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

Abstract

Oxidative stress resulting from reactive oxygen species (ROS) is known to play a key role in numerous neurological disorders, including neuropathic pain. Morphine is one of the commonly used opioids for pain management. However, long-term administration of morphine results in morphine antinociceptive tolerance (MAT) through elevation of ROS and suppression of natural antioxidant defense mechanisms. Recently, mesoporous polydopamine (MPDA) nanoparticles (NPS) have been known to possess strong antioxidant properties. We speculated that morphine delivery through an antioxidant nanocarrier might be a reasonable strategy to alleviate MAT. MPDAs showed a high drug loading efficiency of ∼50%, which was much higher than conventional NPS. Spectral and in vitro studies suggest a superior ROS scavenging ability of NPS. Results from a rat neuropathic pain model demonstrate that MPDA-loaded morphine (MPDA@Mor) is efficient in minimizing MAT with prolonged analgesic effect and suppression of pro-inflammatory cytokines. Additionally, serum levels of liver enzymes and levels of endogenous antioxidants were measured in the liver. Treatment with free morphine resulted in elevated levels of liver enzymes and significantly lowered the activities of endogenous antioxidant enzymes in comparison with the control and MPDA@Mor-treated group. Histopathological examination of the liver revealed that MPDA@Mor can significantly reduce the hepatotoxic effects of morphine. Taken together, our current work will provide an important insight into the development of safe and effective nano-antioxidant platforms for neuropathic pain management.

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

“…A. Yay and colleagues investigated the antioxidant effect of CA on renal oxidative stress in diabetic rats induced with streptozocin [ 85 ]. Cellular ROS is generally produced at a low level in cells and is vital for maintaining cellular homeostasis and function [ 86 , 87 ]. However, an imbalance in ROS levels promotes the expression of pro-inflammatory cytokines and chemokines.…”

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

“…To examine TEN’s effect against NP, we have developed a PSNT model used in our previous studies [ 34 ]. PSNT is a well-known model for NP.…”

“…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.…”

Hierarchical Two-Dimensional Layered Double Hydroxide Coated Polydopamine Nanocarriers for Combined Chemodynamic and Photothermal Tumor Therapy

“…The presence of the characteristics bands of DOX at 1106 cm −1 and 1420 cm −1 resultant from δ (CH3O-) stretching and δ(N-H) vibration of DOX confirms the successful loading of DOX in CuAl-LDH@DOX (Figure 2A(b,c)) [26]. Furthermore, coating of PDA resulted in additional bands at 1460 and 1630 cm−1 which corresponds to the indole groups in PDA [27,28]. Additionally, characteristic -CH 2 -stretching vibrations are found at 2920 cm −1 in CuAl-LDH@DOX@PDA samples confirming successful adsorption of PDA onto CuAl-LDH@DOX (Figure 2A(d)).…”