Chemotherapy is a common contributor to peripheral neuropathy, and because of this, there have been efforts to both prevent and treat chemo-induced peripheral neuropathy (CIPN).  However, much of the work in this field has been hampered by difficulty in measuring this, as well as trials that are pretty small.

A couple have been the subject of trials that were negative, showing no benefit for the investigational agent, including the radioprotectant amifostine, the calcium channel blocker nimodipine, and some others.

A few have had some mixed and some positive results.  Among these, vitamin E has been suggested in trials to reduce the frequency and severity of CIPN, but as an anti-oxidant, there is some concern that it may compromise the effectiveness of chemotherapy.  Others that have looked favorable in small studies have included glutamine, glutathione, N-acetylcysteine, and calcium and magnesium infusions, though the last have raised some questions about being associated with reducing the efficacy of chemotherapy.   Overall, with most of these being such small trials, and without establishing that prevention of neuropathy occurs without a compromise of the effectiveness of the chemotherapy, none of these has become a standard treatment.   In the meantime, there are ongoing trials looking at whether certain approaches prevent CIPN, including acetyl-L-carnitine, vitamins B6 and B12, and alpha lipoic acid.

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Neuropathic pain is a common pain syndrome for patients with cancer. As I mentioned in my introductory pain post, neuropathic pain is one of the three main types of pain (somatic, visceral, and neuropathic).  It is nerve-related and is typically described as an electrical or burning sensation; it can occur both due to damaged peripheral nerves (outside of the spinal cord and the brain) or damage within the central nervous system (CNS, which includes the spinal cord and brain).   Because of associated nerve injury, some patients can develop decreased sensation or actual muscle weakness.  While there are certainly isolated instances of pure neuropathic pain, often neuropathic pain is part of a “mixed” syndrome in which a patient can have neuropathic pain in conjunction with the other types of pain as well.

Why does this pain develop when a nerve is damaged, even after the injury has occurred?   Nerves that are damaged can begin to have abnormal sensing—the pain fibers in the nerves can become more sensitive due to damage and can also trigger pain spontaneously.   In the spinal cord, the signals from pain can be amplified by nerve damage—this causes the pain response to be much higher than expected to minor stimuli (a bedsheet touching the feet or something cold hitting the skin).

In hearing about neuropathic pain, we often think of the hands and feet being affected and feeling paresthesias (pins and needles) there, but neuropathic pain can occur anywhere there are nerves.   In cancer, the mechanism of nerve injury can occur through three main ways:

1) direct pressing on the nerve by tumor

2) cancer treatments toxic to nerves

3) paraneoplastic syndromes where the cancer causes an abnormal reaction from the body’s autoimmune system against the nerves.  Paraneoplastic syndromes are much less common, so I won’t be discussing this.

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In reviewing posts from GRACE, it’s not surprising to see that pain is major issue for many patients with cancer. Pain is not unique to cancer, but for most patients with cancer, their pain is related to the cancer in some way. In cancer, the causes of pain not only include the disease itself, but also the treatments and procedures involved. There are particular types of pain and pain syndromes that are seen primarily in patients with cancer compared to other illnesses. Within oncology and pain management, cancer pain is so crucial for patient care that it has become essentially its own specialty in recent years. Dr. Janet Abrahm, an oncologist and cancer pain expert at the Dana Farber, has written one of the definitive texts on cancer pain management which is a major reference for this post.

Cancer-related pain can be categorized in several ways into what time course it follows. Patients who have acute cancer-related pain have pain that is expected to improve with cancer-directed therapy or, if it is a treatment-related complication, will resolve after treatment. Chronic cancer-related pain is not expected to resolve or its source cannot be eradicated. This chronic pain is very frustrating; similar to non-cancer patients with chronic pain, treatment focuses on therapies that can help patients function and improve their quality of life.

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