For several years, Dr. Wonders has extensively investigated the effects of exercise on chemotherapy induced peripheral neuropathy and cancer treatment related pain. This blog post summarizes the results of multiple investigations conducted by our lab. Citations of these publications are at the conclusion of this post.
Treating cancer requires an understanding of cellular kinetics.
To break that down means this — In a normal cell cycle, DNA repair is regulated by various checkpoints. However, in cancer cells, DNA mutations often occur during DNA replication. This impacts the regulatory mechanisms and leads to uncontrolled cell division. Ultimately, this leads to tumor growth.
Chemotherapy works by interrupting the cell cycle to prevent cell proliferation. Essentially, the medicine weaves itself into the DNA of the cells and unravels it, so that the cell can no longer divide.
This is very effective at destroying cancer cells.
The downside is that most chemotherapy agents cannot tell the difference between a cancer cell and a healthy cell. It is programed to find every cell in the body that is in one specific stage of division, intercalate its DNA, and destroy that cell. This leads to side effects and long-term morbidities that negatively impact functional ability and quality of life.
The most common neurological side effect of chemotherapy is chemotherapy induced peripheral neuropathy (CIPN). It is estimated that the incidence of CIPN ranges anywhere from 10 to 100%, depending on the type of chemotherapy, dose, and patient factors. Patients at an increased risk for CIPN include those who are previously affected by diabetes, alcoholism, or inherited neuropathies.
CIPN is characterized by damage to the nervous system that is a direct result of certain types of chemotherapy. While all drugs do not have the same potential toxicity, vincristine, paclitaxel, and cisplatin are the most neurotoxic. In most cases, CIPN appears to be dose and duration dependent. However it can evolve even after a single drug application.
Often, the damage to the central nervous system pain pathways observed with CIPN results in neuropathic pain, frequently described as burning, paroxysmal, stabbing, or electric shock-like, and is accompanied by pins-and-needles sensations and itching.
The presence and severity of neuropathic pain is often shown to be associated with impairments in walking, general activities, sleep, work, mood, enjoyment of life, and relationships with others. This negatively impacts quality of life, and often leads to depression and anxiety in patients.
Due to the wide variety of symptoms and their negative impact on quality of life, treatment of neuropathic pain due to CIPN often requires a multidisciplinary approach. Effective treatment strategies may include a combination of pharmacological agents and exercise rehabilitation.
Pharmacological agents often are associated with many negative side effects that could further interfere with quality of life. Therefore, this post will focus on the safety and effectiveness of exercise oncology programs.
While the mechanisms underlying the role of exercise in neuroprotection are unclear, several theories have been circulated.
- Muscle Weakness: With neuropathy, muscle atrophies and causes significant decreases in muscular strength. This decline in strength appears to be slow and progressive, affecting distal muscle groups more so than proximal muscles. Researchers have indicated that this muscle weakness translates into impaired motor performance skills and a reduced exercise capacity. However, several studies have reported improvements in muscular strength following moderate resistance exercise programs in patients with hereditary motor and sensory neuropathies, as well as diabetic neuropathies, and those associated with Fibromyalgia and chronic fatigue.
Moderate to intense strength training and aerobic exercise appears to be well tolerated by patients with CIPN, and is associated with improvements in motor function and nerve conduction velocity, as well as improved muscle reinnervation and increased axon regeneration. Specifically, research has demonstrated that low intensity treadmill exercise promoted Schwann cell proliferation in an injured peripheral nerve.
In light of these findings, it is feasible to assume that an individual who has experienced a reduction in muscular strength and functional ability due to CIPN may experience similar improvements following an exercise program.
- Decrease in Pain Perception: A second benefit of exercise rehabilitation in the CIPN population may be a reduction in pain associated with peripheral neuropathy. This pain has long been recognized as one of the more difficult types of pain to treat, and often is so severe that it interferes with an individual’s quality of life.
In healthy subjects, both aerobic and resistance exercise have been shown to transiently decrease pain perception; a condition referred to as Exercise-Induced Hypoalgesia (EIH).
EIH has also been observed in breast cancer patients diagnosed with CIPN who met the amount of recommended physical activity levels. Specifically, unpleasant skin sensations and sensitivity related to neuropathic pain were attenuated following chronic exercise training.
Exercise Program Recommendations
The goals of the exercise program should be to maximize functional capacities, prolong or maintain independent function, and improve quality of life. It should also help patients adapt to changes in physical functioning.
Previous studies indicate that low to moderate intensity resistance training result in strength gains that improve functional ability. However, it is important to watch for signs that indicate that the muscles are being over-exercised. Symptoms of this would include muscle weakness within 30 minutes of the completion of exercise and excessive muscle soreness between 24-48 hours after the bout of exercise.
Aerobic exercise training should also be part of an exercise program, with the intent to increase cardiovascular performance and pain tolerance, and decrease fatigue and depression scores. Available data suggests that the endurance exercise program should be low impact; approximately 50% of the patient’s heart rate reserve and must include a proper warm up and cool down component.
In closing, CIPN is a dose-limiting effect of cancer therapy that has negative implications on a patient’s quality of life. While much effort has been made to explore pharmacological therapies aimed at cancer patients, exercise rehabilitation is one lifestyle modification that safely and positively impacts the lives of patients with CIPN.
Exercise is Medicine!
Further your understanding of this topic by reviewing our published research on this topic:
Wonders, K.Y., Stout, B. (2016). The Role of Exercise in Chemotherapy-Induced Peripheral Neuropathy. Neurooncology. In Tech.
Wonders, KY (2014). The Effect of Supervised Exercise Training on Chemotherapy-Induced Peripheral Neuropathy. International Journal of Physical Medicine and Rehabilitation. 2:(4) 210-215.
Wonders, KY, Bergman, D., & Drury, DG (2014). An Investigation of the Maxagrip Handle Design on Muscular Strength and Gripping Comfort: A Pilot Study. Journal of Exercise Physiology, Online. 17(3):46-57.
Wonders, KY, Whisler, G., Loy, H., Holt, B., Bohachek, K., Wise, R. (2013). Ten Weeks of Home-Based Exercise Attenuates Symptoms of Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer Patients. Health Psychology Research Journal, 1(3):149-153.
Wonders, KY & Drury, DG (2012). Current exercise behaviors of breast cancer patients diagnosed with chemotherapy-induced peripheral neuropathy. Journal of Integrative Oncology, 1(1): 103-107.
Wonders, KY & Drury, DG. (2011). Exercise intensity as a determinant of exercise induced hypoalgesia. Journal of Exercise Physiology online,14(4):134-144
Wonders, KY. Reigle, BS, & Drury, DG. (2010). Treatment strategies for chemotherapy-induced peripheral neuropathy: Potential role of exercise rehabilitation. Oncology Reviews, 4(2): 117-25.
Wonders, KY & Drury, DG. (2010). Orthostatic-induced hypotension attenuates cold pressor pain perception. Journal of Exercise Physiology, online, 13(1): 21-32.