What Is Pain?

Steven G. Kamerling

James N. Moore

The International Association for the Study of Pain describes pain as an unpleasant sensory and emotional experience associated with actual or imminent tissue damage.¹ However, this definition continues to be debated. Although most agree that pain is “perceived” by organisms that have a nervous system, the degree of “suffering” experienced by various animals is controversial. In human medicine many believe that pain must be defined in the context of intelligence, consciousness, and the memory of painful experiences. However, pain reactions are readily recognizable in large animals and are clearly “remembered” by animals that have experienced them. Perhaps what differentiates humans and other animals is the complexity and manner in which pain is expressed. In verbally competent humans, linguistically reported pain is the gold standard. In human neonates and animals, recognition of pain reactions or behaviors becomes of paramount importance. Despite phylogenetic differences among members of the animal kingdom, it is incumbent on the veterinary practitioner to presume that large animals perceive, react to, and suffer from painful stimuli and experiences.

Nociceptors and Nociception

The International Association for the Study of Pain’s definition of pain highlights two important aspects of pain, namely a sensory discriminative component and an emotional, or affective, component. The sensory component of pain is often referred to as nociception, or the sensory reception of noxious or injurious stimuli by nociceptors. Nociceptors are sensory neurons having free, unmyelinated nerve endings. These nociceptors respond selectively to noxious stimuli but cannot be characterized based purely on histology. The three main functional types of nociceptors are mechanical, thermal, and chemical. Anatomically they are classified as A-delta or C-polymodal. A-delta nociceptors are unimodal, high-threshold, small-diameter, myelinated fibers that respond to deforming mechanical stimuli such as tissue compression. They typically do not respond to excessive temperatures or chemicals unless sensitized. C-polymodal nociceptors are small-diameter, unmyelinated, slowly conducting fibers that respond to chemical, thermal, and mechanical extremes. Thermal nociceptors, typically present in skin, respond to temperatures exceeding 45° C. For example, radiant heat sufficient to raise the temperature of the skin over the withers (44° to 50° C) elicits the protective twitch reflex within 5 seconds. Chemical nociceptors respond to noxious chemicals (e.g., caustics, acids, bases, hypertonic solutions) or inflammatory mediators (e.g., prostaglandins, bradykinin). Nociceptors exist in muscles, the skin, the periosteum, most internal organs, the tooth pulp, the cornea, and the meninges. With the exception of pain in the meninges (i.e., headache), “pain” in these tissues can be readily recognized.

Nociceptors serve to warn an animal of imminent or ongoing tissue injury. This warning typically elicits protective reflexes, such as the skin twitch reflex described previously, that attempt to separate the animal from the noxious stimulus. The limb withdrawal reflex after the application of a hoof tester can be used as a measure of pain threshold in horses.² Pain threshold can be defined as the stimulus intensity (e.g., temperature, pressure) that is sufficient to elicit a behavioral pain response. Nonsteroidal antiinflammatory analgesics increase the amount of hoof compression tolerated by laminitic horses,³ and opioid analgesics lengthen the time required to produce the limb withdrawal and skin twitch reflexes in horses exposed to noxious heat.⁴ Because these analgesics act preferentially on nociceptors and their peripheral and central pathways, these reflexes represent true “pain responses” by the horse. Clearly, such reflexes are critical in protecting horses from hostile environmental insults.

Inflammatory Pain and Hyperalgesia

The reflexes discussed previously signal imminent tissue injury; but what happens when tissues actually are damaged? The sensitivity of damaged tissues (especially the skin) to pain and other stimuli differs from that of normal intact tissue. The first phenomenon observed in injured tissues is allodynia, the production of pain by a stimulus that previously was nonpainful. For example, lightly probing the withers of a horse does not usually elicit a response. However, gently stroking the same site in horses with severe dermatophylosis can elicit a vigorous, attention-getting twitch response. This is an example of allodynia. The second phenomenon is hyperalgesia, which occurs when previously painful stimuli produce pain of greater magnitude, duration, or area. Osteoarthritis is a condition associated with inflammatory hyperalgesia, in which weight bearing on already painful joints results in a greater degree of pain. Nonsteroidal antiinflammatory drugs are particularly effective in reducing hyperalgesia but have little effect on pain sensitivity in healthy tissues.

The phenomenon of hyperalgesia is a subject of considerable research. Current theories suggest that persistent tissue injury is mediated by numerous endogenous chemicals, which alter both the peripheral and the central nervous systems. Peripheral hyperalgesia occurs at the site of injury and is mediated by the release and conversion of arachidonic acid into prostaglandins (mainly PGE₂) and leukotrienes (mainly LTB₄ products). Together with bradykinin and histamine, these mediators render nociceptors hyperresponsive to noxious stimuli. Serotonin from platelets and mast cells, interleukins 1 and 8, and tumor necrosis factor from immune cells contribute to hyperalgesia. Retrograde release of substance P and calcitonin gene-related peptide from neighboring nociceptors amplifies the hyperalgesia. The sympathetic nervous system appears to be involved in hyperalgesia, as norepinephrine, released from sympathetic efferents, provides additional amplification. In fact, sympathectomies have been used to minimize certain types of intractable pain.

More recently adenosine (and other products of adenosine triphosphate [ATP] metabolism) and the excitatory amino acid glutamate have been implicated in the pain amplification cascade. The short-lived gaseous neurotransmitter nitric oxide is produced at inflammatory sites and by pain neurons in the central nervous system. Nitric oxide is formed by the action of nitric oxide synthase, an enzyme, on L-arginine. In fact, nitric oxide synthase inhibitors (e.g., L-NAME) reduce inflammatory pain in several laboratory animal species. Nerve growth factor has also been recognized as contributing to hyperalgesia. A number of these mediators appear to exist in horses and other species. Currently they are targets for pharmacologic intervention in the pain process.⁵

Hyperalgesia also appears to occur centrally within the spinal cord, mirroring the peripheral event. Many of the same transmitter substances released peripherally by nociceptors are released in the spinal cord. Persistent tissue damage triggers the release of substance P, and glutamate/aspartate from the intraspinal terminals of the nociceptors, activating NK-1 and NMDA/AMPA receptors, respectively. These powerful excitatory transmitters appear to lower the response thresholds of second-order dorsal horn neurons. This process appears to mediate both allodynia and hyperalgesia and is often referred to as secondary or central hyperalgesia. Recent evidence suggests that prostaglandins are also released into the spinal cord from peripherally activated nociceptors. Therefore nonsteroidal antiinflammatory drugs that inhibit prostaglandin synthesis may act at the site of injury and centrally to relieve inflammatory pain. Lastly, persistent tissue inflammation may recruit previously inactive neurons or silent nociceptors, which are quiescent in normal tissue. These nociceptors may further enhance the excitability of the spinal cord to peripheral pain.

The prevention of secondary hyperalgesia is of great interest in human and veterinary medicine. It has been proposed that if the barrage of sensory impulses from damaged tissue can be prevented from influencing the spinal cord, less central hyperalgesia should occur. This has been supported by the results of several studies. For example, intra-spinal administration of local anesthetics and opiates to animals before surgery results in less postoperative pain than if the same drugs are administered postoperatively. Thus, the preemptive use of analgesics and anesthetics may reduce postoperative pain and improve recovery from surgery. The relatively common procedure of lumbar puncture should lend itself well to preemptive analgesic therapy in horses and other large animals. From these approaches, it has been suggested that the developing nervous system remembers pain. Stated another way, pain changes the nervous system. Consequently, the long-term impact of surgery-induced pain should perhaps be reexamined.

Pain Transmission Within the Central Nervous System

The simplest pain responses are unconscious motor reflexes. These reflexes are segmentally controlled within the spinal cord and do not require conscious intervention. Animals whose spinal cords have been severed can still demonstrate withdrawal reflexes below the level of transection. Such reflexes normally serve to protect animals from injury.

Noxious stimuli are initially transduced by A-delta and C nociceptors, which then synapse with spinal cord dorsal horn neurons in several of the layers or laminae. Lamina I (i.e., the marginal zone), the most superficially located layer, receives A-delta and C fibers that carry pain and temperature information. Lamina II (i.e., the substantia gelatinosa) consists mostly of interneurons that integrate information from A-delta and C fibers from Lissauer’s tract. Warmth, cold, and pain are integrated and modulated in laminae III and IV. Lamina V and VI neurons are critical in pain processing and modulation. They receive information primarily from thermosensitive and mechanosensitive nociceptors and may project directly to the thalamus and brain. These neurons also receive input from descending brainstem pathways capable of modulating pain signals.⁶ The relatively superficial location of the pain pathways in the spinal cord helps explain the rapid and selective analgesia achieved after intrathecal administration of local anesthetics in horses.

The dorsal column pathway and spinothalamic tract are involved in conveying pain signals from the spinal cord to the brainstem or brain. There are species differences in the roles of each of these pathways. For example, the spinothalamic tract is more important in pain transmission in primates than in nonprimates. The dorsal column-medial lemniscus pathway carries information about pain, touch, and pressure. It is unique in that some nociceptors travel directly to the brainstem via this pathway, resulting in rapid contact between periphery and brain. The brainstem plays a key role in the autonomic responses to pain (see later). Cells from the medial lemniscus synapse with the intralaminar nuclei of the thalamus. The spinothalamic tract carries information about pain, temperature, and to some extent touch. However, spinothalamic tract cells originate mainly in lamina V and do not synapse with the brainstem. Instead they innervate the ventral posterior and other nuclei of the thalamus. The trigeminal nerve contains nociceptors that convey temperature and pain information from the face, jaw, teeth, tongue, and lips. These trigeminal nociceptors synapse with the nucleus of the spinal tract (similar to the spinothalamic tract) and go on to form the trigeminothalamic tract. This is a particularly important pathway in horses, considering that orofacial pain, applied through a bit, is used to command attention and control motor behavior. The spinothalamic tract pathways appear to play an important, albeit not exclusive, role in chronic burning pain states especially involving the polymodal nociceptors. Overall, it is generally believed that the lateral thalamus is involved in the discriminative sensory component of pain, whereas the medial thalamus mediates the emotional and motivational aspects of pain.⁷

Processing of pain in cortical sites may to some extent underlie species differences in the experience and expression of pain. Clearly the relative size and complexity of the cerebral cortex differs among animals. Modern functional imaging studies show that painful stimuli activate subcortical regions such as the periaqueductal gray, the hypothalamus, the amygdala, and the cerebellum. However, painful stimuli selectively activate cortical sites such as the insular and cingulate cortices, which receive input from the thalamus. It is interesting to note that the frontal and cingulate cortices of the cerebrum seem to be necessary for experiencing suffering. Early human studies have indicated that patients receiving frontal lobotomies were able to describe a painful stimulus but not to be concerned about it.^7,8

Types of Physical Pain

Pain has often been categorized as superficial, deep somatic, and visceral. Cutaneous or superficial pain tends to be definitive, well localized, and constant and may follow the distribution of somatic nerves. Deep somatic and visceral pain tends to be diffuse, dull, poorly localized, and periodic and elicits more pronounced autonomic changes. Visceral pain may also be referred to other deep or cutaneous sites.

It may be more relevant for the practitioner to identify pain in terms of its site of origin. Visceral, musculoskeletal, and cutaneous areas are perhaps the most recognizable sites for pain in large animals. Rapid distention, ischemia, pulling on the root of the mesentery, or high luminal pressure in any portion of the hollow viscus elicits pain behavior in horses and cattle. This is most rapidly characterized by biting, looking at, or kicking at the abdomen or thorax and probably reflects an attempt to remove the painful stimulus from the referred site. Dorsolateral rolling, whole body hyperextension, and groaning can be observed in horses with severe intestinal colic. Muscle pain can be induced by strenuous exercise, trauma, or sustained contraction. Alterations in weight bearing, abnormal body postures, and lameness and tenderness on palpation are the most recognizable signs. Severe rhabdomyolysis (“tying up”) certainly initiates dramatic changes in muscle tension. Joint pain accompanies acute traumatic, infectious, and degenerative arthritis and is associated with decreased range of motion, hypoactivity, and lameness. Cutaneous pain usually results from traumatic skin injury, bite wounds, or infections. Typically these sites of injury may be guarded, scratched, or licked. Exaggerated withdrawal or evasive reflexes may occur in an attempt to remove the noxious stimulus. Corneal pain can be elicited by chemical, thermal, or mechanical stimuli and is often accompanied by increased tear production and blinking. Dental pain, perhaps the only sensation in teeth, is difficult to detect in large animals but has been associated with head tossing, jaw opening, or mandibular activation. Whereas headache pain is of considerable concern in human medicine, there have been no systematic attempts to identify or characterize this phenomenon in large animals.

Autonomic and Emotional (Affective) Components of Pain

Affective, or emotional, responses to painful stimuli appear to vary widely in the animal kingdom and within a species. The neuroanatomic correlates of emotional pain involve higher brain functions and add another dimension to simple reflex responses. Humans experiencing pain often use terms such as exhausting, terrifying, sickening, cruel, and vicious. Changes in facial expression, body posture, and gestures signaling disgust, fear, and anger have also been described.⁹ These expressions serve to alert others to an individual’s condition of pain. Some of these human “emotions” may have large-animal counterparts. In addition to site-related motor responses, changes in temperament have been described.¹⁰ Animals showing aggression in the form of kicking, biting, striking, head butting, teeth grinding, fighting, and escaping may be in pain. Grunting, moaning, or squealing may be heard. On the other hand, some individuals may appear docile and defeated. Changes in facial expression such as dull eyes; drooping eyelids, ears, and head; excessive tears; and hyperresponsiveness to light or sound may be observed. Thus, animals and humans may share the fear-, anxiety-, and anger-associated expressions of pain.

Along with the expression of pain behaviors, autonomic disturbances in homeostasis occur. It is worth noting that some nociceptive dorsal horn neurons synapse with the pontine and midbrain reticular formation, the lateral periaqueductal gray, the ventral medulla, and the hypothalamus. Nociceptive activation of the ventral medulla results in increases in heart rate, respiratory rate, and blood pressure. Activation of the hypothalamus results in the release of vasopressin and adrenocorticotropic hormone (ACTH), which affect hemodynamics and blood glucose concentration. Stimulation of the reticular formation results in enhanced vigilance and attention. Activation of the periaqueductal gray results in recruitment of an endogenous, descending pain suppression system (see endogenous pain suppression later), which “attempts” to modulate the intensity of painful stimuli at the level of the spinal cord. These gross autonomic and metabolic responses contribute to the aversive and arousal nature of the painful experience.

In addition to its aversive quality, pain can motivate and be learned and avoided by animals. The application of acute pain is used universally to control equine behavior. Common examples include the use of a bit to coerce movement, the application of a whip to increase racing performance, the application of a twitch for restraint, and sole “soring” to increase gait animation. There is little doubt that the average horse learns and remembers the aversiveness of these stimuli and “works” to avoid them. However, acute pain (e.g., kicking, biting) is inflicted conspecifically to establish social and reproductive dominance within a herd. Pain can also be used to subdue adversarial predators. Past experiences can profoundly influence the affective response to pain. Factors such as anticipation, anxiety, and fear can negatively influence future pain response. Horses that appear “head shy” after years of abuse have learned, all too well, how to detect and avoid imminent tissue injury.

Acute Pain

Pain of short duration alerts animals to potential injury and is adaptive for survival. It is also a signal to stop using injured tissues, to promote healing. Acute pain usually elicits quick behavioral action and resolves without a significant disruption in homeostasis. Acute pain may be caused by environmental stimuli, trauma, surgery, acute medical conditions, or normal physiologic processes (e.g., parturition). A common constellation of signs may be seen in large animals. Neurologic signs include behavioral excitement, confusion, tremors, rigidity, twitching, hyperreflexia, and ataxia or immobility, paralysis, and inertia. Cardiorespiratory signs include hypertension, tachycardia, vasospasm, venous stasis, and tachypnea. Gastrointestinal hypomotility or hypermotility, urinary retention, sweating, and hyperthermia may also occur. Acute pain of a more debilitating nature may produce more profound changes in posture, temperament, and locomotion. Head and neck ptosis, rolling on the ground, hyperextension or hyperflexion of the body and neck, widened stance, and prolonged sternal or lateral recumbency may be observed. A spectrum of emotional reactions from aggressiveness, anxiety, self-mutilation, and vocalization (moaning, grunting) to marked depression may occur. Specific lamenesses and weight-bearing deficits may accompany more specific musculoskeletal insults.¹⁰

Chronic Pain

Fortunately, most acute pain resolves and homeostasis is restored. However, extensive tissue injury or disease may result in pain that persists for days or weeks. Such pain is often associated with inflammation and accompanying allodynia and hyperalgesia. Pain states that persist for months, even after healing has occurred, are classified as chronic. Chronic pain often includes a continuation of the acute manifestations described previously. However, more global, systemic changes emerge as unabated pain continues.

Chronic pain can be best assessed by noting changes in eating, sleeping, social behavior, reproductive activity, personality, growth and performance, body position, and activity level and certain physiologic signs. Chronic unrelieved pain may result in depression, inappetence, weight loss, and reduced growth or milk production (e.g., in cows or goats). Musculoskeletal pain may actually impair mobility and prevent normal social competition for food, contributing to further weight loss. Disruption in sleep-wake cycles may add to the overall debility. Psychologic alterations expressed as personality changes toward an owner or cohort may emerge, along with a positional change in the herd hierarchy. Conspecific grooming and other social interactions may decline as well. Signs of psychomotor stress may develop including trembling and rigidity, as well as stereotypies such as pacing, head shaking, pawing, scratching, and stall walking.

The persistent disruption in homeostasis may have serious long-term consequences. Increased release of cortisol, catecholamines, and renin is associated with pain and other forms of distress. These hormonal responses can impair normal cardiovascular function and may contribute to hypertension. In fact, acute changes in plasma concentrations of cortisol, catecholamines, glucagon, blood glucose, insulin, β-endorphin, lactate, and growth hormone have been used as indirect measures of pain. Depending on the site of pain or injury, prolonged recumbency in large animals can result in pulmonary congestion, hypoxemia, pneumonia, and altered thermoregulation. Data also suggest that chronic pain may be immunosuppressive.

Although the use of analgesics for pain relief is not discussed in this chapter, it is worth noting that analgesics can be used to diagnose pain. Opiates elevate the nociceptive threshold by preferentially inhibiting dorsal horn neurons in pain reflex pathways. This in part explains their ability to dull pain sensations. This occurs without altering other sensory modalities (e.g., touch, pressure). Opiates also activate (1) descending brainstem inhibitory pathways, which alter spinal pain transmission, and (2) ascending pathways to the nucleus accumbens, amygdala, frontal cortex, striatum, thalamus, hypothalamus, and ventral hippocampus.¹¹ These latter sites are intimately associated with emotionality and the affective and autonomic responses to pain. Therefore, relief of the aforementioned behavioral signs and symptoms by opioids is indirect evidence that pain contributed to their expression.

Are Animal and Human Pain Equivalent?

Whether nonhuman animals feel pain the way humans do continues to be debated, along with the need for analgesics. Arguments favoring a difference include the following:

The relative speed with which animals recover from major surgery

Stoicism in the face of severe injury

Anatomic differences in pain pathways

Lesser-developed cortices in nonhuman animals

Unusual responses to some analgesic drugs

Arguments favoring a similarity include the following:

The hypothesis that stoicism is adaptive and reflects a difference in pain expression rather than perception.

Acute and chronic pain symptoms and sequelae are similar.

Autonomic and endocrine responses to pain are similar.

The same chemical, thermal, and mechanical stimuli elicit pain in humans and animals.

The same pain-mediating neurotransmitters and modulators are present in humans and animals.

There are qualitative similarities in the neuroanatomic pain pathways.

Surgical procedures (e.g., auricular, thoracotomy) and diseases (e.g., arthritis, pancreatitis, colic) that are painful to humans are also painful to animals.

Opioids are universally analgesic.

Although these arguments persist, many large animal practitioners avoid using analgesics because they mask symptoms and impair the diagnosis of underlying disease. Drugs such as nonsteroidal antiinflammatory drugs may also produce serious side effects such as gastric and abomasal ulcers. On the other hand, public and regulatory agencies insist that animal pain be recognized, avoided, and treated whenever possible.

Endogenous Pain Suppression

The expression of pain seems to differ widely across and within animal species. Some animals (and humans) cry out at the slightest provocation, whereas others seem to endure traumatic insults interminably. Most veterinary practitioners have had the misfortune of observing a horse finish or perhaps win a race, undeterred, with a fractured cannon bone. One may ask how this occurs. There is growing neurochemical and neuroanatomic evidence for the existence of an endogenous pain suppression system with segmental and suprasegmental components.

The segmental component is thought to exist within the dorsal horn of the spinal cord. It is probably this system that we activate when we lightly but vigorously rub a recently acquired bruise for pain relief. The licking or light rubbing of a fresh wound by an animal would represent the corollary process. The light touch or vibration stimulates larger-diameter, A-beta mechanoceptive afferents at or near the site of injury. At the same time, A-delta and C fibers are transmitting nociceptive signals from the injured site. These fibers somatotopically converge on a common spinothalamic tract cell. However, the A-beta fiber is thought to activate an inhibitory interneuron en route to the spinothalamic tract cell. Thus, the large fiber damps down or closes the gate to pain signals delivered by the neighboring nociceptor. This formed the basis of the Gate Control Theory of Pain by Melzack and Wall.¹² This theory has also been advocated to explain the operation of transcutaneous electrical nerve stimulation devices. These devices deliver nonnoxious electrical stimuli to the skin via electrodes placed at or near injured or inflamed sites. The direct current (DC) electrical current activates mainly large-diameter, cutaneous, low-threshold mechanoceptors, which damp down nociceptor input from converging dermatomes. Variations in impulse magnitude, shape, frequency, and duration are selected to maximize this effect. Transcutaneous electrical nerve stimulation devices are used routinely in human medicine and by racetrack practitioners to reduce inflammatory pain.

For function in the face of severe pain and distress, certain endogenous coping mechanisms exist that modulate the intensity and quality of pain. The best understood of these is the descending pain suppression system. This system consists of a family of descending neurons from the hypothalamus, midbrain periaqueductal gray, rostral ventromedial medulla, and dorsolateral pontine tegmentum. These pathways form a cascading neuronal circuit that ultimately influences activity in pain-sensitive spinothalamic tract cells in the spinal cord dorsal horn. The neuronal components of this descending system are activated by pain and other stressful stimuli.¹¹

The command center of the system is the periaqueductal gray. The periaqueductal gray contains both opiate receptors and enkephalins. Enkephalins are small, short-acting peptides that bind to opiate receptors and mimic the actions of morphine. In fact, the name is derived from the term endogenous cephalic peptide. Activation of or application of morphine or enkephalin into the periaqueductal gray activates the rostral ventromedial medulla. The rostral ventromedial medulla then releases serotonin from its terminals in the spinal cord dorsal horn. Serotonin is an indoleamine neurotransmitter involved in the control of mood, vigilance, sleep, and pain threshold. Once released into the spinal cord, serotonin activates specific dorsal horn interneurons that contain enkephalin. The enkephalins then act on opioid receptors located on pain-responsive neurons in the spinal cord. Stimulation of these opioid receptors inhibits the pain-responsive cells, rendering them less excitable by nociceptive signals from the periphery. The periaqueductal gray also activates the dorsolateral pontine tegmentum, which sends its norepinephrine-releasing neurons to the dorsal horn as well. The norepinephrine acts on α₂-receptors also located on pain-sensitive neurons, inhibiting them. Thus, three separate neurotransmitter systems play a role in endogenous pain modulation-serotonin, enkephalin, and norepinephrine. Activation of these systems ultimately results in inhibition of pain reflexes and pain sensations (i.e., analgesia).¹¹ This mechanism not only explains how pain can induce endogenous analgesia, but also how intrathecal and systemically administered morphine and xylazine relieve pain.

Another important morphine-like peptide involved in the production of endogenous analgesia is β-endorphin. Pain, parturition, exercise-stress, acupuncture, and surgery increase circulating levels of this pituitary hormone along with ACTH. β-Endorphin, which can be detected in plasma and cerebrospinal fluid, is larger and longer-acting than enkephalin and also binds to opioid receptors. It produces analgesia when administered, and its effects can be blocked by the opioid antagonist naloxone. Endorphins are involved in regulating pain threshold in horses, as they follow the same diurnal rhythm.¹³ Plasma concentrations of endorphins and pain threshold also appear to increase after strenuous exercise in thoroughbred horses.¹⁴ Endogenous opioids are also present in the gastrointestinal tract and are thought to modulate muscle tone and possibly sensation. We believe that this system is operative in the horse, as we have observed colic pain and diarrhea in horses receiving the opioid antagonist naloxone.¹⁵

Approach to Diagnosis of Abdominal Pain

Diseases characterized by abdominal pain occur commonly in horses and ruminants. In most instances the painful stimuli originate secondary to an intestinal obstruction or malposition (Boxes 3-1 and 3-2). In male or castrated male sheep and goats, the most common cause of abdominal pain is urolithiasis. When the pain is intestinal in origin, there may be distention of the intestinal wall with gas or ingesta, increased tension on the mesentery, or ischemia of the intestine. The clinical signs exhibited by the animal depend on the species, the age of the particular animal, and the severity of the underlying cause. The presence of abdominal pain may be characterized by outward clinical signs ranging from mild depression to repeated pawing or stamping of the feet to violent behavior. For example, in the horse many problems can cause abdominal pain, ranging from distention of the cecum with gas to simple obstruction of the intestinal lumen with ingesta to strangulation obstruction of the intestine (see Colic, Chapter 7). Consequently the clinical signs exhibited by the horse may range from repeated pawing with a front foot and turning around to look at the abdominal region to uncontrollable rolling and thrashing. Although the severity of the clinical signs exhibited by the horse tends to correlate with the severity of the underlying problem, exceptions to this rule occur commonly. Thus, the importance of performing a thorough physical examination in these instances cannot be overstated. Finally, the age of the animal must be considered in light of the clinical signs manifested. For example, the foal frequently swishes its tail from side to side and rolls up onto its back as part of its characteristic response to the presence of abdominal pain. In addition, bruxism is not an uncommon manifestation of pain in foals. Abdominal pain caused by liver disease is uncommon; however, it can occur in cases of severe hepatic lipidosis (especially in ponies and miniature horses). In horses with cholelithiasis, intermittent abdominal pain is the most common clinical sign, presumably resulting from bile duct distention.¹⁶

Approach to Diagnosis of Chest Pain

Generally pain associated with conditions involving the pleural cavity is severe. The painful stimuli usually originate from the inflamed parietal pleura because few nociceptors are present in the visceral pleura. Because of the primary involvement of the parietal pleura, the pain is referred to a site directly overlying the thoracic wall. Consequently, if the focus of inflammation is relatively well localized, as occurs with traumatic reticuloperitonitis-pericarditis, sensitivity to externally applied pressure may be restricted to one area of the chest wall (Box 3-3). If, however, the inflammation is generalized, as in equine pleuropneumonia, pain may be elicited by applying digital pressure over several sites. Similarly, because movement of the inflamed tissue accentuates the production of painful impulses, the animal remains stationary and is reluctant to lie down; the elbows are abducted; the chest wall is splinted; and the respiratory excursions are shallow, rapid, and accompanied by grunting. It is common that the severity of pain is reduced as the volume of pleural effusion increases.

Chest pain may also develop acutely as a result of pulmonary arterial thromboembolism in cattle (Box 3-4). Presumably the acute development of pulmonic ischemia in such instances causes the local generation and release of several proinflammatory substances. Most of these problems occur secondary to thrombosis of the caudal vena cava.

Although less dramatic than that accompanying either pleuropneumonia or thromboembolism, pain also accompanies pneumonia and pulmonary contusions. The pain associated with pneumonia occurs secondary to pleural irritation and is well localized only if the parietal pleura is involved. Because the pain appears to be most evident during forced respiratory excursions, splinting of the thorax is common. Chest pain may also occur secondary to traumatic incidents. Although rib fractures occur rarely in horses and ruminants, they must be given some consideration in an animal exhibiting clinical signs of chest pain. Rib fractures occur more commonly in neonatal foals during birth and may result in respiratory distress. Obviously the force required to fracture a rib will cause severe bruising and inflammation of the underlying pleura.

Approach to Diagnosis of Pain in the Extremities

Although the reflex contraction of flexor muscles occurs with all types of pain, this reflex is most evident with pain in the extremities. Thus, as a result of a painful stimulus and to minimize the continued stimulation of the nociceptors in the affected area, the animal alters its stance or gait to protect the source of pain. Therefore, it is vital that the animal be inspected initially from a distance to determine which limb is involved. It may be necessary to move the animal at either a walk or a faster gait to identify the affected limb. It is important for the clinician to recognize that (1) the painful impulses may originate from several tissues in the extremity, including the skin, joint, periosteum, muscle, and the sensitive laminae of the distal phalanx; and (2) several factors may be contributing to the source of the pain. These factors may represent a particular conformational, breed, or familial predisposition toward development of the condition, the effects of nutritional imbalances on the development or stability of either bone or soft tissue, the effects of the use or performance of the animal, the possible involvement of infectious agents, and the effects of trauma (Boxes 3-5 and 3-6).

Careful palpation of both the soft tissues and the bones of the limbs must be performed to identify sources of inflammation or pain. Furthermore, the responses, if any, to flexion and extension of the joints must be evaluated, and the examination performed in a systematic manner. It may be necessary to inject a local anesthetic over a sensory nerve or into a synovial structure (joint, tendon sheath, bursa) to prevent the conduction of pain impulses to the central nervous system. The judicious use of local anesthesia combined with a careful physical examination should allow the affected site to be identified. On the basis of this information, the clinician can then make efficient use of other diagnostic aids (radiography, synovial fluid analysis, scintigraphy, ultrasonography) to determine the underlying cause of the pain and direct therapy accordingly.

Approach to Diagnosis of Back and Neck Pain

The association between pain arising from either the back or the neck and irritation of spinal nerve roots has not been as well established in large animal species as it has in small animals and people. However, there is considerable evidence that muscle damage, ligamentous strain, sacroiliac strain, and either fracture or overriding of the dorsal spinous processes of the thoracic vertebrae cause varying degrees of back pain in horses.^17,18 Attention must be given to the detection and treatment of exertional rhabdomyolysis in horses and postanesthetic myopathy in horses and cattle (Boxes 3-7 and 3-8). Each of these conditions is characterized by painful impulses originating from ischemic or damaged muscles. Similarly, the development of nutritional myopathy associated with selenium deficiency must be considered in horses and ruminants in certain areas of the country. All large animals are susceptible to traumatic incidents that may result in fracture of either cervical or sacral vertebrae. Horses occasionally rear up and fall over backward, fracturing the sacrum or dorsal processes of the thoracic vertebrae. Cattle fracture the pelvis or develop sacroiliac luxations when they slip on concrete floors, often when mounting is occurring during estrus.

Neck pain is frequently manifested by splinting and unwillingness to eat from the ground or assume any but the most benign neck position. Trauma is the most common cause, but meningitis may also cause severe neck pain.

Approach to Diagnosis of Pain on Urination

Although the term dysuria means difficult urination, its use has become synonymous with pain on urination. The painful impulses may arise from distention of the wall of the urethra, bladder, or pelvis of the kidney or irritation or spasm of the urethra. The most common causes of dysuria are inflammatory or obstructive conditions involving the urethra (Boxes 3-9 and 3-10). Thus, care must be exercised to identify uroliths, strictures, urethritis, vaginitis, neoplasia, or fractures involving the pelvic bones. Because urethritis may coexist with other inflammatory conditions involving the urinary tract (e.g., cystitis, pyelonephritis), the diagnostic plan should include physical and laboratory assessments of the kidneys, ureters, and bladder. Urine should be collected for urinalysis, culture, and sensitivity testing. A rectal examination should be performed to detect vesical calculi, tumors, and alterations in the architecture of the kidneys or the size of the ureters. In many cases ultrasonography will be used to evaluate the kidney. Because the severity of pain can resemble that associated with acute abdominal obstruction, the physical examination must be thorough.

Urolithiasis occurs more commonly in ruminants than in horses. Of the ruminants, young feedlot steers less than 18 months of age and male sheep and goats (intact or castrated) appear to be at the highest risk. There is an association among sorghum feeds, diets high in magnesium, and the development of the condition. In horses, urinary calculi occur most commonly in geldings, and straining to urinate is the most common clinical sign. Rectal examination of the bladder, endoscopic examination of the urethra, and urinalysis are important aspects of the diagnostic plan. Most calculi in horses are rough, calcium carbonate stones, whereas most calculi in ruminants are magnesium ammonium phosphate, calcium phosphate, carbonate, or silicate in composition (see Chapter 32). Rupture of the bladder, the urethra, or occasionally the ureter may occur secondary to the obstruction.

Straining to urinate is a common clinical sign in newborn foals with a ruptured bladder. This condition generally occurs after the first 24 hours of life, occurs most commonly in males, and involves the dorsal aspect of the bladder. Presumably the rupture occurs during parturition. The diagnosis is facilitated by comparison of creatinine concentration in the blood and peritoneal fluid and by determination of serum electrolyte status. Most foals with the condition are hyperkalemic, hyponatremic, and hypochloremic.