Paclitaxel acute pain syndrome

Paclitaxel produces a disabling syndrome of subacute aches and pains in a majority of patients, which had been commonly referred to as arthralgias and myalgias. These symptoms generally begin 1 to 3 days after administration and are self-limited, usually resolving within a week. Symptoms have been described in large axial muscular and joint regions and generally are not accompanied by objective musculoskeletal or neurologic examination changes.The symptom location, temporal relationship, and self-limited nature of the syndrome make paclitaxel-induced acute pain syndrome (APS) distinct from paclitaxel-associated peripheral neuropathy. In the more distant past, the exact characterization of paclitaxel-induced APS had not been well defined. There had been very little known about how exactly patients characterize these symptoms or how these symptoms compare or contrast to symptoms of neuropathy. Given that paclitaxel, administered to rats, causes dorsal root ganglion injury by 24 hours, it was hypothesized that the APS may well be related to nerve pathology, as opposed to muscle and/or joint pathology. To address this topic, 18 patients, who noted the presence of subacute aches and pains following paclitaxel, participated in structured interviews to characterize their symptoms. Eighty-three percent of the patients (15/18) specifically denied joint or muscle pain. The pain commonly started 1 to 2 days after the paclitaxel infusion, with the median duration of pain being 4 to 5 days. Patients commonly described the discomfort as “aching” or “deep pain” that was “radiating,” “stabbing,” or “shooting.” The pain was usually generalized and located in the back, hips, shoulders, thighs, legs, and feet and, at times, radiated down the legs, arms, or back. It was concluded that the subacute paclitaxel-induced pain appeared to be related to a pathologic process in nerve tissue (e.g., sensitization of nociceptors or nociceptive fibers) as opposed to a musculoskeletal injury. Although this hypothesis has not yet been confirmed by neurological testing in humans, new supporting data has revealed that the degree of APS pain after the first dose of paclitaxel, in individual patients, positively correlates with the degree of more classic peripheral neuropathy 12 to 18 weeks later. Opioid medications are helpful for the treatment of this problem. 

Suggested Readings

Loprinzi CL, Maddocks-Christianson K, Wolf SL, et al. The Paclitaxel acute pain syndrome: sensitization of nociceptors as the putative mechanism. Cancer J. 2007;13:399-403. PMID: 18032978.