Neuropathy, neuropathic pain, and sickle cell disease

describe pain and other non-neurological adverse events in children with sickle cell anemia (SS) and previous stroke who received hydroxyurea and phlebotomy or standard therapy with chronic transfusion and chelation. These children were recruited from the previously reported SWITCH study The primary endpoint of the study was to compare standard therapy (transfusions and chelation) with the alternative therapy (hydroxyurea and phlebotomy) in preventing secondary stroke and the reduction of transfusional iron overload in children with SS and previous stroke. The authors compared the rates of vaso-occlusive pain and other non-neurological adverse events such as acute chest syndrome, infection, infestation, etc. in each treatment arm. They showed that blood transfusion was more effective than hydroxyurea in reducing the painful episodes. In another article, also in this issue of the journal, Oliveros at al. Although thalassemia is not typically associated with pain, the authors report that of the 252 participants, 56% reported pain at least once over the course of the study, with 32% reported severe pain. Additionally, the pain burden increased with increasing age in patients with thalassemia. Moreover, the report by Oliveros et al. The effect of age on the frequency and severity of pain in SS, however, is not well studied and seems to be more complex. In one of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) follow-up studies, the utilization of analgesics at home (which is a surrogate measure of pain) reached a peak at the age of 30-35 years and decreased after the age of 35 years especially in males. Moreover, in all the studies mentioned above, neuropathy and neuropathic pain were not mentioned, described, or diagnosed thus raising the question whether they do not complicate SS and thalassemia or whether their diagnosis is missed. The known types of pain in patients with sickle cell disease (SCD) in general and SS in particular include the recurrent vasoocclusive crises (VOC), the persistent pain between crises, chronic pain, pain due to therapy, and pain due to co-morbid conditions. Anecdotally, therapy with opioids may be occasionally associated with hyperalgesia associated with some neuropathic features. Peripheral neuropathy has been described in SS but neuropathic pain has not been well documented to date. This commentary will critically analyze this issue, review the definitions, and describe the diagnostic criteria of neuropathy and neuropathic pain and their relation to SCD.