C. Vance

Release of GABA and activation of GABAA in the spinal cord mediates the effects of TENS in rats

Transcutaneous electrical nerve stimulation (TENS) is a commonly utilized non-pharmacological, non-invasive treatment for pain. GABA is a neurotransmitter in the dorsal horn of the spinal cord that mediates analgesia locally, and also through activation of supraspinal sites. TENS reduces hyperalgesia through activation of receptor-mediated pathways at the level of the spinal cord, and supraspinally. The current study tested the hypothesis that either high or low frequency TENS applied to the inflamed knee joint increases GABA in the spinal cord dorsal horn and activates GABA receptors spinally. We utilized microdialysis to sample the extracellular fluid before, during and after TENS and analyzed GABA in dialysates with high performance liquid chromatography. We analyzed the extracellular GABA concentrations in animals with and without knee joint inflammation induced by intra-articular injection of kaolin and carrageenan. We further tested if spinal blockade of GABA receptors prevents the antihyperalgesia produced by TENS in rats with joint inflammation. We show that high frequency TENS increases extracellular GABA concentrations in the spinal cord in animals with and without joint inflammation. The increases in GABA do not occur in response to low frequency TENS, and there are no increases in glycine in response to low or high frequency TENS. However, the reduction in primary hyperalgesia by both high and low frequency TENS is prevented by spinal blockade of GABA(A) receptors with bicuculline. Thus, high frequency TENS increases release of GABA in the deep dorsal horn of the spinal cord, and both high and low frequency TENS reduce primary hyperalgesia by activation of GABA(A) receptors spinally.

High-frequency, but not low-frequency, transcutaneous electrical nerve stimulation reduces aspartate and glutamate release in the spinal cord dorsal horn

Transcutaneous electrical nerve stimulation (TENS) is a commonly utilized non‐pharmacological treatment for pain. Studies show that low‐ and high‐frequency TENS utilize opioid, serotonin and/or muscarinic receptors in the spinal cord to reduce hyperalgesia induced by joint inflammation in rats. As there is an increase in glutamate and aspartate levels in the spinal cord after joint inflammation, and opioids reduce glutamate and aspartate release, we hypothesized that TENS reduces release of glutamate and aspartate in animals with joint inflammation by activation of opioid receptors. Using microdialysis and HPLC with fluorescence detection, we examined the release pattern of glutamate and aspartate in the dorsal horn in response to either low‐frequency (4 Hz) or high‐frequency (100 Hz) TENS. We examined the effects of TENS on glutamate and aspartate release in animals with and without joint inflammation. High‐frequency, but not low‐frequency, TENS significantly reduced spinal glutamate and aspartate in animals with joint inflammation compared with levels in those without joint inflammation. The reduced release of glutamate and aspartate by high‐frequency TENS was prevented by spinal blockade of delta‐opioid receptors with naltrindole. Thus, we conclude that high‐frequency TENS activates delta‐opioid receptors consequently reducing the increased release of glutamate and aspartate in the spinal cord.

A new transient sham TENS device allows for investigator blinding while delivering a true placebo treatment

UNLABELLED This study compared a new transient sham transcutaneous electrical nerve stimulation (TENS) that delivers current for 45 seconds to an inactive sham and active TENS to determine the degree of blinding and influence on pain reduction. Pressure-pain thresholds (PPT), heat-pain thresholds (HPT), and pain intensities to tonic heat and pressure were measured in 69 healthy adults before and after randomization. Allocation investigators and subjects were asked to identify the treatment administered. The transient sham blinded investigators 100% of the time and 40% of subjects compared to the inactive sham that blinded investigators 0% of the time and 21% of subjects. Investigators and subjects were blinded only 7% and 13% of the time, respectively, with active TENS. Neither placebo treatment resulted in significant changes in PPT, HPT, or pain intensities. Subjects using higher active TENS amplitudes (> or =17 mAs) had significantly higher PPTs and lower pain intensities to tonic pressure than subjects using lower amplitudes (<17 mAs). HPTs and pain intensities to tonic heat were not significantly changed. The transient TENS completely blinds investigators to treatment and does not reduce pain, thereby providing a true placebo treatment. PERSPECTIVE This article presents the benefits of a new transient sham TENS device for use in prospective, randomized, clinical trials. This device facilitates blinding of subjects and investigators to eliminate expectation bias and determine the true efficacy of TENS for use in clinical populations.

An investigation of the development of analgesic tolerance to TENS in humans

&NA; Transcutaneous electrical nerve stimulation (TENS) is a noninvasive modality used to control pain. Animal models show that repeated TENS application produces analgesic tolerance and cross‐tolerance at spinal opioid receptors. The aim of the present investigation was to examine whether repeated application of TENS produces analgesic tolerance in humans. One hundred healthy subjects were randomly assigned to 1 of 4 groups: control, placebo, low‐frequency (4 Hz) or high‐frequency (100 Hz) TENS. TENS was applied daily for 5 days to the nondominant upper limb; pressure‐pain threshold (PPT) measurements were recorded before and after TENS. Temporal summation to mechanical stimulation was recorded on days 1 and 5, before and after TENS. Diffuse noxious inhibitory control (DNIC) was tested on day 5 using the cold pressor test and PPT measurements. There was an initial increase in PPTs in both low‐ and high‐frequency TENS groups when compared with placebo or control groups. However, by day 5 this TENS‐induced increase in PPT did not occur, and there was no difference between active TENS and placebo or control groups. High‐frequency TENS decreased temporal summation on day 1 when compared with day 5. DNIC increased the PPT similarly in all groups. These data suggest that repeated daily application of TENS results in a decrease in its hypoalgesic effect by the fifth day and that the tolerance‐like effect to repeated TENS results from tolerance at centrally located opioid receptors. The lack of change in DNIC response suggests that TENS and DNIC utilize separate pathways to produce analgesia. Repeated high‐frequency and low‐frequency transcutaneous electrical nerve stimulation produce analgesic tolerance in humans by the fourth and fifth day of treatment, respectively.

Transcutaneous electrical nerve stimulation reduces pain, fatigue and hyperalgesia while restoring central inhibition in primary fibromyalgia

Summary Pain and fatigue during movement, but not at rest, are reduced by a onetime 30‐m treatment with active transcutaneous electrical nerve stimulation (TENS) in individuals with fibromyalgia. Abstract Because transcutaneous electrical nerve stimulation (TENS) works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double‐blinded randomized, placebo‐controlled cross‐over design to test the effects of a single treatment of TENS with people with fibromyalgia. Three treatments were assessed in random order: active TENS, placebo TENS and no TENS. The following measures were assessed before and after each TENS treatment: pain and fatigue at rest and in movement; pressure pain thresholds, 6‐m walk test, range of motion; 5‐time sit‐to‐stand test, and single‐leg stance. Conditioned pain modulation was completed at the end of testing. There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS. Pressure pain thresholds increased at the site of TENS (spine) and outside the site of TENS (leg) when compared to placebo TENS or no TENS. During active TENS, conditioned pain modulation was significantly stronger compared to placebo TENS and no TENS. No changes in functional tasks were observed with TENS. Thus, the current study suggests TENS has short‐term efficacy in relieving symptoms of fibromyalgia while the stimulator is active. Future clinical trials should examine the effects of repeated daily delivery of TENS, similar to the way in which TENS is used clinically on pain, fatigue, function, and quality of life in individuals with fibromyalgia.

Adjusting Pulse Amplitude During Transcutaneous Electrical Nerve Stimulation (TENS) Application Produces Greater Hypoalgesia

UNLABELLED Transcutaneous electrical nerve stimulation (TENS) is a noninvasive technique used for pain modulation. During application of TENS there is a fading of current sensation. Textbooks of electrophysical agents recommend that pulse amplitude should be constantly adjusted. This seems to be accepted clinically despite the fact that there is no direct experimental evidence. The aim of the current study was to investigate the hypoalgesic effect of adjusting TENS pulse amplitude on pressure pain thresholds (PPTs) in healthy humans. Fifty-six healthy TENS naïve participants were recruited and randomly assigned to 1 of 4 groups (n = 14 per group): control, placebo TENS, fixed pulse amplitude TENS, and adjusted pulse amplitude TENS. Both active and placebo TENS were applied to the dominant forearm. PPTs were recorded from 2 points on the dominant forearm and hand before, during, and after 40 minutes of TENS. TENS increased the PPTs on the forearm (P = .003) and hand (P = .003) in the group that received the adjusted pulse amplitude when compared to all other groups. The mean final pulse amplitude for the adjusted pulse amplitude TENS group was 35.51 mA when compared to the fixed pulse amplitude TENS group, which averaged 31.37 mA (P = .0318). PERSPECTIVE These results suggest that it is important to adjust the pulse amplitude during TENS application to get the maximal analgesic effect. We propose that the fading of current sensation allows the use of higher pulse amplitudes, which would activate a greater number of and deeper tissue afferents to produce greater analgesia.

Using TENS for pain control: the state of the evidence

Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological intervention that activates a complex neuronal network to reduce pain by activating descending inhibitory systems in the central nervous system to reduce hyperalgesia. The evidence for TENS efficacy is conflicting and requires not only description but also critique. Population-specific systemic reviews and meta-analyses are emerging, indicating both HF and LF TENS being shown to provide analgesia, specifically when applied at a strong, nonpainful intensity. The purpose of this article is to provide a critical review of the latest basic science and clinical evidence for TENS. Additional research is necessary to determine if TENS has effects specific to mechanical stimuli and/or beyond reduction of pain and will improve activity levels, function and quality of life.

Transcutaneous Electrical Nerve Stimulation at Both High and Low Frequencies Reduces Primary Hyperalgesia in Rats With Joint Inflammation in a Time-Dependent Manner

Background and Purpose Clinical studies of transcutaneous electrical nerve stimulation (TENS) have used a variety of outcome measures to assess its effectiveness, with conflicting results. It is possible that TENS is effective on some measures of pain and not on others. The purpose of this study was to test the hypothesis that TENS reduces primary hyperalgesia of the knee induced by joint inflammation. Subjects Male Sprague-Dawley rats were used in this study. Methods Inflammation of the knee joint was induced by intra-articular injection of a mixture of 3% kaolin and 3% carrageenan. Primary hyperalgesia was measured as the compression withdrawal threshold of the knee joint before and after the induction of inflammation (4 hours, 24 hours, and 2 weeks) and after sham TENS treatment, treatment with high-frequency TENS (100 Hz), or treatment with low-frequency TENS (4 Hz). Results The compression withdrawal threshold was significantly reduced at 4 hours, 24 hours, and 2 weeks after the induction of inflammation. Either high-frequency TENS or low-frequency TENS completely reversed the compression withdrawal threshold when applied at 24 hours or 2 weeks after the induction of inflammation but not when applied at 4 hours after the induction of inflammation. Discussion and Conclusion These data suggest that TENS inhibits primary hyperalgesia associated with inflammation in a time-dependent manner after inflammation has already developed during both acute and chronic stages.

Mechanical hyperalgesia and reduced quality of life occur in people with mild knee osteoarthritis pain.

Objectives:This study determined whether individuals with mild knee pain due to osteoarthritis (OA) experience hyperalgesia and central sensitivity by comparing them with age-matched and sex-matched control participants and determined whether these levels are associated with pain intensity. This study also determined whether these individuals experience significantly poorer quality of life than age-matched and sex-matched controls and whether pain and function predict quality of life. Methods:Quantitative sensory tests (QSTs), including punctate pain intensity (PPI), pressure pain threshold (PPT), and heat pain threshold, tolerance, and temporal summation, were measured in 75 individuals with mild knee OA pain and 25 age-matched and sex-matched controls. Pain intensity, walking function, and quality of life were also assessed. Results:Significant differences were found for PPI at all sites, for PPT at the affected knee, and for quality of life. QST measures significantly correlated with pain intensity. Pain, but not function, predicted quality of life. Discussion:Individuals with mild knee pain due to OA experience mechanical (but not thermal) hyperalgesia that relates to pain intensity. They have a reduced quality of life that is predicted by pain intensity. More aggressive pain management for mild knee OA pain is indicated to improve the quality of life for individuals who are not yet candidates for joint replacement.

Transcutaneous Electrical Nerve Stimulation and Conditioned Pain Modulation Influence the Perception of Pain in Humans.

Research in animal models suggests that transcutaneous electrical nerve stimulation (TENS) and conditioned pain modulation (CPM) produce analgesia via two different supraspinal pathways. No known studies have examined whether TENS and CPM applied simultaneously in human subjects will enhance the analgesic effect of either treatment alone. The purpose of the current study was to investigate whether the simultaneous application of TENS and CPM will enhance the analgesic effect of that produced by either treatment alone.