Development of diabetic sensory polyneuropathy is associated with alterations in intracellular calcium homeostasis in primary and secondary nociceptive neurons. We have shown previously that in a model of streptozotocin (STZ)-induced diabetes, the calcium signal is prolonged and calcium release from ryanodine-sensitive calcium stores down-regulated in neurons of the nociceptive system. The aim of the present study was a more detailed characterization of calcium homeostasis in primary (dorsal root ganglia, DRG) and secondary (dorsal horn, DH) nociceptive neurons in STZ-induced diabetes. Fluorescence video-imaging was used to measure free cytosolic [Ca2+] ([Ca2+]i) in lumbar nociceptive neurons of control and streptozotocin-diabetic rats. Resting [Ca2+]i rose progressively in these neurons with the duration of diabetes and calcium mobilization from the endoplasmic reticulum (ER) decreased during diabetes. The amplitude of calcium release from both ryanodine- and IP3-sensitive calcium stores induced by caffeine, ionomycin, ATP or glutamate was significantly (P<0.01) lower in DRG and DH neurons from 6-week STZ-diabetic rats. Diabetes-induced changes in the calcium homeostasis were similar in DRG and DH neurons indicating that they might be general for many types of neurons from the central and peripheral nervous systems.

Understanding the origin of and discovering a treatment for neurological complications in diabetes mellitus is one of the most important challenges facing both experimental investigation and clinical practice because of their severity and the large numbers of patients affected. Nevertheless, the mechanisms of the development of distal diabetic neuropathy, in particular the incidence of hyperalgesia and allodynia, pain syndromes or, the opposite, loss of sensitivity are not well understood. In particular, data about the changes of intracellular metabolism in nociceptive neurons under diabetic conditions are scarce, especially about changes in intracellular calcium signalling which could be quite important for Diabetologia (2001) 44: 1302±1309 Diabetes-induced changes in calcium homeostasis and the effects of calcium channel blockers in rat and mice nociceptive neurons

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