ELECTROPHYSIOLOGICAL CHANGES PROMOTED BY HIGH-FREQUENCY TRIGGING IN THE SCIATIC NERVE OF CONTROL AND DIABETIC MICE

Diabetes Mellitus (DM) affects more than 540 million people and 10% of pre-diabetics already have nerve damage. The Ischiatic Nerve (NI) is used to study diabetic neuropathy, not only for its sensitive and motor innervation, but also for its extension. Often, neuropathic patients report symptoms such as paresthesia, allodynia and hyperalgesia, which may be associated with neuronal hyperactivity. Thus, investigating the effects of high-frequency stimulation on the NI of diabetic animals is essential to clarify the pathophysiology of this comorbidity. Forty-two female Swiss mice, with body mass between 25 and 30g, were divided into two groups: Control (CT) and Diabetic (DB). The DB group received intraperitoneally 150 mg/kg of streptozotocin diluted in sodium citrate (0.1 M; pH 4.5). Weekly, mass and blood glucose were measured, in addition to mechanical sensitivity tests (Von Frey filaments). After the fourth week of induction, both groups were sacrificed. Then, the extracellular recording of the Compound Action Potential (CAP) was used for the electrophysiological evaluation, where the IN was subjected to a pulse of 40V and duration of 1ms. The frequencies used were: 0.2Hz, 20Hz, 50Hz, 100Hz and 200Hz. We used two-way ANOVA followed by an appropriate contrast test to compare groups. All mice in the DB group showed DM characteristics, such as: weight loss, which lasted until the 2nd week (Day 0: 29.6±0.4g; Day 30: 30.1±0.7g); hyperglycemia (Day 0: 111.5±4.6mg/dL; Day 30: 361.6±43.9mg/dL) and sensory changes demonstrated by the paw withdrawal threshold: (Day 0: 4.0±0.3g , Day 28: 4.5±0.1g). Compared to CT data (Mass: Day 0: 28.8± 0.3g; Day 30: 31.5±0.3g; Blood glucose: Day 0: 103.8± 3.0mg/dL; Day 30: 123 ,8±3.1mg/dL; paw withdrawal threshold: Day 0: 4.1±0.4g, Day 28: 5.1±0.2g), the use of the Swiss mouse, proved to be effective as a model of diabetic neuropathy, since the changes promoted by DM were effective and similar to those found in humans . With regard to electrophysiological data, CAP records were obtained consisting of three peaks, called components. In all PAC records, the 1st and 2nd components were observed, the CT group presented the 3rd component in all its records, unlike the DB group, which presented the 3rd component in only 50% of the records. Unpublished data from our laboratory demonstrate the same scenario in NI of diabetic rats. We believe that DM promotes a desynchronization of fiber conduction velocities, consequently this 3rd component would be veiled by the 2nd. This data has not yet been described in the literature. Regarding stimulation with different frequencies, the nerves of the groups behaved similarly. However, in the immediate recovery period, CT PACs exhibited component separation. In the DB group, this separation occurred in only 17% of the nerves, suggesting that diabetes promotes fiber adaptation to high-frequency stimulation. This finding agrees with the sensory alterations presented, which demonstrate hyposensitivity followed by hypersensitivity in mice with only four weeks of DM. Thus, we concluded that the Swiss mouse represents a good model for the study of diabetic neuropathy and that DM made nerve fibers more resistant to high-frequency stimulation.