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L i s te n to T h e A B M P Po d c a s t a t a b m p.co m /p o d c a s t s o r w h e reve r yo u a cce s s yo u r favo r i te p o d c a s t s 33 A LITTLE NERVOUS SYSTEM REVIEW To talk about CIPN and the role massage therapy might play in this context, it will be useful to do a short review of some structure and function of the nervous system. Leaving out higher levels of consciousness (involving emotion, memory, learning, executive function, and all the fun stuff ), the nervous system operates in three main functional domains: motor function, sensory function, and autonomic function. Motor function describes how voluntary and reflexive messages that initiate in the central nervous system are passed along neuron fibers that carry those messages to muscles and glands. The muscles and glands then contract or secrete. They stop contracting and secreting when the impulses stop. Sensory function describes how impulses are generated in the body and passed via both simple and complex pathways up the spinal cord and into the brain. There, they are sorted, recognized, and assigned meaning. Sometimes that meaning elicits a motor response that initiates in the spinal cord, brain, or both. Autonomic function involves both sensory and motor fibers that help regulate our autonomic nervous system. These sympathetic and parasympathetic responses allow us to adapt and respond to our environment while we try to maintain a steady internal state. Neurons in the peripheral nervous system may be classified as small- and large- fiber neurons, which refers to their diameter and whether they are myelinated. Large-fiber neurons are myelinated, so their impulses travel quicker than the small-fiber neurons. Motor neurons that carry messages to muscles are large-fiber neurons. Sensory neurons that carry messages about position in space, vibration, and touch are also large-fiber neurons. Small-fiber neurons carry sensory messages about damage (nociception) and temperature. Some autonomic motor messages are also carried via small- fiber neurons. These messages control sweating, blood pressure, GI tract activity, and other autonomic functions. CIPN PATHOPHYSIOLOGY CIPN can develop with several different classes of chemotherapy agents, and the nerve damage can take several different forms. Unfortunately, depending on the type of cancer, the most effective chemotherapy drugs are often the most neurotoxic. Neuron damage can involve microtubule disruption (these are the organelles that deliver molecules through the long axons of peripheral nervous system neurons); oxidative stress that accompanies mitochondrial damage; and changes to the function of ion channels along the cell membranes, damage to myelin sheaths, and neuroinflammation, among other issues. CIPN can develop with a single treatment of a specific drug, or it can develop over time as a chemotherapy treatment course progresses. CIPN can be severe enough that patients need to delay their treatment while they recover, and, of course, this may have negative consequences for patient outcomes. But perhaps the most insidious aspect of CIPN is that, for many patients, it only develops after their chemo has concluded—and then continues to get worse for weeks, months, or longer. CIPN is extremely resistant to treatment with conventional interventions. This means a lot of cancer patients successfully conclude their treatment, which is great, but they now have a long-term, sometimes permanent, challenge with nerve damage. A handful of small-scale studies, including case reports and clinical trials, suggest that skilled massage therapy could have a positive impact on CIPN, both as a treatment and as a possible preventive measure. CIPN SYMPTOMS CIPN symptoms can include any combination of problems with sensation, motor control, and autonomic function. However, sensory problems are the most commonly reported symptom. Some versions of CIPN appear to target small-fiber neurons, while others target large-fiber neurons, and some affect both. The symptoms patients experience reflect what kinds of neurons have been affected. Damage to large-fiber neurons can affect motor function, where reflexes may be slowed. And impaired large-fiber sensation feels like the person is always wearing thick gloves or socks. Perception from the skin is dulled and imprecise, and it is difficult to perform fine motor skills like buttoning a shirt or picking up coins if sensation is muffled in this way. And because proprioceptors may also be affected, the sense of position in space may be altered, which raises the risk for falls. Damage to small-fiber sensory neurons can change the way temperature is interpreted (it could be hyper- or hyposensitive). Nociception may be accentuated, and signals can occur without any stimulus, which is called spurious sensation. Allodynia, the experience of pain