Pain Management
L. Koranteng1 and N. Moryl1,2, 1Memorial Sloan Kettering Cancer Center, New York, NY, United States, 2Medicine Weill Cornell Medical College, New York, NY, United States
Abstract
Pain is one of the common symptoms that clinicians manage in the field of palliative medicine. Clinicians managing patients with pain need to do so as best as they can to ensure that each patient has a quality of life that is acceptable to them, their caregivers, and family members. This chapter is to serve as a quick guide for the radiation oncologist to use in managing the pain experienced by their patients.
While radiation helps with pain, other modalities are considered to help with pain such as pharmacologic options (opioids and nonopioids) and other nonpharmacologic options. The radiation oncologist managing a patient with pain should be aware of all these modalities.
Keywords
Acute pain; chronic pain; neuropathic pain; opioids
Introduction
Pain is one of the common symptoms reported by cancer patients. This handbook chapter is a practical and quick guide to use while assessing and managing patients with cancer pain. We offer medication options to consider when treating patients as well as offer nonpharmacologic options worth considering.
What Is Pain?
Pain is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. While it is unquestionably a sensation in part or parts of the body, it is always unpleasant and therefore, an emotional experience” [1]. The above definition addresses the physical and emotional aspects of pain, however, we should also be cognizant of the concept of total pain [2], which addresses other components such as the psychological, social, financial, cultural, and spiritual aspects of pain.
Common Pain Terminology
• Acute pain—It is pain that “follows injury to the body and generally disappears when the bodily injury heals.” It can be associated with objective physical signs of sympathetic nervous system activity including tachycardia, hypertension, diaphoresis, mydriasis, and pallor [3].
• Chronic pain—Acute pain that persists for three months or longer [3]. Objective physical signs of sympathetic nervous system activity that may be associated with acute pain are likely to disappear in chronic pain (the patient with chronic pain may not appear to be in pain).
• Central pain—According to Chekka et al. [4], it is “regional pain caused by a primary lesion or dysfunction in the central nervous system usually associated with abnormal sensibility to painful (hyperalgesia) and nonpainful (allodynia) stimulation.”
• Neuropathic pain—Pain that results from a primary lesion in the nervous system [1]. Often associated with sensory changes (decreased sensation, allodynia, hyperalgesia, and other sensory changes).
• Nociceptive—Pain caused by noxious stimuli [5].
Pain Assessment
• Pain is a subjective experience and performing a thorough assessment is one of the key steps in managing a patient’s pain [6].
• Multiple scales exist; most of them document the patient’s own self-reported level of pain and some of the scales document the patient’s report of pain interference with activities and quality of life.
• It is essential to perform a pain assessment at the initial and every consecutive visit using the same scale.
• The following are the most commonly used pain assessment scales that can be used in clinical practice [7]:
Patient rates pain using a numerical figure usually from “0” being no pain to “10” being the worst pain imaginable.
Limited as it captures one dimensional aspect of pain.
Wong-Baker FACES Scale [8] (Fig. 6.1)
Patient chooses the face that best depicts their level of pain. Useful in patients greater than 3 years of age.
Can also be used in the elderly.
Edmonton Symptom Assessment Scale: Pain is one of the 9 symptoms assessed with a scale 0 to 10 [9].
Brief Pain Inventory [10]
• Measures pain intensity and interference of pain in patient’s life, as well as pain relief, pain quality, and patient perception of the cause of pain.
• Minimum requirements for pain assessment must include pain location, intensity, aggravating and alleviating factors, pain trajectory, and current pain regimen. One example of this is PQRST characteristics of pain [11]:
Palliating or precipitating factors (P)—“what makes it better or worse?”
Quality of pain (Q)—“what is it like?”
Region and/or Radiation (R)—“does it spread anywhere?”
Severity (S)—“How severe is it?”
Temporal factors (T)—“Is it there all the time, or does it come and go?”
• Other points to keep in mind:
The type of pain being treated (acute, chronic, acute on chronic) and how long it is anticipated to last for.
Safety and other concerns related to the prescribed pain regimen such as:
– Opioids—Drug abuse potential, constipation, respiratory depression, and adverse effects.
– NSAIDs—GI, renal, and other toxicity.
– Antidepressants—Multiple drug–drug interactions.
– Antiepileptics—Dose restrictions in renal failure and other concerns.
• Recommended screening tools to be used for the patients with substance abuse history:
Opioid risk tool [12].
CAGE substance abuse screening tool [13].
• Conduct an interview about any personal and/or family history of substance abuse and personal history of anxiety, depression or other.
• Tips to consider when managing patients with increased risk of opioid use disorder:
Use only one prescriber (or one team if a group practice).
Always consult with prescription monitoring programs if available in your state.
Contact retail/dispensing pharmacy if there is a high suspicion of opioid use disorder and the patient reports challenges/issues such as lost prescriptions.
Consider transdermal formulations such as the Fentanyl transdermal patch as they are difficult to tamper with. Consider other tamper-proof opioids, such as methadone or morphine (lowest street value medications).
For patients with repeated suspicious behavior (running out of medications, reports of repeated loss of medications or prescriptions), you may need to give a limited amount for 3–7 days instead of monthly refills (more time-consuming, more complex with insurance coverage, higher copays for the patient).
Factors that increase risk for opioid overdose include history of overdose, substance abuse disorder, higher opioid dosages, and concurrent benzodiazepine use.
Engage other members of a multidisciplinary team, e.g., social worker, psychiatry, patient representative, if needed, an addiction counselor.
Consider a peer review process for complex cases.
Establish goals of opioid treatment, timeline, and the plan of tapering at the first appointment and reinforce at each visit.
• Address potential system barriers such as:
Access to analgesics of choice.
Patient Reported Outcomes
Patient-reported outcomes (PROs) such as pain and other symptoms are commonly measured not only in research, but more commonly now in routine clinical care for symptom screening and to enhance communication, particularly those addressing chronic illnesses that impact patient quality of life and their activities of daily living. Use of PROs in performance evaluation is closely related to a growing interest in integrating PROs into electronic health records systems and patient portals [14]. Evidence demonstrates that patient reporting can improve communication, satisfaction, and symptom management [15,16]. There is evidence to support PRO in assessing baseline pain and changes in pain, analgesia, and analgesic-induced side effects in an effort to improve analgesia [17] (Tables 6.1 and 6.2).
Table 6.1
Opioids—Initial Dosing Recommendations for Opioid-Naïve Patientsa
| Medication (Common Brand Name) | Oral | Parenteral |
| Morphine | 7.5–15 mg q 3–4 h | 2.5–5 mg q 3–4 h |
| Hydromorphone | 2 mg q 3–4 h | 0.2 mg q 3 h |
| Oxymorphone | 5–10 mg q 3 h | 0.5–1 mg q 3 h |
| Levorphanol | 2 mg q 6 h | – |
| Codeine | 30–60 mg q 3–4 h | 15–30 mg q 3–4 h |
| Hydrocodone | 5/325 mg q 4 h | – |
| Oxycodone | 5–10 mg q 4 h | – |
| Tramadol | 25–50 mg q 6 h | – |
aas needed for pain.
Table 6.2
| Equianalgesic Doses (mg) | Caution in: | ||
| Drug | Parenteral Dose | Oral Dose | |
| Morphine | 10 | 30 | Renal insufficiency—avoid or dose reduce |
| Fentanyla | 0.1 | ||
| Hydrocodone | NA | 30 | |
| Hydromorphone | 1.5 | 7.5 | Renal insufficiency—dose reduce |
| Methadoneb | 1 | 2 | |
| Levorphanol | 2 | 4 | |
| Oxycodone | 10 | 20 | Renal insufficiency—dose reduce |
| Oxymorphone | 1 | 10 | Renal insufficiency—dose reduce |
| Tramadol | 100 | 120 | Renal insufficiency—dose reduce |
aUnidirectional rotation. If opioid-naïve patients, consider, 10 mg IV morphine being equivalent to 100 mcg of fentanyl. If opioid-tolerant, 10 mg of IV morphine is equivalent to approximately 250 mcg of IV/transdermal fentanyl 19.
bSee Table 6.3 for dose-dependent methadone conversion ratios. This is unidirectional.
Source: Miaskowski C, Bair M, Chou R, D’Arcy Y, Hartrick C, Huffman L, et al. Principles of analgesic use in the treatment of acute pain and cancer pain. 6th ed. American Pain Society; 2008.
Management of Pain
Pain management includes both the use of pharmacological and nonpharmacological approaches.
Pharmacologic Management of Pain
• The World Health Organization (WHO) and National Comprehensive Cancer Network (NCCN) Adult Cancer Pain Management have developed guidelines for the pharmacologic management of pain [18,19].
• The WHO analgesic “ladder” for cancer pain relief in adults recommends starting with a nonopioid then gradually escalating to a mild opioid and further escalating to a strong opioid as necessary [18].
Step 1: Use acetaminophen, NSAIDS or adjunct analgesic.
Step 2: Use a mild opioid with or without an adjunct analgesic.
Step 3: Use a strong opioid (e.g., morphine, hydromorphone, fentanyl, and hydrocodone) with or without an adjunct analgesic (variety of drug classes including anticonvulsants, antidepressants, muscle relaxants, and corticosteroids) (Table 6.3).
Table 6.3
Suggested Starting Doses for Nonopioids
| Medication | Oral | Parenteral |
| Acetaminophen | 650–1000 mg every 8 h | 650–1000 mg every 8 h |
| Ibuprofen | 400–600 mg every 6 h | N/A |
| Ketorolac | – | 15–30 mg every 6 h (limit to 3–5 days) |
| Gabapentin | 100–300 mg at bedtime | N/A |
| Pregabalin | 150 mg daily | N/A |
| Dexamethasone | 4 mg every 12 h | 4 mg every 12 h |
| Cyclobenzaprine | 5 mg every 8 h | N/A |
• Have a long-term treatment plan: prescribing medications, when and how to increase or decrease the dose of medications, and the frequency of follow-up appointments for monitoring of outcomes, side effects, and risk factors. Communicate this plan to the patient clearly. For example, patients treated for acute pain on opioids will more often than not be titrated off these medications slowly to avoid withdrawal.
• The FDA does not mandate any specific time interval to manage patients on controlled substances. Follow the administrative requirement for controlled substance prescribing in your respective state. For example, in New York State, the Prescribing Monitoring Program Registry (PMP) is an electronic system used to review a patient’s prescription history of controlled substances [20].
• Be aware of important drug–drug interactions
Example: Patients being initiated on methadone who are currently on antidepressants with CYP3A4 inhibiting activity. These antidepressants could slow the metabolism of methadone and potentially increase serum levels and possibly cause toxicity issues.
Nonpharmacologic Management of Pain
• Other nonpharmacologic approaches to managing pain include alternative and complementary medicine, which includes guided imagery, music therapy, acupuncture, and massage therapy [21–23]. These various modalities have been shown to improve pain when used either alone or in combination with pharmacologic approaches.
• Acupuncture has been shown to be effective for cancer-related pain and postoperative pain [24]. Pain intensity levels decreased by 36% by 2 months from baseline in the treatment group compared to placebo [25].
• Music therapy is also able to relax patients and make pain bearable [26].
• Interventional pain management
Certain procedures (radiotherapy, nerve blocks, e.g., celiac plexus blocks for pancreatic cancer patients, intrathecal pump placements) can alleviate pain in oncology patients.
The appropriate service should be consulted when a patient is being considered for these alternative options for pain management.
Patient Case 1.1
Mr. RJ is a 71-year-old man with a newly diagnosed locally advanced SCC of the supraglottic larynx. He has a sore throat and has trouble swallowing due to pain and mechanical dysphagia. The plan is to start radiation therapy. The following information is gathered during his pain assessment.
• Location of pain: Base of throat
• Intensity: 7/10 on the numerical pain rating scale
• Aggravating factors: Swallowing
• No prior or current substance abuse, psychiatric history, or psychosocial issues
Mr. RJ also reports that he has tried over-the-counter acetaminophen and ibuprofen with not much relief. What pain medication would you recommend?
• Based on Mr. RJ’s assessment, a short-acting opioid to be administered as needed may be worth considering. (See Table 6.1 for opioid options to consider as needed for opioid naïve patients.)
morphine 7.5–15 mg by mouth every 3–4 hours as needed for pain.
oxycodone 5 mg PO q 3–4 h as needed for pain.
Hydromorphone 2–4 mg PO every 3–4 hours as needed for pain.
In the setting of aggravated dysphagia or where the patient is unable to swallow tablets, consider the liquid formulation.
It may be appropriate to start a constipation prophylaxis regimen particularly if the patient is taking the opioids frequently. Consider a stimulant laxative and a stool softener.
Maintain a pain diary to document usage and side effects.
Counsel patient to store opioids in a safe place, not to share medications with others.
Patients on opioids can experience various side effects such as nausea, vomiting, itching, dizziness, confusion, hallucinations, and constipation (Table 6.4).
Table 6.4
Opioid Adverse Effects and Possible Treatment Options
Patient Case 1.2
Mr. RJ returns in 1 week with reports of good analgesia and some constipation. He states he is afraid to fall asleep because of increased pain should he miss a dose of the short-acting opioids. He reports that he is taking medications every 3 or 4 hours around the clock. What would be an appropriate next step?
• This patient would benefit from a long-acting opioid and a short-acting opioid for breakthrough pain
• Calculate the total effective 24 hour opioid dose.
• Give this dose in a long-acting opioid formulation, e.g., Morphine extended release, oxycodone extended release, and fentanyl transdermal patches.
• Give 10–20% of the 24 hour total opioid dose of the long-acting opioid every 3 or 4 hours as needed for pain.
• In patients with dysphagia, the fentanyl transdermal patch might be an option to consider (avoidance of oral route). Methadone is available in liquid form, and may be appropriate for patients with difficulty swallowing tablets, however, some patients might not tolerate the taste (some patients find it bitter).
Start a scheduled constipation prophylaxis regimen, e.g., a stimulant laxative such as Senna 8.6 mg by mouth every 12 hours with a stool softener such as Docusate sodium 100 mg by mouth every 12 hours. Senna may be titrated up to four tablets twice daily as tolerated.
Maintain a pain diary to document usage and side effects.
Counsel patient to store opioids in a safe place, not to share medications with others.
Patient Case 1.3
Mr. RJ starts radiation therapy and reports mucositis pain, skin pain, and allodynia and more opioid requirements.
• May consider starting gabapentin and titrating to effect (maximum dose 3600 mg). Gabapentin has been showing promising results and possibly reduces opioid requirements for patients with mucositis pain [27].
• Assess and escalate opioids as needed following the plan in case 1.2.
Patient Case 1.4
Mr. RJ calls the doctor’s office with a report of 10/10 pain rating. He sounds confused and is unable to report the location of his pain. He reports that he is unable to swallow much and unable to take his medications and he sounds very distressed.
• Mr. RJ might need an inpatient admission due to dose-limiting side effects (his medications might be causing confusion) and uncontrolled pain.
• Consider opioid rotation and IV administration of opioids.
• Opioid Rotation: In certain cases, a patient may need to be switched to another opioid due to a number of reasons (inadequate pain control, or intolerance to an opioid due to side effects). Additionally when converting from one opioid to another, one would need to factor in incomplete cross-tolerance. Using Table 6.2 for converting to another opioid, consider a 25–50% dose reduction in the total 24 hour opioid dose.
Calculate the total effective 24 hour opioid dose.
Choose another opioid and convert using conversion tables above.
Dose reduce by at least 25% to factor for incomplete cross-tolerance.
Patient Case 1.5
Radiation is completed for Mr. RJ and he would like to know how long his pain will last for.
Patient Case 1.6
You start to taper Mr. RJ off opioids as his pain symptoms have improved. After about 48 hours of tapering, the patient calls to complain of diarrhea, yawning, sweating, and dysphoria.
• This is physical withdrawal which is expected and a slower taper is required.
• Symptoms of withdrawal include dysphoric mood, nausea or vomiting, muscle aches, lacrimation or rhinorrhea, pupillary dilation, piloerection or sweating, diarrhea, yawning, fever, and insomnia, and may present after discontinuation of opioids.
• Clonidine for withdrawal may be considered, and acetaminophen as needed.
• In some situations, one may need to refer to an addiction specialist for further opioid tapering.
Patient Case 1.7
Mr. RJ comes back 6 months later with recurrent disease and complains of pain. What pain medication do you start with?
• Assume he is opioid naïve and start with PRN opioids.
• Additional general tips for prescribing opioids:
Be cognizant of controlled substance prescribing [28].
The recommended starting doses of common opioids are presented in Table 6.1.
Comparable doses of opioids with each other are presented in Table 6.2. These equianalgesic data are based on single dose studies and cannot be relied upon solely.
Clinicians should monitor their patients on opioids and dose carefully in renally or hepatically impaired patients.
For patients with mucositis pain and being managed with systemic opioids, may consider topical opioids. Opioids may be combined with magic mouthwash and patients instructed to swish and spit for pain relief of mucosal ulcers however this remedy may or may not be helpful to all patients [29].
Topical anesthetics although widely used have not been shown to be effective with larger studies.
Opioids can cause adverse effects including sedation, opioid neurotoxicity, urinary retention, nausea, vomiting, delirium, constipation, and respiratory depression. These side effects are treatable and can be prevented [30].
In pain crisis, consider referring patient to the hospital for rapid opioid titration using IV medications including PCAs.
Methadone is a long-acting medication with complicated pharmacokinetic and pharmacodynamic properties and it may be safe to consider consultation with a pain management specialist (Tables 6.5–6.7).
• For further assistance with pain, consider consultation with pain management specialists especially if:
Unfamiliar with medication/dose.
Need help with pain diagnosis.
Table 6.5
Advantages and Disadvantages of Analgesics
| Medication/Medication Class | Advantage(s) | Disadvantage(s) |
| Nonopioid—Acetaminophen | No damage to gastric mucosa, no cognitive side effects, no constipation, minimal risk of addiction | No antiinflammatory effects, hepatotoxic at high doses; ceiling effect for analgesia |
| Nonopioid–NSAIDS | Antiinflammatory effects, no physical dependence, no cognitive side effects, no psychological dependence | Hematological effects, GI effects, cardiovascular effects (prothrombotic), renal effects, CNS dysfunction, bone density effects, ceiling effect for analgesia |
| Opioids | No ceiling effect | Constipation and other side effects (see Table 6.2), tolerance, addiction |
| Coanalgesics—Gabapentinoids | Minimal drug–drug interactions; may be particularly helpful for neuropathic pain; may reduce opioid requirements in radiation induced mucositis | May take 3–7 days after reaching therapeutic doses (often requires 2700–3600 mg/day for gabapentin) to achieve expected analgesia, need dose adjustment in RI |
| Coanalgesics—antidepressants | May be particularly helpful for neuropathic pain | Potential for more drug–drug interactions, e.g., tamoxifen with SSRI’s (decrease effect of tamoxifen), fentanyl with SSRI’s (risk of SS); may take 3–7 days after reaching therapeutic doses to achieve expected analgesia |
Table 6.6
| 24-h Oral Morphine (mg) | Oral Morphine:Methadone Ratio |
| 30–90 | 4:1 |
| 90–300 | 8:1 |
| >300 | 12:1 |
| >1000 | 20:1 (please consider pain specialist consult) |
| >2000 | 30:1 (please consider pain specialist consult) |
Important notes about Methadone
• Methadone is a long-acting opioid (half-life 15–60 h) with a duration of analgesia od 6–12 h.
• Methadone can prolong the QTC interval; may order baseline EKG at the initiation of methadone.
• Methadone should be administered every 8 or 12 h. Will recommend a short-acting opioid to be given for breakthrough pain. If methadone is given for breakthrough pain, consider 10% of the daily methadone dose.
• Strongly consider consult with a pain specialist when initiating patients on methadone, unless you have had prior training.
• Often requires hospital admission for IV admin by designated pain specialists.
Table 6.7
Adjuvant Analgesics and Their Use in Various Types of Pain
| Neuropathic pain | Gabapentinoids, antidepressants, ketamine*, anticonvulsants, lidocaine (topical) |
| Bone pain | Corticosteroids (e.g., dexamethasone; bone modifying agents such as bisphosphonates or denosumab; NSAIDS) |
| Muscle spasms | Muscle relaxants (e.g., cyclobenzaprine) |
Conclusion
There are several modalities to use in the management of pain. While there are general suggestions provided, treatment should be individualized for each patient. The most ideal pain management treatment plan should be multimodal in nature and incorporate both pharmacologic and nonpharmacologic approaches.
Glossary
Breakthrough pain: Pain that flares in a patient on chronic opioid daily treatment.
Equianalgesic dose: An equivalent dose of a medication when compared to the dose of another medication.
High risk behavior: According to the Substance Abuse and Mental Health Services Administration, it includes:
Stealing or borrowing another patient’s drugs;
Obtaining prescription drugs from nonmedical sources (friends, family, street);
Concurrent abuse of related illicit drugs;
Multiple unsanctioned dose escalations;
Incomplete cross-tolerance: An increased response to the new opioid when you change from an existing opioid to a new one (opioid rotation).
Opioid rotation: In certain cases, a patient may need to be switched to another opioid due to a number of reasons (inadequate pain control, or intolerance to an opioid due to adverse effects).
Opioid-tolerant: Using the Food and Drug Administration (FDA) definition, opioid-tolerant patients are taking 1 week or longer of at least:
Opioid-naïve: Patients who do not meet the above definition of opioid-tolerant, and who have not taken opioid doses at least as much as those listed above for 1 week or longer.
Tolerance: Requiring increased amounts of opioids to achieve desired effect or a diminished response in analgesia with continued use of the same dose of an opioid.
Withdrawal: The development of the following symptoms after discontinuation of opioids: dysphoric mood, nausea or vomiting, muscle aches, lacrimation or rhinorrhea, pupillary dilation, piloerection or sweating, diarrhea, yawning, fever, and insomnia.
List of Abbreviations
COPD chronic obstructive pulmonary disease
NSAIDS nonsteroidal antiinflammatory drugs