Effects of acupuncture stimulation of the sacral region on EEG and urinary bladder activity in rats

Objective To observe the effect of acupuncture stimulation of the sacral segment on the excitability of the cerebral cortex and the activity of the urinary bladder and the involvement of the cholinergic neurons in the laterodorsal tegmental （LDT） nucleus of the brainstem in acupuncture-induced electroencephalogram （EEG） changes. Methods A total of 109 SD rats were used in the present study. Under anesthesia （urethane）, a pair of stainless steel electrodes was separately implanted into the frontal and parietal bony sutures to record EEG. Glass microelectrodes were used to record extracellular discharges of single neuron of the LDT nucleus in the brainstem. Urinary bladder pressure was recorded through a catheter inserted in the bladder and the contraction was induced by infusion of normal saline. A filiform acupuncture needle was inserted into the sacral segment Ecorresponding to Zhongliao （中髎BL 33）] and rotated manually for 1 min. Results In 27 rats whose bladder was full of normal saline, acupuncture stimulation of the sacral region suppressed the contraction activity of the bladder, the fast EEG with lower amplitude and higher frequency tuned into slow EEG with higher amplitude and lower frequency in 6 cases （22.2%）. The inhibitory effect occurred from 45 s to 12 min after acupuncture manipulation. In 82 rats whose bladder was empty, acupuncture stimulation caused the fast EEG to turn into slow EEG in 71 cases （86.6%）. Simultaneously, LDT cholinergic neurons reduced their firing rates from （2.9±1.5） Hz to （1.2±0.6） Hz （n = 12, P〈0.05）, and the reduction of LDT neuronal discharge was earlier in time than the change of EEG. Conclusion Acupuncture stimulation of the sacral region can lower the excitability of the cerebral cortex and suppress bladder activity, which is closely associated with its resultant inhibitory effect on the electrical activity of LDT cholinergic neurons.

Inhibition of LIM kinase reduces contraction and proliferation in bladder smooth muscle

Overactive bladder(OAB)is the most bothersome symptom in lower urinary tract symptoms(LUTS).Current pharmacologic treatment aims to inhibit detrusor contraction;however,shows unsatisfied efficacy and high discontinuation rate.LIM kinases(LIMKs)promote smooth muscle contraction in the prostate;however,their function in the bladder smooth muscle remains unclear.Here,we studied effects of the LIMK inhibitors on bladder smooth muscle contraction and proliferation both in vitro and in vivo experiments.Bladder expressions of LIMKs are elevated in OAB rat detrusor tissues.Two LIMK inhibitors,SR7826 and LIMKi3,inhibit contraction of human detrusor strip,and cause actin filament breakdown,as well as cell proliferation reduction in cultured human bladder smooth muscle cells(HBSMCs),paralleled by reduced cofilin phosphorylation.Silencing of LIMK1 and LIMK2 in HBSMCs resulted in breakdown of actin filaments and decreased cell proliferation.Treatment with SR7826 or LIMKi3 decreased micturition frequency and bladder detrusor hypertrophy in rats with bladder outlet obstruction.Our study suggests that LIMKs may promote contraction and proliferation in the bladder smooth muscle,which could be inhibited by small molecule LIMK inhibitors.LIMK inhibitors could be a potential therapeutic strategy for OAB-related LUTS.