CXCL10 and CXCR3 in the Trigeminal Ganglion Contribute to Trigeminal Neuropathic Pain in Mice.

PURPOSE: Trigeminal neuropathic pain is very common clinically, but effective treatments are lacking. Chemokines and their receptors have been implicated in the pathogenesis of chronic pain. This study explored the role of the chemokine CXCL10 and its receptor, CXCR3, in trigeminal neuropathic pain in mice. MATERIALS AND METHODS: Trigeminal neuropathic pain was established by partial infraorbital nerve ligation (pIONL) in wild-type and Cxcr3 -/- mice. Facial mechanical allodynia was evaluated by behavioral testing. A lentivirus containing Cxcr3 shRNA (LV-Cxcr3 shRNA) was microinjected into the trigeminal ganglion (TG) to knock down Cxcr3 expression. Quantitative polymerase chain reaction assays and immunofluorescence staining were used to examine Cxcl10/Cxcr3 mRNA expression and protein distribution. Western blotting was performed to examine activation of extracellular signal-regulated kinase (ERK) and AKT in the TG. Intra-TG injection of an AKT inhibitor was performed to examine the role of AKT in trigeminal neuropathic pain. RESULTS: pIONL induced persistent trigeminal neuropathic pain, which was alleviated in Cxcr3 -/- mice. Intra-TG injection of LV-Cxcr3 shRNA attenuated pIONL-induced mechanical allodynia. Furthermore, pIONL increased the expression of CXCR3 and its major ligand, CXCL10, in TG neurons. Intra-TG injection of CXCL10 induced pain hypersensitivity in wild-type mice but not in Cxcr3 -/- mice. CXCL10 also induced activation of ERK and AKT in the TG of wild-type mice. Finally, pIONL-induced activation of ERK and AKT was reduced in Cxcr3 -/- mice. Intra-TG injection of the AKT inhibitor alleviated pIONL-induced mechanical allodynia in WT mice but not in Cxcr3 -/- mice. CONCLUSION: CXCL10 acts on CXCR3 to induce ERK and AKT activation in TG neurons and contributes to the maintenance of trigeminal neuropathic pain.

A numerical simulation method of natural fragment formation and injury to human thorax.

OBJECTIVE: Fragment injury is a type of blast injury that is becoming more and more common in military campaigns and terrorist attacks. Numerical simulation methods investigating the formation of natural fragments and injuries to biological targets are expected to be developed. METHODS: A cylindrical warhead model was established and the formation process of natural fragments was simulated using the approach of tied nodes with failure through the explicit finite element (FE) software of LS-DYNA. The interaction between the detonation product and the warhead shell was simulated using the fluid-structure interaction algorithm. A method to simulate the injury of natural fragments to a biological target was presented by transforming Lagrange elements into smooth particle hydrodynamics (SPH) particles after the natural fragments were successfully formed. A computational model of the human thorax was established to simulate the injury induced by natural fragments by the node-to-surface contact algorithm with erosion. RESULTS: The discontinuous velocities of the warhead shell at different locations resulted in the formation of natural fragments with different sizes. The velocities of natural fragments increased rapidly at the initial stage and slowly after the warhead shell fractured. The initial velocities of natural fragments at the central part of the warhead shell were the largest, whereas those at both ends of the warhead shell were the smallest. The natural fragments resulted in bullet holes that were of the same shape as that of the fragments but slightly larger in size than the fragments in the human thorax after they penetrated through. Stress waves propagated in the ribs and enhanced the injury to soft tissues; additionally, ballistic pressure waves ahead of the natural fragments were also an injury factor to the soft tissues. CONCLUSION: The proposed method is effective in simulating the formation of natural fragments and their injury to biological targets. Moreover, this method will be beneficial for simulating the combined injuries of natural fragments and shock waves to biological targets.

[Feasibility of sewage sludge used as filling material in permeable reactive barrier].

Permeable reactive barriers (PRB) have been used widely as an alternative technique to treatment of acid mine drainage (AMD). Selection of the appropriate filling materials is the most important procedure to application of this treatment. Batch adsorption tests and bacteria culture batch tests were conducted to assess the possibility of sewage sludge served as filling material for PRB. Results from batch adsorption tests showed that the maximum adsorption capacities of the sewage sludge were 13.62 mg x g(-1) (Zn2+) and 15.60 mg x g(-1) (Cd2+). Bacteria culture batch tests indicated that SO4(2-) concentrations in reactors decreased from initial concentrations of 700 mg x L(-1) to below 300 mg x L(-1). Sulfate removal efficiency ranged from 60% to 70%. Fe and heavy metals, including Zn and Cd, were removed completely in two reactors. This study suggested that sewage sludge is a suitable filling material for PRB.

[Oxidation buffer capacity of sewage sludge barrier for immobilization of heavy metals].

Benefit from the microbial activities especially the anaerobic sulfate reduction processes, sewage sludge could be used as a barrier to immobilize the heavy metals leached from tailings. With respect to the redox reaction between sewage sludge and acid mine drainage (AMD), oxidation titration test was carried out to study the effect of oxidation buffer capacity (OBC) of sewage sludge on the immobilization of heavy metals. Test results showed that OBC of sludge suspensions was decreased slightly with the solid-liquid ratio of the suspensions, but increased with the anaerobic incubation time, and that more than 50% of OBC was contributed by the sludge existed in strongly-reduction conditions (Eh < or = - 150 mV). During oxidation titration test, Zn was released obviously when Eh > or = - 150 mV, while Cu and Pb released obviously when Eh > or = 150 mV. According to the test results, a mathematical model was established to predict the OBC consumption of the sludge barrier under AMD penetrating conditions. The simulation results showed that a sludge barrier with 2m thickness, even undergone 38 787-years oxidation by AMD under 10m water head, keep in a strongly-reduced condition and, therefore, promote an immobilization of heavy metals from AMD in the barrier.

[Acid buffer capacity of sewage sludge barrier for immobilization of heavy metals].

Employing the anaerobic activities of microorganisms, sewage sludge can be used as a barrier to immobilize the heavy metals leached from tailings. Due to the interactions between sewage sludge barrier and acid mine drainage (AMD), it is possible that the heavy metals that have been immobilized previously might be released out. The acid buffering capacity (ABC) of sewage sludge suspensions with various anaerobic incubation time and the effect of ABC on the mobility of heavy metals were investigated by acid titration tests. Test results showed that ABC of sewage sludge suspensions was increased with the solid-liquid ratio of the suspensions and the anaerobic incubation time, and that carbonate and organics play an important role in acid buffer of sewage sludge suspensions. During the acid titration test, Zn, Pb and Cu were released out obviously following the order of Zn > Cu > Pb as pH was decreased less than 6.2. A mathematical model was established to predict the ABC consumption of the sewage sludge barrier under AMD penetration condition. The simulation results showed that a sewage sludge barrier with 2.0 m thickness, even undergoing 666-years acidification by AMD under 10.0 m water head, can maintain a condition of pH > or = 6.2 and, therefore, keep immobilize the heavy metals of AMD in the barrier.