Persistent pain is an important health problem. Based on representative samples (age range: 18-65 years) in 15 centres in Asia, Africa, Europe and the Americas, the prevalence of persistent pain averaged 22%. The most common forms were: back pain (47.8%), headaches (45.2%) and joint aches (41.7%). A characteristic feature of chronic pain is the loss of quality of life, mainly due to psychological illness and limitations in daily activities (1).

In diabetic patients pain is a particularly frequent and severe problem. As a consequence of the metabolic derangement, symptomatic peripheral neuropathy developed in 16.2% of a community based sample of diabetics, while in the non-diabetics, the prevalence was 5% (2). Advanced neuropathic deficits are in many cases a forerunner of foot ulcers and amputations. The prevalence of peripheral neuropathy is related to the duration of diabetes (2). In a large United Kingdom hospital population study, there was also a clear association with patient age (3). In the age group 70-79 years the prevalence of peripheral neuropathy was 44.2%. In the U.S. population, symptoms of neuropathy affected up to a third of adults with non-insulin dependent diabetes mellitus (4).

In end-stage renal failure, more than 50% of patients complain of pain symptoms. Among the causes, musculoskeletal disorders dominate. Peripheral neuropathy and pain from peripheral vascular ischemia average about 13% and 10%, respectively (5).

In the treatment of pain, electro-medical approaches were implemented as early as the 5^th century BC. Plato (427-347 BC) and Aristotle (384-322 BC) discovered that contact with the ”black torpedo”, an electric ray fish, has pain-relieving properties. These fish are capable of generating electrical charges of up to 220 V (6).

In modern medicine, the most frequently non-pharmacological methods in pain treatment are: the transcutaneous electrical nerve stimulation (TENS), the percutaneous electrical nerve stimulation (PENS), functional electrical stimulation (FES), and the spinal cord stimulation (SCS).

In the first form of electro-medical therapy, TENS, a battery-powered electrical unit with electrodes is placed on the skin, above the underlying, painful nerve fibres. The therapy was shown to be very effective in patients with painful peripheral diabetic neuropathy (7). In a placebo-controlled, randomised study, a beneficial effect of TENS was observed in patients with diabetic neuropathy (8). In another study by the same research group, it was demonstrated that TENS may be ”a useful adjunctive modality” in combination with a pharmacological agent, i.e. amitriptyline (9). In this group of patients, about 85% reported symptom improvement. An analgetic effect of electrotherapy was also reported in patients suffering from pain associated with arthritis and rheumatological conditions (10).

PENS, another kind of electro-medical stimulation, combines both TENS and electroacupuncture-like needle probes (”transcutaneous hyperstimulation”) to stimulate sensory nerves innervating the region of neuropathy. In a sham-controlled cross-over study, it lowered extremity pain and improved physical activity (7).

Functional electrical stimulation (FES) employs electrical currents to activate nerves which innervate extremities affected by paralysis resulting from spinal cord injury, head injury, stroke or other neurological disorders, i.e. to restore function in people with disabilities (11).

A very effective form of electrostimulation in chronic pain is the spinal cord stimulation (SCS). Here, an epidural electrode is placed in an appropriate spinal cord segment and connected with a permanent pulse generator in the flank. A relief of pain symptoms has been described in severe diabetic neuropathy, painful ischemic peripheral artery disease, phantom limb pain, and refractory angina pectoris. SCS has been successfully used in patients with peripheral artery occlusive disease, i.e. in patients unsuitable for vascular reconstruction. It markedly reduced pain and may delay or even prevent the amputation of extremities (12).

The effect of SCS has been evaluated in 8 chronic hemodialysis patients with critical lower limb ischemia (Leriche-Fontaine stage 3 or 4). A dramatic lowering of pain, an improved quality of life and a noteworthy reduction in the use of pain medication could be observed. The benefits persisted for a further 6-12 months. The authors assume that an earlier treatment of peripheral artery occlusive disease (Leriche-Fontaine stage 2 or 3) might delay the amputation of extremities of dialysis patients (13). The favourable effects of SCS could be attributed to a vasodilating effect, on the one hand, as demonstrated by an improved microvascular blood flow in severe limb ischemia (14). On the other hand, it has been suggested that electrical stimulation activates the dorsal columns and inhibits C-fibres with a subsequent decrease in pain perception (15).

Comparably beneficial actions could be achieved by SCS in patients with intractable angina pectoris, for whom angioplasty or coronary bypass graft surgery could not be performed. The results showed a reduction of angina, an enhanced exercise capacity, less ST segment depression and improvement of myocardial blood flow (16). The treatment was as effective as coronary artery bypass surgery (17). The beneficial long-term effects of SCS on angina were recently underlined (18).

However, SCS therapy is not without complications. In 3-4% there is an SCS device failure. Infections occur in 3-5% of patients implanted with such a device. The most common complication (11-36%) concerns external electrode dislocation and breaks. Further complications include cerebrospinal fluid leak (1%) and meningitis (0.5%) (19).

An innovative type of electrotherapy is the so-called ”high-tone external muscle stimulation” (HTEMS). In this special electro-medical approach, the electrical frequency varies in short intervals (3 sec.) between 4100 and 33 000 Hz. Another novelty of this method is the fact that amplitude and electrical frequency are modulated simultaneously.

The mechanisms behind the efficacy of HTEMS are still not fully understood. It is hypothesized that at the high frequency the smaller charged molecules in the muscle tissue fluids may resonate and oscillate, while the larger charged molecules may do so at the low frequency. These oscillations may enhance blood flow, metabolic processes and accelerate the removal of waste products and inflammatory cytokines.

There are only a few contraindications of HTEMS: e.g. active bacterial infections, presence of a pacemaker, pregnancy, recent fractures, acute thrombosis, epilepsy and implants.

In a direct comparison between TENS and HTEMS, the HTEMS was nearly 3 times as effective as the TENS. In this study of the German Diabetes Institute in Düsseldorf, diabetic patients were treated in a randomised fashion with one of the two electrotherapies (30 min) on 3 consecutive days (20). These results were confirmed and extended at the University of Heidelberg. Here, 92 type 2 diabetic patients with different neuropathic symptoms were included in a prospective uncontrolled trial. The patients were treated twice weekly for a total of 4 weeks with HTEMS, whereby the symptoms were graded on numeric scales at baseline, before the second and the eighth visit. A marked improvement of symptoms (pain, paresthesia, numbness, burning sensation, and sleeping disturbance) was documented in 73% of the patients. This subjective treatment response was positively and directly associated with symptom intensity but independent of disease extent, metabolic factors, age, or gender. Patients in the upper tertile of symptom intensity showed significant improvement of paresthesia, pain, numbness and most pronounced for burning sensations and sleeping disturbances. The authors concluded that HTEMS ”seems to be an effective treatment for symptomatic neuropathy in patients with type 2 diabetes, especially in patients with strong symptoms” (21).

We performed a non-controlled, multi-centre study on the effect of HTEMS in a total of 40 hemodialysis patients with symptomatic peripheral polyneuropathy (PPN) (25 with diabetic and 15 with uremic PPN). Both lower extremities were treated intradialytically with HTEMS for 30-60 minutes, three times a week. The patients´ degree of neuropathy was graded at baseline before and after 3 months of HTEMS treatment, using the 10-point Neuropathic Pain Scale of Galer and Jensen (Neurology 48:332-338, 1997). Five neuropathic symptoms (pain, tingling, burning, numbness, numbness in painful areas) as well as sleep disturbances were measured. A positive response was defined as the improvement of one symptom or more, by at least 3 points. HTEMS led to a significant improvement in all five neuropathic symptoms, and to a significant reduction in sleep disturbances for both diabetic and uremic PPN. The responder rate of 73%t was independent of the patients´ age. This pilot study showed for the first time that HTEMS can ameliorate the discomfort and pain associated with both diabetic and uremic PPN in hemodialysis patients, and could be a valuable supplement in the treatment of their pain and neuropathic discomfort (22). These findings have recently been confirmed by the research group of Prof. Guido Bellinghieri (Messina, Italy, personal communication).