A-Fibers Mediate Cold Hyperalgesia in Patients with Oxaliplatin-Induced Neuropathy.

Cold hyperalgesia is a common side effect of oxaliplatin treatment; still, the pathophysiological and molecular mechanisms as well as the contribution of different primary afferent fiber systems are unclear. Therefore, patients with oxaliplatin-induced acute neuropathy with (n = 6) and without (n = 7) cold hyperalgesia were tested by applying a preferential blockade of peripheral myelinated A-fiber afferents in combination with quantitative sensory testing. Additionally, an interview-based questionnaire assessed the severity of symptoms and the impact on daily activities. Results indicate a deficit of cold perception in patients without cold hyperalgesia compared to patients with cold hyperalgesia prior to A-fiber blockade. In patients with cold hyperalgesia, a preferential blockade of A-fibers abolished cold hyperalgesia. This suggests that oxaliplatin-induced cold hyperalgesia is mediated by A-fibers and that a deficit in A-fiber function might prevent the development of cold hyperalgesia. The work supports findings in rodents and in human sural nerve biopsies indicating that oxaliplatin interferes with axonal ion conductance in intact A-fibers by sensitizing potassium and/or sodium channels. Drugs that act on these molecular targets might be of potential value to treat oxaliplatin-induced cold hyperalgesia.

Changes of Somatosensory Phenotype in the Course of Disease in Osteoarthritis Patients.

To investigate sensory changes, physical function (pF), quality of life (QoL) and pain intensity of patients with osteoarthritis (OA) in the natural course of disease, and patients undergoing total joint replacement therapy (TJR) 31 (20 females, mean age 64.6 ± 10.4 years), patients with OA were investigated with questionnaires and quantitative sensory testing (QST) in the area of referred pain at the thigh at baseline and follow-up 22-49 weeks later; changes were analyzed separately for patients with (n = 13) and without TJR (n = 18). In patients without TJR pain intensity, pF, QoL did not improve, and increased pain sensitivity to cold and a stronger loss of detection were observed. In patients after TJR, however, a reduction in mechanical pain sensitivity and allodynia occurred in accordance with a reduction of pain intensity and improvement of functionality while QoL did not improve. Additionally, an increased sensitivity to heat pain and a more pronounced loss of mechanical detection could be observed in this group. TJR seems to stop peripheral pain input leading to a reduction of pain intensity and central sensitization, but surgery-induced sensory changes such as peripheral sensitization and loss of detection occur. Furthermore, TJR has favorable effects on pain intensity and functionality but not QoL.

Historical aspects of immunization and vaccine safety communication.

It has been a long journey starting from the beginnings of variolation [3] leading up to the greatest success in the history of immunization: the eradication of smallpox [39]. Today, vaccines are an acknowledged important medical advance [40]. Nevertheless, immunization has been the subject of public controversy on several occasions [15, 24, 31]. This article shall provide a short overview of some aspects of the early stages of immunization in Western countries, including some examples of vaccine safety controversies in the past.

Phenotyping neuropathic pain patients: implications for individual therapy and clinical trials.

PURPOSE OF REVIEW: The sensory phenotype can be used as a surrogate marker of underlying mechanisms of pain generation and is assessed by tools like the Quantitative Sensory Testing, Patient Reported Outcomes or the Capsaicin Response Test. In order to establish an individualized, mechanism-based treatment of pain, it has to be demonstrated that subgroups of patients with a distinct sensory phenotype respond differently to a certain treatment. RECENT FINDINGS: Retrospective analyses of several clinical trials revealed that the presence of certain somatosensory abnormalities in the painful area was associated with a better treatment outcome. Examples will be discussed in this article, showing that somatosensory phenotyping of patients with neuropathic pain is a promising method to subgroup patients in order to predict their response to treatment. SUMMARY: The discussed trials show the importance of the development of an individualized pain therapy. Up to now, no clinical trial has prospectively used the sensory phenotype as an inclusion or stratification criterion. Academic researchers and pharmaceutical industry should be encouraged to implement this approach in future trial designs.