Page 307 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

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Supportive Care for the Cancer Patient

plasticity. Cancer models of pain in rodents have shown that per-
SECTION A: MANAGEMENT OF CHRONIC sistent noxious signals can lead to genetic alterations that modify
CANCER PAIN the synaptic ultrastructure of spinal neurons (e.g., recruitment of
wide dynamic range neurons in the superficial spinal cord) and
induce dysregulation of the neuron–glia–immune system and the
MICHAEL W. NOLAN, CONSTANZA descending inhibitory/facilitatory system. 10–16 It has been hypoth-
MENESES, TIMOTHY M. FAN, AND esized that these events could preserve the nociceptive transmis-
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B. DUNCAN X. LASCELLES sion without the need for algesic mediators. Currently, the exact
intracellular signaling pathways that explain the interconnected
This chapter explains the underlying mechanisms of cancer- mechanisms among all these elements remains unclear. However,
induced pain. It also provides a guide for assessment and treat- new research has identified the potential role of various therapeu-
ment of pain in canine and feline cancer patients. Finally, the tic targets for cancer pain management (see the section Future
future of analgesic therapies is discussed. Given the modicum of Analgesic Therapies later in the chapter). The failure of clinical
clinical studies in dogs and cats, the information in this chapter studies regarding this signaling pathway might be representative of
cannot be based solely on peer-reviewed investigations. Rather, it the current limitation of translating data from the commonly used
is a combination of the authors’ experiences and the experiences of animal models to humans, as has been discussed in several reviews
others who collectively are contributing to the treatment of can- of translational pain research. 17–20
cer patients. It also is based on considered extrapolations from
physician-based medicine and from veterinary research on other Pain as a Consequence of Cancer Therapy
chronically painful conditions, such as osteoarthritis (OA).
Clinical interventions represent an important and often underap-
Mechanisms of Cancer-Induced Pain preciated source of discomfort in patients. Invasive diagnostic inter-
ventions, such as tumor biopsy and bone marrow aspiration, are
In veterinary medicine several types of tumors have been associ- obvious examples, but other potential sources for at least transient
ated with painful symptoms (Table 16.1). However, the presence iatrogenic pain include positioning for radiographic studies (which
and manifestation of pain in cancer patients are not predictable, could exacerbate or upset orthopedic diseases such as OA) and phys-
and its prevalence and severity depend on numerous factors com- ical examination (e.g., digital rectal examination, tumor palpation).
monly linked to the characteristics of the patient, the cancer type, Surgery is perhaps the most obvious cause for treatment-related
the anatomic location, and associated therapeutic interventions. pain in cancer patients. Surgery is the most common treatment for
The generation of noxious (painful) signals generally starts in canine and feline tumors, and it causes a visible wound. The con-
the peripheral nervous system (PNS), triggered by tissue com- trol of acute perioperative pain in cancer patients is very impor-
promise, invasion, and injury generated by the tumor itself. Pro- tant, and readers are referred to appropriate texts for information
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nociceptive mediators (e.g., cytokines, interleukins, chemokines, on perioperative pain control. Though phantom limb pain is
prostanoids, endothelins, and growth factors) can be released by commonly discussed with regard to amputation of tumor-bearing
both cancer cells and the immune cells that infiltrate the tumor limbs, little is known about the epidemiology of pain in animals
microenvironment. 1–7 The release of these factors sets off an related to chronic tumor surgery.
inflammatory signaling cascade, which modifies the intracellular Radiation therapy (RT) can also cause painful side effects.
homeostasis of the surrounding sensory neurons’ primary afferent Late radiation-induced neuropathies and tissue fibrosis can cause
fibers and cell bodies located at the level of the dorsal root ganglia significant disability. Fortunately, although those late effects are
(DRG). This powerfully modulates excitatory synaptic transmis- both chronic and progressive, they are also uncommon, affecting
sion in the central nervous system (CNS), sensitizing spinal cord about 5% of patients 2 to 3 years after finishing a typical defini-
neurons and enhancing nociceptive transmission within supraspi- tive course of RT. Uncomfortable acute radiation side effects,
nal circuits. 4,8,9 such as dermatitis and oral mucositis, are far more common. The
Central neuronal plasticity and hyperexcitability can originate incidence and severity of these side effects depend on a variety of
either from increased and sustained peripheral inputs or from factors, including the radiation prescription, the planning tech-
primary or metastatic CNS tumors, or both. Significant overlap nique and treatment delivery modality, and the anatomic site and
is seen between mechanisms underlying peripheral and central species. In veterinary medicine radiation-induced pain is more

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