**3. Impact on quality of life**

The use of chemotherapeutic agents works by disrupting the cell cycle to prevent cell proliferation before it begins [4]. The negative of systemic chemotherapeutic agents is that normal cells, as well as malignant cells, are disrupted. This leads to untoward effects and longterm morbidities [4] that negatively impact functional ability and quality of life. Chemother‐ apy-induced peripheral neuropathy (CIPN) is the most common neurological side effect of chemotherapy [5]. This condition is characterized by damage to the nervous system that is a direct result of the medications associated with chemotherapy. Often, this damage to the central nervous system pain pathways results in neuropathic pain [6], frequently described as burning, paroxysmal, stabbing, or elective shock-like [7], 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

Little is known about the mechanisms responsible for the development of CIPN [4]. The peripheral toxicity involved with CIPN is specific to each chemotherapy drug class and appears to be dose and duration dependent. However, it can evolve even after a single-drug application [9]. The type and cause of neuropathy are dependent on the chemotherapy agent administered, with vincristine, paclitaxel, and cisplatin being the most neurotoxic [10].

Currently, prophylactic and symptomatic treatments have been ineffective because the neurobiology underpinning CIPN is not fully understood [11]. Thus, the purpose of this chapter was to outline the differences in treatment options available to patients with CIPN and analyze the benefits of exercise in the management of symptoms related to this disorder.

In healthy individuals, peripheral and central nervous system pain pathways function in a protective and adaptive manner [12]. The transduction, conduction, and transmission of nociceptor activity involve these pathways when carrying out activity within the cell. Whether induced by cancer or its treatments, damage to these pathways can result in neuropathic pain [13]. Discontinuation of treatment can result in the development of acute and chronic neurotoxic effects, and these effects can be seen immediately or within weeks or months after discontinuation. Symptoms seen immediately following the first course of treatment can often be contributed to vincristine and oxaliplatin-based regimens. Though both regimens typical‐ ly produce symptoms immediately following treatment, these symptoms vary between treatments. Vincristine use typically involves the cranial nerve and can lead to symptoms such as seizures, quadriparesis, and numbness. In contrast, oxaliplatin use often produces acute sensory symptoms seen in the mouth or throat that can be intensified by exposure to cold [14]. Regimens that do not present symptoms for up to several weeks after the final treatment may

Incidence of CIPN is estimated to range anywhere from 10 to 100%, depending on the antineoplastic agent, dose, and other factors as presented by the patient [16]. Patients previ‐ ously affected by diabetes, alcoholism, or inherited neuropathies may be at an increased risk

induce a length-dependent neuropathy on small fibers [15].

life, and relationships with others [2, 8].

436 Neurooncology - Newer Developments

**2. Etiology of CIPN**

Neuropathic pain negatively affects health-related quality of life. Specifically, decrements to physical [20–22], emotional [20, 21, 23], and social functioning [21, 22, 24] are noted in patients with CIPN. In addition, sleep [20, 21, 24, 25] and global quality of life [3, 26] are disturbed. The presence and severity of pain was reported to cause depression and anxiety in patients [20, 21, 23].
