Introduction
Pain is a common and troubling symptom among pediatric cancer patients in both the inpatient and outpatient settings. , In this chapter we will provide a comprehensive overview of chronic pain and its management in pediatric cancer patients. We will also discuss pediatric palliative care and how it can be of great benefit to this vulnerable population.
Pain Presentations
Pain is a complex entity that can manifest in many ways even within the same patient. It can present as acute or chronic pain. Acute pain is typically related to a specific insult and is self-limited, lasting no more than 3–6 months. Specifically, in cancer, it is usually related to tumor invasion or invasive interventions such as procedures or surgery. Acute pain occurs when the body sends signals to the brain to indicate injury, and it also occurs during the processes of preservation and repair. Treatment of acute pain is aimed at minimizing the pain perception while primarily treating the underlying etiology. Chronic pain can develop from long-standing tumor expansion, compression, or destruction of surrounding structures or their treatment. Chronic pain is generally defined as lasting for greater than 6 months and the treatment goals are markedly different, as often the underlying etiology cannot be reversed. While acute pain focuses on alleviating pain and treating the root cause, management of chronic pain focuses on maintaining function, while decreasing pain to a tolerable level. There is also an acute on chronic pain presentation that is unique to chronic conditions such as malignancy. Also called breakthrough pain, acute on chronic pain presents as an episodic, significant increase in pain above the patient’s baseline chronic pain. It is usually exacerbated by a specific event such as a surgical intervention, side effect of treatment, or progression of disease. The treatment for this type of pain is similar to that of acute pain, in which decreasing pain to baseline is the goal. In this chapter we will focus on chronic pain presentations, as these are common in the pediatric cancer population.
Types of Pain
Nociceptive pain is subdivided into somatic and visceral types and is caused by direct injury to anatomic structures, including internal organs (visceral pain) or connective tissues, muscles, and bone (somatic pain). Patients, who experience nociceptive visceral pain describe it as achy, crampy, and poorly localized. Examples of visceral pain are pancreatitis secondary to chemotherapy or bowel obstruction from tumor growth. Nociceptive somatic pain is described as sharp, stabbing, throbbing, or a pressure sensation and can be seen with bone metastases or leukemic skin infiltration. Neuropathic pain is characterized as sharp, electrical, shooting, tingling, or numbness and is the result of damage to the central and/or peripheral nervous system by direct tumor invasion, surgical trauma to nerves, or medication-induced neurotoxicity that leads to abnormal processing of somatosensory stimuli.
It is important to note that there are other types of pain, such as spiritual, psychologic, and social, that may manifest or be interpreted as physical pain by the child or their caregivers. Dame Cicely Saunders, the founder of modern hospice and palliative care, described a holistic concept of total pain in which pain affects different aspects of quality of life (physical well being and functioning, psychologic well being, social well being, and spiritual well being), and these aspects, in turn, affect the perception and presentation of pain. This is well established in the literature, and other authors have built on this work. A consequence of undertreated, nonphysical pain is usually an increase in the expression of physical pain. Early assessment and treatment of nonphysical pain may be helpful in minimizing confounding factors during the management of physical pain.
Chronic Pain Etiologies
Chronic pain can be the result of the malignancy or the treatment of the malignancy. Tumor extension can cause pain, as it puts pressure on solid organs or adjacent nerves. Direct infiltration into connective tissues, bone marrow, bones, or muscles can also produce long-standing pain, especially in patients with refractory, metastatic, or inoperable disease. Blockage of blood flow or lymphatics can lead to accumulation of fluid in the form of peripheral edema, ascites, or pleural effusions, which can also cause pain. Chronic neuropathic pain can also present after surgical interventions such as limb amputation (phantom limb), limb salvage, hemipelvectomies, or thoracotomies.
Pathologic fractures secondary to tumor invasion can produce chronic pain. Multimodal cancer therapy with a combination of chemotherapy, radiation, and/or surgery can be a source of great pain burden for patients. Chemotherapy can have painful side effects. For example, vincristine or paclitaxel can cause peripheral neuropathy that can lead to chronic pain. Osteopenia or osteoporosis secondary to chronic steroid use can result in vertebral body fractures, which in turn leads to chronic back pain. Radiation can produce many painful side effects, such as dermatitis and mucositis, which can be significant and prolonged. Iatrogenic procedures, such as indwelling catheters for pleural or ascitic fluid drainage or G-tubes for venting/feeding, can also be sources of chronic pain for patients. Central lines, which are commonplace for cancer treatment, can lead to thrombus or nerve damage.
Chronic Pain Evaluation
Chronic pain management requires not only a thorough physical and historical evaluation of the pain trajectory but also an understanding of both the physical and emotional burden on the patient and their family. Parents, as well as the patient, may experience significant distress that can impact their perception of pain. An example would be parent catastrophizing of a child’s pain. This is when parents hold certain thoughts or beliefs that magnify the threat value of pain, and this has been found to be a significant predictor of adolescent somatic symptoms. Wilson et al. described that parental catastrophizing increases the likelihood that adolescents will also catastrophize their pain, which in turns leads to more disability. Additionally, it will be helpful to understand the status of the patient’s primary malignancy, as this can greatly affect pain presentation, goals of care, and ultimately, management.
Pain assessment tools can be helpful in obtaining a subjective measurement of a patient’s pain experience if the patient is able to self-report. For very young children, this may be impossible or very difficult, thus one has to rely on parent-proxy reports. The setting in which the pain evaluation takes place is also important. Depending on the developmental stage of a child, they may experience significant stranger anxiety and an accurate assessment of pain will be difficult by a medical provider that is unfamiliar to the child. In these situations the best strategy is to evaluate the child while they are held by a parent or simply by observing the child.
Many different pediatric pain scales exist for various chronologic and developmental age groups. For example, infant pain can be assessed through observations of the baby crying, grimacing, body stiffening, and withdrawal from painful stimuli. Several scales exist for neonatal pain assessment; for example, the Neonatal Pain, Agitation, and Sedation Scale (N-PASS) or the Neonatal Infant Pain Scale (NIPS) can be used for neonates, while the Premature Infant Pain Profile (PIPP) can be used for premature infants. For toddlers, parent-proxy reports will still be the most helpful, and tools, such as the Faces, Legs, Activity, Cry, and Consolability Scale (FLACC), can be helpful. Preschool children can have limited self-reporting abilities, and these should still be supplemented with parent’s reports of pain or limitations. For children in this age group, the Wong-Baker FACES or Oucher pain rating scales can be used reliably. Most children aged 9 years and older can use the numerical (0–10) pain rating scale.
Although these pain scales are used primarily for assessment of acute pain, they may still be useful for periodic assessment of chronic pain. It is important that medical providers are aware that many of the typical pain signs and symptoms may be attenuated or absent in the chronic pain setting. For instance, children with chronic pain may not exhibit changes in vital signs or crying. They may have adapted to function with pain, and thus their functional status, emotional demeanor, and vital signs will not reflect their true level of pain.
Chronic Pain Management
Chronic pain management differs from that of acute pain in that the goal is to decrease pain to a tolerable level, not to alleviate it completely. Reducing pain allows increases in daily function and improvements in quality of life. It is very important to converse with parents and the child to set realistic expectations and establish goals. Goals should be life-centered and personalized to each patient.
General Strategy
The general strategy for management of chronic cancer pain in children is to use a minimum number of medications at the lowest effective dose in order to reduce pain and increase function. Treatment should be multimodal and include pharmacologic as well as nonpharmacologic interventions.
Nonpharmacologic Management
Nonpharmacologic therapies play a key role in the management of chronic pain. Physical and occupational therapies can offer patients exercises and stretches that can help decrease pain and improve mobility and function. Not only can these be performed with a skilled professional in the inpatient or outpatient setting but the therapist can also teach the patient and their caregivers exercises for the child to do on their own. This can be very helpful for children, as it gives them another method to control their pain. In a patient with advanced cancer that may have limited mobility, these therapies can also help prevent or alleviate painful contractures. Integrative medicine therapies, such as yoga, meditation, aromatherapy, acupuncture, massage, and guided imagery, are additional tools to help decrease pain without the use of medications.
Children with terminal cancer can suffer from severe pain and palliative surgical measures may provide adequate benefit to justify their use. For example, pleural, pericardial, or peritoneal effusion-related pain can be improved with catheter drain placement and improve respiratory status. Similarly, percutaneous gastrostomies for venting may be helpful in gastrointestinal obstructions secondary to tumor invasion. A more invasive but inarguably palliative measure is surgical debulking or stabilization of bones in the setting of terminal cancer. Refractory disease may be very painful due to direct tumor invasion into bones, body cavities, or solid organs. This progression can cause bowel obstruction or gross tumor burden that can perforate bowel or even skin. It is important to be mindful of the risks associated with surgery when planning these palliative interventions. Poor wound healing, infection, and significant pain among others may outweigh the benefits of the surgery. Radiation therapy can often also provide pain relief by decreasing tumor burden or growth rate without significant side effects or toxicity and often using less than five fractions.
Pharmacologic Management
Management of chronic pain will frequently require administration of pain-relieving medications. As is the general rule in pediatrics, medications should be dosed by weight and should not exceed maximal starting adult doses in opioid-naive patients. Oral medications should be the first choice but this can be transitioned to other routes, such as intravenous, transdermal, sublingual, subcutaneous, or even rectal, if the patient is unable to tolerate oral intake. Intravenous may be the route of choice in the case of severe, excruciating pain that requires immediate relief. Often, more than one medication may be needed to achieve adequate pain relief. Combination regimens, which may include both opioids and nonopioid medications, may be helpful for opioid-sparing effects but can also lead to polypharmacy, which can have numerous complications such as nephrotoxicity, hepatotoxicity, and oversedation among others. The decision to use combination pain regimens should be made by physicians with experience with these medications, their side effects, and possible interactions with other medications. Consultation with a palliative care physician or pain specialist is recommended. Finally, the pain medication choice and dose will, in part, depend on the patient’s age, as this will affect their ability to take certain formulations. Liquid formulations or medication compounding may be necessary in children requiring small doses or unable to swallow pills.
The World Health Organization proposed a pain management plan that starts with nonopioid medications and escalates to stronger opioids. This pain ladder can serve as a guide to initiate a pain regimen and then it can be titrated to effect. The correct dose of opioid will provide adequate analgesic effect with minimal toxicity. Common opioid toxicities include nausea, pruritus, and constipation. Less often and usually with larger doses, toxicities may include sedation, respiratory depression, myoclonus, and hallucinations. When toxicity outweighs the analgesic benefit, the provider may consider changing to a different opioid, also known as opioid rotation. Because the body becomes tolerant to opioids due to constant effect at its specific receptor, the analgesic effect may decrease over time while the side effect profile may increase. Changing to a different opioid that will affect a different receptor will increase the analgesic benefit and may decrease the side effect burden. Of note, opioid rotation requires conversion of the opioid dose to the new opioid dose using standardized tables and a 20%–30% dose reduction, as tolerance to the new opioid is generally incomplete (incomplete cross-tolerance).
Chronic cancer pain that is present on most days will require long-acting, in combination with short-acting, pain medications. The long-acting pain medication will provide a baseline level of pain relief and should be taken on a scheduled basis. The long-acting pain medication doses should be titrated to provide pain relief to a tolerable level. In addition, a short-acting pain medication will be necessary for breakthrough pain. This medication should be taken as needed only. The dose should be titrated to decrease pain to the baseline level. In the hospital setting, this combination of long- and short-acting pain medication can be delivered via a patient-controlled analgesia (PCA) pump. This method provides a continuous or basal dose of an opioid at a low rate, while allowing the patient to administer an additional dose for breakthrough pain at set intervals. The benefits of this method include faster pain medication delivery.
In general, opioids are the mainstay of cancer pain treatment; however, nonopioid medications also play a strategic role, as they can help spare opioid use. For mild pain, acetaminophen or nonsteroidal antiinflammatory medications should be the drugs of choice if no contraindications are present. For neuropathic pain, antiepileptic medications such gabapentin, serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine, and low-dose methadone may be helpful. Methadone is particularly effective in relieving chronic cancer pain with minimal side effects; however, dosing is complicated and should be performed by an experienced provider or in consultation with a palliative care or pain physician. Other medications, such as topical lidocaine for mucosal pain, may be indicated depending on the child’s pain or other comorbidities.
As mentioned earlier, opioids can be an important component of chronic cancer pain management and should be used with great care in order to avoid toxicity or disordered use. See Tables 51.1 , 51.2 , and 51.3 for opioids, neuropathic agents, and other adjuvant therapies used in pediatric cancer patients.
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