INTRODUCTION

The body is a complex mechanism, and the ways in which the various electrophysical agents discussed in this book interact with it are still being investigated. In particular, the relationship between the thermal and so-called ‘non-thermal’ effects that can arise is still a matter of debate.

The thermal changes that can occur following the use of hot packs, infrared irradiation, ultrasound and shortwave diathermy and other agents are outlined in Chapter 7. Although these effects are significant, heating is not the only way in which physiological changes can be brought about in body tissues by electrophysical agents. Other effects include the use of low-frequency currents to produce stimulation of muscle or nervous tissue, whereas wound repair can be stimulated by electromagnetic fields and currents. Finally, certain high-frequency agents, such as ultrasound, pulsed shortwave diathermy and light, are used by practitioners in very low and/or pulsed doses to facilitate tissue repair and reduce pain.

The term ‘non-thermal’ is frequently used in clinical practice to mean a treatment that does not result in the patient being conscious of any warming. It must be remembered, however, that all forms of energy can degrade ultimately into heat energy, although the level may be extremely low. Although there is clear evidence of the non-thermal effects of agents such as ultraviolet irradiation, visible light, X-rays and gamma rays, there is currently much controversy surrounding the possible existence of such effects from the use of low-intensity, non-ionizing radiations and mechanical waves in physiotherapy practice and further a field. The press and academic literature continues to report research about the possible effects on people of many devices that we encounter regularly, such as power cables, mobile telephones (e.g. effects on brain tissue; Ferreri et al 2006), transmission masts and televisions.

Arguments for and against the existence of these effects arose early in clinical practice (e.g. with ultrasound and pulsed shortwave diathermy) and controversies have continued. For example, in 1990 Frizzell and Dunn believed there to be no evidence of biological effects arising with the use of low-energy ultrasound. By contrast, Mortimer and Dyson (1988) reported changes in the permeability of the cell membrane to calcium ions, while Dyson et al (1974) noted the temporary banding at half wavelength intervals of blood cells and endothelial cell damage within blood vessels exposed to ultrasound in a stationary wave field in vivo.

Similarly, Barker and Freestone (1985) and Barker (1993) had reservations with respect to pulsed shortwave diathermy, and many people have doubted the benefits of therapeutic laser. Although for many years the American Food and Drug Administration (FDA) was unconvinced of the clinical efficacy of low-level laser therapy (LLLT), this has now changed due to an increase in scientifically valid clinical trials. In 2002 the FDA granted approval for some LLLT devices to be marketed for specific indications, such as ‘adjunctive use in providing temporary relief of minor chronic neck and shoulder pain of musculoskeletal origin’ and for ‘adjuncted use in the temporary relief of hand and wrist pain associated with carpal tunnel syndrome’ (Swedish Laser Medical Society 2004).

A variety of suggestions has been made about the underlying ways in which predominantly non-thermal effects may occur. Many of those postulated are based on the suggestion that electrophysical agents can influence the mechanisms that lead to cell communication. Tsong (1989) suggested that cells communicate both directly through chemical means and indirectly through the influence of electrical, physical and acoustic signals, and it seems that electrophysical agents may produce physiological changes through these mechanisms.

Work in this area has gained momentum recently, particularly as knowledge of growth factors and their role in tissue repair and function increases, as research workers have examined the possible effects derived from using electromagnetic fields to stimulate cell activity. Recent work, using a variety of field parameters, has examined changes in growth-factor production, signalling pathways (e.g. Ca²⁺ mediated), cell growth and survival, cell cycle distribution, cyclic AMP content and gap-junction-mediated communication between cells (e.g. George et al 2002, Schimmelpfeng et al 2005, Takashima et al 2006).

For any agent to be effective it must be active through one of more sites, or components, of tissues. It is generally considered that these sites are intracellular, although energy transduction within extracellular molecules such as collagen might also be involved and lead to the activation of these intracellular sites, here termed interactive targets.

INTERACTIVE TARGETS

‘Interactive targets’ are cellular components that may be receptive to interventions. These interactive targets include the plasma membrane of the cell, also termed the cell membrane, and intracellular structures such as the intracellular membranes, microtubules, mitochondria, chromophores, cell-associated ions and the nucleus.

PLASMA MEMBRANE

The cell was described in terms of its electrical structure and function in Chapter 3, and it will be recalled that the plasma membrane consists of a bilayered, phospholipid structure which surrounds the cell and is studded with transmembranous proteins (Alberts et al 1994). These proteins have a number of functions: they strengthen the membrane; they transport substances such as proteins, sugars, fats and ions across the membrane; and they form specialist receptor sites for hormones, neurotransmitters and enzymes. In addition, the plasma membrane is electrically charged, possessing a negative charge on its internal surface and a positive charge on its external surface. The resulting potential difference of approximately 70mV is maintained through the passive and active movement of ions across the cell membrane.

A number of electrophysical agents are thought to effect changes at the level of the plasma membrane. For example, Adey (1988) postulated the transduction of a pulsed magnetic field (PMF) signal across the cell membrane and regarded this structure as the primary site of interaction between the oscillating electrical field and the cellular components of the tissue. Adey suggested that a large amplification of an initial weak trigger can occur as the result of the binding of hormones, antibodies and neurotransmitters to their specific binding sites on the cell membrane owing to the effects of magnetic fields.

Other workers, such as Tsong (1989), Westerhoff et al (1986) and Astumian et al (1987), have postulated that proteins can undergo conformational changes as a result of interaction with an oscillating electrical field. For this to occur with any degree of efficiency, the frequency of the field must match the kinetic characteristics of the reaction and be at an optimum field strength (Tsong 1989). This reaction can result in pumping effects, with substances being actively transported across the cell membrane, leading to subsequent ATP synthesis. Although none of these researchers has specifically examined the effects of agents used in clinical practice, it might be that pulsed shortwave diathermy acts upon cells in one or more of these ways.

Mechanical energy might also effect changes in cell membrane behaviour; such changes have been shown to occur when therapeutic levels of ultrasound are applied to cells in vitro. Hill and ter Haar (1989) state that acoustic cavitation results in sound energy being converted into other forms of energy, including shear energy. The sound energy induces the oscillation of minute bubbles within the tissues, which in turn induce microstreaming of liquids both around the bubbles themselves and around the cell walls (further details are provided in Chapter 12). Some writers, such as Repacholi (1970) and Repacholi et al (1971), suggest that microstreaming may alter membrane permeability and secondary messenger activity and be responsible for changes in the surface charge of cells, resulting in the transduction of signals. This view has been reinforced by both Dyson (1985) and Young (1988), who have suggested that microstreaming (at therapeutic doses) may influence cell function by reversibly affecting the permeability of the plasma membrane and modifying the local environment through mechanisms such as altered cell metabolite gradients. Mortimer and Dyson (1988) have demonstrated that therapeutic levels of ultrasound can induce permeability changes to calcium ions, and that this is associated with cavitation.

Finally, writers such as Smith (1991a, b) have suggested that infrared, low-level laser radiation may initiate reactions at the cell membrane level, possibly through photophysical effects on Ca²⁺ channels. This suggestion has been supported by the work of other groups. In 1997, Lubart et al reported changes in calcium transport in plasma membranes caused by 780nm irradiation. In 2004, Kujawa et al (2004) reported that low-intensity (3.75–25J/cm²) near-infrared (810nm) laser irradiation of erythrocytes induces long-term conformational plasma membrane transitions related to changes in the structural states of both membrane proteins and the lipid membrane; these resulted in changes in the activity of membrane ion pumps and, therefore, in plasma membrane permeability to ions. It has been proposed that optimization of the structure and function of the erythrocyte plasma membrane may be the basis for improvement of cardiac function in patients undergoing laser therapy (Kujawa et al 2004). Some of the cellular effects of LLLT can be mediated by nitric oxide (NO; Karu et al 2005); in erythrocytes this may be released by LLLT from NO-haemoglobin (Vladomirov et al 2000).

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