Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis

Abstract

BackgroundNonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis.Materials and methodsTwenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types Aα and Aβ fibers) with a large conduction velocity (70–120 m/s), and the second component originated from fibers (Type Aγ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed.ResultsWe observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed.ConclusionOur data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders.

Sepsis-induced encephalopathy impairs descending nociceptive pathways in rats

“…Previous studies regarding pain and an immune challenge have different results concerning nociception alterations (de Goeij et al, 2013;Diniz et al, 2018;Reeve et al, 2000;Seo et al, 2008). We believe that these diversified data result from the distinct models used (CLP, LPS injection, or cytokine administration), the dose of LPS, the route of administration (intraperitoneally, intravenous, intracerebroventricular) and the time points analyzed (minutes, hours or days after the Fig.…”

“…Previous studies regarding pain and systemic inflammation showed that endotoxemia by lipopolysaccharide (LPS) injection could play some role in sensory pain modulation, possible due to its peripheral impairment of sensory neurons (Calil et al, 2014;Hsieh et al, 2018;Meseguer et al, 2014;Ruiz-Miyazawa et al, 2015;Sun et al, 2015). Moreover, in the sciatic nerve was found that the CLP (cecal ligation and puncture) model-induced excitability impairment may enhance mechanical antinociception in the von Frey test (Diniz et al, 2018); although the authors did not state the role of central descending pain modulation in the sepsis model. Leading the same way, Imamura et al (2016) had also shown thermal antinociception on hot plate test in animals with systemic inflammation induced by LPS.…”

The Influence of Pain and Analgesia in Rodent Models of Sepsis

“…Within 24 h of cecal ligation and puncture (CLP), a model of sepsis, rats display decreased sciatic nerve excitability due to inactivation of sodium channels. 20,55 The electrophysiologic changes occur before notable histologic findings and are associated with higher thresholds for paw withdrawal in response to von Frey filaments. 20 Simultaneously, there is an increase in vagal nerve excitability, which is known to modulate the immune system and have antiinflammatory effects in sepsis.…”

“…20,55 The electrophysiologic changes occur before notable histologic findings and are associated with higher thresholds for paw withdrawal in response to von Frey filaments. 20 Simultaneously, there is an increase in vagal nerve excitability, which is known to modulate the immune system and have antiinflammatory effects in sepsis. 40,42,85 These findings suggest that pain perception is actually reduced in the early phases after CLP in rats.…”

Catestatin Enhances Neuropathic Pain Mediated by P2X4 Receptor of Dorsal Root Ganglia in a Rat Model of Chronic Constriction Injury

“…Before starting the trials, we kept the room at 20-25 °C and gave all rats a few minutes to explore and acclimate to the new environment. The paw withdrawal response is known to be a positive response [16,17]. We used an Electrical Mechanical Analgesia Tester (BME-404, Tianjin, China) to stimulate their operated hind paws with pressure (range: 0 -50 g).…”