Impairment of cellular ionic homeostasis is one of the causes of several diabetic complications including neuropathies. We have previously shown certain changes of intracellular calcium signalling in nociceptive neurones in rats with streptozotocin (STZ)-induced diabetic neuropathy. In this study we have investigated possible effects of prolonged rat treatment with the L-type calcium channel blocker nimodipine on diabetic-induced changes in intracellular Ca²⁺ ([Ca²⁺]_i) signalling and neuropathic symptoms.

Experiments were conducted on isolated neurones from dorsal root ganglia (DRG) and dorsal horn (DH) neurones from thin spinal cord slices of the lumbar L4ÐL6. Animals were anaesthetised (isofluorane) during preparative surgery and then humanely killed in accordance with the Bogomoletz Institute’s animal care guidelines. Diabetes was evoked by a single I.P. injection of STZ (80 mg kg^-1). [Ca²⁺]_i was measured by microfluorescence technique using fura-2 and indo-1.

After 3 weeks of diabetes development young diabetic rats (6Ð7 weeks old) were treated with nimodipine (40 mg kg^-1 per day) over the next 3 weeks. We examined the effects of nimodipine treatment on Ca²⁺ release from the intracellular calcium stores of DRG and DH neurones in diabetic animals compared with those observed in neurones from control and non-treated diabetic animals. Caffeine (20 mM) application to DRG neurones induced a transient elevation of [Ca²⁺]_i with an amplitude of 943 ± 73 nM (n = 26) in control, 357 ± 51 nM (n = 16) under diabetes and 796 ± 67 nM (n = 39) in neurones from nimodipine-treated diabetic animals. The difference in [Ca²⁺]_i elevations between control and nimodipine-treated rats was not significant (P > 0.07). Caffeine application to DH neurones induced [Ca²⁺]_i rise with an amplitude (nM) of 196 ± 17 (n = 16), 107 ± 14 (n = 17) and 145 ± 12 (n = 36) in control, diabetic and nimodipine-treated diabetic neurones, respectively. Thus in DH neurones nimodipine treatment partially restored the amplitude of responses to caffeine; the recovery is statistically significant (P < 0.04, Student’s unpaired t test). Ionomycin (500 nM) application in Ca²⁺-free extracellular solution induced [Ca²⁺]_i elevation in DRG neurones with amplitudes of 236 ± 20 (n = 19), 116 ± 26 (n = 16) and 238 ± 25 (n = 32) in control, diabetic and nimodipine-treated diabetic neurones, respectively. Nimodipine treatment completely restored to control level the amplitude of responses to ionomycin; the difference was not significant (P > 0.95). Nimodipine also partially reversed STZ-induced thermal hypoalgesia in diabetic rats: diabetic nimodipine-treated animals displayed increased withdrawal latency to painful thermal stimuli, when placed on a hot (48 °C) surface, compared with the non-treated age-matched diabetic rats. The results of this study suggest that chronic nimodipine treatment may be effective in reducing diabetes-induced thermal hypoalgesia, as well as in recovery of calcium-regulating mechanisms of the endoplasmic reticulum affected by diabetes.

This work was supported by JDFI and CRDF grants to N.V.

All procedures accord with current local guidelines.