| According to the International Association for the Study of Pain(IASP),pain is the fifth vital sign of the human body after blood pressure,pulse,respiration and body temperature.Pain,as an important symptom of various clinical diseases,not only brings physical torture to patients,but also has varying degrees of negative impact on patients' mental,psychological,working life and other aspects,such as anxiety,depression,insomnia,Even mental breakdown,which directly reduces the patient's sense of wellbeing.According to statistics,the current number of chronic pain patients in China has exceeded 100 million,and is still in sustained growth.Therefore,analgesia is particularly important,effective analgesic strategy can not only effectively promote the rehabilitation of patients with diseases,but also greatly reduce the family,social medical costs,optimize the allocation of medical resources.Transcutaneous electrical nerve stimulation(TENS)is a noninvasive analgesic therapy that activates peripheral nerve fibers by current pulses.It has many advantages such as non-pharmacological,safety and noninvasiveness,low cost and so on.Currently,TENS has been used in many types of clinical pain relief,such as the use of TENS after acute trauma,which can effectively promote the recovery of patients and reduce the use of analgesics;TENS in patients with chronic low back pain can effectively relieve pain and promote rehabilitation of motor function;pregnant women use TENS during childbirth,which can effectively reduce labor pains and shorten the delivery time.However,there is a large difference in the clinical analgesic effect of TENS,which may be due to the fact that TENS under different stimulation parameters involves different mechanisms of analgesia.At present,TENS according to the different parameters can be divided into two categories: high-frequency low-intensity TENS and low-frequency highintensity TENS.High-frequency,low-intensity TENS selectively activates nonnociceptive afferent nerves(A? fibers)in the human body,thereby inhibiting the uptake of harmful information by A? and C fibers into central nervous system.Therefore,within the same dermatome,high-frequency low-intensity TENS often can get a good analgesic effect.The low-frequency high-intensity TENS mainly activates the smaller diameter of the A? and C fibers,activating the body pain top-down inhibit pathway,promote the release of opioids,resulting in the diffuse noxious inhibitory controls.However,researchers remain controversial about the mechanism of analgesia in highfrequency and low-frequency TENS.According to Melzack and Wall's theory of pain gate control,high-frequency TENS suppresses A? and C fibers by activating A? fibers,resulting in a segmental analgesic effect that concentrates the analgesic effects on the same dermal TENS-stimulated Involved in the regulation of the high center.In recent years,some researchers have used animal models to question this traditional view.The researchers found that the analgesic effect of high-frequency TENS can be reversed by opioid antagonists(naloxone),and that depressing the analgesic effect of high-frequency TENS can be significantly suppressed if large amounts of rat brain serotonin are consumed.These findings suggest that the mechanism of analgesia by TENS is still not fully revealed and no consistent conclusions have been reached by animal experimenters.In addition,many studies have used non-pain-specific stimuli,such as: electrical stimulation,thermal stimulation or stress stimulation.These stimuli activate the nonnociceptive?? fibers while activating the nociceptors A? and C fibers,and the conclusions reached do not fully reflect the analgesic effect of TENS on pain-specific stimuli,which are mixed with pain stimulus itself tactile influence.In the meantime,most of the previous studies on TENS used animal models or rat-based neuropathic pain models.However,it remains controversial whether the conclusions drawn from animal models can be directly transferred to human experiments.In addition,the TENS study of existing human subjects is often selected patients with chronic pain or the elderly,its research purpose is to test the TENS analgesic efficiency of various chronic pain,reflecting the TENS to a chronic pain analgesic effect.Few studies have used health subjects to study the mechanism of analgesia of TENS.It is very necessary to use healthy subjects in pain research.Using healthy people as subjects can exclude other subjects' pain and thus interfere with the experimental results,Let us study the TENS analgesic mechanism more accurately and controllably.Aim of Investigation: Transcutaneous Electrical Nerve Stimulation(TENS),delivering electrical stimuli to the skin,activates peripheral somatosensory afferents and inhibits nociceptive afferent information.It has been commonly used as a nonpharmacological approach to relieve both acute and chronic pain,and the most common types of TENS are “conventional” TENS(high-frequency and low-intensity TENS,~50-100 Hz)and “acupuncture-like” TENS(low-frequency and high-intensity TENS,~2-4 Hz).Animal studies have well demonstrated that both types of TENS have analgesic effect,and relate to different mechanisms.“Conventional” TENS is usually related to the “gate control” theory,while “acupuncture-like” TENS is more related to the diffuse noxious inhibitory control phenomenon.Nevertheless,TENS induced analgesic effect on pain in healthy participants and chronic pain patients are largely conflicting and not conclusive,which could be due to the inherent difference between species,as well as the fact that animal TENS effects are typically detected in anaesthetized or “spinal” animals.Thus,the present study aimed to investigate the neurobiological mechanism of high-and lowfrequency TENS induced analgesic effects on healthy human subjects.Methods: Eighty healthy subjects were randomly allocated into four experimental groups: high-frequency(100 Hz,30 mins,eliciting a strong but comfortable tingling sensation)and low-frequency(4 Hz,30 mins,eliciting a painful but tolerable sensation)active TENS,and their respective sham TENS,with twenty subjects in each group.TENS induced changes of spontaneous brain activities were assessed by comparing the ongoing electrocortical oscillations between pre-and post-TENS sessions,and TENS induced analgesic effects were assessed by comparing the changes of subjective ratings of pain perception(intensity and unpleasantness)and electrocortical responses elicited by nociceptive stimulation,between pre-TENS and post-TENS sessions.Results: Whereas high-frequency active TENS did not elicit any overt change of spontaneous brain activities,low-frequency active TENS resulted in a clear enhancement of ongoing alpha oscillations over the primary sensorimotor cortex contralateral to the side of TENS application,as well as a significant enhancement of functional connectivity between the medial prefrontal cortex(m PFC)and the primary sensorimotor cortex contralateral to TENS.In addition,even both types of active TENS significantly reduced subjective ratings of pain(intensity and unpleasantness)than sham TENS,the analgesic effect of high-frequency active TENS was present when nociceptive stimuli were delivered homotopically to TENS,i.e.,a more segmental analgesic effect,whereas the analgesic effect of low-frequency active TENS was equally strong regardless of where nociceptive stimuli were delivered,i.e.,a more diffuse analgesic effect.Importantly,such different spatial features of analgesic effects between high-and low-frequency active TENS were further confirmed and supported by nociceptive stimuli evoked brain responses(N2 and P2 waves of the laser-evoked brain responses).Conclusion: Both high-and low-frequency active TENS has analgesic effect,but displays different spatial features,which can be subserved by distinctive neurobiological mechanisms.This understanding can guide clinicians in choosing the appropriate set of TENS parameters to maximize the analgesic effect in different patients. |
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