Lowering plasma 1-deoxysphingolipids improves neuropathy in diabetic rats.

1-Deoxysphingolipids (1-deoxySLs) are atypical neurotoxic sphingolipids that are formed by the serine-palmitoyltransferase (SPT). Pathologically elevated 1-deoxySL concentrations cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), an axonal neuropathy associated with several missense mutations in SPT. Oral L-serine supplementation suppressed the formation of 1-deoxySLs in patients with HSAN1 and preserved nerve function in an HSAN1 mouse model. Because 1-deoxySLs also are elevated in patients with type 2 diabetes mellitus, L-serine supplementation could also be a therapeutic option for diabetic neuropathy (DN). This was tested in diabetic STZ rats in a preventive and therapeutic treatment scheme. Diabetic rats showed significantly increased plasma 1-deoxySL concentrations, and L-serine supplementation lowered 1-deoxySL concentrations in both treatment schemes (P < 0.0001). L-serine had no significant effect on hyperglycemia, body weight, or food intake. Mechanical sensitivity was significantly improved in the preventive (P < 0.01) and therapeutic schemes (P < 0.001). Nerve conduction velocity (NCV) significantly improved in only the preventive group (P < 0.05). Overall NCV showed a highly significant (P = 5.2E-12) inverse correlation with plasma 1-deoxySL concentrations. In summary, our data support the hypothesis that 1-deoxySLs are involved in the pathology of DN and that an oral L-serine supplementation could be a novel therapeutic option for treating DN.

Omalgia pruriginosa / Pruriginous omodynia

La notalgia parestésica es una mononeuropatía sensitiva producida por atrapamiento de los ramos dorsales de las raíces espinales de D2 a D6, debido a que estos nervios se angulan 90° al pasar por la musculatura paraespinal. Se desconoce su causa, pero se ha visto relacionada con alteraciones en la estática de la columna a ese nivel (artrosis, escoliosis). Parestesias, prurito y quemazón son los síntomas más frecuentes y, junto con el hallazgo de una placa hiperpigmentada en dicha localización, constituyen los pilares de su diagnóstico. La electroneurografía muestra signos de denervación en las raíces afectadas. Únicamente la capsaicina tópica ha demostrado eficacia en ensayos clínicos. Otras terapias descritas en la literatura son la acupuntura, el bloqueo anestésico paravertebral local, la fisioterapia y la oxcarbazepina (AU)

Notalgia paresthetica is a sensory mononeuropathy producedby the dorsal spinal nerve root branch entrapmentfrom D2 to D6 because these nerves are angles 90° when passingthrough the paraspinal musculature. Its cause is unknownbut it has been observed to be related with alterationsin the spinal cord statics at this level (arthritis, scoliosis). Paresthesias,pruritus and burning sensation are the most frequentsymptoms. Together with the finding of a hyperpigmentedplaque at that location, they are the mainstay of itsdiagnosis. The electroneurography shows signs of denervationin the affected roots. Only topical capsaicin has beenshown to be effective in clinical trials. Other therapies describedin the literature are acupunture, local paravertebralblock anesthesia, physical therapy and oxcarbazepine (AU)