Pain Management for the Cancer Patient

Elaine R. Caplan, DVM, Dipl. ACVS, ABVP
Capital Area Veterinary Specialists
Round Rock, Texas

 

Cancer frequently causes pain in veterinary and human patients. Pain may be a direct effect of the cancer, paraneoplastic syndrome, or induced by diagnostic procedures and treatments. Bone pain is the most common type, followed by tumor infiltration of nerve and hollow viscous. Cancer therapy results in pain in about 15-25% of patients receiving chemotherapy, surgery, or radiation therapy. Sixty to ninety percent of patients with advanced terminal disease experience moderate to severe pain. It is estimated that 67% of cancer patients with metastatic suffer from pain and 36% of these experience pain that interferes with quality of life. Pain caused by non-cancer related problems (e.g. degenerative joint disease, degenerative disk disease) is estimated to be present in 3-10% of patients. Physiologic manifestation of untreated pain cam be widespread with resulting poor survival time and response to therapy.

It is assumed that animals suffer to the same extent from cancer pain because anatomic structures and neurophysiologic mechanisms that lead to pain perception (nociception) are similar in humans and animals. Veterinarians are ethically committed to relieve suffering and pain. Unfortunately, veterinarians tend to lag behind pain management and end of life care. Many of our clients experience feelings of guilt, sadness, anger, and fear about suffering and pain associated with cancer and treatment. Owners may choose euthanasia over treatment due to fear of their beloved pet suffering from pain. Cancer pain should be anticipated, recognized, and treated in order to relieve suffering and stress, and improve quality of life. Also, owners must be educated, and encouraged to actively participate in the treatment of their pet’s disease. Ideally, a team involving the owner; medical, surgical, and radiation oncologists; pain specialists; physical therapists, and social workers would ultimately fulfill the goals of maximum comfort with minimal pain and stress.

Classification of cancer pain is according to duration and origin. Pain can be classified as acute or chronic. Acute pain lasts for moments to several weeks and is associated with objective and subjective clinical signs such as tachycardia, tachypnea, hypertension, vocalization, abnormal posture, and alterations in stress related hormones (cortisol, epinephrine, and norepinephrine). Acute pain can be self limiting and responds to symptomatic therapy, and treatment of the underlying cause. Common causes include direct tumor invasion, paraneoplastic syndromes, surgery and diagnostic procedures. Chronic pain is defined as the presence of pain for more than 3 months with a less well defined onset. Sensitization of peripheral receptors or central nervous system sensitization “wind-up” results in abnormal processing of afferent stimuli along the nociceptive pathway. There is expansion of peripheral receptor fields of the dorsal horn neurons. When the endogenous inhibitory mechanisms are diminished, the inhibition of excitability is reduced. Continued afferent activity can lead to a nervous system that exaggerates and prolongs noxious information. Pain can increase with cancer progression and decrease with tumor regression. In humans, pain is associated with poor quality of life factors including anxiety, depression, and anorexia. Pain activates the neuroendocrine system favoring gluconeogenesis due to an imbalance between insulin and glucagons, excessive catecholamines and cortisol. This results in impaired metabolism despite adequate intake, and ultimately catabolism and cachexia.

Pain can be classified according to pathophysiologic pathways of nocoception. This includes somatic, visceral, and neuropathic nociceptor activation. Somatic pain is described as sharp, aching, or throbbing and is well localized. It arises from skin, skeletal, and peritoneum. Examples of somatic pain are primary or metastatic bone cancer pain and postsurgical incisional pain. Visceral pain is not well localized and is experienced as cramping or gnawing sensation as result of obstruction of a hollow organ. Mesenteric involvement can manifest as aching, sharp, or throbbing. Visceral nociceptors are stimulated in the thoracic, abdominal, or pelvic viscera by compression, stretching, infiltration, or expansion of a tumor. Inflammation also sensitizes nociceptors and contributes to pain.

Direct damage to peripheral or central nervous structures by infiltration or compression of axons and nerve membranes may sensitize them, inducing neuropathic pain. Central neuronal hyperactivity in the spinal cord and thalamus may be part of the process. Burning, lancinating, or shooting pain with deficits in sensory, motor, or autonomic areas characterizes neuropathic pain. Allodynia is a type of excruciating neuropathic pain resulting from a stimulus that does not normally produce pain. Neuropathic pain is more difficult to control compared to visceral or somatic pain and often requires analgesic adjunctive therapy (local nerve blocks, antidepressants, radiation, neurosurgery) in addition to commonly used analgesic agents. Nonsteroidal anti-inflammatory drugs (NSAIDS) are no longer effective and resistance to opioids occurs.

Bacterial infections, fever, and paraneoplastic syndromes may also produce pain. Pulmonary hypertrophic osteopathy (HO) is a paraneoplastic syndrome that produces a periosteal proliferation originating in the digits and extending proximally to include the femur and humerus. HO is seen with primary or metastatic lung and urinary tract tumors and resolves after excision of the tumor. Myopathy is a syndrome associated with thymomas and neuromyopathies can be seen with pulmonary carcinomas. Because cancer patients can be immunosuppressed from cancer or from chemotherapeutic agents, infections can occur after surgery, diagnostics, or radiation therapy. The tumor itself may become necrotic and form an abscess.

Pain associated with therapy can be a result of administration of chemotherapy and radiation therapy. Analgesics and tranquilizers help minimize stress and pain in patients receiving repeated venipuncture for chemotherapeutic protocols. Extravasation of chemotherapeutic drugs such as doxorubricin, vincristin, vinblastin, and actinomycin can cause severe inflammation and sloughing of tissues.

Mucositis of the oral cavity, esophagus, and pharynx usually occurs within 1 to 2 weeks after radiation therapy begins and continues 2 to 4 weeks after completion. To prevent anorexia, infection, and pain, oral rinses are used. Oral formulations include chlorhexidine rinse, viscous lidocaine, and green tea. At the University of Illinois Cancer Care Clinic, the oral cavity is rinsed with weak green tea, which helps to gently debride plaques. This followed by an analgesic rinse consisting of equal volumes of viscous lidocaine, Benedryl ® elixir, and Maalox®liquid. Sucralfate slurries help to control esophagitis. Gastrostomy tubes may be necessary if anorexia persists. Radiation effects of skin include erythema, moist desquamation, pruritis, and necrosis of superficial and deep skin layers. Oral analgesics, antihistamines, anti-inflammatory doses of corticosteroids, e-collar, and aloe vera gel help with healing and pain control. Excessive rubbing and removal of scabs may result in damage to the basement membrane. These effects can subside 2-3 weeks after therapy ends. Bone necrosis can also occur leading to sequestra. Blepharitis, blepharospasm, conjunctivitis, keratoconjunctivitis sicca, and corneal ulcers are painful ophthalmologic sequela of radiation therapy and need to be treated promptly. Due to the painful sequela expected from radiation therapy, owners should be well informed of anticipated side effects and reassured that this painful period is expected to be limited. During this time, analgesic and adjunctive therapies will be necessary.

Assessment of cancer pain must be a joint effort between the veterinarian and the client. The veterinarian performs a thorough evaluation including history, physical examination, diagnostic tests (to evaluate sources of pain), and response to therapy on a regular basis. Owners should be encouraged to evaluate, monitor, and record the animal’s pain relief. This involvement in pain control can diminish the owner’s feelings of helplessness in not being able to control the pet’s pain. Owners often best monitor changes in the animal’s level of activity, mood, and appetite. To daily monitor efficacy of the pain management plan, clients can use the Oxford Pain Chart.

Management of cancer pain is based on guidelines set by the World Health Organization (WHO) for the treatment of human cancer. The “3 step analgesic ladder” bases recommendations on 3 levels of pain: mild, moderate, and severe. Combination of agents from different drug classes is used in order to maximize analgesia, reduce the dose of drugs (which act synergistically), and minimize side effects. This system has been successfully used in successful controlling 70-90% of cancer-associated pain in humans. NSAIDs, opioids, and adjuvant drugs are the most common therapies used. Neurosurgery, physical therapy, complementary/alternative therapies including acupuncture, massage, and herbal medications (e.g. St. John’s Wort) can also be used. Cancer pain management should be individually tailored  each patient so that the choice of drug matches the intensity of the pain.

The first step in the “analgesic ladder” is the treatment of mild pain with an NSAID with or without an adjunctive drug. Common NSAIDs recommended include carprofen, etodolac, meloxicam, ketoprofen, piroxicam, and acetaminophen. Use of acetaminophen is contraindicated in the cat. NSAIDs decrease the production of prostaglandins by inhibiting cyclooxygenase (COX). COX-2 is thought to be responsible for pain and inflammation. COX-1 is the beneficial type present in many organs including kidney, gastrointestinal tract, and platelets. Newer NSAIDs (carprofen, etodolac) are believed to preferentially inhibit COX-2. Gastrointestinal ulceration, renal dysfunction, and bleeding are potential adverse side effects. Patients must be well hydrated. H2 blocking agents, sucralfate, omeprozole, and misoprostol can be used to treat or prevent gastrointestinal side effects.

The second step involves the treatment of mild to moderate pain. In this case, pain persists or increases in spite of NSAIDs used alone. A weak opioid or a combination of a weak opioid with an NSAID is used. Examples are aspirin or acetaminophen plus an oral opioid like codeine or oxycodone. Butorphanol is an oral opioid agonist/antagonist and buprenorphone is a partial opioid agonist used parenterally. These two drugs have a ceiling effectso should not be used for severe cancer pain. They should also not be used with a pure opioid agonist.

The third step in the pain ladder is when pain persists or increases requiring pure opioids to control pain. Opioids when combined with an NSAID increases analgesia efficacy. Opioids produce analgesia by binding to opioid receptors in the brain and spinal cord. Since pure opiods do not have a ceiling effect with respect to analgesia, doses can be increased with increased pain levels. Mu receptor activation results in the most effective analgesia with a linear dose curve. The most common opioids used are morphine, fentanyl, hydromorphone, oxycodone, and oxymorphone. Potential side effects include respiratory and cardiovascular depression, systemic hypotension, dysphoria, agitation, and excitement. Opioids are kept to the lowest dose necessary to control the level of pain. This is best accomplished by adding an NSAID or an anxiolytic drug such as acepromazine.

Adjunctive analgesics are drugs that have weak or non-existent analgesic action when used alone but can enhance analgesic actions when co-administered with known analgesic agents. They may be the first line approach in some chronic pain syndromes. This is very important when dealing with severe refractory cancer pain. Adjunctive therapies include corticosteroids, tricyclic antidepressants, anticonvulsants, local anesthetics, antihistamines, neuroleptics (acepromazine), dissociative anesthetics, and alpha-2 agonists. Other types of therapy include palliative radiation therapy, physical therapy, acupuncture, transcutaneous electrical nerve stimulation (TENS), neutroceuticals, and herbal therapy.

Hospice or home care for the terminally ill patient involves pain control at home. These animals may need combinations of analgesic classes. These may include oral NSAIDs, opioid/NSAID combinations, fentanyl patch, and other adjuvant therapies, which may improve quality of life. Clean thick bedding, bladder/bowel management, adequate nutritional support, and hydration are all important in hospice care. Veterinary technicians may have an important role in hospice care in the future; helping with administration of medication, subcutaneous fluids, and management of feeding tubes.

Cancer pain management needs to be incorporated into all cancer protocols. Ignoring existence of pain only increases and prolongs suffering. Pain management needs to be individualized and tailored to the level of pain based on the WHO “3 step analgesic ladder.” Owners should be part of the cancer treatment team by using pain scoring systems at home. Adjuvant and alternative therapies may provide additional pain relief when conventional drugs are no longer efficacious. By providing adequate pain management, veterinarians reduce pain and suffering, reduce client fears, and improve the quality of life of patients.