Effects of Personal Low-Frequency Stimulation Device on Myalgia: A Randomized Controlled Trial

Electrotherapy is commonly used for myalgia alleviation. Low-frequency stimulation (LFS) is primarily used for controlling acute and chronic pain and is a non-invasive therapy that can be easily performed with electric stimulation applied on the skin. However, little evidence exists regarding the pain alleviation effects of personal low-frequency stimulation device for home use. Moreover, no studies have compared myalgia alleviation effects between personal low-frequency stimulation (PLS) and physical therapy (PT), which are most commonly used for patients with myalgia in hospitals and clinics. Therefore, we aimed to investigate the pain alleviation effects of PLS in patients with myalgia and compare these effects with those of conventional PT (transcutaneous electrical nerve stimulation + ultrasound). In total, 39 patients with myalgia in the neck, shoulder, back, and waist areas were randomly assigned to the personal low-frequency stimulation group (PLSG: n = 20) and physical therapy group (PTG: n = 19). Both groups were treated for 3 weeks (20 min per session and 5 sessions per week). Patients were assessed for pain intensity by surface electromyography (sEMG), visual analogue scale (VAS) and a short-form McGill pain questionnaire (SF-MPQ) before and after the intervention period. Our results showed that PLSG showed a tendency of muscle relaxation with a significant decrease in sEMG in the neck (p = 0.0425), shoulder (p = 0.0425), and back (p = 0.0046) areas compared to the control group. However, there was no significant difference in waist area. Additionally, VAS scores significantly decreased between pre- and post-treatment in both PTG (p = 0.0098), and PLSG (p = 0.0304) groups, but there was no significance difference between the groups. With respect to SF-MPQ, the PLSG showed greater pain alleviation (5.23 ± 0.25) effects than the PTG (6.23 ± 0.25). Accordingly, our results suggest that PLS treatment using a home device might offer positive assistance in pain alleviation for patients with myalgia that is as equally effective as conventional PT treatment. However, further detailed studies are required considering larger samples to fully claim the effectiveness of this device.

Behavioural responses of threespine stickleback with lateral line asymmetries to experimental mechanosensory stimuli

Behavioural asymmetry, typically referred to as laterality, is widespread among bilaterians and is often associated with asymmetry in brain structure. However, the influence of sensory receptor asymmetry on laterality has undergone limited investigation. Here we use threespine stickleback (Gasterosteus aculeatus) to investigate the influence of lateral line asymmetry on laterality during lab simulations of three mechanosensation-dependent behaviours: predator evasion, prey localization and rheotaxis. We recorded the response of stickleback to impacts at the water surface and water flow in photic conditions and low-frequency oscillations in the dark, across four repeat trials. We then compared individuals’ laterality to asymmetry in the number of neuromasts on either side of their body. Stickleback hovered with their right side against the arena wall 57% of the time (P<0.001) in illuminated surface impact trials and 56% of the time in (P=0.085) dark low-frequency stimulation trials. Light regime modulated the effect of neuromast count on laterality, as fish with more neuromasts were more likely to hover with the wall on their right during illumination (P=0.007) but were less likely to do so in darkness (P=0.025). Population level laterality diminished in later trials across multiple behaviours and individuals did not show a consistent side bias in any behaviours. Our results demonstrate a complex relationship between sensory structure asymmetry and laterality, suggesting that laterality is modulated multiple sensory modalities and temporally dynamic.

Synaptotagmin-7 enhances phasic dopamine release

Dopamine released from substantia nigra pars compacta (SNc) neurons modulates movement, motivation, and reward. In addition to their tonic firing pattern, dopamine neurons also fire high-frequency bursts that cause superlinear increases in dopamine release. To examine this poorly understood form of short-term plasticity, we used the fluorescent dopamine sensor dLight1.3b to examine the role of the calcium-binding protein synaptotagmin-7 (SYT7). We report that SYT7 mediates a hidden component of facilitation, which was unmasked by lowering initial release probability, or by low-frequency stimulation of nerve terminals. In Syt7 KO neurons, there was profound synaptic depression that significantly reduced release during stimulations that mimic in vivo firing patterns of SNc neurons. D2-mediated inhibitory postsynaptic currents in the SNc revealed a similar role for SYT7 in somatodendritic release. Our results indicate that SYT7 drives short-term facilitation of release from dopamine neurons, which likely underlies frequency-dependence of dopamine signaling in vivo.

Low-Frequency Stimulation Prevents Kindling-Induced Impairment through the Activation of the Endocannabinoid System

Background. Cannabinoid system affects memory and has anticonvulsant effects in epileptic models. In the current study, the role of cannabinoid 1 (CB1) receptors was investigated in amelioration of the effects of low-frequency stimulation (LFS) on learning and memory impairments in kindled rats. Methods. Electrical stimulation of the hippocampal CA1 area was employed to kindle the animals. LFS was applied to the CA1 area in four trials following the last kindling stimulation. One group of animals received intraperitoneal injection of AM251 (0.1 μg/rat), a CB1 receptor antagonist, before the LFS application. Similarly, CB1 agonist WIN55-212-2 (WIN) was administrated to another group prior to LFS. The Morris water maze (MWM) and the novel object recognition (NOR) tests were executed 48 h after the last kindling stimulation to assess learning and memory. Results. Applying LFS in the kindled+LFS group restored learning and memory impairments in the kindled rats. There was a significant difference between the kindled and the kindled+LFS groups in learning and memory. The application of AM251 reduced the LFS effects significantly. Adversely, WIN acted similarly to LFS and alleviated learning and memory deficits in the kindled+WIN group. In addition, WIN did not counteract the LFS enhancing effects in the KLFS+WIN group. Conclusions. Improving effects of LFS on learning and memory impairments are mediated through the activation of the endocannabinoid (ECB) system.

High-Frequency Stimulation of Ventral CA1 Neurons Reduces Amygdala Activity and Inhibits Fear

The hippocampus can be divided into distinct segments that make unique contributions to learning and memory. The dorsal segment supports cognitive processes like spatial learning and navigation while the ventral hippocampus regulates emotional behaviors related to fear, anxiety and reward. In the current study, we determined how pyramidal cells in ventral CA1 respond to spatial cues and aversive stimulation during a context fear conditioning task. We also examined the effects of high and low frequency stimulation of these neurons on defensive behavior. Similar to previous work in the dorsal hippocampus, we found that cells in ventral CA1 expressed high-levels of c-Fos in response to a novel spatial environment. Surprisingly, however, the number of activated neurons did not increase when the environment was paired with footshock. This was true even in the subpopulation of ventral CA1 pyramidal cells that send direct projections to the amygdala. When these cells were stimulated at high-frequencies (20 Hz) we observed feedforward inhibition of basal amygdala neurons and impaired expression of context fear. In contrast, low-frequency stimulation (4 Hz) did not inhibit principal cells in the basal amygdala and produced an increase in fear generalization. Similar results have been reported in dorsal CA1. Therefore, despite clear differences between the dorsal and ventral hippocampus, CA1 neurons in each segment appear to make similar contributions to context fear conditioning.

Short-Term Amygdala Low-Frequency Stimulation Does not Influence Hippocampal Interneuron Changes Observed in the Pilocarpine Model of Epilepsy

Temporal lobe epilepsy (TLE) is characterized by changes in interneuron numbers in the hippocampus. Deep brain stimulation (DBS) is an emerging tool to treat TLE seizures, although its mechanisms are not fully deciphered. We aimed to depict the effect of amygdala DBS on the density of the most common interneuron types in the CA1 hippocampal subfield in the lithium-pilocarpine model of epilepsy. Status epilepticus was induced in male Wistar rats. Eight weeks later, a stimulation electrode was implanted to the left basolateral amygdala of both pilocarpine-treated (Pilo, n = 14) and age-matched control rats (n = 12). Ten Pilo and 4 control animals received for 10 days 4 daily packages of 50 s 4 Hz regular stimulation trains. At the end of the stimulation period, interneurons were identified by immunolabeling for parvalbumin (PV), neuropeptide Y (NPY), and neuronal nitric oxide synthase (nNOS). Cell density was determined in the CA1 subfield of the hippocampus using confocal microscopy. We found that PV+ cell density was preserved in pilocarpine-treated rats, while the NPY+/nNOS+ cell density decreased significantly. The amygdala DBS did not significantly change the cell density in healthy or in epileptic animals. We conclude that DBS with low frequency applied for 10 days does not influence interneuron cell density changes in the hippocampus of epileptic rats.