Abstract
Our previous studies have revealed the ultrasmall superparamagnetic iron oxide in the amine group USPIO-101 has an analgesic effect on inflammatory pain. Here, we further investigated its effect on the spinal cord and brain via electrophysiological and molecular methods. We used a mouse inflammatory pain model, induced by complete Freund’s adjuvant (CFA), and measured pain thresholds via von Frey methods. We also investigated the effects of USPIO-101 via an extracellular electrophysiological recording at the spinal dorsal horn synapses and hippocampal Schaffer collateral-CA1 synapses, respectively. The mRNA expression of pro-inflammatory cytokines was detected by quantitative real-time polymerase chain reaction (RT-qPCR). Our results showed intrathecal USPIO-101 produces similar analgesic behavior in mice with chronic inflammatory pain via intrathecal or intraplantar administration. The potentiated low-frequency stimulation-induced spinal cord long-term potentiation (LTP) at the spinal cord superficial dorsal horn synapses could decrease via USPIO-101 in mice with chronic inflammatory pain. However, the mRNA expression of cyclooxygenase-2 was enhanced with lipopolysaccharide (LPS) stimulation in microglial cells, and we also found USPIO-101 at 30 µg/mL could decrease the magnitude of hippocampal LTP. These findings revealed that intrathecal USPIO-101 presented an analgesia effect at the spinal cord level, but had neurotoxicity risk at higher doses.
Highlights
We revealed further analgesic evidence for using ultrasmall superparamagnetic iron oxide (USPIO)-101 at the spinal cord and the possible neurotoxicity that should be concerned for future application
Electrophysiological results, reactive oxygen species (ROS) level, or mRNA expression were analyzed by one-way analysis of variance (ANOVA) followed by Newman–Keuls multiple comparisons test for post-hoc analyses
The analgesic effect of USPIO-101 was measured in mice with chronic inflammatory pain via different administration routes, intrathecal or intraplantar injection
Summary
Pharmaceutics 2022, 14, 366 inflammatory pain [5] This analgesic response probably happens by attenuating inflammatory cell infiltration and reducing reactive oxygen species (ROS) production in the paw [5]. This was the first report to demonstrate that USPIO itself could have analgesic ability not in conjugation with other pain-relieving drugs. Superparamagnetic iron oxide (SPIO) administration, either locally or systemically, gave an acute inflammatory response [12]. These reports inspired us to consider that USPIO-101 could probably have neurotoxicity in neuronal cells. We revealed further analgesic evidence for using USPIO-101 at the spinal cord and the possible neurotoxicity that should be concerned for future application
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