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Activation of CX3CR1 in microglia plays an important role in the development of neuropathic pain. Here, we investigated whether neuropathic pain could be attenuated in spinal nerve ligation (SNL)-induced rats by reducing microglial activation through the use of poly(D,L-lactic-co-glycolic acid) (PLGA)-encapsulated CX3CR1 small-interfering RNA (siRNA) nanoparticles. After confirming the efficacy and specificity of CX3CR1 siRNA, as evidenced by its anti-inflammatory effects in lipopolysaccharide-stimulated BV2 cells in vitro, PLGA-encapsulated CX3CR1 siRNA nanoparticles were synthesized by sonication using the conventional double emulsion (W/O/W) method and administered intrathecally into SNL rats. CX3CR1 siRNA-treated rats exhibited significant reductions in the activation of microglia in the spinal dorsal horn and a downregulation of proinflammatory mediators, as well as a significant attenuation of mechanical allodynia. These data indicate that the PLGA-encapsulated CX3CR1 siRNA nanoparticles effectively reduce neuropathic pain in SNL-induced rats by reducing microglial activity and the expression of proinflammatory mediators. Therefore, we believe that PLGA-encapsulated CX3CR1 siRNA nanoparticles represent a valuable new treatment option for neuropathic pain.

Rheumatoid arthritis (RA) is a chronic inflammatory disease involving multiple joints. The cervical spine is often affected, and cases involving atlantoaxial joint can lead to instability. Anterior atlantoaxial subluxation in RA patients can lead to posterior neck pain or occipital headache because of compression of the C2 ganglion or nerve. Here, we report the successful treatment of a RA patient with occipital radiating headache using pulsed radiofrequency therapy at the C2 dorsal root ganglion.

BackgroundThis study compared intubating conditions and the onset time associated with administration of cisatracurium, a nondepolarizing neuromuscular blocker with a relatively slow onset, according to prior injection of one of two intravenous anesthetic agents: propofol or etomidate.MethodsForty-six female patients, undergoing general anesthesia and endotracheal intubation for elective surgery, were randomized to two groups; group P were administered propofol (2 mg/kg) prior to cisatracurium (0.2 mg/kg); group E were administered etomidate (0.3 mg/kg) prior to cisatracurium (0.2 mg/kg). We measured intubating conditions and the onset time according to the types of intravenous anesthetic administered. Measurements of heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were taken immediately prior to induction; immediately and 1 min after IV anesthetic administration; and immediately and 1, 2, 3, 4, 5, 7, and 15 min after endotracheal intubation.ResultsIntubating conditions were superior in group E compared with group P (P = 0.009). The average onset time of cisatracurium was more rapid in group E (155.74 ± 32.92 s vs. 185.26 ± 38.57 s in group P; P = 0.008). There were no group differences in SBP, DBP, and HR following intravenous anesthetic drug injection and endotracheal intubation. However, SBP and DBP were substantially higher in group E after endotracheal intubation.ConclusionsEtomidate improves intubating conditions and provide a more rapid onset time of cisatracurium during anesthetic induction compared to propofol.

Monoamine oxidase (MAO) inhibitors have been investigated for the treatment of neuropathic pain. Here, we assessed the antiallodynic effects of a novel MAO-B inhibitor, KDS2010, on paclitaxel (PTX)-induced mechanical hypersensitivity. Oral administration of KDS2010 effectively relieved PTX-induced mechanical hypersensitivity in a dose-dependent manner. KDS2010 (25 mg/Kg) significantly prevented and suppressed PTX-induced pain responses with minimal effects on the body weight, motor activity, and working memory. KDS2010 significantly reduced reactive astrocytosis and reactive oxygen species (ROS) level in the L4–L6 spinal cord of PTX-treated mice. Furthermore, KDS2010 reversed the attenuation of GABAergic spontaneous inhibitory postsynaptic current (sIPSC) frequency in spinal dorsal horn neurons, although it failed to restore the reduced tonic GABAA inhibition nor the increased GABA transporter 1 (GAT1) expression in PTX-treated mice. In addition, bath application of a reactive oxygen species (ROS) scavenger (PBN) restored the sIPSC frequency in PTX-treated mice but not in control and PTX + KDS2010-treated mice. These results indicated that the antiallodynic effect of KDS2010 is not due to a MAO-B-dependent GABA production. Finally, PBN alone also exerted a similar analgesic effect as KDS2010, but a co-treatment of PBN with KDS2010 showed no additive effect, suggesting that inhibition of MAO-B-dependent ROS production is responsible for the analgesic effect by KDS2010 on PTX-induced allodynia. Overall, KDS2010 attenuated PTX-induced pain behaviors by restoring the altered ROS level and GABAergic inhibitory signaling in the spinal cord, suggesting that KDS2010 is a promising therapeutic strategy for chemotherapy-induced peripheral neuropathy.

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.