The onset speed of hyperglycemia is important to the development of neuropathic hyperalgesia in streptozotocin‐induced diabetic rats

Abstract

Diabetic neuropathic hyperalgesia is one of the most common diabetes complications. The physiopathological mechanism of hyperalgesia and the reason by which this condition affects only part of the diabetic patients still unclear. We tested whether an adaptation of primary afferent neurons to hyperglycemia could prevent the development of hyperalgesia. Hyperglycemia was induced in male Wistar rats by a daily administration of a low dose of streptozotocin (STZ), during five consecutive days. Glycemia and mechanical nociceptive thresholds were measured at days 0, 3, 7 and 14 after starting the streptozotocin treatment. In parallel, dorsal root ganglia (DRG) neurons were collected from healthy male Wistar rats and cultured in different glucose concentrations (mimicking slow or fast increase of hyperglycemia), and used for calcium imaging and Western blot analyses. Rats with a slow increase of glycemia did not develop hyperalgesia, while rats with a fast increase of glycemia developed hyperalgesia. DRG neurons suddenly incubated in DMEM containing a high glucose concentration showed a significant increase of calcium influx. However, DRG neurons incubated in DMEM and receiving increasing doses of glucose had the same calcium influx observed in control neurons. The activation of AMPK (α1/ α2) was greater in L5-L6 DRG of hyperglycemic and non-hyperalgesic rats, when compared with hyperglycemic and hyperalgesic rats. Our data suggest that the onset speed of hyperglycemia could be related to the development of diabetic neuropathic | 3643 do PRAdo et Al.

Anti-diabetic Potential Properties of Two Edible Omani Wild Plants (Pteropyrum scoparium and Oxalis corniculata)

“…Furthermore, our study revealed amelioration in the fasting blood glucose levels of all the treated diabetic groups. In contrast to our findings with respect to Oxalis corniculata, it was demonstrated that a single daily oral administration of an aqueous extract of Oxalis corniculata (100 mg/kg body weight) caused a significant reduction in the blood glucose in Alloxan-induced diabetic mice when treated for a period of ten days (do Prado et al, 2020). The results observed in our study are based on a different dose and feeding duration.…”

“…On the other hand, there were no studies to compare the results obtained from treating diabetic animals with Pteropyrum scoparium or the mixture of two plants. Long term of untreated hyperglycemia in diabetes is as- Al-Qalhati, Waly, Al-Subhi, Al-Attabi sociated with oxidative stress generating from glucose autoxidation, protein glycation and glycoxidation leading to tissue injury and damage (do Prado et al, 2020). Induction of STZ generates H2O2 and increased the production of free radicals in vitro as well as in vivo increasing the oxidative stress level (Balaji et al, 2020).…”

New Advances on Pathophysiology of Diabetes Neuropathy and Pain Management: Potential Role of Melatonin and DPP-4 Inhibitors

“…DM is known to damage various regions of the brain, including the hippocampus, cortex, and cerebellum, due to the excessive oxidative stress ( do Prado et al, 2020 ; Tong & Cheng, 2005 ). Melatonin is shown to protect the brain from DM-stimulated glial cell activation and ROS in STZ-induced diabetic rats ( Barber et al, 2000 , Antonetti, Gardner, and Penn State Retina Res, 2000; Renno, Alkhalaf, Afsari, Abd-El-Basset, & Mousa, 2008 ) ( La Morgia et al, 2010 ; Galley et al, 2017 ).…”

Photoacoustic Spectroscopy and Hyperglycemia in Experimental Type 1 Diabetes

“…It has been shown that slow increase of glycemia produced by several daily small doses of STZ allows adaptation to nociceptive stimuli producing less pain; in contrast, sudden high hyperglycemia produced by higher STZ doses reduced such adaptation. 39 Such adaptation is like the phenomenon named preconditioning. In fact, animals that are separated from their original cages are stressed.…”

“…41 Decreased adaptation during hyperglycemia has been attributed to mitochondrial dysfunction. 39 Moreover, STZ has direct (effects on lymphocytes producing lymphopenia) and indirect (hyperglycemia) immunosuppressive activity. 42 Therefore, changes of heme, Hb, oxyHb, and p450 in the first two weeks after STZ could be due to lack of adaptation and immunosuppression.…”