 Nonsteroidal Antiinflammatory Drugs

NSAIDs are very useful analgesic drugs that have been shown to work synergistically with opioids when used together. NSAIDs are thought to work by inhibiting an enzyme called cyclooxygenase (COX). Two forms (COX-1 and COX-2) of cyclooxygenase exist. COX-1 maintains physiologic functions such as modulation of renal blood flow and synthesis of gastric mucosa and is sometimes called the constitutive form (Paddleford, 1999). COX-2 is considered the induced (by tissue injury) form that promotes the formation of prostaglandin from cell membrane arachidonic acid (Figure 14-4). Generally, inhibition of COX-2 is responsible for effectiveness of NSAIDs whereas inhibition of COX-1 is associated with side effects. NSAIDs that selectively inhibit COX-2 are thought to produce fewer gastrointestinal side effects. Recent research has suggested that this scheme may be an oversimplification and that COX-2 may be constitutive in some tissues (Budsberg, 2009). COX-1 versus COX-2 selectivity may depend on the drug, the dose, and the species (Claude, 2013). Because the degree of COX-1 and COX-2 inhibition for many of the newer NSAIDs is not well-defined, preferential COX-2 inhibitor may be chosen over selective COX-2 inhibitor because some inhibition of COX-1 and COX-2 may occur (Boothe, 2012). COX-1 sparing has the same connotation as preferential COX-2 inhibitor.

Glucocorticoids exert their effects by blocking phospholipase, an enzyme necessary for the production of both prostaglandins and leukotrienes (intervention is provided earlier in the sequence of the formation of inflammatory mediators). Because the inflammatory reaction is blocked earlier by glucocorticoids, they are more effective antiinflammatory agents than are NSAIDs (Langston and Mercer, 1988). NSAIDs are often preferred, however, because they have fewer side effects and they promote analgesia and fever reduction. At this time, it is not known why glucocorticoids do not induce the analgesic and antipyretic effects of NSAIDs. It is also unknown why some NSAIDs provide relief of only mild pain (aspirin) and others provide relief of moderate to severe pain (flunixin). Some clinicians speculate that NSAIDs may act to varying degrees centrally to modulate spinal transmission of pain impulses (Paddleford, 1999).

The most common side effects of the NSAIDs are gastrointestinal ulceration and bleeding, which probably result from interference with the normal mucous coating of the stomach. Other side effects may include hepatotoxicity, nephrotoxicity, inhibition of cartilage metabolism, bone marrow suppression, and bleeding tendencies (from reduced platelet aggregation).

All pets should undergo a thorough physical examination and history, as well as appropriate laboratory tests, before NSAIDs are initiated. Clients should be advised to stop the use of these drugs and to contact their veterinarian if they observe side effects in their pets that are receiving NSAIDs. Pets receiving long-term treatment with NSAIDs should have periodic evaluations of liver and kidney function performed. Clients should be advised to watch their pets for anorexia, vomiting, changes in bowel movements, bloody or tarry stools, lethargy or other changes in behavior, seizures, jaundice, changes in urination (frequency, color, or smell), or changes in the condition of the skin.

 Technician Notes

• NSAIDs should be used with caution in geriatric animals.

• Combining NSAIDs or combining NSAIDs with corticosteroids should be done with great caution or avoided.

Salicylates

Aspirin, a salicylate, is also known as acetylsalicylic acid. Its actions include the following:

• Relief of pain (analgesia)

• Reduction in fever (antipyrexia)

• Inhibition of inflammation (antiinflammatory effect)

• Reduction in platelet aggregation (blood-thinning effect)

These effects are thought to occur as a result of the ability of aspirin to inhibit an enzyme (COX) that is responsible for the synthesis of prostaglandin. Prostaglandin is a chemical mediator of the processes that lead to pain, fever, inflammation, and platelet aggregation. Its inhibition results in diminishing of each process.

Clinical Uses

Clinical uses of aspirin exist for most animal species and may include the following:

• Relief of mild to moderate pain caused by musculoskeletal conditions such as arthritis and hip dysplasia

• Postadulticide treatment for heartworm disease

• Analgesia/antipyrexia

• Treatment of cats with cardiomyopathy

• Treatment of endotoxic shock

Dosage Forms

These include plain uncoated tablets, buffered uncoated tablets, enteric-coated forms, and boluses (large-animal applications). Many generic or brand names are available in many different strengths, including the following:

• Aspirin bolus; horses and cattle

• Aspirin tablets; dogs

• Aspirin gel; dogs

• Aspirin granules; horses

Adverse Side Effects

Adverse side effects of aspirin include gastric irritation, which can lead to ulceration and bleeding. Cats are highly susceptible to aspirin overdosage because of their inability to metabolize it rapidly; they should receive this drug only under the supervision of a veterinarian.

 Technician Notes

• Enteric-coated aspirin, such as Ecotrin, may be used to prevent gastric irritation.

• A 1-grain “baby” aspirin contains 65 mg; a 1.25-grain baby aspirin contains 81 mg.

• Aspirin has no withdrawal time in food animals.

Pyrazolone Derivatives

Phenylbutazone

Phenylbutazone, a pyrazolone derivative, is an NSAID that is commonly used in veterinary medicine. Its actions include the following:

• Analgesia for mild to moderate pain

• Antiinflammatory action

• Antipyrexia

Clinical Uses

These include relief of inflammatory conditions of the musculoskeletal system of horses and dogs. Phenylbutazone is used extensively in horses for the treatment of lameness and for the relief of pain associated with colic. It sometimes is used in dogs and cattle for its antiinflammatory, analgesic, and antipyretic effects.

Dosage Forms

Dosage forms of phenylbutazone include parenteral injection, tablets, boluses, an oral paste, an oral gel, and powder.

• Phenylbutazone, tablets, boluses, paste, injection

• Phenylzone Paste

• Equi-Phar ButePaste

• ButaJect

• Phenylbute Paste

Adverse Side Effects

These include gastrointestinal bleeding and bone marrow suppression.

 Technician Notes

• Phenylbutazone injection should be administered by the intravenous route only. Subcutaneous and intramuscular injection may lead to sloughing of tissue.

• Prolonged use or an overdose can lead to bone marrow suppression in humans.

• Prolonged use also may lead to ulcer formation.

• Because of possible bone marrow suppression and potential ulcer formation, animals that are receiving long-term treatment with phenylbutazone should be monitored carefully.

Flunixin Meglumine

Flunixin is an NSAID that is labeled for use in horses and cattle. It has extralabel uses in other species. Its actions are related to its ability to inhibit COX and include the following:

• Analgesia

• Antipyrexia

• Antiinflammatory effects

Clinical Uses

Clinical uses of flunixin in horses include alleviation of pain associated with musculoskeletal disorders and colic. (Flunixin apparently has great ability to inhibit visceral pain.) Other uses in horses and other species include treatment of the following:

• Disk disease

• Endotoxic shock

• Calf diarrhea

• Parvovirus disease

• Heatstroke

• Ophthalmic conditions

• Postsurgical pain

Dosage Forms

Dosage forms of flunixin include injectable, oral paste, and oral granule formulations.

• Banamine Injection

• Banamine Oral Paste

• Banamine Oral Granules

• FlunixiJect

• Flunazine Injection

Adverse Side Effects

These are limited in horses but may include swelling at the injection site and sweating. In dogs, vomiting, diarrhea, nephrotoxicity, and gastric ulceration may occur with long-term use.

 Technician Notes

• Flunixin is labeled for intravenous and intramuscular use in horses.

• Some equine clinicians believe that flunixin relieves abdominal pain so well in horses that it may cause a sense of false security about the condition of an animal with colic.

• Small-animal patients receiving flunixin should be well-hydrated and should be given intravenous fluids and ulcer prophylaxis (Paddleford, 1999).

Dimethyl Sulfoxide

DMSO is a clear liquid that was originally developed as a commercial solvent. It is noted for its antiinflammatory action and its ability to act as a carrier of other agents through the skin. Its antiinflammatory actions may be related to its ability to trap products associated with the inflammatory response. DMSO causes vasodilation when applied topically.

Clinical Uses

Clinical uses of DMSO are varied; however, the only labeled use for DMSO is for topical application to reduce acute swelling resulting from trauma in dogs and horses. DMSO has reportedly been used as the following:

• An adjunct to intestinal surgery (intravenously)

• A treatment for cerebral edema or spinal cord injury (intravenously)

• A treatment for perivascular injection of chemotherapeutic agents or other irritating substances (topical)

• A carrier of drugs across the skin

< div class='tao-gold-member'>

Only gold members can continue reading. Log In or Register to continue