An Updated Understanding of the Mechanisms Involved in cHemotherapy-Induced Neuropathy

Abstract

The burdensome condition of chemotherapy-induced peripheral neuropathy occurs with various chemotherapeutics, including bortezomib, oxaliplatin, paclitaxel and vincristine. The symptoms, which include pain, numbness, tingling and loss of motor function, can result in therapy titrations that compromise therapy efficacy. Understanding the mechanisms of chemotherapy-induced peripheral neuropathy is therefore essential, yet incompletely understood. The literature presented here will address a multitude of molecular and cellular mechanisms, beginning with the most well-understood cellular and molecular-level changes. These modifications include alterations in voltage-gated ion channels, neurochemical transmission, organelle function and intracellular pathways. System-level alterations, including changes to glial cells and cytokine activation are also explored. Finally, we present research on the current understanding of genetic contributions to this condition. Suggestions for future research are provided.

Long-Lasting and Additive Analgesic Effects of Combined Treatment of Bee Venom Acupuncture and Venlafaxine on Paclitaxel-Induced Allodynia in Mice

“…Nevertheless, 7 out of 10 patients receiving paclitaxel develop a devastating dose-limiting side effect, paclitaxel-induced peripheral neuropathy [ 2 ]. The representative clinical manifestations of this unwanted neuropathy include overt numbness, tingling, ongoing pain, and allodynia, most of which progress symmetrically from the feet and hands [ 3 , 4 ]. This burdensome neurotoxic state can be sufficiently distressing to lead to temporary cessation or even termination of life-saving therapy, thereby ultimately affecting the survival likelihood [ 1 , 4 ].…”

“…The representative clinical manifestations of this unwanted neuropathy include overt numbness, tingling, ongoing pain, and allodynia, most of which progress symmetrically from the feet and hands [ 3 , 4 ]. This burdensome neurotoxic state can be sufficiently distressing to lead to temporary cessation or even termination of life-saving therapy, thereby ultimately affecting the survival likelihood [ 1 , 4 ]. Unfortunately, a satisfactory gold-standard monotherapy protocol is not currently available [ 5 ].…”

Inhibitory Effects of Columbianadin on Nociceptive Behaviors in a Neuropathic Pain Model, and on Voltage-Gated Calcium Currents in Dorsal Root Ganglion Neurons in Mice

“…Oxaliplatin is a platinum-based chemotherapeutic agent commonly used in the treatment of colorectal cancer. However, use of oxaliplatin causes a peripheral neuropathy that is associated with a characteristic sensory hypersensitivity triggered or exacerbated by cold temperature (Argyriou et al, 2013;Boyette-Davis et al, 2018). Like other types of neuropathic pain, current treatments for oxaliplatininduced pain are often not effective or with serious side effects.…”

Comparison of Chemotherapy Effects on Mechanical Sensitivity and Food-Maintained Operant Responding in Male and Female Rats

“…hypersensitivity is a sign of neuropathic pain, then one might also expect concurrent expression of other clinically relevant signs of pain, such as behavioral depression sufficient to interfere with activities of daily living (Dworkin et al, 2008). Moreover, insofar as chemotherapy-induced neuropathic pain manifests primarily as spontaneous shooting, throbbing, or stabbing pain (Kanbayashi et al, 2010;Pachman et al, 2016;Boyette-Davis et al, 2018), one might expect behavioral disruptions in the absence of explicit eliciting stimuli such as the probing with von Paclitaxel in male rats was the only treatment to produce a sustained decrease in foodmaintained responding that could potentially be related to sustained neuropathic pain. However, even with paclitaxel, this decrease in responding observed under the FR 5 schedule was relatively small compared to decreases produced at earlier times by other drugs, was not accompanied by a significant decrease in the reinforcing efficacy of food as assessed by behavioral economic analysis, was not associated with a decrease in sucrose preference, and was not apparent in females.…”