Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients

Abstract

Taxol produces neuropathic pain with three distinct zones of involvement in the extremities. Most distally is an area of on-going pain and proximal to this is a zone of sensory disturbance but not overt pain. These two areas were confined in all but one case to the glabrous skin of the hands and/or feet. More proximal is an area not recognized by the patients as involved with pain or sensory disturbance yet wherein quantitative sensory tests nevertheless reveal altered sensibility. Impairment of perception to light touch, normally conveyed by myelinated fibers, was dramatically altered in all three areas, being approximately 50-fold greater than normal in areas of pain and sensory disturbance as well as in areas of skin perceived by the patients as not affected. Impairment of perception to sharpness, normally conveyed by small myelinated fibers, was most pronounced in areas of on-going pain, intermediate in areas of sensory disturbance and near baseline in more proximal skin of chemotherapy patients. In contrast to mechanical sensibility, thermal thresholds for warm and heat pain detection were normal throughout. Finally, chemotherapy patients showed paradoxical burning pain to skin cooling that was most pronounced in proximal areas of skin thought to be unaffected by the patients, intermediate in the border zone of altered sensibility and least pronounced in areas of on-going pain. These data suggest that taxol produces a neuropathy characterized by pronounced impairment of function in A-beta myelinated fibers, intermediate impairment of A-delta myelinated fibers, and a relative sparing of C-fibers.