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Veterinary Forum March 2008 (Vol 25, No 3)

Share Their Pain: Science and art combine to control the many pathways of pain

by Paul Basilio

    Sometimes change can be painful. In the field of pain management, however, a little change can bring welcome relief.

    Not long ago, veterinarians were taught that a little pain was good — pain would keep the patient still and it would be less likely to reinjure itself.

    This is no longer the case. Changes in the field of veterinary pain control are similar to those made in human pediatric medicine, according to Cindy Hatfield, DVM, MSc, assistant professor of anesthesiology at the Virginia-Maryland Regional College of Veterinary Medicine in Blacksburg, Va. "Only 10 to 20 year ago, the thought was that young children did not feel pain," she says. When infants were circumcised, it was assumed they did not need analgesia because their nervous system was not fully developed.

    Today, both physicians and veterinarians are more aware of how animals and infants feel pain, and they feel it to the same degree as adult humans do.

    "I think you have to anthropomorphize," says Karol Mathews, DVM, DVSc, DACVECC, professor and service chief, emergency and critical care medicine at the Ontario Veterinary College in Guelph, Ontario, Canada. "The pain pathways are similar in cats, dogs and humans. Cats and dogs will withdraw from a given stimulus that causes pain at a similar point that a human would. Therefore, an assumption can be made that if it hurts us, it will hurt them."

    The benefits of pain relief go beyond the simple reduction of physical pain, Mathews says. "The neuro­endocrine response to pain, which is fired up constantly during times of pain, results in a profound catabolic state as a result of the added stress. In addition, the response to ongoing pain causes the heart rate to remain high, which eventually results in a lower cardiac output because of increased myocardial oxygen consumption and insufficient time for ventricular filling.

    "It's like a sprinter," Mathews says. "The work the heart has to undergo and the oxygen consumption are maximal. Can you imagine trying to sustain those? Just because the animal is not running doesn't mean its body is not undergoing the same processes."

    An animal can end up being consumed by the ambience of pain, she adds. "There isn't enough reserve to deal with the normal healing process, so delayed healing occurs and because of a blunted immune response, the animal becomes more susceptible to infection."

    Mathews recommends automatically presupposing that an animal is in pain, especially in the case of inflammatory medical pain (e.g., pancreatitis) or trauma as well as following any surgical procedure.

    The difficulty most veterinarians face is that animals can't verbally express their pain. Veterinarians, therefore, must rely on behavior and physiologic responses that aren't dependable — another similarity between pediatric and veterinary pain management.

    It's a barrier that frustrates and discourages many veterinarians from focusing on pain, which is now referred to as the fifth vital sign.

    "You may not always see a patient vocalize, but rather a depressed patient that is motionless," Mathews says, noting that animals, particularly cats, can be sitting quietly in a cage while feeling pain and then suddenly start thrashing around. "Interacting with patients is very important, as their responses usually will let you know if they hurt before the pain becomes severe. However, a tail wag from a dog may still indicate pain, and a motionless cat may still purr when it is in pain, so you can't use these behaviors as a guarantee that pain doesn't exist."

    Veterinarians should search for pain in every examination, according to Karen Faunt, DVM, MS, DACVIM, vice president and chief medical officer at Banfield, The Pet Hospital. "You can look for clues," she says. "You can see how the pet moves around the examination room and how it interacts with you — whether it is seeking attention or hiding. If the client notices a change in behavior or activity level, that can be a sign of pain. If you're anticipating pain, you can usually find it based on how the pet is trying to relate to you."

    Technicians also play a large part in pain detection and management, experts say.

    "They are often the ones who are on the front line, sitting with the pet while it recovers, taking it for walks or cleaning out its cage," Faunt says. "They are usually the ones who can notify the doctor that Sparky isn't sleeping well or is starting to whine, and they may see other unusual behaviors and know that it's time to reevaluate pain control."

    Mathews agrees: "Because technicians spend more time with the patient, they can see progression or regression. If they tell you that you need to give Bozo an analgesic, then you should give Bozo an analgesic. Technicians play a huge role in pain management."

    However, it can be difficult to distinguish pain from anxiety. Physical markers, such as excessive panting, vocalization and increased respiratory or heart rate, can be present with either. Physiologic markers, such as high cortisol levels, are unreliable because they occur in response to pain and anxiety.

    "We have to assume that some animals are going to be upset about where they are," Mathews says. "If we've given an appropriate amount of analgesic for the procedure performed [and they still appear nervous], we will give them a sedative. The combination of an analgesic and a sedative works well."

    Some veterinarians were taught that analgesics can mask other problems, Mathews continues. "But actually they unmask problems. You can't blame pain for causing a high heart rate [after giving appropriate pain medication], so you have to look for something else, such as low blood pressure. If no other problems are identified, then further analgesic requirement must be considered."

    Faunt says that when in doubt, administer pain control and wait for improvement. "In general, if you feel a pet may be in pain, it's much better to treat it and see if the pain goes away than to wait and continually wonder if the animal is still in pain."

    The highways and roadblocks

    Pathophysiologic pain occurs after tissue injury, something that happens each time an animal has surgery or is involved in a traumatic event.

    "This type of pain serves no purpose except to tell you that it's there," Mathews says.

    When tissue is injured initially, transduction occurs. Cutaneous or visceral nociceptors transmit a signal up the peripheral nerve to the spinal cord dorsal horn, which acts as a junction for pain transmission to the thalamus. Before the sensation moves to the brain, N-methyl-d-aspartate (NMDA) receptors in the dorsal horn receive the pain signals through various chemicals, facilitating transmission along the spinal cord, where modulation occurs, and then onto the thalamus and cortex, where pain is perceived.

    The dorsal horn is an important area where "windup" occurs. "If I keep hitting you with a hammer, you're going to have all these signals going to the dorsal horn," Mathews says. "Various transmitter and chemical interactions occur to increase the excitability of neurons and enhance recruitment of wide dynamic-range neurons — called central sensitization — so more signals travel through the spinal cord to the brain, where it is perceived as worsening pain. What we need to do is stop this because that's what heightens the sense of pain, or hyperalgesia."

    Windup pain can be difficult to treat both during and after surgery, and the pharmacologic approach to managing pain is to consider what pain the animal is already experiencing and for how long, as well as what pain can be expected postoperatively.

    "When we're looking at selecting an anesthetic or analgesic after surgery and want to stop this windup from carrying on, we include ketamine," Mathews says, noting that ketamine blocks these receptors before pain signals can reach the brain. Many drugs can block transmission to the brain, such as local anesthetics, NSAIDs and opiates, but low-dose ketamine is often effective when included in a multimodal analgesic plan, she says.

    "Often we'll see orthopedic cases in which a dog is hit by a car 2 or 3 days before presentation," Hatfield says. "These are difficult pain control cases because they haven't had adequate pain management and have experienced a lot of central sensitization. It takes much higher doses of both opioids and anesthetic gas to keep them comfortable in surgery. You see a difference in pain level from a routine elective orthopedic case as opposed to a fracture that has been cooking for a couple days before the animal goes to surgery. There is a lot of windup at the level of the dorsal horn in those particular animals."

    Peripheral nerves serve two functions, Mathews says. The A-delta and C fibers transmit pain, but the A-beta pathways generally do not. These pathways inform the brain that the body is touching a desk or walking by a doorway, for example. "If I tap you, it's not going to hurt — but if I thump you, it's the first two pathways that send this message to the brain," she explains. "With constant pain, the A-beta pathways are recruited and begin to transmit pain, making every sensation hurt, which is called allodynia. This also is part of the neuropathic pain complex.

    Chronic pain can become established in animals that did not receive adequate pain medication for surgical procedures. This has been reported in humans, Mathews says, but there is no way to prove this in animals, although she has suspected it in some cases. "And the thing is," she says, "there's no way to correct this. The animal is hardwired for that now. Even though the initiating peripheral component is cured, the 'pain' program is established in the thalamocortex."

    Mathews offers that the brain is like a major metropolitan city — one with several major highways leading into it. If you block one highway, traffic can still get in another way. To block traffic completely, you need to block as many of the highways as possible. "It's exactly the same approach with pain," she says. "You have to block all pain highways to eliminate the pain, and each highway can be blocked by administering a different drug."

    Anesthesia and analgesia can play a large role in blocking those roads and managing postoperative pain.

    "We can inhibit the impulse condition at the site of surgery using local anesthesia techniques," Hatfield says. "For example, we can inhibit the transduction of pain and peripheral sensitization of nociceptors with the use of preoperative NSAIDs, opioids and regional local anesthetic blocks. We can work on the level of the spinal pathways to modulate the central sensitization with locals, opioids and epidurals."

    By using small amounts of different drug classes, Hatfield says anesthesiologists can provide patients with better overall intra- and postoperative pain management than could be achieved by using only one.

    "When I was training about 11 years ago," she adds, "we gave a little bit of preemptive analgesia before surgery, ran lots of gas and then gave the patient something to wake up on."

    Hatfield explains that by using small amounts of opioids incrementally and with a constant-rate infusion of drugs like ketamine, anesthesiologists can use a much lower minimum alveolar concentration (MAC) for patients, which means the animals wake up quicker, are more comfortable and are not as hypotensive or cold. Animals also are having pain pathways continuously blocked pre-, intra- and postoperatively.

    Hatfield related a case involving a dog with a radius"ulna fracture that was given 0.75% isoflurane and a RUMM block for the radial, ulnar, median and musculocutaneous nerves on the medial and lateral sides of the distal humeral epicondyles using bupivacaine. "The dog had an opioid [before anesthesia] and a little bit of acepromazine, but we were able to manage it on a significantly lower inhalant concentration than we would have had we not followed that technique." With appropriate postoperative pain medication, animals can actually use the limb postsurgery.

    Mathews adds: "Most of these drugs prevent the transmission [of pain signals] to the brain. The relay station to the cortex is the thalamus. It's important to try to block that. The gas anesthetics only block transmission from the thalamus to the cortex — perception — during the surgical procedure but will not prevent establishment of pain through other pathways to the thalamus, which will be felt when the gas anesthetic is removed."

    Fear of the art

    The science of pain management is inexact, and the looming dread of overdosing a patient sits heavily with some veterinarians.

    "A lot of it is science, and a lot is art," Hatfield says. "I think it comes with experience. I have met practitioners who still think that a little bit of pain is good and are reluctant to give opioids for fear of respiratory depression and further debilitation of the animal."

    She notes that there have been reports of respiratory depression in some of the higher published doses, but for an animal in extreme pain, it is not a big concern, even in cats. "I have never seen a cat that truly was in pain become dysphoric on opioids," she explains. "If they start to get a little wound up, it's usually because they have been slightly overdosed or the dosing interval hasn't been long enough, and you can treat that with some sedation to get them over the rough part."

    Hatfield says that some veterinarians tend to withhold opioids in cats because they fear the drug will make the patient "crazy," but she warns that a cat with a severe fracture or that is undergoing involved abdominal surgery will need more than an NSAID for proper pain management.

    "Sometimes what we end up doing is experimenting [with dosing]," Mathews says. "If a patient vocalizes after repeated opioid administration, you'll say, 'Okay, I've given him two lots of this stuff, and this procedure shouldn't require any more of it, so maybe he is anxious. I'll give him a little sedative, and if that doesn't settle him down, then maybe I've given him too much of the opiate so I'll titrate a diluted opiate reversal agent very carefully and observe the response.' It's like baking. You need a little more of this and a little more of that, then you've put too much of one thing in and now you need some more flour." With a little experience, she says, the art of pain management becomes easier.

    For veterinarians who haven't focused enough on pain, experts agree that continuing education is vital. "Many of the patients are in the hospital for something that has to do with pain," Hatfield says. "One of the major things a veterinarian should focus on is understanding and being comfortable with treating them for pain."

    Mathews says that some fears that veterinarians associate with pain management can be traced to a patient's adverse reaction to a treatment in the past or to the potential adverse effects noted with all analgesics.

    "Just because an unpleasant experience happens should not deter a doctor from trying again. The first time I started using various analgesics in the 1980s I was a little apprehensive, too, about drugs I was unfamiliar with. But by understanding, recognizing, treating and stopping pain, one gains confidence in its management. Now when I see an animal in pain, my goal is to stop it, whatever drug it takes."

    Drs. Mathews, Hatfield and Faunt reported no potential conflict of interest relevant to this article.

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