Radiotherapy and Cancer Pain Syndromes

Treatment-induced acute pain syndromes are associated with most treatment modalities, including chemotherapy, hormone therapy, surgery, and radiotherapy. They range from postsurgical pain syndromes to chemotherapy-induced headaches, oral mucositis, toxic peripheral neuropathy, joint or muscle pain, diffuse (non-localized) bone pain, and hand-foot syndrome, which involves painful rashes on the palms and foot soles (sometimes associated with liposomal doxorubicin and capecitabine).2,3 

Up to 40% of patients undergoing palliative radiation for bone metastases experience a transient increase in bone pain, the severity of which might be reduced with dexamethasone.3 Radiation-induced neuropathy results from radiation damage to peripheral nerves.

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There are several types of radiotherapy-induced acute pain syndromes, including radiation mucositis; radiation cystitis (inflammation of the bladder or urethra); radiation enteritis and proctitis, affecting patients undergoing abdominal or pelvic radiotherapy; and radiation-induced neuropathy.2,6,8 Acute radiation oral mucositis involves radiation damage and painful inflammation of the wet mucous membrane lining the oral cavity, and can make swallowing painful, leading to dehydration and malnutrition.

Radiation mucositis can also become a chronic complication of radiation, persisting after treatment.8 More than 80% of patients undergoing radiotherapy for head and neck cancers will experience radiation oral mucositis.8 It often leads to the use of feeding tubes.

Chronic or late, postradiation pain syndromes include radiation-induced dermatitis, lymphedema (a complication of irradiation to the breast, shoulder, or pelvis6), neuropathy (which can be progressive, irreversible, and resists most treatments), peripheral nerve entrapment or compression, radiculopathy (resulting in numbness, pain, or weakness of the wrist and hand), spinal myelopathy (a rare complication of irradiation of the spine9), osteonecrosis (also known as osteoradionecrosis, bone death) and osteoporosis, noncardiac chest pain, and pelvic pain syndromes.2,6,8 Radiation-induced plexopathy (RIP) is a rare delayed chronic condition that can result from irradiation of the chest wall or neck.6

These radiation-induced chronic pain syndromes will become more common in the coming years as the population ages, survivorship improves, and more survivors undergo radiation oncology care.8

Radiation-induced neuropathy is rare but potentially catastrophic for patients who have undergone radiotherapy; it emerges after treatment, is progressive, and can be irreversible and frequently resistant to treatment.

Identification of cancer pain syndromes involves differential diagnosis of possible syndromes based on tumor biology and treatment. Keep in mind that new forms of pain in patients with cancer is not always caused by cancer. Particularly in elderly patients, bone pain can be caused by metastatic tumors or it can be caused by osteoporosis-associated fractures.2

Managing Cancer Pain Syndromes

There is no one-size-fits-all solution to managing cancer pain, and the evidence base for treating cancer pain syndromes is limited compared to the clinical evidence for cancer treatment. Treatment options depend on the pathophysiological causes of a patient’s pain, and patient preferences and goals.

For mild to moderate pain, acetaminophen (up to a maximum dose of 4000 mg) or aspirin, sometimes in combination with opioids such as codeine, hydrocodone, or oxycodone, can offer relief.2 Severe pain is more commonly managed with morphine, hydromorphone or oxycodone, methadone, or fentanyl, with switching or rotation between opioids or dose reduction when efficacy wanes or dose-limiting side effects occur. Doses should be escalated incrementally for breakthrough pain.2 (Adverse effects of opioid treatment can include confusion, constipation, and nausea or vomiting, which can be treated with medications.2)

Adjuvant analgesics include topical viscous lidocaine for radiation mucositis-associated ulcerations of the mouth and pharynx, and corticosteroids, particularly in cases of inflammation- or intracranial pressure-associated pain, spinal cord compression, metastatic bone pain, tumor-caused neuropathic pain, or lymphedema.2 Low dose dexamethasone (1-2 mg twice daily) can help ease pain in patients with advanced-stage cancers, and higher doses might offer temporary respite from opioid-resistant and severe acute pain caused by spinal cord compression, or very severe bone pain.

Neuropathic pain syndromes are more treatment resistant than others. Some antidepressant tertiary amine tricyclic medications, like amitriptyline, can offer analgesia for neuropathic pain.2

Palliative anticancer treatment can slow tumor growth or temporarily reduce tumor mass, reducing tumor-caused pain. Palliative or analgesic radiotherapy can be used to target pain syndromes specifically related to tumor growth, for example.2 Radiotherapy is a gold standard treatment for painful bone and cerebral brain metastases. For obstructive visceral pain, surgery is sometimes attempted. Refractory limb tumor causing severe pain is sometimes treated with amputation, but the pain-relief benefits are complicated by surgical risks, postsurgical hospitalization and rehabilitation, and whether or not other metastatic tumors limit the likely benefits of such a radical step.2


1. Yang GS, Barnes NN, Lyon DE, Dorsey SG. Genetic variants associated with cancer pain and response to opioid analgesics: implications for precision pain management. Semin Oncol Nursing. 2019;35(3):291-299. doi:10.1016/j.soncn.2019.04.011

2. Cherny N, Carver A, Newton HB. Chronic cancer pain syndromes and their treatment. In: Newton HB, Malkin MG, eds. Neurological Complications of Systemic Cancer and Antineoplastic Therapy, 2nd ed. Elsevier/Academic Press; London, UK; 2022:587-610.

3. Brant JM. The assessment and management of acute and chronic cancer pain syndromes. Semin Oncol Nursing. 2022;38(1):151248. doi:10.1016/j.soncn.2022.151248

4. Strang P. Existential consequences of unrelieved cancer pain. Palliat Med. 1997;11(4):299-305. doi:10.1177/026921639701100406

5. Arnstein P. Adult cancer pain: an evidence-based update. J Radiol Nursing. 2018;37(1):15-20. doi:10.1016/j.jradnu.201.10.009

6. Portenoy RK, Ahmed E. Cancer pain syndromes. Hematol Oncol Clin North Am. 2018;32(3):371-386. doi:10.1016/j.hoc.2018.01.002

7. Webb JA, LeBlanc TW. Evidence-based management of cancer pain. Semin Oncol Nursing. 2018;34(3):215-226. doi:10.1016/j.soncn.2018.06.003

8. Karri J, Lachman L, Hanania A, et al. Radiotherapy-specific chronic pain syndromes in the cancer population: an evidence-based narrative review. Adv Ther. 2021;38(3):1425-1446. doi:10.1007/s12325-021-01640-x

9. Radiation Myelopathy. Accessed November 22, 2022.