Defining the pathophysiology of the paclitaxel-acute pain syndrome

Abstract

19613 Background: Paclitaxel therapy often results in a unique sub-acute pain syndrome, whose pathophysiology is unknown. While this syndrome is often termed as a ‘myalgia’ or ‘arthralgia’, it has not been demonstrated to be associated with any structural injury of muscles or joints. Identifying the pathophysiology mechanisms that result in the paclitaxel-acute pain syndrome might be a positive step in the development of effective prevention and/or treatment strategies. With the hypothesis that the paclitaxel-acute pain syndrome occurs as a result of nerve injury, an observational study to clarify the clinical characteristics of this syndrome was initiated. Methods: Oncology patients who were treated with at least one dose of paclitaxel and reported developing sub-acute pain were questioned using a detailed structured interview. Various aspects of the pain, including the time of onset, duration, location, severity, and exacerbating factors were evaluated. Data were tabulated descriptively. Results: Eighteen patients were interviewed. The onset of pain typically occurred 1–2 days after therapy and lasted for a median of 4–5 days. Pain was most commonly located in the back, hips, shoulders, thighs, legs and feet, with the most common descriptors used being ‘aching’ or ‘deep pain’. Commonly used adjectives to describe the pain were: ‘radiating’, ‘shooting’, ‘aching’, ‘stabbing’ and ‘pulsating’. Some patients described increased pain with weight bearing or walking. Fifteen of 18 patients specifically denied localization of pain to either joints or muscles. Conclusions: The nature of the pain, i.e. , generalized, deep aching pain, the notation of increased sensitivity with weight bearing (mechanical hyperalgesia) and the lack of localization to joints or muscles, support the hypothesis that the paclitaxel-acute pain syndrome results from a hyperalgesic dysfunction of nociceptive receptors, their fibers, or the spinothalamic system. These clinical conclusions are supported by the recent findings that markers of cellular injury can be identified in peripheral nerve tissues shortly following paclitaxel administration in an animal model (Peters CM, et al., Exp Neurol. 2007 Jan;203(1):42- 54). No significant financial relationships to disclose.