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Many chemotherapy regimens can damage nerves that serve most of the body, called peripheral nerves. This damage, technically called chemotherapy-induced peripheral neurotherapy (CIPN), causes pain in about 60% of chemotherapy- treated patients.1 While it often begins after the later cycles, it can linger for years.
Current pharmaceutical medications provide marginal relief or have risk for unacceptable side effects. New treatment ideas are needed.
Adenosine, a structural component of your DNA, acts as a signaling molecule of injury or stress. Study contributor Dr. Janes2 says that “it plays an important role in many processes including pain. [Its] extracellular concentration can increase up to 1000 fold.” These high concentrations of adenosine can activate nerve cells from the central nervous system (neurons, astrocytes, and microglia cells) that can signal pain. At least three main types of receptors exist for adenosine. Understanding these receptors may be key for combating nerve pain as a result of chemotherapy.
Scientists and clinicians worked for a decade on compounds that blocked two types of receptors for adenosine: A1AR, A2AR. However, these compounds showed too many cardiovascular side effects.
In contrast, Dr. Salvemini and her group reported in a study that activating a third type of adenosine receptor, A3AR, could alleviate persistent pain—chronic pain.3 Dr. Salvemini says that “We have identified selective orally bioavailable A3AR agonists as potent non-narcotic analgesics.”2 They have tested the receptors in animal models and found that they can reduce pain caused by chemotherapy.2
Update: The A3AR receptors are being tested in phase II/III clinical trials currently.2
What causes peripheral pain?
Peripheral pain is linked to:
- activation of cells called astrocytes,
- high levels of inflammation,
- low levels of compounds (IL-10, IL-4) that turn off inflammation,
- and a feedback loop in glial cells (cells that live in the central nervous system) that amplifies the inflammatory signals and helps the pain become and stay chronic.2
Can other things affect these inflammatory signals also?
Yes. A class of essential nutrients, omega-3 oils act as building blocks for mediators that turn off or dim the fires of inflammation. Membranes of our cells contain mixtures of essential fats, including omega-3 oils and omega-6 oils, cholesterol, etc. Most Americans eat too many foods containing lots of omega-6 oils (vegetable oils), which are found especially in processed foods. Thus, it may be useful to eat enough natural foods to reach a healthy ratio of beneficial oils which is approx 4 units of Omega 6 oils to 1 unit of omega-3 oils. Eating more foods rich in omega-3 oils may help reduce inflammation: foods like wild salmon, cod, walnuts, and freshly ground flaxseed.
Vitamin Bs are also important for calming the inflammatory response. For example, “the grade 3/4 toxicities of the combination arm, particularly leucopenia, neutropenia and diarrhea, were found to be greatly improved by the addition of vitamin B12 and folic acid” states Dr. Dundar.4
Two tips for some immediate relief:
1. Check your eating habits now. Do you eat foods with at least 2 grams of omega -3 oils daily? If not, adding a serving of cod, or wild caught salmon or a small handful of walnuts may help. Since the ratio of types of fats is also very important, consider replacing processed foods like potato chips with a baked potato or a baked sweet potato. Start by replacing one processed food a day with a piece of fruit, a vegetable like raw carrot, few slices of cucumbers, handful of nuts, etc.
2. Eat meals with foods that contain the nutrients you need, especially omega-3 oils and vitamin Bs, which are found in shellfish, fish, meats, whole grains, and green leafy greens.
Janes K, Esposito E, Doyle T et al. A3 adenosine receptor agonist prevents the development of paclitaxel-induced neuropathic pain by modulating spinal glial-restricted redox-dependent signaling pathways. Pain 2014;155(12):2560-2567.
Janes K, Wahlman C, Little JW et al. Spinal neuroimmune activation is independent of T-cell infiltration and attenuated by A3 adenosine receptor agonists in a model of oxaliplatin-induced peripheral neuropathy. Brain Behav Immun 2015;4491-99.
Little JW, Ford A, Symons-Liguori AM et al. Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states. Brain 2015;138(Pt 1):28-35.
Dundar Y, Bagust A, Dickson R et al. Pemetrexed disodium for the treatment of malignant pleural mesothelioma: a systematic review and economic evaluation. Health Technol Assess 2007;11(1):1-90.
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