Analgesic Effects of Interferential Current Therapy: A Narrative Review

Background and Objectives: Transcutaneous electrical stimulation of low- and medium-frequency currents is commonly used in pain management. Interferential current (IFC) therapy, a medium frequency alternating current therapy that reportedly reduces skin impedance, can reach deeper tissues. IFC therapy can provide several different treatment possibilities by adjusting its parameters (carrier frequency, amplitudemodulated frequency, sweep frequency, sweep mode or swing pattern, type of application (bipolar or quadripolar), time of application and intensity). The objective of this review article is to discuss the literature findings on the analgesic efficacy of IFC therapy. Conclusions: According to the literature, IFC therapy shows significant analgesic effects in patients with neck pain, low back pain, knee osteoarthritis and post-operative knee pain. Most of the IFC parameters seem not to influence its analgesic effects. We encourage further studies to investigate the mechanism of action of IFC therapy.


Introduction
Interferential current (IFC) therapy is a simple, non-invasive and non-pharmacological treatment commonly used in clinical practice to alleviate pain, mainly of musculoskeletal origin, for muscle strength production, edema reduction, autonomic effects (control of incontinence, heart rate variability, blood flow velocity and vessel size), tissue repair and spasticity treatment after a cerebrovascular accident [1][2][3][4][5][6], mostly in the United Kingdom, other European countries and Australia [7]. It is a medium-frequency alternating current, and although commercial units allow several parameter adjustments, the rationale behind each parameter effect has been based on textbooks and the clinical experience of physical therapists rather than well-controlled studies [8].
Skin impedance (resistance) is inversely proportional to the frequency of an applied current [9]. The fundamental aspects of IFC therapy involve reducing cutaneous nerve stimulation and maximizing the current that permeates the tissues [3] with a higher carrier frequency, making it more suitable for treating deeper tissue layers [10]. Below, we present the definition, history, physiological effects and parameters of IFC therapy. The IFC units contain several parameters that can be adjusted, and our aim is to show the differences for each parameter.

Methods
In this narrative review, a literature search was performed using PubMed, Embase and PEDro to identify studies reporting on the definition, physiological effects, parameters and analgesic efficacy of IFC therapy. The following search terms were used: interferential current, medium-frequency currents, burst-modulated alternating current, medium-frequency The two out-of-phase medium-frequency alternating currents (4000 Hz and 4100 Hz) "interfere" within the tissues and produce an amplitude-modulated frequency (AMF) of 100 Hz. The resulting frequency is 4050 Hz, and the duration of each burst is 10 milliseconds (ms). Hz: hertz. The IFC is an example of a burst-modulated alternating current (BMAC) with sinusoidal modulation, also known as kilohertz-frequency alternating current, and is reportedly more comfortable, reaches deeper tissues and induces greater muscle torque than low-frequency pulsed currents [7]. Nevertheless, it is important to exercise caution in relation to muscle force production, because Bellew et al. (2012) observed that the IFC actually produced a higher percentage of maximal voluntary isometric force of the knee extensors in healthy subjects when compared to the Russian current; however, there was no significant difference between the IFC and burst-modulated low-frequency biphasic pulsed currents [11].

History
IFC therapy was developed by Dr. Hans Nemec in the early 1950s in Vienna and has since been extensively used in Europe (Austria, Germany, Bulgaria and France). The aim of crossing two medium-frequency alternating currents was to utilize the concept that the skin offers little ohmic resistance to the passage of medium frequencies (two digits), whereas direct currents and low frequencies encounter very high ohmic resistance (between 2000 and 4000 ohms) [12,13].

Physiological Effects of IFC Therapy
Although IFC therapy has been used for the past several decades, the physiological effects are not established enough to explain the analgesic effect [14]. Goats (1990) reported that IFC therapy decreases the stimulation of cutaneous sensory nerves close to the electrodes while increasing the effect on deep tissues [3]. Some theories have been proposed to explain the analgesic effect, such as the gate control theory, descending pain suppression pathway, physiological blockage and placebo effect [14].

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Gate control theory of pain perception: Proposed by Melzack and Wall in 1965 [15], it has been suggested that an IFC frequency of 100 Hz can activate the large-diameter, lowthreshold nerve fibers and that it uses the "pain-gating" system to achieve analgesia [14]. • Descending pain suppression pathway: Involves endogenous opioid (endorphins, dynorphins and enkephalins) release from periaqueductal grey matter (PAG) and the rostral ventral medulla (RVM) (nucleus raphe magnus (NRM), reticular nuclei and the spinal dorsal horn) [14,16]. These endogenous opioids play an important role in the control of nociceptive messages from primary afferent nerves [14]. A pulse duration range of 100-200 µs may activate large-diameter fibers, once their threshold is lower than that of the small-diameter A-delta and C fibers. Most IFC devices have a fixed pulse duration of 125 µs. However, it is not clear how IFC therapy can selectively activate the different nerve fiber types [14]. • Physiological blockage (Wedensky inhibition): C and Aδ fibers may not conduct nociceptive impulses after frequency stimuli greater than approximately 15 Hz and 40 Hz, respectively [3,14]. • Placebo effect: Refers to the patient-therapist relationship and types of modalities used during treatment. IFC devices are technically advanced and visually impressive, which may help convince patients that they are receiving an effective treatment [14].
It is important to highlight that to date, there has been no experimental research investigating the mechanism of action of IFC therapy for pain relief. IFC therapy has often been used for pain disorders; however, there is a lack of literature to explain its use. Some authors have based their claims on studies that investigated the mechanism of action of TENS. Goats et al. (1990) claimed that IFC therapy has a powerful placebo effect [3]. Thus, studies are needed to investigate the analgesic mechanism of action of IFC therapy. In addition, it is important to conduct more randomized clinical trials investigating the temporal summation of pain or conditioned pain modulation to assess the pain modulatory system of IFC therapy, such as in studies that have investigated other therapies [17,18].

IFC Parameters
There are several parameters that can be adjusted in IFC devices, including the carrier frequency, amplitude-modulated frequency (AMF), sweep frequency, sweep mode or swing pattern (slope), application type (bipolar or quadripolar application) and application time and intensity. There are a wide range of options for each one, all of which can be adjusted.
Most therapists select IFC parameters by trial and error, and some researchers believe that IFC therapy may be effective for a variety of diseases; the interference wave mediates the physiological and clinical effects, while different physiological effects are produced according to different amplitude-modulated wave frequencies [19]. Some of these claims about the effectiveness of IFC therapy have been based on personal experience [19]. Given the wide variety of parameters, it is important to understand the different effects of varying dosages, while the choice of parameters should be based on the findings of randomized clinical trials and systematic reviews. As such, it is relevant to discuss the current scientific evidence.

Carrier Frequency
The carrier frequency refers to a medium-frequency alternating current or kilohertzfrequency alternating current [1]. This frequency range of 1 to 10 kHz can be adjusted in modern IFC devices [20]. Some studies have investigated the effects of different carrier frequencies: • Venancio et al. (2013) studied the effects of the carrier frequency on the pressure pain threshold (PPT) and sensory comfort in healthy subjects. One hundred and fifty subjects were randomly allocated to 1 of 5 groups according to carrier frequency (1 kHz, 2 kHz, 4 kHz, 8 kHz and 10 kHz). An AMF of 100 Hz was used for 20 min with two self-adhesive electrodes placed on the lateral aspect of the forearm, and the current amplitude was increased until a strong but comfortable paresthesia was reached. The authors found that a 1 kHz carrier frequency increased the PPT during and after stimulation compared to 8 kHz and 10 kHz. In addition, carrier frequencies of 1 kHz and 2 kHz were more uncomfortable compared to those of 4, 100 Hz) on subjects with chronic low back pain. One hundred and seventy-five subjects were randomly allocated to 1 of 5 groups (2 kHz, 100 Hz, sensory level; 2 kHz, 2 Hz, motor level; 4 kHz, 100 Hz, sensory level; 4 kHz, 2 Hz, motor level; placebo). IFC was applied with 4 electrodes on the lumbar area for 30 min. It was observed that 4 kHz with 100 Hz provided better analgesic effects in subjects with low back pain [22].
These studies demonstrated that the carrier frequency of 1 kHz with AMF of 100 Hz increased the PPT in healthy subjects [20], while carrier frequencies of 1 and 4 kHz with AMF of 100 Hz seem to promote higher analgesic effects, such as increased PPT and decreased analgesic consumption, pain intensity and temporal summation of pain in individuals with chronic low back pain [21,22]. In addition, the higher carrier frequencies (8 kHz or 10 kHz) present in some devices appeared to be less effective, albeit more comfortable [20].

Amplitude-Modulated Frequency (AMF)
The interference of two sinusoidal alternating currents can be constructive (waves in phase, producing a wave with a greater amplitude) and destructive (out-of-phase waves, when the rising segment of one coincides with the falling segment of another) [3]. The rate of resultant amplitude is equal to the difference in frequency between the two original waves and is called the "beat frequency" [3]. The amplitude-modulated frequency is a low-frequency current (1-250 Hz) generated by the interaction between two out-ofphase medium-frequency currents [23]. The literature on IFC therapy states that different parameters, such as the AMF, can cause different physiological effects (e.g., 130 Hz is more sedative; 0-100 Hz is more stimulating; 10-150 Hz increases blood flow; 50-100 Hz has sedative and spasmolytic effects) [24]. However, these claims seem to be based more on the personal and clinical experience of authors than on scientific evidence [24].
According to the literature, studies have been performed to investigate the analgesic and physiological effects of different AMFs in healthy subjects [23][24][25] and individuals with knee osteoarthritis [26] and chronic low back pain [22].

Sweep Frequency (Delta F-∆F)
The sweep frequency means that the AMF can fluctuate between pre-determined upper and lower limits in an interchangeable manner [27]; in other words, ∆F is a variation of an AMF pre-set in the device. This means that with an AMF of 100 Hz and a ∆F of 50 Hz, the AMF variation will be between 100 and 150 Hz. This parameter is used to avoid sensory habituation [28]. However, Pivetta and Bertolini (2012) evaluated the duration of IFC habituation and how often it occurred in a crossover trial with 15 subjects. They received 10 min of IFC in the lumbar area with the following parameters: 4 kHz, 100 Hz (AMF), 1:1 (slope) and ∆F was adjusted according to the group (0 ∆F null = 0, ∆F low = 30% or ∆F high = 70%). There were no differences in habituation threshold or in how many times sensory habituation occurred between groups. Thus, it was concluded that the variation in AMF has no effect [28]. In addition, Dounavi et al. (2012) found no segmental or extrasegmental hypoalgesic effect using a pressure algometer to compare sweep AMF (80-110 Hz-within 6 s), constant AMF (110 Hz), placebo and control groups. A carrier frequency of 4 kHz (a strong and uncomfortable intensity) was applied for 30 min on the dominant forearm. The findings of this study were the same, regardless of the sweep AMF.

Sweep Mode (Slope) or Swing Pattern
This parameter is used to change the AMF between the lower and upper frequency limits on a fixed timeline [27]. The aim is to prevent the sensory habituation of the nervous system to repetitive electrical currents [27]. There are several types of swing pattern delivery ramps, such as 1:1 (variation every 1 s) (Figure 2A), 1:5:1 (frequencies increase and decrease in 1 s and remain stable for 5 s) ( Figure 2B) and 6:6 (frequencies increase and decrease in 6 s) ( Figure 2C) [29]. According to the literature, different swing patterns do not interfere in the analgesic effect or in sensory habituation in healthy subjects or individuals with low back pain, as described below: •  compared the analgesic effects of different IFC swing patterns on cold-induced pain in healthy subjects. Forty subjects were randomized into 1 of 4 treatment groups: burst, 1:1, 6:6 and 6 6 ( = jumping, AMF remains at the lower frequency for 6 s before jumping to the upper frequency for 6 s). The IFC parameters were 4 kHz and an AMF of 100 Hz for 20 min with current intensity adjustment up to "strong but comfortable electrical paresthesia without visible muscle contraction". The subjects completed 6 cycles of the cold-induced pain test: 2 pretreatments, 2 during treatment and 2 post-treatments. The changes in pain threshold and pain intensity were evaluated. In conclusion, there were no intergroup differences in the hypoalgesic effects of different swing patterns [30]; • Adedoyin et al. (2005) examined the effects of different IFC swing patterns in subjects with low back pain. Thirty-nine subjects were allocated to three intervention groups based on three IFC patterns: 1:1, 6:6 or 6 6 ( = jumping, AMF remains at the lower frequency for 6 s before jumping to the upper frequency for 6 s). The carrier frequency was fixed at 4 kHz and the AMF at 100 Hz for 20 min. Two electrodes, secured in place by Velcro straps and well-padded with lint, were positioned on the spinal nerve root corresponding to the painful area of the low back. The treatment was performed twice a day (2 times a week) for 3 weeks. No significant swing pattern differences were found for pain modulation in low back pain patients [27]; • Guerra and Bertoline (2012) evaluated the onset times of the first sensory habituation and the number of times it occurred during 10 min of IFC, varying the delta F (∆F) delivery ramps. Eighteen healthy women were randomized into 3 groups: A (1:1; 1:5:1; 6:6), B (1:5:1; 6:6; 1:1) and C (6:6; 1:1; 1:5:1). IFC therapy was applied for 3 days according to the delta F specified. The IFC parameters were: 100 Hz of AMF, 50% of delta F and intensity above the sensory threshold. The first sensory habituation and how many times it occurred were recorded. There were no differences in sensory habituation threshold, although the 1:5:1 ramp had the lowest number of sensory habituations when compared to the 6:6 ramp [29].

Type of Application
IFC is applied transcutaneously with electrode pads (bipolar or quadripolar) [31].

Bipolar Application
Two electrodes are used in this method, whereby amplitude modulation occurs within the stimulator [31] and the output is pre-modulated or exogenous IFC [1]. The signal leaving the equipment is modulated. With respect to bipolar application, the modulation depth in the tissue is the same in all directions-the modulation depth is always 100%.

Tetrapolar (Quadripolar) Application
Four electrodes are used in this application, and interference occurs within the tissues [31]. It is also known as true or endogenous IFC [1]. The modulation depth depends on the direction of the currents and can vary from 0 to 100%. The region of maximum interference develops at 45 degrees diagonally between the two sets of electrodes, representing the region of therapeutic effect, which is static and situated deep in the tissues [3]. Since the tissues are not homogenous in relation to the electrical conductivity, the region of maximum stimulation tends to be more irregular [1].

Tetrapolar (Quadripolar)-Automatic Vector Scan
The automatic vector scan makes it possible to increase the area of effective stimulation. The current intensity (amplitude) in the red circuit varies slowly between 50 and 100% of the maximum established value, and in the black circuit it is set automatically to 75% of the maximum current in the varying circuit. The direction in which the modulation depth is 100% depends on the ratio between the two currents. As a result, the area of maximum stimulation rotates back and forth in the region of intersection. Accurate positioning of the electrodes is important, since there are zones in which stimulation is not optimal. The patient must experience varying sensations of the current.
To date, we have found only two studies that have investigated the differences between bipolar and tetrapolar parameters: • Ozcan et al. (2004) compared bipolar and tetrapolar applications and determined differences in the motor-to-sensory threshold ratio, maximum electrically induced torque and the comfort of each stimulation. Twelve healthy subjects received 4 different IFCs in a randomly allocated order: tetrapolar and crossed currents; bipolar and crossed currents; tetrapolar and parallel currents; bipolar and parallel currents. Four electrodes were attached to the right lower limb. A carrier frequency of 4 kHz and AMF of 50 Hz were used. According to the results, crossed currents did not show higher depth efficiency than their parallel counterparts, and bipolar application exhibited higher maximum electrically induced torque and less discomfort than its quadripolar counterpart. Thus, the authors concluded that tetrapolar is not superior to bipolar application in terms of the depth efficiency, torque production or comfort [

Practical Applicability
The electrodes are positioned on the skin after being cleaned with soap and water to decrease linear electrical resistance, and arranged so that the two currents intersect in the treatment area [3]. Current intensity is increased until the patient reports that it is strong but comfortable [3].

Contraindications
Patients with tumor, fever, acute inflammation, cardiac pacemaker, pregnant women and individuals with an aversion to electrical current therapy must be treated with caution [3].

Systematic Reviews
We found 4 systematic reviews that investigated the efficacy of IFC for musculoskeletal pain [32,33] and knee osteoarthritis [9,34]. , and noninvasive interactive neurostimulation (NIN)) with a control group in the pain relief of subjects with knee osteoarthritis. Twenty-seven studies were included, and IFC was the only effective pain therapy when compared to controls. Thus, IFC therapy seems to be the best electrical stimulation option for pain relief in subjects with knee osteoarthritis [34]; • Hussein et al. (2021) analyzed the efficacy of IFC therapy in relieving musculoskeletal pain. Thirty-five trials were included, 19 of which were selected for meta-analysis. They concluded that IFC therapy alone reduced pain compared to placebo. Nevertheless, there were no significant differences between IFC and other interventions, such as laser, TENS or cryotherapy; IFC therapy plus standard treatment and placebo IFC therapy plus standard treatment; or IFC therapy plus standard treatment and standard treatment [33].
According to the systematic reviews presented, IFC therapy seems to be an effective analgesic electrical current, mainly for subjects with musculoskeletal pain or knee osteoarthritis.

Randomized Clinical Trials
Randomized clinical trials have been performed to evaluate the analgesic effects of IFC therapy in healthy subjects and those with pain disorders. The results in healthy subjects [31,35] are controversial. No positive IFC therapy results have been found for shoulder disorders [36,37]. Nevertheless, IFC therapy has shown analgesic effects for neck pain [38,39], low back pain [21,22,[40][41][42], knee osteoarthritis [26,27,[43][44][45] or postoperative knee pain [4,46]. Most of these studies have used the following parameters: carrier frequency of 4 kHz, AMF between 30-180 Hz, for 20-40 min with a strong but comfortable intensity. More details on these studies are presented in Table 1.

Conclusions
Clinical decisions about the use of IFC and its parameters should be based on scientific evidence. We hope that this review will be useful for physical therapists. IFC showed significant analgesic effects in patients with neck pain, low back pain, knee osteoarthritis and post-operative knee pain. Most IFC parameters seem not to influence the analgesic effect of this electrical current, except for carrier frequencies of 1 or 4 kHz with 100 Hz of AMF, which appear to promote greater analgesic effects than higher, more comfortable carrier frequencies. We encourage further studies to investigate the mechanism of action of IFC.