Effects of hyperglycemia on rat cavernous nerve axons: A functional and ultrastructural study

Abstract

The present study explored parallel changes in the physiology and structure of myelinated (Aδ) and unmyelinated (C) small diameter axons in the cavernous nerve of rats associated with streptozotocininduced hyperglycemia. Damage to these axons is thought to play a key role in diabetic autonomic neuropathy and erectile dysfunction, but their pathophysiology has been poorly studied. Velocities in slow conducting fibers were measured by applying multiple unit procedures; histopathology was evaluated with both light and electron microscopy. To our knowledge, these are the initial studies of slow nerve conduction velocities in the distal segments of the cavernous nerve. We report that hyperglycemia is associated with a substantial reduction in the amplitude of the slow conducting response, as well as a slowing of velocities within this very slow range (<2.5 m/sec). Even with prolonged hyperglycemia (> 4 months), histopathological abnormalities were mild and limited to the distal segments of the cavernous nerve. Structural findings included dystrophic changes in nerve terminals, abnormal accumulations of glycogen granules in unmyelinated and preterminal axons, and necrosis of scattered smooth muscle fibers. The onset of slowing of velocity in the distal cavernous nerve occurred subsequent to slowing in somatic nerves in the same rats. The functional changes in the cavernous nerve anticipated and exceeded the axonal degeneration detected by morphology. The physiologic techniques outlined in these studies are feasible in most electrophysiologic laboratories and could substantially enhance our sensitivity to the onset and progression of small fiber diabetic neuropathy.

The Impact of Low-Dose Insulin on Peripheral Nerve Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats

“…In the present study, IENFD appeared to increase despite the early development of nociceptive dysfunction in STZ-induced diabetic rats, suggesting the development of a functional, but not structural, abnormality of small sensory fibers in this model. Although some researchers [39], [40] reported a reduction in IENFD in STZ-induced diabetic rats, the present finding is consistent with previous studies showing a trend toward increases in myelinated [41], [42] and unmyelinated fiber number/density [43], [44] in the peripheral nerves of STZ-induced diabetic rats. In humans, IENFD decreases in the early period of type 2 diabetes or even in prediabetes [45]-[48].…”

Noninvasive Evaluation of Nerve Conduction in Small Diameter Fibers in the Rat

“…At the early stage of degeneration (10 days), C fibers demonstrated a re-distribution of MUA toward a slower range NCV, in addition to a decrease in total magnitude of the response. Similar signs of dysfunction were observed in distal diabetic autonomic neuropathy [77]. …”

“…To balance the difference between the time periods of faster and slower velocities (e.g., 3 ms for 1.5-2 m/s and 20 ms for 0.5-1 m/s), the response integrated over each range of NCV was divided by the number of time bins (voltage samplings) within this range. The integrated MUA signal was expressed as a magnitude of response over the range of 0.5-2 m/s with respect to the level of spontaneous activity in the pre-stimulation epoch [76-77]. …”

Sinusoidal Constriction and Vascular Hypertrophy in the Diabetes-Induced Rabbit Penis

“…Several epidemiological studies have assessed the correlation between DM and ED (8). Evaluation of animal models demonstrated that neural (9) and vascular (10) changes seen with DM may be associated with ED. Vascular diseases such as microangiopathy, atherosclerosis, and hypertension are often observed in patients with DM.…”