Department of Biomedical Sciences, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, QC, Canada
Cancer is the leading cause of mortality in dogs older than two years of age and cancer-associated pain is a major symptom in these patients.1 Cancer pain leads to stress, suffering and low quality of life, and untreated pain in humans is one of the most feared and debilitating symptoms among cancer patients.2 In these patients, pain scores on a Numerical Rating Scale (NRS) from 0 to 10 generally vary from 4 to 6, with exacerbations as high as 7.2 Furthermore, meta-analysis studies have revealed that 64% of human patients with end-stage cancer experience pain before death.3 Given that dogs and cats frequently present with advanced-stage cancer at initial evaluation and based on similar cancer biology when compared with humans, it is reasonable to presume that canine and feline patients will experience pain at some point in the progression of the disease.1
The nature of cancer-related pain is multidimensional. Pain may originate from the primary tumor due to tumor necrosis and nerve involvement. Primary tumor pain may affect up to 68% of human patients.2 Other sources of pain include metastatic disease, cancer therapies (e.g., surgery, chemotherapy, radiation, etc.) and diagnostic procedures (e.g., surgical biopsies). Finally, cancer patients are also normally affected by other concomitant painful conditions such as osteoarthritis (OA) for example.
Cancer pain may vary greatly in nature and intensity depending on the location of the tumor as each tumor type will behave differently and will cause different types and levels of pain. For example, a dog with osteosarcoma will be clinically very distinct from a cat with oral squamous cell carcinoma, and different functions will be affected in each case. Additionally, tumours that affect internal organs result in diffuse visceral pain, whereas skin tumors are more likely to trigger focal pain.
With all these in mind, it becomes clear that cancer-related pain is therefore a result of a mixture of different types of pain. An example of that is a tumor causing nerve compression. Tumor necrosis will cause inflammatory/nociceptive pain, and nerve compression will cause neuropathic pain. In this case, central sensitization likely results from the chronic nociceptive input to the spinal cord and patients may develop hyperalgesia or even allodynia. Finally, for all the reasons above discussed, it should be considered that in cancer patients, both acute (clinically manifested as `breakthrough pain`) and chronic pain may be present, but the latter is much more prevalent.
The nature and intensity of cancer-related pain has not been characterized in dogs or cats and the prevalence of concomitant "non-cancer" pain is also unknown. This lack of knowledge impairs proper recognition and treatment of pain.1,4,5 Veterinarians have therefore the responsibility to appropriately recognize and assess pain in cancer patients, as this is the first step to an adequate pain management.5
Pain is now considered as the 5th vital sign, and its assessment should be incorporated into the clinical evaluation of all patients.5 The clinical signs of pain in cancer patients will greatly vary on a case-by-case basis as they depend on the primary cause of the pain. However, in most cases the signs are related to changes from normal behavioural that are reported by the owner. In this sense, the owners play a crucial role in the assessment of cancer-related pain as well as monitoring of treatment efficacy. A thorough physical examination including orthopedic and neurological examination should always be performed. During examination, close attention should be given to the expression of pain behaviors such as tensing of the body, resisting manipulation, abnormal physiological reactions, vocalization, attempt to escape, aggression, among others.
In humans, the correlation between chronic pain and negative psychological effects is well recognised, and patients generally self-report suffering, anxiety, impaired mobility, depression and isolation. It may be reasonable to assume that animals are similarly affected. A general assessment of quality of life may be performed during the history taking.6
The treatment of cancer pain comprises a multimodal approach using pharmacological and non-pharmacological options.5 With regards to pharmacological treatment, the World Health Organization proposes a stepwise pharmacologic approach (three-steps) for the management of cancer pain. Therefore, human patients with mild pain are administered non-steroidal anti-inflammatory drugs (NSAIDs), and patients with moderate to severe pain are administered opioids in combination with adjuvant analgesics.
Opioids are the cornerstone of acute pain treatment; nevertheless, in veterinary medicine, oral administration of opioids do not seem to produce consistent and sufficient clinical effects. In addition, opioids are controlled drugs with limited availability world-wide and potential for abuse. Their use for cancer-related pain should be limited to the hospital setting. On an outpatient basis, opioids are not recommended for cancer-related pain.7
Unless there is a contra-indication, NSAIDs are a viable treatment option for cancer pain. They exert their effects via inhibition of the expression of cyclooxygenase (COX) enzymes in cell membranes and are excellent analgesics for inflammatory pain. Close monitoring of adverse effects is imperative.5
Amitriptyline is a low-cost tricyclic antidepressant largely used for the treatment of human neuropathic pain and has been recommended for use in veterinary patients with chronic cancer pain.1,8 Its analgesic effects result from the inhibition of the reuptake of serotonin and norepinephrine in the central nervous system.9 Gabapentin is an anticonvulsant drug with analgesic properties that are mediated via calcium channels.9 This drug is commonly recommended as an adjuvant for the treatment of neuropathic pain in humans.2,3 Tramadol is a centrally acting analgesic that activates µ-opioid receptors and inhibits serotonin and norepinephrine reuptake. Amantadine exerts its analgesic effects by the antagonism of NMDA receptors and by increasing dopamine concentrations in the central nervous system.
All the aforementioned adjuvant analgesics may be considered for the treatment of cancer pain. Since they have different mechanisms of action, different drug associations may be used and chosen depending on the type of pain and treatment response. Nevertheless, little scientific evidence is available for their use in clinical cancer pain in small animals.
Local anesthetics may be an option for long-term treatment when administered via transdermal patches, but their efficacy greatly varies among patients. Local anesthetic techniques that require veterinarian skills should only be used in the event of breakthrough pain.
In patients with primary or secondary bone cancer, biphosphonates (pamidronate, zoledronate, etc.) may provide analgesia by inhibition of bone resorption due to osteoclast activity.
Euthanasia comprises a treatment option and should be considered in cases with poor prognosis, impossibility to treat due to owner's ability, financial constraints, lack of response to therapy, etc.
The benefits of non-pharmacological treatment options should not be underestimated. Although there is lacking scientific evidence on the efficacy of these techniques in veterinary patients, their importance in the treatment of chronic pain in humans has been increasingly recognised as it decreases pain, suffering and anxiety in several patients.
Several non-pharmacological options exist and should be considered depending on the clinical case, availability, acceptance by the patient and the owner. These options include acupuncture, physiotherapy, environmental enrichment, massage, natural products, among others.
Last but not least, continuous 'tender loving care' is essential for cancer patients. It will play a role in the patient's welfare and will strengthen the human-animal bond.
References
1. Fan TM. Pain management in veterinary patients with cancer. Vet Clin North Am Small Anim Pract. 2014;44:989–1001.
2. PDQ® Supportive and Palliative Care Editorial Board. PDQ cancer pain. http://www.cancer.gov/about-cancer/treatment/side-effects/pain/pain-hp-pdq. Published 2016. Updated 10 March 2016. Accessed 31 May 2016.
3. van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007;18:1437–1449.
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5. Mathews K, Kronen PW, Lascelles D, et al. Guidelines for recognition, assessment and treatment of pain: WSAVA Global Pain Council members and co-authors of this document. J Small Animal Pract. 2014:55:E10–68.
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8. Gaynor JS. Control of cancer pain in veterinary patients. Vet Clin North Am Small Anim Pract. 2008;38(6):1429–1448.
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