<p>Manganese Oxide Nanozymes Ameliorate Mechanical Allodynia in a Rat Model of Partial Sciatic Nerve-Transection Induced Neuropathic Pain</p>

Abstract

Background: Reactive oxygen species (ROS) induced oxidative stress is linked to numerous neurological diseases, including neuropathic pain. Natural ROS scavenging enzymes like superoxide dismutase (SOD) and catalase have been found to be efficient in alleviating neuropathic pain. However, their sensitivity towards extreme pH and a short half-life limit their efficacy in vivo. Manganese oxide nanoparticles (MONPs) are recently known to possess ROS scavenging properties. In this study, MONPs were examined for their therapeutic effect on neuropathic pain. Methods: The MONPs were synthesized by a hydrothermal method. The synthesized MONPs were characterized by UV/Vis, TEM, SEM, FTIR, NTA and XRD. The biocompatibility of the nanoparticles is evaluated in neural cells using LDH assay. MONPs were evaluated for their antioxidant activity by DPPH assay. In addition, in vitro ROS scavenging properties were examined in bone marrow-derived macrophage (BMDM) cells using 2ʹ,7ʹdichlorofluorescin diacetate (DCFDA) assay. To evaluate the in vivo efficacy of nanoparticles, neuropathic pain was induced in Wistar rats by partial sciatic nerve transection (PSNT). On post-transection days 14 to 18, rats were intrathecally injected with MONPs and paw withdrawal threshold was measured. The spinal cords were collected and processed for Western blotting and histological analysis. Results: The synthesized MONPs were biocompatible and showed effective antioxidant activity against DPPH free radical scavenging. Further, the nanoparticles scavenged ROS efficiently in vitro in BMDM and their intrathecal administration significantly reduced mechanical allodynia as well as the expression of cyclooxygenase-2 (COX-2), an important mediator of chronic and inflammatory pain in the spinal dorsal horns of PSNT rats. Conclusion: As ROS play a significant role in neuropathic pain, we expect that MONPs could be a promising tool for the treatment of various inflammatory diseases and might also serve as a potential nanocarrier for the delivery of analgesics.

Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System

“…Partial sciatic nerve transection surgery was performed by following the procedure reported previously [ 33 , 34 ]. The sciatic nerve from the left leg was carefully pulled until mid-thigh level, then a prolene 7-0 needle was introduced into the nerve just cranially to the branch stretching to the musculus biceps femoris, half of the nerve was transacted in a ventrocranial way up to the ligature.…”

Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain

“…Partial sciatic nerve transection (PSNT) surgery was performed by following our previous protocols [ 31 , 33 , 34 ]. The sciatic nerve from the left leg of rats was gently exposed, and a prolene 7-0 needle was inserted carefully and semi-transected, in an intracranial direction.…”

p66shc siRNA-Encapsulated PLGA Nanoparticles Ameliorate Neuropathic Pain Following Spinal Nerve Ligation

“…Although many underlying mechanisms, related to the onset and development of neuropathic pain, have been suggested, mitochondrial dysfunction may be one of the most important pathophysiological mechanisms of neuropathic pain [3,4]. Our and other previous studies reported that mitochondrial reactive oxygen species (ROS) levels are increased in the neuropathic spinal cord, and that removal of ROS in neuropathic pain can lead to recovery of central sensitization and hyperalgesia to normal levels [5][6][7][8]. In addition to mitochondrial functions and ROS, autophagy has been regarded as one of the most important mechanisms for understanding neuropathic pain.…”