Dexmedetomidine Attenuates Neuropathic Pain by Inhibiting P2X7R Expression and ERK Phosphorylation in Rats

α2-Adrenoceptor agonists attenuate hypersensitivity under neuropathic conditions. However, the mechanisms underlying this attenuation remain largely unknown. In the present study, we explored the potential roles of purinergic receptor 7 (P2X7R)/extracellular signal-regulated kinase (ERK) signaling in the anti-nociceptive effect of dexmedetomidine in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. An animal model of CCI was adopted to mimic the clinical neuropathic pain state. Behavioral hypersensitivity to mechanical and thermal stimuli was determined by von Frey filament and Hargreaves' tests, and the spinal P2X7R expression level and ERK phosphorylation were analyzed using western blot analysis and immunohistochemistry. In parallel with the development of mechanical and thermal hyperalgesia, a significant increase in P2X7R expression was noted in the ipsilateral spinal cord on day 7 after CCI. Intrathecal administration of dexmedetomidine (2.5 µg) for 3 days not only attenuated neuropathic pain but also inhibited the CCI-induced P2X7R upregulation and ERK phosphorylation. Intrathecal dexmedetomidine administration did not produce obvious effects on locomotor function. The present study demonstrated that dexmedetomidine attenuates the neuropathic pain induced by CCI of the sciatic nerve in rats by inhibiting spinal P2X7R expression and ERK phosphorylation, indicating the potential therapeutic implications of dexmedetomidine administration for the treatment of neuropathic pain.

Effects of bacterial biofilm on hearing restoration with titanium partial ossicular prosthesis replacement / 医用生物力学

Objective To study effects of the bacterial biofilm at different growth stages on dynamic behavior of the titanium partial ossicular replacement prosthesis (PORP), so as to provide theoretical references for clinical treatment of diseases such as secretory otitis media. Methods Based on the CT scan images of normal human right ear and combined with the self compiling program, a 3D finite element model of the ear was reconstructed for dynamic analysis on sound conduction, and compared with the experimental data. The model was computed by harmonic response analysis method, and the sound conduction effect of bacterial biofilm grown on PORP at different growth stages was analyzed. Results The simulated amplitude of umbo and stapes footplate was in accordance with experimental measurements, which confirmed the validity of this numerical model. The existence of biofilm would cause 0-1.6 dB hearing loss at low frequencies. The growth of biofilm in the radial direction of PORP would cause 0-12 dB hearing loss at intermediate and high frequencies, especially at 8 kHz, and the hearing loss could be as high as 11.2 dB. Conclusions The bacterial biofilm has an impact on hearing by reducing the hearing at low frequencies while raising a little at high frequencies. The biofilm grown in the radial direction of PORP will reduce hearing, and affect the working efficiency of PORP on hearing restoration.