Paclitaxel, an effective anti-neoplastic agent in the treatment of solid tumors, produces a dose-limiting painful peripheral neuropathy in a clinically significant number of cancer patients. Prior work has demonstrated paclitaxel-induced neurodegeneration and sensory loss in laboratory rodents. We describe here an experimental paclitaxel-induced painful peripheral neuropathy. Adult male rats were given four intraperitoneal injections on alternate days of vehicle or 0.5, 1.0, or 2.0 mg/kg of paclitaxel (Taxol). Behavioral tests for pain using mechanical and thermal stimuli applied to the tail and hind paws, and tests for motor performance, were taken before, during and after dosing for 22-35 days. All three doses of paclitaxel caused heat-hyperalgesia, mechano-allodynia, mechano-hyperalgesia, and cold-allodynia, but had no effect on motor performance. Neuropathic pain began within days and lasted for several weeks. We did not detect any dose-response relationship. Tests at the distal, mid, and proximal tail failed to show evidence of a length-dependent neuropathy. Vehicle control injections had no effect on any measure. No significant systemic toxicities were noted in the paclitaxel-treated animals. Light-microscopic inspection of the sciatic nerve (mid-thigh level), L4-L5 dorsal root ganglia, and dorsal and ventral roots, and the gray and white matter of the L4-L5 spinal cord, showed no structural abnormalities. Electron microscopic examination of the sciatic nerve (mid-thigh level) and the L4-L5 dorsal root ganglia and dorsal horns demonstrated no degeneration of myelinated and unmyelinated axons in the sciatic nerve and roots, but revealed endoneurial edema. This model may be useful in understanding a significant source of pain in cancer patients, and in finding ways to avoid the neurotoxicity that limits paclitaxel therapy.

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Symptoms reported by patients themselves provide the necessary and different insight into cancer and its treatment, compared with those observed by clinicians. The use of patient-reported symptoms should be incorporated into routine clinical practice and not just research studies.

Collaborative on Countering the US Opioid Epidemic [8] has been focusing on comprehensive and collaborative efforts to fundamentally address the opioid epidemic crisis. All of these major initiatives emphasize pain education as a key component in the fight against the dual crises of chronic pain and the opioid epidemic. I am honored to represent the AAPM on the HHS Pain Management Task Force and the NAM Action Collaborative and contribute to these important initiatives of our nation on your behalf.