Possible Mechanisms for the Effects of Sound Vibration on Human Health

This paper presents a narrative review of research literature to “map the landscape” of the mechanisms of the effect of sound vibration on humans including the physiological, neurological, and biochemical. It begins by narrowing music to sound and sound to vibration. The focus is on low frequency sound (up to 250 Hz) including infrasound (1-16 Hz). Types of application are described and include whole body vibration, vibroacoustics, and focal applications of vibration. Literature on mechanisms of response to vibration is categorized into hemodynamic, neurological, and musculoskeletal. Basic mechanisms of hemodynamic effects including stimulation of endothelial cells and vibropercussion; of neurological effects including protein kinases activation, nerve stimulation with a specific look at vibratory analgesia, and oscillatory coherence; of musculoskeletal effects including muscle stretch reflex, bone cell progenitor fate, vibration effects on bone ossification and resorption, and anabolic effects on spine and intervertebral discs. In every category research on clinical applications are described. The conclusion points to the complexity of the field of vibrational medicine and calls for specific comparative research on type of vibration delivery, amount of body or surface being stimulated, effect of specific frequencies and intensities to specific mechanisms, and to greater interdisciplinary cooperation and focus.

1.2.2. Current Therapeutic Application Concepts for Vibration

Whole body vibration (WBV), also referred to as whole body periodic acceleration (WBPA) is one type of application that grew out of the 18th and 19th century interest in vibration. WBV, a mechanical vibration typically created with stand-on oscillating platforms, developed largely in response to concerns about the effect of weightlessness in space on bone and muscle and then was quickly applied in sports [22]. Although current WBV platforms can produce vibration frequencies up to 100 Hz, frequencies below 30 Hz are most commonly used. The past 20 years has seen growing interest in the effects of WBV on bone density, orthopaedic, and neurological concerns [23,24].

More in keeping with the early uses of tuning forks for sensory stimulation is the practice of low frequency sound therapy (and most closely related to music therapy) that has developed in the past 50 years and is now commonly known as vibroacoustic therapy (VAT). WBV typically uses frequencies below 30 Hz while VAT uses 30-120 Hz. Olav Skille in Norway and Petri Lehikoinen in Finland were the leaders in this use of sinusoidal sound to stimulate the body for therapeutic purposes. Skille placed particular emphasis on single pitches at 40, 52, 68, and 86 Hz modulated with a steady rise and fall of amplitude at a rate of about 6.8 s from peak to peak. A noteworthy application of this method in research was done by Wigram [25,26]. Instead of single frequencies, Lehikoinen used constant frequency scanning with the intent to treat muscles at their particular resonance frequency, slow power pulsation to prevent muscle contraction, and at times directional movement and sound. Lehikoinen developed the  NextWave chair system that was Federal Drug Administration (FDA) and British Standards Institution (BSI) approved in 1996 for three claims related to physioacoustic therapy: increased blood and lymphatic circulation, decreased pain and stress, and increased muscle relaxation and mobility [28]. Numerous devices that include chairs, chair backs, beds, mats, pillows, backpacks, and smaller hand-held units have been developed since then.

1.3. Definitions, Clarifications, and Terminology

1.3.1. Source of Pulsed Stimulation: Sound Waves or Mechanical Compression

To review the literature related to vibration, one of the fundamental questions requiring clarification is whether the stimulation of the body with sound waves is different in some way from mechanical vibration. Since people hear sound waves and feel mechanical vibrations, an easy conclusion is that the two are categorically different. However, sound in essence is mechanical vibration that transmits through a medium [29]. In the medium of air, the sound actuator creates a vibration that results in regular compressions and decompressions of air molecules that travel to the receiving surface on the body such as the ear’s tympanic membrane or the mechanoreceptors in the skin. In water a rapidly oscillating membrane would create compressions and decompressions of water molecules. Once in contact with the body, the compression and decompression of the surface of the body is transmitted through bone and tissue and may be sensed by a set of mechanoreceptors or by our auditory system.

At a cellular or molecular level in the body there is probably no difference between activation by air molecules applying regular sine wave pressure on the body, by a surface applying oscillatory pressure stemming from a rotating motor shaft, or by the body itself moving against gravity on an oscillating platform. Another way to understand this can be in comparing the application of sound to produce vibration and the application of vibration to produce sound. Sound, which propagates through a material can vibrate the material and be physically felt like a massage, such as in a vibroacoustic device [30]. Mechanical vibration can also produce sound. Bone conduction headphones are commercially available and are built to be positioned along the skull. The mechanical vibration of the bones of the skull propagate to the inner ear and are perceived as sound (31). Therefore the interchange of sound and mechanical vibration demonstrate that they are in essence the same thing.

1.3.2. Vocabulary and inclusion

Clarification is needed about the vocabulary used in this field. We have already explained VAT and WBV. Another term used is rhythmic sensory stimulation (RSS) and is inclusive of multiple types of pulsed (rhythmic) stimulation. RSS includes whole body rhythmic movement, vibrotactile stimulation of all or part of the body, auditory pulses delivered as individual sound units (like hits on a drum, plucks of a string, interaction “waves” resulting from binaural detunement, or isochronous amplitude modulated sound trains) or as molecular compressions that create continuous sound (research usually focusing on low frequency sound 20–130 Hz), and visual light flashes or flicker. Pulsed ultrasound can also be regarded as a type of vibrational mechanical stimulation and is typically applied in 2 ms bursts but with varying ratios of sound to silence from 1:1 (250 Hz) to 1:20 (45 Hz).

When considering the use of rhythmic pulses to stimulate to the body, one question is whether electric stimulation and pulsed ultrasound are comparable to mechanical vibration. Bartel et al. [32] drew parallels between pulsation frequencies used in electric stimulation and pulsed ultrasound with frequencies for VAT. Many years ago Charcot postulated that the vibration stimulation was not unlike electric stimulation and showed similar results [21]. In this paper the review of specific mechanisms activated by vibration will be restricted to studies using various sonic and mechanical vibratory means from general body vibration to focused points of vibration delivered with pencil-like probes. However, a future more extensive review of the mechanisms activated by pulsed stimulation might include electrical and pulsed ultrasound stimulation as well.

A final question is whether whole body vibration (WBV) is fundamentally different from vibroacoustic therapy (VAT) and, therefore, WBV studies cannot be mixed with VAT in the examination of mechanisms. First, although many applications of WBV use frequencies in the level of infrasound (1–15 Hz) they also use higher frequencies (e.g., 20–40 Hz) in the same range that VAT frequently uses. Music stimulation and VAT can employ pulsed sound units at 1–15 Hz and, in fact, “rhythm” in music is primarily in that frequency. So, there is no set frequency that makes it one or the other. Secondly, the axis of the applied vibration may be a discriminator between approaches (e.g., vertical (axial), horizontal, or multidirectional) but at the mechanism level there does not appear to be strict differentiation. For example, with blood flow slow axial (direction of the spine) WBV creates pulsatile stress on endothelial cells and so enhances blood flow at 1 or 2 Hz [33] but also with sound stimulation at 50 Hz [34]. Rhythmic driving of oscillatory coherence happens with rhythmic pulses at 1 or 2 Hz (delta entrainment, e.g., RAS effects) and at 10 Hz (alpha), 20 Hz beta, or 40 Hz gamma, etc. Consequently, at the level of the mechanism, WBV and VAT will be considered within the same domain of pulsed stimulation.

1.4.2. Mechanisms of Response to Vibration

The auditory and vibrotactile stimulation from low frequency sound shows effects that are essentially the result of two categories of mechanisms: (1) physical, through muscular and cellular means, and (2) neurological, through sensory-based stimulation of nerves and receptors. At the physical level sound vibration is sensed by tactile receptors in the outer skin (Merkel disks—sensing vibratory strength and responding most to 5–15 Hz), inner skin (Meisner corpuscles—sensing vibratory frequency and responding most to 20–50 Hz), and in deeper tissues (Pacinian corpuscles—sensing acceleration and responding most to 60–400 Hz) [35,36]. To avoid numbing of these sensors, VAT is usually constantly varied in amplitude (power pulsation) and/or frequency (scanning). A physical therapeutic effect can be obtained at a cellular and lymphatic level due to increased fluid and cellular waste transport, increased cellular metabolism [37,38], increased blood circulation, and muscular relaxation due to a resonance response. Within the brain, vibration hypothetically enhances flow of cerebrospinal fluid and speeds removal of metabolic waste [39]. Most research with VAT has not explored neural oscillatory effects but recent studies show [40,41,42,43,44] potential brain effects, especially through prolonged application of a single frequency (e.g., 40 Hz).

2. Hemodynamic Effects

2.1. Basic Mechanism: Stimulation of Endothelial Cells

2.1.1. Submechanism: Nitric Oxide

pGz on eNOS and antioxidants. The subjects were given pGz for an hour a day and tissue was tested after one, two, and four weeks. The pulsed stimulation resulted in significant expression of antioxidants including glutathioneperoxidase1 (GPX-1), catalase (CAT), superoxide, and superoxide dismutase 1 (SOD1). It also decreased reactive oxygen species (ROS).

2.1.2. Submechanism: Adrenomedullin

In addition to the release of nitric oxide, the vibratory stimulation of endothelial cells has been shown to release the cell protecting mediator, adrenomedullin (AM). It may function as a hormone in controlling circulation and vasodilation but also serves to stimulate angiogenesis—the growth of new blood vessels—and combats oxidative stress in cells. In this way AM can have a positive effect in cardiovascular disease including hypertension, myocardial infarction, and chronic obstructive pulmonary disease. However, in its function to extend blood supply in cells it may be a negative factor in relation to cancer. Martínez et al. [64] conducted an animal study to examine the effect of one hour of pGz stimulation on AM and found that immediately after the stimulation blood pressure was significantly reduced (from 115 ± 10 to 90 ± 8) and AM level was significantly increased and remained so for 3 h (from 776 ± 176 pg/mL baseline to 1584 ± 160 pg/mL, p < 0.01).

2.1.3. Submechanism: Antioxidants

Many disease conditions are linked to oxidative stress. These include cancer, Alzheimer’s and Parkinson’s disease, diabetes, and cardiovascular conditions like high blood pressure, atherosclerosis, and stroke. Release of nitric oxide into circulation is known to have some antioxidant properties. Uryash et al. [65], in a study with mice with high oxidative stress, specifically looked for the effect of pGz on eNOS and antioxidants. The subjects were given pGz for an hour a day and tissue was tested after one, two, and four weeks. The pulsed stimulation resulted in significant expression of antioxidants including glutathioneperoxidase-1 (GPX-1), catalase (CAT), superoxide, and superoxide dismutase 1 (SOD1). It also decreased reactive oxygen species (ROS).

2.2. Basic Mechanism: Vibropercussion

One of the features of vibration is that it results in one material striking against another—whether molecule to molecule or cell to cell or bone to bone, etc. The essentially mechanical action can produce health-related effects.

3. Neurological Effects

Effects of sound vibration stimulation on the neurological system are many and wide-ranging with multiple complex mechanisms involved. Most of these mechanisms are not yet fully understood but we will point to how the mechanisms at a cellular level seem to function and are related to sound vibration.

3.1. Basic Mechanism: Protein Kinases Activation

One of the questions of neuroscience is whether there is a way to regenerate or repair neural damage from neurodegeneration, stroke, transected nerve ends, etc. Electrical stimulation [71] is one intervention that has shown some success in creating axonal regeneration and neurite outgrowth. Low frequency sound vibration also appears to have potential at stimulating neurite outgrowth and neuronal differentiation.

Koike et al. [72], motivated by the intent to find why music therapy might be useful for Alzheimer’s disease (AD) patients, conducted a study to determine if vibratory sounds might enhance neurite outgrowth. They focused on an in-vitro examination of PC12m3 cells known to be sensitive to nerve growth factor (NGF) that induces differentiation of nerve cells and neurite extension. They looked specifically at the p38 mitogen-activated protein kinase (MAPK) activity that has been shown by research with electrical stimulation [71] to be a pathway to enhancing PC12m3 cell growth, and which also appears enhanced in AD. They found that vibratory sound in the 10–100 Hz range had a positive effect on neurite growth with the strongest effect being at 40 Hz whereas vibratory sound at 150 Hz and 200 Hz had little effect. They found that 40 Hz stimulation enhanced p38 MAPK activity indicating that the neural outgrowth they observed was induced through the p38 MAPK pathway.

3.2. Basic Mechanism: Nerve Stimulation

Evidenced-based research repeatedly shows positive clinical effects from the application of pulsed stimulation of the body. This applies in varied neurological conditions including cerebral palsy [76], multiple sclerosis [77], and chronic musculosleetal pain [78]. way from a stimulation of the nervous system and if so, how does that occur. How pervasive is a system to respond to vibration? In the living body transmission of sensory information depends on sensory neurons and mechanosensation at axonal terminals in peripheral nerves. Different types of sensing neurons include mechanosensors detecting external signals, proprioceptors receiving internal body signals, and many types of nociceptors that detect noxious body-threatening stimuli. Usoskina et al. [79] examined the molecular mechanisms activated in the process of cells detecting vibration. By observing calcium ion transients in the somata of neurons, they saw that neurons reliably detected every individual stimulus (e.g., each molecular compression in a sound wave) and then converted these into specific firing patterns in the nerves. Given this basic mechanism, we next look at several categories in which this is applied.

3.2.1. Submechanism: Sensitization of the Proprioception System

The body’s proprioception system gathers and processes information about changes in the position of joints and limbs and, therefore, is strongly involved in the control of posture and movement. Proprioceptors are mechanosensory neurons in the skin (Merkel disks and Meissner’s and Pacinian corpuscles), muscles (spindles), tendons (Golgi tendon organs), and joints.

This proprioception system involving receptors, nerves, spinal cord, and pathways of the central nervous system terminates within the thalamus and cerebral cortex [36]. The proprioception system is very sensitive to vibration and, since it is an important factor in motor control, the effect of vibration has been the subject of considerable research, especially the effect of whole body vibration on the rehabilitation of neurological disorders [80]. The stimulation or sensitization of the proprioception system appears to engage a mechanism that retrains the body-mind strategies of motor control or establishes greater consonance between input from the senses and output to the motor system at the cortical level [81]. Perhaps pointing to a cascade effect in this proprioceptive mechanism, which is not fully understood, Delecluse et al. [82] propose that vibration may enhance corticospinal cell connectivity to spinal motor neurons.

Application: Complex Regional Pain Syndrome (CRPS)

Gay et al. [81] postulated that CRPS type I may be caused by a sensory input–output mismatch that leads to motor programming disorganization in cortical structures. They hypothesized that enhancing proprioceptive feedback with vibratory stimulation would minimize pain and increase range of motion. The study by Gay et al. [81] applied sinusoidal vibration at 86 Hz to the hand and wrist of patients with CRPS for 20 min a day, five days a week for 10 weeks in addition to conventional rehabilitation sessions. The control group received only the conventional treatment. The results showed that pain severity was lower by close to 50% and range of motion improved by about 30% in the treatment group. They attributed this result to a reestablishment of sensory input–output consonance.

Application: Cerebral Palsy

The research of Katusic et al. [80] proceeded on the premise that proprioception is crucial to motor control and hypothesized that sound-based vibration can resonate through the body and enhance sensation of body position, location, and orientation. Further they accepted the premise of Delecluse et al. [82] that vibration could alter corticospinal cell and spinal motor neuron connectivity and that this stimulation of the proprioceptive pathways could rearrange motor control strategies resulting in better postural stability. To test this Katusic et al. [80] did a three month study with 89 children with spastic cerebral palsy (CP) randomized to a physiotherapy only group and to physiotherapy plus vibration group. The vibration treatment, applied with a mat they could lie on, consisted of 40 Hz sine waves for 20 min, two times a week for 12 weeks. The vibration treatment group improved significantly in both spasticity and in gross motor function.

Ko et al. [83] observe that vibration has recently been shown to improve proprioception and thereby balance and motor skills. They postulate that this may be because vibration stimulates muscles and tendons. To test whether whole body vibration at 20–24 Hz would affect sense of joint position, gait, and balance in children with CP, they randomized 24 children to physical therapy (PT) or traditional PT plus vibration for 20 min (3 min on, 3 min off) two times a week for three weeks. They found significant improvement in joint position sense and improvement in gait variables in the vibration group.

3.2.2. Submechanism: Vagal Nerve Stimulation

The vagus nerve, one of the 12 cranial nerves, serves as a major parasympathetic (efferent) component of the autonomic nervous system and importantly transmits sensory information from much of the body to the brain [84]. It plays a key role in cardiac and gastrointestinal function, in muscle control of mouth and throat, in the neuroendocrine-immune system, and in the regulation of emotion including anxiety and depression. Vagus nerve stimulation (VNS) [84] is a recognized practice commonly done with manual massage or compression, electrical stimulation, or vibration including with the voice or gargling throat or with external vibrotactile devices. However, the spleen has nerve fibers that are integrated with the vagus nerve and studies [85,86] show that anti-inflammatory effects of the vagus nerve rely somewhat on the splenic nerve to the extent that stimulation of the splenic nerve results in immunosuppressive effects comparable to VNS [87]. Vibration at the abdominal level [88] may then be stimulating the splenic–vagal nerve system. Specific applications of VNS include refractory epilepsy, depression, and decreasing inflammation. One of the known mechanisms by which stimulation of the vagus nerve has its effect is the release of the neurotransmitter acetylcholine.

Application: Depression

Sigurdardóttir et al. [88] conducted a study with 38 people with depressive disorder (18 treatment, 20 control) using relaxing music with a specifically created low frequency sound track that activated a vibrotactile transducer at the abdominal level at the back of the chair in which they were seated. The premised mechanism for their intended effect was the activation of Pacinian corpuscles sending an afferent impulse in the vagus nerve to the regions of the brain associated with depression. The vibratory stimulation treatment was applied for 20 min in eight sessions over 3–4 weeks. The authors did not report what specific frequencies they employed but maintain that Pacinian corpuscles stimulated at 240 Hz have a maximal afferent output but afferent output occurs at any frequency below that. Although not a rigorously controlled study and not measuring changes in the vagal tone, the pilot study did find a reduction in depression scores in the treatment group and attributes this to stimulation of the vagus nerve and the central nervous system through the abdomen. A study by Braun Janzen et al. [89] that applied a very similar treatment also found a reduction in depression and anhedonia although it did not premise vagal stimulation.

3.3. Category of Neurological Effects—Pain and Vibratory Analgesia Specific

The pain-reducing effect of vibration is demonstrated in numerous evidencebased research studies [78,94,95,96,97]. Mechanical and acoustic vibrations have been used extensively to address pain and is a treatment technique in orthopedics and low back pain [98,99], physiotherapy [100,101,102], during cosmetic procedures [103], and during orthodontic work and orofacial pain [104,105,106,107]. However, until relatively recently, very little was thoroughly described and understood about pain perception mechanisms. Studies with electrophysiology have shown cortical neurons responding to noxious stimuli, but it has not become clear to what extent this response represents pain or correlates ith it [108]. Consequently, the mechanisms by which vibration acts as an analgesic is less understood.

3.3.1. Basic Mechanism: Gate Control

One of the submechanisms of the general mechanism of nerve stimulation but a basic mechanism of analgesia is focused on the function of the substantia gelatinosa in the dorsal horn and is commonly known as gate control. The theory for this pain mechanism was proposed by Melzack and Wall [109] and postulates that the substantia gelatinosa modulates sensory information being transmitted to the spinal cord and the brain. Specifically, signals from pain receptors are carried to the dorsal horn by small diameter afferent A-delta and C fibers. The signal transmission from the pain receptors can be modulated (inhibited) by the large afferent A-alpha and A-beta fibers transmitting sensory signals from skin sensation such as touch or vibration [78,96,109]. This mechanism known as gate control theory has been subject of considerable criticism and aspects have been questioned [110,111] and enhanced by Melzack’s neuromatrix of pain theory [112] but its fundamental function remains.

Salter and Henry [113] specifically explored the response of wide dynamic range (WDR) spinal neurons in the lumbar dorsal horn to vibration at different amplitudes and frequencies to determine how they might play a role in analgesic effects. They tried a variety of frequencies and intensities and found that WDR neurons entrained to the vibratory frequencies below 80 Hz. Their findings suggest that pain reduction is accomplished by the effect of vibration on Pacinian corpuscle afferents and the WDR neuron response in the dorsal horn but that frequency, location, and intensity of the vibratory stimulus is a factor that needs further clarification.

3.3.3. Basic Mechanism: Neurotransmitters – Pain and Beyond

Unpacking the complexity of the role of neurotransmitters and neuromodulators on the body and brain is beyond the scope of this paper.

However, research has shown instances in which neurotransmitters are stimulated by vibration and these will be described here.