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Figure 3 Pain signaling occurs in four steps: transduction, transmission, modulation, and perception ( Following transduction, conduction occurs as nociceptive signals travel through myelinated A and unmyelinated C fibers toward the spinal cord ( in vitro models suggest that taxanes disrupt this process by impairing axonal transport and growth, reducing axonal length by approximately 50% and altering neuronal morphology ( fibers (active at the beginning and end of a continuous mechanical stimulus) (56) and A , contributing to mechanical allodynia (a non-painful stimulus producing a sharp pain response) and hyperalgesia (increased perception of pain) (57, 58)

doi: 10.1002/jobm.202100248 2 AbbasR.LuoJ.QiX.NazA.KhanI

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