As cancer progresses, tissue destruction occurs, causing the release of cell membranes, cytosolic proteins and nuclei acid. The inflammation created is painful and can stimulate additional angiogenesis, cell cycle initiation and cancer progression.
In this Oncology Outlook, I want to propose a “pain ladder” that provides guidance in the management of cancer pain and reviews measures used in our clinical facility.
The goal of a pain management strategy is to relieve pain and prevent or delay additional complications. In human medicine, the World Health Organization recommends the use of a one through 10 scale to characterize the severity of pain and provide guidance in selecting appropriate pain relief measures.
While many others use scales, algorithms or charts to track an animal’s pain, I propose the following three categories of cancer pain and suggest some measures for additional relief.
Mild to Moderate Pain: This occurs as a tumor compresses surrounding tissues and is possibly warm to the touch, but the general aches or stiffness do not limit a pet’s duration of normal activity. Cautious but regular use of a non-steroidal anti-inflammatory drug would be the first choice.
Following some reconstructive surgical procedures or definitive radiation protocols, using antioxidants can prevent or lessen the severity of mild to moderate pain.
Moderate to Severe Pain: When the pain behavior is not relieved by an NSAID or when the pain begins to severely limit daily activities then opiods should be considered. Opiates may include codeine, hydrocodone, fentanyl, torbutrol and tramadol.
The selection may limited by the cost. This makes tramadol an attractive option for pain relief, but the responses are quite variable. More consistent pain relief occurs when an opiate is combined with an NSAID.
Severe Pain: Intestinal or pelvic obstruction, bone pain from a primary or metastatic tumor and oral ulceration are a few of the causes of severe pain in cancer patients. In some circumstances, the type or dosage of NSAID and opiate combination can be modified to provide temporary relief.
To obtain durable pain relief and to arrest cancer progression, tumor irradiation or intravenous bisphosphonates are indicated.
When the primary or metastatic tumor lesion does not represent an immediate risk of rupture (oral melanoma), obstruction (bladder tumor) or fracture (osteosarcoma) then radiation can be effective in reducing pain and tumor progression.
In our practice, nearly 80 percent of dogs experience pain relief after at least three treatments of eight Gy irradiation at weekly intervals.
The median duration of pain relief is three months. However, when six Gy are given in weekly intervals for a total of six treatments, the median duration approaches eight months (ranging from two to 15 months). Longer times were observed when chemotherapy was administered concurrently.
The general mechanism of action on how radiation reduces acute pain is unknown. One hypothesis is that ionizing radiation destroys the inflammatory cell population and reduces the amount of prostaglandin production. This may explain the sudden relief of pain noted in most dogs within 24 hours.
Another hypothesis for pain relief in patients with bone cancer is that ionizing irradiation inhibits the recruitment and activation of osteoclasts, thus reducing cytokine production, metalloproteinase secretion and bone resorption.
This has been proved in many models but showed reduced quantities of urinary markers of bone resorption in humans and dogs.
We are all familiar with the sudden onset pain arising from a primary bone tumor. But bone pain arising from the formation of multiple metastatic lesions is difficult to localize without advanced imaging techniques such as nuclear medicine or computed tomography. Treating multiple skeletal sites with irradiation becomes impractical.
The action of bisphosphonates, like radiation in the relief of bone pain, is mostly unknown, but this class of drugs continues to show promise for use in veterinary medicine. There are two groups of bisphosphonates, non–amino-bisphosphates and amino-bisphosphonates. The amino-bisphosphonates have greater antiresorptive capabilities and represent a newer generation of bisphosphonates.
These are effective for pain relief in dogs that have multiple sites of involvement and because no specialized equipment or advanced delivery techniques are needed. Nearly one-third of dogs with primary bone cancer show clinical improvement following a single administered intravenous dosage. Some also report clinical improvement in patients with hypercalcemia of malignancy.
Although bisphosphonates are regarded as metabolically inert in the body, adverse effects do occur and include anaphylaxis, acute gastritis, renal insufficiency and delayed healing. Bisphosphonate drugs that are FDA-approved in humans for the treatment of cancer-related skeletal complications include Zometa (zoledronic acid) and Aredia (pamidronate).
Pain Inevitable, Suffering Optional
Providing pain relief is part of our commitment to helping animals. In the course of our day-to-day practice, each of us has developed predetermined thresholds for the levels of pain we are willing to accept in our patients before recommending euthanasia.
It is not the purpose of this forum to recommend one NSAID or opiate over another in the management of cancer pain. Likewise, it is not my intention to recommend heroic measures.
Yet, thankfully, there are many choices to consider as an alternative to euthanasia so that the family can enjoy additional quality time with their loved one.