Temporal Dynamics of Adverse Effects across Five Sessions of Transcranial Direct Current Stimulation.

(1) Background: Transcranial direct current stimulation (tDCS) is a safe intervention, only producing mild and transient adverse effects (AEs). However, there is no detailed analysis of the pattern of adverse effects in an application transferable to the clinic. Therefore, our objective is to describe the AEs produced by tDCS and its temporal evolution. (2) Methods: A total of 33 young volunteers were randomized into a tDCS or sham group. Participants performed a hand dexterity task while receiving the tDCS or sham intervention (20 min and 1 mA), for five consecutive days. AEs were assessed daily after each intervention and classified as somatosensory, pain, or other effects. (3) Results: The number of AEs was generally increased by tDCS intervention. Specifically, tDCS led to more frequent somatosensory discomfort, characterized by sensations like itching and tingling, alongside painful sensations such as burning, compared to the sham intervention. Additionally, certain adverse events, including neck and arm pain, as well as dizziness and blurry vision, were exclusive to the tDCS group. Interestingly, tDCS produced similar AEs across the days; meanwhile, the somatosensory AEs in the sham group showed a trend to decrease. (4) Conclusions: tDCS produces mild and temporary somatosensory and pain AEs during and across sessions. The different evolution of the AEs between the tDCS and sham protocol could unmask the blinding protocol most used in tDCS studies. Potential solutions for improving blinding protocols for future studies are discussed.

Blood flow effects of percutaneous peripheral nerve stimulation. A blinded, randomized clinical trial.

BACKGROUND: The vasculature function is mainly regulated by the autonomic nervous system. Importantly, the sensory-motor nervous system also innervates peripheral vessels and has the capacity to modulate vascular tone. Here we investigated the effects of electrical stimulation of a mixed nerve trunk on blood flow in deep arteries and muscle perfusion. Our hypothesis is that stimulation of a mixed nerve can modify blood flow. METHODS: Twenty-nine healthy participants were included into a randomized-crossover and blinded clinical trial. Each subject received a placebo and two percutaneous peripheral nerve stimulation (pPNS) protocols on the median nerve: Pain Threshold continuous Low Frequency (PT-cLF) and Sensory Threshold burst High Frequency (ST-bHF). Blood flow was then assessed bilaterally using Power Doppler Ultrasonography at the main arteries of the arm, and blood perfusion at the forearm muscles. Afterwards, blood flow was quantified using a semi-automatized software, freely shared here. RESULTS: Placebo, consisting in needle insertion, produced an immediate and generalized reduction on peak systolic velocity in all arteries. Although nerve stimulation produced mainly no effects, some significant differences were found: both protocols increased the relative perfusion area of the forearm muscles, the ST-bHF protocol prevented the reduction in peak systolic velocity and TAMEAN of the radial artery produced by the control protocol and PT-cLF produced a TAMEAN reduction of the ulnar artery. CONCLUSIONS: Therefore, the arterial blood flow in the arm is mainly impervious to the electrical stimulation of the median nerve, composed by autonomic and sensory-motor axons, although it produces mild modifications in the forearm muscles perfusion.

Endogenous Pain Modulation in Response to a Single Session of Percutaneous Electrolysis in Healthy Population: A Double-Blinded Randomized Clinical Trial.

The purpose of this double-blinded randomized controlled trial was to investigate whether percutaneous electrolysis (PE) is able to activate endogenous pain modulation and whether its effects are dependent on the dosage of the galvanic current. A total of 54 asymptomatic subjects aged 18-40 years were randomized into three groups, receiving a single ultrasound-guided PE intervention that consisted of a needle insertion on the lateral epicondyle tendon: sham (without electrical current), low-intensity (0.3 mA, 90 s), and high-intensity (three pulses of 3 mA, 3 s). Widespread pressure pain thresholds (PPT), conditioned pain modulation (CPM), and temporal summation (TS) were assessed in the elbow, shoulder, and leg before and immediately after the intervention. Both high and low intensity PE protocols produced an increase in PPT in the shoulder compared to sham (p = 0.031 and p = 0.027). The sham group presented a significant decrease in the CPM (p = 0.006), and this finding was prevented in PE groups (p = 0.043 and p = 0.025). In addition, high-intensity PE decreased TS respect to sham in the elbow (p = 0.047) and both PE groups reduced TS in the leg (p = 0.036 and p = 0.020) without significant differences compared to sham (p = 0.512). Consequently, a single PE intervention modulated pain processing in local and widespread areas, implying an endogenous pain modulation. The pain processing effect was independent of the dosage administrated.

Epithelial and sensory mechanisms of nasal hyperreactivity.

"Nasal hyperreactivity" is a key feature in various phenotypes of upper airway diseases, whereby reactions of the nasal epithelium to diverse chemical and physical stimuli are exacerbated. In this review, we illustrate how nasal hyperreactivity can result from at least three types of mechanisms: (1) impaired barrier function, (2) hypersensitivity to external and endogenous stimuli, and (3) potentiation of efferent systems. We describe the known molecular basis of hyperreactivity related to the functional impairment of epithelial cells and somatosensory innervation, and indicate that the thermal, chemical, and mechanical sensors determining hyperreactivity in humans remain to be identified. We delineate research directions that may provide new insights into nasal hyperreactivity associated with rhinitis/rhinosinusitis pathophysiology and therapeutics. The elucidation of the molecular mechanisms underlying nasal hyperreactivity is essential for the treatment of rhinitis according to the precepts of precision medicine.

Deciphering the Action of Perfluorohexyloctane Eye Drops to Reduce Ocular Discomfort and Pain.

Perfluorohexyloctane (F6H8) eyedrops have been recently introduced in Europe as a product to treat dry eye disease, based on its ability to reduce tear film instability in Meibomian gland dysfunction and evaporative dry eye disease, although its mechanism of action is still unknown. In the present pilot study, we evaluated the effects of the ocular instillation of a single drop of commercial F6H8 eyedrops in 20 healthy humans (9 women/11 men), measuring: (a) Corneal surface temperature (CST) from infrared video images; (b) tear volume using phenol red threads; (c) blinking frequency; and (d) ocular surface sensations (cold, dryness, pricking, foreign body, burning, itching, gritty, eye fatigue, watering eyes, and light-evoked discomfort sensations; scored using 10 cm Visual Analog Scales), before and 5-60 min after F6H8 or saline treatment. CST decreased and tearing and blinking frequency increased significantly after F6H8 but not after saline solution. When applied unilaterally, CST decreased only in the F6H8-treated eye. No sensations were evoked after F6H8 or saline. The corneal surface temperature reduction produced by topical F6H8 does not evoke conscious ocular sensations but is sufficient to increase the activity of corneal cold thermoreceptors, leading to an increased reflex lacrimation and blinking that may relieve dry eye condition thus reducing ocular discomfort and pain.

Effects of Percutaneous Electrolysis on Endogenous Pain Modulation: A Randomized Controlled Trial Study Protocol.

Percutaneous electrolysis consists of the application of a galvanic electrical current throughout an acupuncture needle. It has been previously hypothesized that needling procedures' neurophysiological effects may be related to endogenous pain modulation (EPM). This protocol study describes the design of a double-blind (participant, assessor) randomized controlled trial with the aim to investigate whether percutaneous electrolysis is able to enhance EPM and whether the effect is different between two applications depending on the dosage of the galvanic electrical current. Seventy-two asymptomatic subjects not reporting the presence of pain symptoms the previous 6 months before the study, aged 18-40 years, are randomized into one of four groups: a control group who does not receive any intervention, a needling group who receives a needling intervention without electrical current, a low-intensity percutaneous electrolysis group (0.3 mA × 90 s), and a high-intensity percutaneous electrolysis group (three bouts of 3 mA × 3 s). Needling intervention consists of ultrasound-guided insertion of the needle on the common extensor tendon of the lateral epicondyle. The primary outcome is conditioned pain modulation (CPM), and secondary outcomes include widespread pressure pain sensitivity (pressure pain thresholds (PPT) over the lateral epicondyle, the cervical spine, and the tibialis anterior muscle) and temporal summation (TS). We expected that percutaneous electrolysis would have a greater influence on CPM than an isolated needling procedure and no intervention. In addition, we also postulated that there might be differences in outcome measures depending on the intensity of the electrical current during the percutaneous electrolysis application. This study makes a new contribution to the field of neurophysiological effects of percutaneous electrolysis and needling interventions.

Reversed Polarity bi-tDCS over M1 during a Five Days Motor Task Training Did Not Influence Motor Learning. A Triple-Blind Clinical Trial.

Transcranial direct current stimulation (tDCS) has been investigated as a way of improving motor learning. Our purpose was to explore the reversal bilateral tDCS effects on manual dexterity training, during five days, with the retention component measured after 5 days to determine whether somatosensory effects were produced. In this randomized, triple-blind clinical trial, 28 healthy subjects (14 women) were recruited and randomized into tDCS and placebo groups, although only 23 participants (13 women) finished the complete protocol. Participants received the real or placebo treatment during five consecutive days, while performing a motor dexterity training program of 20 min. The motor dexterity and the sensitivity of the hand were assessed pre- and post-day 1, post 5 days of training, and 5 days after training concluded. Training improved motor dexterity, but tDCS only produced a tendency to improve retention. The intervention did not produce changes in the somatosensory variables assessed. Thus, reversal bi-tDCS had no effects during motor learning on healthy subjects, but it could favor the retention of the motor skills acquired. These results do not support the cooperative inter-hemispheric model.

Static magnetic stimulation in the central nervous system: a systematic review.

OBJECTIVE: To systematically review the literature on the use of the transcranial static magnetic stimulation (tSMS) technique in humans and animals, its effects on different areas of the central nervous system (CNS), its influence on neural excitability and on the subject's behavior, and its biological effects and future possibilities. All static magnetic field applications that can be considered to have a physiologically similar effect have been reviewed. METHODS: We searched studies using key terms in NCBI PubMed, Scopus, PEDro, SciELO, Cochrane, and links to publications (inception to September 2019). Three reviewers independently selected the studies, extracted data, and assessed the methodological quality of the studies using the recommendations described in the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines. RESULTS: We analyzed 27 studies. The reviewed literature suggests that the use of these magnetic fields has an inhibitory effect on different areas of the CNS, such as motor, somatosensory, and visual cortex, cerebellum, and spinal cord. Regarding subject's behavior, the different effects of tSMS appear to be transient and dependent on the stimulated area, such as loss of visual discrimination or improvement of somatosensory perception. In addition, the technique has some therapeutic utility, specifically in pathologies with cortical hyperexcitability. CONCLUSIONS: These results suggest that tSMS may be a promising tool to modulate cerebral excitability in a safe and non-invasive way. Further investigations could give a better explanation of its precise mechanisms of action and applications.