We give and receive love and companionship from animals, have them as members of our families and know that they can suffer pain, fear and distress. Animal pain may very well be worse than human pain since animals cannot speak and cannot reason or understand why they hurt. The outdated premise that animals don’t feel pain or that pain is good because it keeps them from ruining the veterinarian’s work or that we should make an animal prove it is painful rather than giving it the benefit of the doubt by treating it are thankfully considered unethical these days. Lack of pain management in animals not only damages the health and well-being of animals, but it also can cause stressors that affect wound healing, resistance to infection and even death. Animals do fear pain. Pain management is fast becoming one of the most important areas of veterinary medicine today. The veterinarian's and the veterinary technician's oaths both pledge "...the protection of animal health and welfare, the prevention and relief of animal suffering." Being members of the veterinary profession obligates us to eliminate or at least manage pain and doing so should be one of our top priorities.
Pain is considered the fifth vital sign after temperature, heart rate, respiratory rate and blood pressure. The International Association for the Study of Pain's widely used definition states: "Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." Pain can serve as the body’s warning system. Most pain will resolve once the cause is removed and the body is allowed to heal. Sometimes however, pain continues even after the painful stimulus is removed and healing has occurred. Some types of pathologic pain will occur without an apparent stimulus, physical pathology, damage or injury. Pain can be divided into three categories: physiologic, inflammatory and neuropathic. Physiologic pain, like that from a needle prick, exists to protect the animal. Inflammatory pain is caused by tissue damage. Neuropathic pain is a syndrome that is caused by abnormal somatosensory processing by the peripheral and central nervous system. The focus of this article is to introduce the reader to the pathology behind neuropathic pain as well as to explore treatment options.
Pathophysiology of Neuropathic Pain
Neurons in the pain pathway communicate information by chemical signaling using neurotransmitters. These chemicals have receptors and become potential targets for drugs to provide analgesia. We can think of these neurotransmitters as a sensitizing soup that contains hydrogen and potassium ions, enzymes such as proteases, cyclo-oxgenase2 (COX-2), nitric oxidase synthase (NOS), prostaglandins, cytokines (interleukin-1, interleukin-6, tumor necrosis factor), growth factors (nerve growth factor), histamine, bradykinin, serotonin and noradrenaline. This soup not only stimulates nociceptors in the area but also lowers the pain threshold of these nociceptors. There are excitatory and inhibitory neurotransmitters involved in pain transmission and modulation that dampen or amplify pain signals. These chemicals are produced, stored and released in the terminals of afferent nerves entering the spinal cord and interneurons in the dorsal horn. When the pain pathways become stimulated and continue to be stimulated, they can show changes in how they respond such that what might typically be a non-painful stimulus (such as the touch of a feather) becomes a painful sensation. When a stimulus that is generally non-painful becomes painful, that is termed allodynia. Hyperalgesia is an increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves. Hyperpathia is a clinical symptom of certain neurological disorders where painful stimuli produce exaggerated levels of pain.
Hyperalgesia and allodynia together make up what is called central sensitization or dorsal horn wind-up. It is important to remember that although general anesthetics block the perception of pain, the events in the dorsal horn are not blocked. The potential for central sensitization is always present unless steps are taken to prevent it. Once wind-up (central sensitization) has been established during a surgical procedure, it will continue to evolve after removal of the general anesthetic and into recovery if nothing is done to prevent it.
Neuropathic pain has no beneficial purpose and can be difficult to diagnose in veterinary patients. We can see different symptoms due to the various sensory pathways affected. We can see the emotional aspects of pain, in addition to the sensation of pain producing a change in personality. Sometimes it is dullness or aggression, along with obvious pain signs like whining, that we notice. Neuropathic pain is frequently associated with chronic pain, but it can occur in the acute setting as well. The best way to help prevent neuropathic pain in the acute setting is to ensure appropriate intervention is used before, during and after the surgery or painful stimulus to prevent debilitating neuropathic pain from developing.
In humans, neuropathic pain is diagnosed based on history and examination findings. Five out of eight of the following are required to diagnose neuropathic pain in humans:
- History consistent with nerve injury
- Pain within but not necessarily confined to an area of sensory deficit
- Pain in the absence of ongoing tissue damage
- Character of pain: burning, pulsing, shooting or stabbing
- Paroxysmal or spontaneous pain
- Associated dysesthesias (abnormal sensations)
- Allodynia, secondary hyperalgesia, or hyperpathia
- Associated autonomic features
Obviously it is difficult to apply all of the above criteria to veterinary patients but select parameters can be applied. With diligent history taking and a thorough sensory examine, the above criteria can be loosely applied to veterinary patients. There are many opportunities for neuropathic pain to develop in veterinary patients. The following are just a few scenarios: amputation, lumbosacral lesions, limb nerve entrapment during fracture repair, nerve entrapment in pelvic trauma or fracture, tumors involving the peripheral nervous system, spinal cord injury, intervertebral disc herniation, diabetic neuropathy, tumors of the central nervous system, vasculitis involving the meninges and spinal cord, feline interstitial cystitis, inflammatory bowel disease and pancreatitis. However, this list is by no means all-inclusive.
Therapeutic Approach to Neuropathic Pain
The best way to treat neuropathic pain and central sensitization is to prevent it with the many modalities at our disposal. Central sensitization or wind-up pain can become nonresponsive and produce chronic intractable pain, particularly if it is left untreated. The purpose of multimodal analgesia or balanced analgesia is to block the pain pathway at several levels. The complexity of the pain pathway involving many different neural mechanisms, neurotransmitters and receptors in the periphery and up in the spinal cord and brain require a diverse assortment of drugs to effectively block and provide pain relief.
Pure mu agonists should be the foundation, along with NMDA receptor antagonists like ketamine that can be used at sub-anesthetic doses in CRIs. Amantadine, an oral NMDA antagonist is similar to ketamine and when used in combination with other medications can be powerful in treating chronic neuropathic pain. Sodium channel blockers, like lidocaine given intravascularly in dogs, can help prevent neuropathic pain. Alpha-2 agonists, such as dexmedetomidine, can be administered by epidural, intra-articular, perineural and parenterally alone or in combination with other medications. Regional analgesia can provide significant benefits to prevent neuropathic and wind-up pain. Epidurals, peripheral nerve blocks and wound soaker catheters are examples of local techniques. NSAIDS provide anti-inflammatory actions in the periphery as well as have direct spinal cord action by helping prevent hyperalgesia. When NSAIDS are used along with opioids, even greater benefits are seen. Gabapentin blocks calcium channels at the spinal and supraspinal levels and blocks spinal cord central sensitization. Studies have shown that perioperative administration of gabapentin for procedures with the potential for nerve injury may reduce the incidence for neuropathic pain. Gabapentin is typically given with or without an opioid and an NSAID. In some animals the opioid or NSAID may be tapered and gabapentin will be effective as the sole analgesic chronically. There is a very wide dose range for gabapentin. It is usually dosed to effect with the limiting factor being sedation. Pregabalin is similar to gabapentin and is used to treat neuropathic pain in humans. It causes less mental confusion and sedation than gabapentin, however it is more expensive. Tricyclic antidepressants like amitriptyline block the reuptake of catecholamines and are also NMDA receptor antagonists. When combined with other analgesics, often times, the synergy results in improvement in 48 hours. Tramadol, a synthetic opioid, does not make the opioid metabolite in dogs and can be hit or miss on providing effective analgesia, depending on the dog. In some dogs it is still an effective pain medication, and in others, it seems to have little effect. It has some SRI (serotonin reuptake inhibitor) and NRI (norepinephrine reuptake inhibitor) activity. Tramadol may have other activities that are not entirely well characterized in dogs. Tramadol often seems to work well for some when given over a short period of time for acute pain or acute flare-ups of chronic pain. When given long term, its efficacy seems to diminish.
Lidocaine dermal patches produce a low systemic dose of lidocaine as well as greater localized results that can be very effective in blocking pain pathways in the peripheral nervous system. Studies show that peak concentrations occur at 9.5-12 hours and steady state concentrations occur between 24-48 hours with efficacy decreasing starting at 60 hours.
Adequan®, (polysulfated glycosaminoglycan) given IM or SQ can relieve pain and reduce inflammation of the synovial membrane. Its purpose is to restore synovial fluid lubrication to improve joint movement. Adequan® has been shown to stimulate cartilage repair by blocking destructive enzymes and helping to reverse degenerative joint disease to help restore the natural balanced wear and repair cycle within the joint.
Hyperbaric oxygen therapy is a relatively new modality for treating chronic pain in veterinary patients and has been shown to provide anti-inflammatory, antimicrobial and tissue-healing benefits. Patients are placed in a tank containing pressurized air, which delivers more oxygen to the body’s organs and tissues, reducing pain and increasing range of motion.
When faced with a case of intractable neuropathic pain in a patient, it can be necessary to reset the central nervous system by giving the patient a pain vacation or holiday. Admitting the patient to the hospital for 36-48 hours, administering a CRI of morphine (fentanyl works well also), plus or minus lidocaine and a sub-anesthetic dose of ketamine until the pain has resolved, is an effective way to wipe the slate clean and reset the CNS. Then the patient can be sent home with a multimodal analgesic plan to block various pain pathways of sensory transmission. Many patients will derive benefits from the pain vacation for as long as ten months.
Rehabilitation therapy for patients with chronic pain with or without a neuropathic component can be key in decreasing pain levels and increasing quality of life. Weight loss, controlled exercise, soft supportive bedding away from cold drafty areas, physical therapy, hydrotherapy, passive range of motion exercises, ramps and slings to help with mobility, raised water and food dishes, innovative prosthetic and orthotic solutions can all improve the patient's quality of life. Traction devices or carpeting/rugs to help avoid slippery surfaces are some ways to aid the chronic pain patient. Exercise and movement can help keep a painful body part or limb moving, improving blood flow and decrease circulatory symptoms. Controlled exercise can also help improve the affected body part or limb’s flexibility, strength and function. Rehabilitation can help to prevent or reverse the secondary brain changes that are associated with chronic pain. Nutraceuticals, omega-3 fatty acids, joint diets, chiropractic care, acupuncture, trigger point therapy, cold laser therapy, shock wave therapy, and pulsed electromagnetic field therapy are all additional adjunctive therapies that can be added to a well-planned pain management strategy for patients suffering with chronic and/or neuropathic pain.
Pain management can be viewed as a three-legged stool. When different modalities are combined and used together (generally three or more) the stool is sturdy. If only one or two modalities are used, then the stool falls over. No single strategy will work for every patient, but I hope that you can see there are many options available to veterinary professionals for the management of pain. As society increases its knowledge about animal welfare and pain management, demand increases for pain control education and options for their companions. It is our responsibility and moral imperative to lead the way, help educate the public, and alleviate and control pain in animals. When we took the oath, we promised we would.