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What is cancer-related neuropathic pain? How many patients suffer from cancer-related neuropathies?
Almost 50% of patients with cancer complain of chronic and persistent pain, of which, 20% of the individuals report having a neuropathic type of pain, compared to 7-8% in the general population. Approximately 39% of patients with cancer report a mixed type of pain, which typically include neuropathic and nociceptive types of pain. Neuropathic pain is characterized by a sensation of sharp, pricking, burning, electric or pins and needles, and may include additional symptoms such as loss of touch and pain or redness and swelling (aka autonomic symptoms). On the other hand, nociceptive pain typically refers to a ‘nociceptive’ input perceived by the body’s pain receptors which may occur when a tumor starts encroaching nearby tissues causing the receptors to be activated. The nociceptive type of pain can, therefore, originate from musculoskeletal (muscles, bone), cutaneous (skin), or visceral (inner organs and their linings) tissues. Read more about the different types of cancer-related pain here.
Neuropathic pain can develop either (a) from a growing tumor or cancerous tissue compressing the surrounding nerves or (b) due to cancer-related treatments such as chemotherapy and radiotherapy. Better understanding of the origin and contributing factors to the cancer-related pain improves the effectiveness of cancer management, and therefore, is considerably beneficial to both – the individuals suffering from cancer and who have survived cancer. Since almost 40% of patients have mixed neuropathic and nociceptive types of pain, cancer-related pain management can be of complex nature and continue to have a substantial impact on the lives of individuals with cancer.
Para neoplastic Neurological Syndromes (PNS) are rare autoimmune disorders associated with cancer, which are typically not caused by direct invasion, metastasis or consequences of treatment. Often, the PNS precedes the manifestations of cancer and can affect the function of nervous system, neuromuscular junction and muscle itself mimicking a ‘neurologic syndrome’. Prompt diagnosis and management includes detection of onconeural antibodies, cancer detection and treatment, immunotherapy and supportive therapies.
Why is it important to identify and treat cancer-related Neuropathic pain?
Cancer-related neuropathic pain is chronic and resistant to over‑the‑counter pain medications (aka analgesics). It can also reduce opioid responsiveness, thus making the management of this pain challenging. Although neuropathic pain is frequently experienced by individuals with cancer, it can remain undertreated due to under-diagnosing or under-reporting. Patients with neuropathic type pain report worse physical, cognitive and social functioning. This type of pain may not only interfere with social activities but also with employment rate and the amount of working hours put in by individuals. Neuropathic pain, therefore, needs optimal diagnosis and management as it amounts to a great economic and social burden on the patients and their community.
How does neuropathic pain secondarily develop from the cancer treatments?
Cancer treatments can result in multiple side effects, one of which is the development of neuropathic type of pain.
Radiotherapy or radiation therapy involves using ionizing radiation to kill malignant cancer cells, and can cause damage to the nervous system, mainly injuring the cranial or peripheral nerves which can clinically present as painful cranial neuralgias, brachial or cervical plexopathies. Radiotherapy induced neuropathic pain can sometimes take months or years to develop after the treatment and is generally severe, persistent and refractory to treatment, therefore, significantly impacting the quality of life of patients with cancer.
Chemotherapy Induced Peripheral Neuropathy (CIPN) is a known side effect of chemotherapy, which presents as numbness or tingling in the ‘stocking and glove’ distribution representing the areas of legs and hands. It can also result in walking difficulties and poor hand function, and is frequently caused by the damage to dorsal root ganglion within the spinal cord. Severe forms of CIPN has been reported in about 3–7% of patients treated with single agents and up to 38% in those treated with multiple chemotherapeutic agents. In a 2014 meta-analysis, CIPN was reported to be experienced by approximately 68% adults in the first month after chemotherapy, 60% at 3 months, and 30% at 6 months or more. Common neurotoxic chemotherapeutics which can result in this dose-dependent side-effect include the platinum drugs, taxanes (paclitaxel and docetaxel), vincristine, bortezomib (protease inhibitor). Currently there is minimal information on the prevention of CIPN and may instead require a chemotherapy schedule modification to limit its severity, which could further limit the treatment effectiveness for cancer.
There are a multitude of treatment approaches to cancer-related neuropathic pain. It’s management typically includes one or more components from the following:
Medical approach:
- Pharmacological:
- Gabapentin , pregabalin, carbamazepine (anti-epileptics)
- Duloxetin, venlafixine (serotonin-norepinephrine reuptake Inhibitors)
- Amitriptylin, nortriptylin (Tricyclic antidepressants).
- Corticosteroids (limited doses)
- Acetylcarnitine (antioxidants) to prevent nerve injury
- Opioids (recommended in severe pain)
- Interventional Pain procedures: Neuromodulation, scrambler therapy (electro-analgesia), chemical neurolysis, radiofrequency ablation of the pain pathways.
Physical or complementary approaches: Since fatigue, lethargy, pain and anxiety are clearly evident in patients with cancer, rest is typically advised. However, current and emerging evidence suggests otherwise.
- Physiotherapy or Physical therapy including balance and muscular strengthening exercises provide a significant analgesic effect in addition to enhancing the overall quality of life in individuals with cancer undergoing chemotherapy as compared to individuals who don’t exercise. Individuals with cancer who may or may not be undergoing cancer treatment significantly improve cancer-related fatigue, mood, sleep, anxiety and toning of their muscles with regular exercises. It has been shown that individuals living with breast cancer who engaged in 2.5-3 hrs/week of moderate level of exercise difficulty reported greater wellbeing, while men living with prostate cancer who walked for >4 hrs/week, decreased their mortality and therefore prolonged their life.
- Occupational therapy can similarly be beneficial in upper extremity strengthening and pain management allowing individuals living with cancer to return to their home activities and work occupations effectively.
- Both physical and occupational therapy can produce various chemicals in our body (including endorphins, serotonin, dopamine and norepinephrine) which reduce the perception of pain (like analgesic medications) and protect the neuron against toxic assaults.
Psychological support: is known to improve emotional well-being by impacting the release of serotonin which leads to a positivity in mindset.
Effective neuropathic pain management helps in improving the quality of life in patients with cancer. An approach tailored to each individual should be adopted combining the use of disease modifying therapies with other complementary and supportive therapies. Why suffer when together we can treat the neuropathic pain!
Dr Abhimanyu Rana
MBBS DNB DA FIPM
Consultant Pain medicine, Medanta hospital Indore. India.
Hina Garg
PT, MS, PhD, NCS, CEEAA
Rocky Mountain University of Health Professions
References
American cancer society guidelines.
Dhawan S, Andrews R, Kumar L, Wadhwa S, Shukla G. A Randomized Controlled Trial to Assess the Effectiveness of Muscle Strengthening and Balancing Exercises on Chemotherapy- Induced Peripheral Neuropathic Pain and Quality of Life Among Cancer Patients. Cancer Nursing. 2020;43(4):269-280.
Singh VK, Shetty YC, Salins N, Jain P. Prescription Pattern of Drugs Used for Neuropathic Pain and Adherence to NeuPSIG Guidelines in Cancer. Indian Journal of Palliative Care. 2020;26(1):13-18.
Tomasello C, Pinto RM, Mennini C, Conicella E, Stoppa F, Raucci U. Scrambler therapy efficacy and safety for neuropathic pain correlated with chemotherapy-induced peripheral neuropathy in adolescents: A preliminary study. Pediatric blood & cancer. 2018;65(7):e27064.
Nyatanga B. Physical exercise for those living with and beyond cancer: Changing perceptions in palliative caring. British journal of community nursing. 2017;22(6):308.
Helen L ,Matthew R. Cancer related neuropathic pain . Cancers(Basel).2019Mar;11(3):373.
Hue Jung Park. Chemotherapy induced peripheral neuropathic pain. Korean J anaesthesiology.2014 Jul; 67(1):4-7
Sudheeran Kannoth. Paraneoplastic neurologic syndrome: A practical approach. Annals of Indian Academy of Neurology. 2012;15(1):6-12.