Acrolein Scavenger Hydralazine Prevents Streptozotocin‐Induced Painful Diabetic Neuropathy and Spinal Neuroinflammation in Rats

Abstract

Diabetes-induced neuropathic pain (DNP) substantially influences people's life qualities. Hyperglycemia-induced excess free radicals have been considered as the most critical mechanisms underlying DNP. As an unsaturated aldehyde and a reactive product of lipid peroxidation, acrolein plays critical roles in diabetic nephropathy and inflammatory pain. We sought to determine whether acrolein is involved in DNP in this study. Diabetes was induced by a single intraperitoneal (i.p.) injection of 60 mg/kg streptozotocin (STZ). An acrolein scavenger hydralazine (5 mg/kg) was administered through a daily injection for 4 weeks, starting immediately within 30 min after STZ injection. Western blot showed that hydralazine could effectively inhibit STZ-induced upregulation of acrolein in the spinal dorsal horn on day 7-28 after STZ injection. Behavioral tests showed that STZ injection induced significant mechanical allodynia and thermal hyperalgesia, which could be alleviated by hydralazine. Immunofluorescent histochemistry and Western blot showed that STZ induced significant microglial activation. ELISA data indicated upregulation of inflammatory cytokines IL-1β and TNF-α expression in the spinal dorsal horn. Furthermore, hydralazine effectively attenuated microglial activation and expression of inflammatory mediators. Our data indicate that acrolein might be involved in the development of neuroinflammation and behavioral consequences of DNP. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1858-1864, 2017. © 2017 Wiley Periodicals, Inc.

KCNQ2/3/5 channels in dorsal root ganglion neurons can be therapeutic targets of neuropathic pain in diabetic rats

“…Although targeting KCNQ2/3/5 channels in DRG neurons is a promising novel approach for relieving diabetic neuropathic pain as shown in our present study, the central mechanism also needs to be explored because of the central sensitization induced indirectly by peripheral nociceptive signaling transmission or directly by high glucose challenges. Upregulation of inflammatory cytokines, 50 alteration of proinflammatory neuropeptides 51 and N-methyl-D-aspartate receptor phosphorylation in spinal dorsal horn, 29 activation of anterior cingulate cortex, 28 and brain-based facilitatory pain mechanism 52 contribute to diabetic neuropathic pain. Combined peripheral and central targeting approach may represent the potential strategy on relieving diabetic neuropathic pain in future.…”

Myocardial Infarction-Related Transcripts (MIAT) Participate in Diabetic Optic Nerve Injury by Regulating Heart Shock Protein 5 (HSPA5) via Competitively Binding to MicroRNA-379

“…A diabetic rat model was established by intraperitoneal injection of streptozotocin (STZ, 60 mg/kg), and control rats received an intraperitoneal injection of citrate buffer (0.1 mol/L). Blood glucose levels of rats higher than 16.7 mM after injection for 72 h were considered as successful construction of the animal model [12]. The db/db mice were fed with high-fat diet, while WT mice were fed with normal diet.…”

Acrolein: A Potential Mediator of Oxidative Damage in Diabetic Retinopathy

“…While acrolein scavengers are still emerging in the field of vision, they are widely investigated in other central nervous system disorders. Treatment with hydralazine, an acrolein scavenger, and an antihypertensive drug demonstrated reduced neuroinflammation and neuropathic pain in a rat model of diabetes [ 136 ]. Hydralazine improved behavioral outcome and reduced myelin damage in an experimental model of multiple sclerosis [ 50 , 137 ] and reduced the neural apoptosis, brain edema, and neurological functional deficits in an experimental model of intracerebral hemorrhage [ 138 ].…”