Streptozotocin-induced mechanical hypernociception is not dependent on hyperglycemia

Abstract

Since streptozotocin (STZ)-induced diabetes is a widely used model of painful diabetic neuropathy, the aim of the present study was to design a rational protocol to investigate whether the development of mechanical hypernociception induced by STZ depends exclusively on hyperglycemia. Male Wistar rats (180-200 g; N = 6-7 per group) received a single intravenous injection of STZ at three different doses (10, 20, or 40 mg/kg). Only the higher dose (40 mg/kg) induced a significant increase in blood glucose levels, glucose tolerance and deficiency in weight gain. However, all STZ-treated rats (hyperglycemic or not) developed persistent (for at least 20 days) and indistinguishable bilateral mechanical hypernociception that was not prevented by daily insulin treatment (2 IU twice a day, sc). Systemic morphine (2 mg/kg) but not local (intraplantar) morphine treatment (8 μg/paw) significantly inhibited the mechanical hypernociception induced by STZ (10 or 40 mg/kg). In addition, intraplantar injection of STZ at doses that did not cause hyperglycemia (30, 100 or 300 μg/paw) induced ipsilateral mechanical hypernociception for at least 8 h that was inhibited by local and systemic morphine treatment (8 μg/paw or 2 mg/kg, respectively), but not by dexamethasone (1 mg/kg, sc). The results of this study demonstrate that systemic administration of STZ induces mechanical hypernociception that does not depend on hyperglycemia and intraplantar STZ induces mechanical sensitization of primary sensory neurons responsive to local morphine treatment.

Streptozotocin Stimulates the Ion Channel TRPA1 Directly

“…TRPA1 is highly conserved between rats and mice (97% identity), and the residues previously proposed to be important for channel activation are identical (6). Previous reports of thermal and mechanical hyperalgesia, which develop both in hyperglycemic and normoglycemic STZ-treated rats, therefore support our behavioral findings (43,44). In this study, the magnitudes of the sensory deficits were similar for at least 10 days following STZ administration.…”

Effect of dipyrone and thalidomide alone and in combination on STZ-induced diabetic neuropathic pain

“…This is in line with various other observations (Kuhad et al 2008;Ohsawa and Kamei 1999). However, some studies suggest that STZ-induced hypernociception is not only associated with hyperglycemia (Romanovsky et al 2004); there is a possibility of STZ sensitizing the peripheral afferent nociceptors and central nociceptive neurons (Cunha et al 2009). Furthermore, diabetic rats showed an increased frequency of flinching following paw formalin injection that is indicative of hyperalgesia in this model (Courteix et al 1993).…”

Immunohistomorphology of Pancreatic Islet Microvasculature and the Immunophenotypic Analysis of CEPC in Adult Diabetic Rats

“…These findings confirm the oedematous effect of CB alone (Cunha et al, 2009) in the rats, and may suggest that the CB used as a solute to dissolve STZ drug does not have any remarkable impact on the histomorphology of STZ treated organs. The severity of STZ-induced diabetes and its effects were apparent on the morphology of the pancreas (Fig.…”