Selective Loss of Calcitonin Gene-Related Peptide-Expressing Primary Sensory Neurons of the A-Cell Phenotype in Early Experimental Diabetes

Jiang, Yun; Nyengaard, Jens Randel; Zhang, Jin Song; Jakobsen, Johannes

doi:10.2337/diabetes.53.10.2669

Cited by 23 publications

(9 citation statements)

References 52 publications

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“…Diabetic neuropathy is also characterized by a reduction in neuropeptide content in sensory ganglia and sensory nerve terminals in the SC dorsal horn. 15 Four weeks after STZ injection, the amount of calcitonin gene-related peptide immunoreactivity in the DRG was significantly reduced in animals when compared with animals not injected with STZ (Supplementary Figures S2c–e). …”

Section: Resultsmentioning

confidence: 98%

Comparative effectiveness of antinociceptive gene therapies in animal models of diabetic neuropathic pain

et al. 2012

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Peripheral neuropathic pain is one of the most common and debilitating complications of diabetes. Several genes have been shown to be effective in reducing neuropathic pain in animal models of diabetes after transfer to the dorsal root ganglion using replication-defective herpes simplex virus (HSV)1-based vectors, yet there has never been a comparative analysis of their efficacy. We compared four different HSV1-based vectors engineered to produce one of two opioid receptor agonists (enkephalin or endomorphin), or one of two isoforms of glutamic acid decarboxylase (GAD65 or GAD67), alone and in combination, in the streptozotocin-induced diabetic rat and mouse models. Our results indicate that a single subcutaneous hindpaw inoculation of vectors expressing GAD65 or GAD67 reduced diabetes-induced mechanical allodynia to a degree that was greater than daily injections of gabapentin in rats. Diabetic mice that developed thermal hyperalgesia also responded to GAD65 or endomorphin gene delivery. The results suggest that either GAD65 or GAD67 vectors are the most effective in the treatment of diabetic pain. The vector combinations, GAD67 + endomorphin, GAD67 + enkephalin or endomorphin + enkephalin also produced a significant antinociceptive effect but the combination did not appear to be superior to single gene treatment. These findings provide further justification for the clinical development of antinociceptive gene therapies for the treatment of diabetic peripheral neuropathies.

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Section: Resultsmentioning

confidence: 98%

Comparative effectiveness of antinociceptive gene therapies in animal models of diabetic neuropathic pain

et al. 2012

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“…Decline in the number of peripheral and central neurons [5-7], decrease of the density of nerve fibres [8], disorganization of the axonal terminals and myelinated nerve fibres [9,10] have been reported in diabetic patients and in animal models of DM. The degenerative effect of DM on neurons and nerves is explained by microvascular insufficiency and biochemical mechanisms [11].…”

Section: Introductionmentioning

confidence: 99%

Remodelling of the intracardiac ganglia in diabetic Goto-Kakizaki rats: an anatomical study

Batulevičius

Frese²,

Peschke

et al. 2013

Cardiovasc Diabetol

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BackgroundAlthough cardiac autonomic neuropathy is one of major complications of diabetes mellitus (DM), anatomical data on cardiac innervation of diabetic animal models is scant and controversial. We performed this study to check whether long-term diabetic state impacts the anatomy of intracardiac ganglia in Goto-Kakizaki (GK) rats, a genetic model of type 2 DM.MethodsTwelve GK rats (276 ± 17 days of age; mean ± standard error) and 13 metabolically healthy Wistar rats (262 ± 5 days of age) as controls were used for this study. Blood glucose was determined using test strips, plasma insulin by radioimmunoassay. Intrinsic ganglia and nerves were visualized by acetylcholinesterase histochemistry on whole hearts. Ganglion area was measured, and the neuronal number was assessed according to ganglion area.ResultsThe GK rats had significantly elevated blood glucose level compared to controls (11.0 ± 0.6 vs. 5.9 ± 0.1 mmol/l, p < 0.001), but concentration of plasma insulin did not differ significantly between the two groups (84.0 ± 9.8 vs. 67.4 ± 10.9 pmol/l, p = 0.17). The GK rats contained significantly fewer intracardiac ganglia, decreased total area of intracardiac ganglia (1.4 ± 0.1 vs. 2.2 ± 0.1 mm2, p < 0.001) and smaller somata of ganglionic neurons. Mean total number of intracardiac neurons in GK rats was 1461 ± 62, while this number in control rats was higher by 39% and reached 2395 ± 110 (p < 0.001).ConclusionsResults of our study demonstrate the decreased number of intracardiac neurons in GK rats compared to metabolically healthy Wistar rats of similar age. It is likely that the observed structural remodelling of intracardiac ganglia in GK rats is caused by a long-term diabetic state.

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“…Diabetes is well known to cause a reduction in the content of CGRP in peripheral nerves (2,3,28), the neurons of the dorsal root ganglia and the dorsal horn of the spinal cord (29). Although physical training has been considered in the treatment of diabetic patients for some time, it was not known, until now, whether training was able to prevent alterations in nociceptive signaling and CGRP content in the spinal cord.…”

Section: Discussionmentioning

confidence: 99%

Exercise alleviates hypoalgesia and increases the level of calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats

Nascimento¹,

Lovatel²,

Ilha³

et al. 2012

Clinics

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OBJECTIVE:The aim of this study was to evaluate the effects of treadmill training on nociceptive sensitivity and immunoreactivity to calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats.METHODS:Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8 weeks. The blood glucose concentrations and body weight were evaluated 48 h after diabetes induction and every 30 days thereafter. The nociceptive sensitivity was evaluated using the tail-flick apparatus. The animals were then transcardially perfused, and the spinal cords were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for calcitonin gene-related peptide analysis was performed on the dorsal horn of the spinal cord.RESULTS:The nociceptive sensitivity analysis revealed that, compared with the control and trained diabetic animals, the latency to tail deflection on the apparatus was longer for the diabetic animals. Optical densitometry demonstrated decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord in diabetic animals, which was reversed by treadmill training.CONCLUSION:We concluded that treadmill training can alleviate nociceptive hypoalgesia and reverse decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord of diabetic animals without pharmacological treatment.

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Selective Loss of Calcitonin Gene-Related Peptide-Expressing Primary Sensory Neurons of the A-Cell Phenotype in Early Experimental Diabetes

Cited by 23 publications

References 52 publications

Comparative effectiveness of antinociceptive gene therapies in animal models of diabetic neuropathic pain

Comparative effectiveness of antinociceptive gene therapies in animal models of diabetic neuropathic pain

Remodelling of the intracardiac ganglia in diabetic Goto-Kakizaki rats: an anatomical study

Exercise alleviates hypoalgesia and increases the level of calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats

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