Autonomic Nervous System and Diabetes: Histological and Histochemical Study of the Autonomic Nerve Fibers of the Urinary Bladder in Diabetic Patients

Faerman, Isaac; Glocer, Leticia; Celener, D; Jadzinsky, Mauricio; Fox, Dora; Maler, Mario; Álvarez, Enrique

doi:10.2337/diab.22.4.225

Cited by 76 publications

(38 citation statements)

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“…The results of the present study are compatible with this idea. It is also of interest that the histological abnormalities found in the present study are similar to those described in the bladder [15], in the corpora cavernosa [16] and in the myocardium [17], all of which are typical sites of diabetic autonomic neuropathy. Thus, autonomic neuropathy is a very common feature in diabetes and an important background to the development of other complications.…”

Section: Discussionsupporting

confidence: 65%

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Autonomic neuropathy in the skin: A histological study of the sympathetic nerve fibres in diabetic anhidrosis

Faerman¹,

Faccio

Calb³

et al. 1982

Diabetologia

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Summary. In diabetics with the anhidrotic syndrome, autonomic nerve fibres were studied in skin biopsies using argentic techniques and light microscopy. The Minor test was used to differentiate normal from anhidrotic skin areas. In the anhidrotic areas, histology of the nerve fibres showed beading, spindle-shaped thickening and fragmentation adjacent to the sweat glands. These changes were similar to those observed in two patients who had previously undergone lumbar sympathectomy. No abnormalities of the sympathetic nerve endings could be found in biopsies taken from normal areas of the forearm of the same patients. We conclude that the diabetic anhidrotic syndrome, a form of diabetic autonomic neuropathy, is due to a lesion of the sympathetic nerve supply to the skin. It is suggested that the Minor test or a skin biopsy should be performed in diabetic patients who are being considered for surgical sympathectomy.Key words: Anhidrosis, sweat secretion, autonomic nerve fibre, sympathetic chain, Minor test, skin biopsy, argentic techniques, sympathectomy, diabetic visceral neuropathy.Alterations in sweating are particularly common in diabetic patients with autonomic neuropathy [1]. The first reference to this anomaly was made by Pryce in 1893 [2], but it was Rundles who published the first clinical description in 1945 [3]. He found that 36 out of 125 patients with diabetic neuropathy had alterations in perspiration and he associated this change with other alterations of the autonomic nervous system, particularly changes in blood pressure and skin temperature. Similar descriptive clinical findings have been documented by several other authors [4,5].Physiological and histological research into changes in sweat production is difficult and this may have contributed to the scarcity of studies on this subject. Normal patterns of sweat production have been determined by List and Peet [6] and by Hyndman and Wolkin [7]. Perhaps the most reliable methods include those described by Minor [8] which depends on the starch-iodine reaction, and the technique of Brown and Adson [9] in which strips of paper soaked with cobalt chloride are applied to the skin. Alternatively, quinarizine may be used, which turns blue on contact with skin moisture [10]. Most of these methods are relatively simple although less accurate than the determination of sweating by galvanic skin resistence techniques.Although not specific, the symptoms suffered by diabetics from sweating disturbances are fairly typical [5]. Initially there is heat intolerance accompanied by hyperhidrosis of the upper half of the body, particularly affecting the face, neck, axillae and hands. It is of interest that these patients rarely perspire excessively below the umbilicus. This diabetic syndrome has been attributed to a lesion of the sympathetic nerve fibres which control sweat secretion [11] and follow the course of the peripheral nerves [12]. This affects the efferent branch of the reflex arch and is identical to that occurring distal to a surgical sympathectomy [13].To ...

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Section: Discussionsupporting

confidence: 65%

“…Two histopathologists (EF and IC) assessed each biopsy independently, without knowledge of the patients' details or site of biopsy. Nerve fibre morphology was considered normal or abnormal according to our previously published criteria [15][16][17].…”

Section: Methodsmentioning

confidence: 99%

Autonomic neuropathy in the skin: A histological study of the sympathetic nerve fibres in diabetic anhidrosis

Faerman¹,

Faccio

Calb³

et al. 1982

Diabetologia

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“…Some markers of innervation include acetylcholinesterase, choline acetyltransferase, and nerve growth factor (NGF). Decreased acetylcholinesterase and choline acetyltransferase staining has been noted in bladders from human and experimental diabetics when expressed as concentration, suggesting that cholinergic innervation is altered by diabetes (Faerman et al, 1973;Lincoln et al, 1984). Buttyan and co-workers found increased bladder NGF mRNA 4 weeks after streptozotocin (STZ) treatment, but a steady decrease in NGF protein up to 8 weeks, suggesting a decreased efficiency of NGF mRNA translation (Te et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Factors underlying the increased sensitivity to field stimulation of urinary bladder strips from streptozotocin‐induced diabetic rats

Tammela

Briscoe

Levin

et al. 1994

British J Pharmacology

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1 The responses of bladder strips from control, streptozotocin-diabetic, and sucrose-drinking rats to electrical field stimulation were investigated. Sucrose-drinking rats were included as additional controls because they have enlarged bladders as a result of non-diabetic diuresis. 2 Bladder strips from diabetic rats developed more spontaneous activity than those from the two control groups. Indomethacin reduced the amplitude and frequency of spontaneous contractions suggesting that they resulted from endogenous prostaglandin formation. Tetrodotoxin (TTX) had little effect, while a,-methylene ATP caused increases in spontaneous activity.3 Bladder strips from diabetic rats responded to field stimulation with greater contractions than controls in the absence of antagonists as well as in the presence of atropine and at,p-methylene ATP.Increasing TTX concentrations caused a step-wise depression of the contractile response to electrical stimulation which was not affected by preincubation with either atropine or a,-methylene ATP.4 Atropine and indomethacin had no effect on stength-duration curves constructed to measure threshold contractile responses to five pulses stimulation. The curves were shifted to the right by both TTX and a,-methylene ATP, indicating that the responses were neurogenic in nature and at least partially, the result of stimulation of P2-purinoceptors. In the absence of drugs, bladder strips from diabetics responded at lower voltages and pulse widths than those of control and sucrose-drinking rats, suggesting that they were more excitable. 5 The response curve of bladder strips from diabetics to field stimulation at increasing voltage was shifted upwards and to the left compared to strips from control or sucrose-drinking rats. 6 Bladder strips from diabetics responded to stimulation at increasing pulse width with greater responses than those from control or sucrose-drinking rats. At 1.0 ms pulse width, the TTX-resistant response of strips from diabetic rats was still greater than that of the other groups, indicating that a myogenic component was also involved. 7 The data suggest that bladder strips from diabetic rats are more excitable than those of control or sucrose-drinking rats. This may result from diabetes-induced decreases in bladder lipid or other membrane changes, and/or be a result of partial depolarization, perhaps related to diabetic neuropathy.

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“…patients with diabetes mellitus (DM) (1)(2)(3)(4)(5)(6). In the early stages of DM, there is a reduction in the sensation of bladder fullness that eventually progresses to bladder atony and urinary retention (7).…”

mentioning

confidence: 99%

Effects of ONO-2235, an Aldose Reductase Inhibitor, on Muscarinic Receptors and Contractile Response of the Urinary Bladder in Rats with Streptozotocin-Induced Diabetes

Kanda¹,

Eto

Tanabe³

et al. 1997

Japanese Journal of Pharmacology

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ABSTRACT-This study was conducted to evaluate effects of the aldose reductase inhibitor ONO-2235 on the contractile response to acetylcholine of the urinary bladder dome of streptozotocin-induced diabetes mellitus (DM) rats and simultaneously observe the changes in the function and number of muscarinic receptors and the sorbitol content of the bladder. The contractile response to acetylcholine increased 51 % in the DM rat bladder dome compared to the normal rats; however, this was attenuated to a 10% increase by administration of 100 mg/kg ONO-2235 for 2 weeks. Treatment with ONO-2235 significantly decreased the specific [3H]quinuclidinyl benzilate binding in DM rats. However there was no significant dose-dependency among the ONO-2235-treated groups. The sorbitol levels of the sciatic nerve and the bladder were higher in the DM rats compared to the control rats; ONO-2235 decreased the level, although it did not completely reverse them to the control level. These results suggest that an aldose reductase inhibitor attenuates the in crease of the muscarinic receptor number and normalizes the enhanced contractile response to acetylcholine caused by hyperglycemia and diuresis, probably through suppression of the polyol-pathway in the DM rat bladder dome.

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Autonomic Nervous System and Diabetes: Histological and Histochemical Study of the Autonomic Nerve Fibers of the Urinary Bladder in Diabetic Patients

Cited by 76 publications

References 4 publications

Autonomic neuropathy in the skin: A histological study of the sympathetic nerve fibres in diabetic anhidrosis

Autonomic neuropathy in the skin: A histological study of the sympathetic nerve fibres in diabetic anhidrosis

Factors underlying the increased sensitivity to field stimulation of urinary bladder strips from streptozotocin‐induced diabetic rats

Effects of ONO-2235, an Aldose Reductase Inhibitor, on Muscarinic Receptors and Contractile Response of the Urinary Bladder in Rats with Streptozotocin-Induced Diabetes

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