Activation of the RAGE/STAT3 Pathway in the Dorsal Root Ganglion Contributes to the Persistent Pain Hypersensitivity Induced by Lumbar Disc Herniation.

BACKGROUND: Clinically, chronic low back pain and sciatica associated with lumbar disc herniation (LDH) is a common musculoskeletal disorder. Due to the unawareness of detailed mechanisms, it is difficult to get an effective therapy. OBJECTIVE: The aim of the present study was to identify the role of the RAGE/STAT3 pathway in the dorsal root ganglion (DRG) on the formation and development of persistent pain hypersensitivity induced by LDH. STUDY DESIGN: Controlled animal study. SETTING: University laboratory. METHODS: After LDH induced by implantation of autologous nucleus pulposus (NP, harvested from animal tail) on the left L5 nerve root was established, mechanical thresholds and electrophysiological tests were conducted at relevant time points during an observation period of 28 days. Protein levels and localization of RAGE and p-STAT3 were performed by using Western blotting and immunohistochemistry, respectively. RESULTS: LDH induced persistent pain hypersensitivity, increased excitability of DRG neurons, and upregulated the expression of RAGE and p-STAT3 in the DRG. Consecutive injection of both RAGE antagonist FPS-ZM1 (i.t.) and STAT3 activity inhibitor S3I-201 (i.t.) inhibited the enhanced excitability of DRG neurons and mechanical allodynia induced by NP implantation. Furthermore, local knockdown of STAT3 by intrathecal injection of AAV-Cre-GFP into STAT3flox/flox mice markedly alleviated NP implantation-induced mechanical allodynia in mice. Importantly, the expression of p-STAT3 was colocalized with that of RAGE in the DRG and inhibition of RAGE with FPS-ZM1 prevented NP implantation-induced STAT3 activation. LIMITATIONS: More underlying mechanism(s) of the role of the RAGE/STAT3 pathway on the formation and development of persistent pain hypersensitivity induced by LDH will be needed to be explored in future research. CONCLUSIONS: These findings suggest activation of the RAGE/STAT3 pathway plays a critical role in persistent pain induced by LDH, and this pathway may represent novel therapeutic targets for the treatment of LDH-induced persistent pain. KEY WORDS: Lumbar disc herniation, persistent pain, RAGE, STAT3, DRG.

Rogue wave triggered at a critical frequency of a nonlinear resonant medium.

We consider a two-level atomic system interacting with an electromagnetic field controlled in amplitude and frequency by a high intensity laser. We show that the amplitude of the induced electric field admits an envelope profile corresponding to a breather soliton. We demonstrate that this soliton can propagate with any frequency shift with respect to that of the control laser, except a critical frequency, at which the system undergoes a structural discontinuity that transforms the breather in a rogue wave. A mechanism of generation of rogue waves by means of an intense laser field is thus revealed.

The effectiveness of functional electrical stimulation based on a normal gait pattern on subjects with early stroke: a randomized controlled trial.

OBJECTIVE: To investigate the effectiveness of four-channel FES based on a normal gait pattern on improving functional ability in subjects early after ischemic stroke. METHODS: Forty-five subjects were randomly assigned into a four-channel FES group (n=16), a placebo group (n=15), or a dual-channel group (n=14). Stimulation lasted for 30 min in each session with 1 session/day, 5 days a week for 3 weeks. All subjects were assessed at baseline, at 3 weeks of treatment, and at 3 months after the treatment had finished. The assessments included Fugl-Meyer Assessment (FMA), the Postural Assessment Scale for Stroke Patients (PASS), Berg Balance Scale (BBS), Functional Ambulation Category (FAC), and the Modified Barthel Index (MBI). RESULTS: All 3 groups demonstrated significant improvements in all outcome measurements from pre- to posttreatment and further gains at followup. The score of FMA and MBI improved significantly in the four-channel group at the end of the 3 weeks of training. And the scores of PASS, BBS, MBI, and FAC in the four-channel group were significantly higher than those of the placebo group. CONCLUSIONS: This study indicated that four-channel FES can improve motor function, balance, walking ability, and performance of activities of daily living in subjects with early ischemic stroke.

Circularly polarized few-cycle optical rogue waves: rotating reduced Maxwell-Bloch equations.

The rotating reduced Maxwell-Bloch (RMB) equations, which describe the propagation of few-cycle optical pulses in a transparent media with two isotropic polarized electronic field components, are derived from a system of complete Maxwell-Bloch equations without using the slowly varying envelope approximations. Two hierarchies of the obtained rational solutions, including rogue waves, which are also called few-cycle optical rogue waves, of the rotating RMB equations are constructed explicitly through degenerate Darboux transformation. In addition to the above, the dynamical evolution of the first-, second-, and third-order few-cycle optical rogue waves are constructed with different patterns. For an electric field E in the three lower-order rogue waves, we find that rogue waves correspond to localized large amplitude oscillations of the polarized electric fields. Further a complementary relationship of two electric field components of rogue waves is discussed in terms of analytical formulas as well as numerical figures.

N-order bright and dark rogue waves in a resonant erbium-doped fiber system.

The rogue waves in a resonant erbium-doped fiber system governed by a coupled system of the nonlinear Schrödinger equation and the Maxwell-Bloch equation (NLS-MB equations) are given explicitly by a Taylor series expansion about the breather solutions of the normalized slowly varying amplitude of the complex field envelope E, polarization p, and population inversion η. The n-order breather solutions of the three fields are constructed using a Darboux transformation (DT) by assuming periodic seed solutions. Moreover, the n-order rogue waves are given by determinant forms with n+3 free parameters. Furthermore, the possible connection between our rouge waves and the generation of supercontinuum generation is discussed.