Peripheral nerve stimulation (PNS) refers to electrical stimulation of the named nerves, plexuses, and branches using implantable hardware; it is a commonly used surgical approach that has many current and potential uses in the care of rehabilitation patients. For example, it has been used to restore breathing in patients with diaphragmatic palsy by stimulating the phrenic nerves, to control seizures and depression by stimulating the vagal nerve, to improve/normalize bowel and bladder function in patients with incontinence and retention by stimulating the sacral nerves, and to control sleep apnea by stimulating the hypoglossal nerve. But, the most established and probably the most underutilized PNS application is related to its ability to control chronic pain.

PNS was introduced for the treatment of chronic pain in the early 1960s [1], even before the “gate-control” theory of pain was conceived and published. As a matter of fact, PNS was used to support this theory when its authors described the pain-relieving effect of PNS with self-experimentation and clinically relevant results in a series of eight patients [2]. Soon thereafter, a novel approach of spinal cord stimulation (SCS) was developed for the treatment of chronic pain. Predictable and reproducible results of SCS lead to its universal acceptance, and by the mid-1970s, SCS eclipsed PNS in clinical practice. The modality was not abandoned completely, and despite the lack of dedicated equipment, there were multiple clinical centers that kept PNS alive, albeit in small volumes and for very specific painful syndromes [1].

Recently, there has been a surge of interest in PNS applications to treat chronic pain for multiple reasons. First, there is a need for a focused neuromodulation approach that would selectively stimulate the nerves that are responsible for pain syndrome (see section on indications below); second, technological advances and creative thinking have resulted in the development of dedicated PNS devices that have been designed to facilitate the implant component of the procedure and to improve long-term outcomes (see sections on procedural details and the future directions); finally, there is now a clear understanding that other modalities, which include SCS, may not be uniformly effective in every clinical situation; furthermore, there are multiple instances where PNS may be significantly superior to everything else, in terms of efficacy and safety (see section on evidence).

Although there are many possible theories explaining the exact way in which PNS suppresses pain, the two most plausible explanations have to do with the frequency of stimulation [3].

The conventional frequency of PNS is in the range of 10–100 Hz; it is usually referred to as “paresthesia-inducing stimulation”, as PNS at this frequency is capable of and is expected to produce paresthesias, which are usually described as a tingling sensation by patients. The Gate Control theory of pain postulates that the presence of non-painful sensation in the area of pain may suppress transmission of nociceptive information toward the central processing regions. Interestingly enough, it appears that the presence of paresthesias in the painful region does not guarantee pain relief, but the absence of paresthesias is all but certain to result in failure of the modality. This, at least in part, may explain the dismal results of PNS seen in patients with complete numbness in the painful region; another explanation may be in the degree of underlying nerve damage, as the injury that is severe enough to make the area numb is likely to make the affected nerve insensitive to electrical stimulation. Paresthesia inducing PNS has been successfully used on a long-term basis in a variety of neuropathic pain conditions.

Another mechanism is observed in the use of a much higher frequency range of 10,000–12,000 Hz (10–12 kHz). Here, it appears that such high frequency stimulation produces complete (but fully reversible) conduction block, which makes the area supplied by the stimulated nerve numb and painless. This PNS approach, described as “high frequency nerve block”, has been successfully used in the treatment of post-amputation pain, with lasting pain relief after intermittent use of stimulation [4].

Most established indications for PNS include pain in the extremities. PNS has been traditionally used to stimulate large named nerves in the arms and legs for a variety of neuropathic pain syndromes. Traumatic or iatrogenic neuropathies, as well as complex regional pain syndromes (type 1, formerly known as reflex sympathetic dystrophy, and type 2, formerly known as causalgia), are considered best indications for PNS [5, 6]. In addition to stimulation of individual nerves, peripheral neuromodulation may also target the brachial plexus and dorsal root ganglia.

Pain in the trunk has been evaluated as an indication for PNS on many occasions. Currently, there is CE (Conformité Européenne) mark for PNS in the treatment of low back pain with neurostimulation from two different companies [7]. Moreover, PNS has been successfully used for the treatment of intercostal neuralgia, abdominal, inguinal and flank pain syndromes, as well as pain in the neck due to cervical spondylosis or following cervical spine surgeries [8].

In terms of head and face pain syndromes, PNS has been used primarily for the treatment of occipital neuralgia [9], cluster headaches, migraine headaches, and trigeminal neuropathic pain [10]. Here, occipital PNS is used for the management of pain syndromes that involve posterior aspects of the head and the upper neck, and stimulation of the trigeminal branches is reserved for pain in the face and frontal part of the head. In addition, occipital PNS has been shown to improve whole body pain in fibromyalgia [11]. Based on several publications, it appears that post-herpetic neuralgia, which frequently presents with chronic pain in trigeminal distribution, is one of those indications for which PNS is less predictable and probably less effective overall [12].

A distinct and relatively new indication for PNS is in the treatment of post-amputation stump pain that may or may not be associated with formation of amputation neuroma, which strongly interferes with the patient’s ability to wear a prosthetic device on the affected limb, and thereby impedes progress in rehabilitation [4]. In these cases, use of a high-frequency nerve block may be a better solution, since making the stump numb does not carry additional functional impairment. Although sometimes considered for the treatment of phantom pain, PNS may not be very effective for this particular indication, which is not unlike other spinal and extra-spinal approaches and is not surprising since it is known that phantom pain is a central phenomenon.

There are many ways that PNS devices may be implanted into the human body. Although the various equipment options may dictate the different procedural details, the general principles remain the same. The stimulating contacts of the electrode lead have to be either in direct contact or in the immediate vicinity of the stimulated nerve. This is accomplished by placing the electrode next to the target nerve by either direct exposure of the nerve (such that the lead may be positioned next to the nerve, or wrapped around the nerve, depending on the lead geometry) or by inserting the electrode lead in the vicinity of the stimulated nerve(s) using a percutaneous approach.

Usually, the implantation of a permanent PNS device is preceded by insertion of temporary electrodes, as a part of so-called “trial” of stimulation. For this, a percutaneous approach is frequently chosen, with or without ultrasound guidance. At the end of the trial, which usually lasts 5–10 days, the temporary leads are removed, and then a permanent device is implanted at the same time or during a separate session. Design of the electrode lead dictates the procedural details. Cylindrical leads may be inserted through an introducer needle; paddle-type flat leads require direct exposure of the stimulated nerve, with the exception of specially designed narrow paddle leads that may be inserted percutaneously through a dedicated insertion tool (Epiducer, St. Jude Medical) [13]; wrap-around leads require not only exposure of the nerve, but also its circumferential dissection. However, the resulting tight direct contact between the nerve trunk and the electrode contacts creates a much more reliable and energy-efficient interface.

Stimulation devices have to be powered and there are different conceptual models to achieve this. Most commonly, the electrode leads are connected to an implanted generator that contains the battery and telemetry/programming units. Such a generator is usually placed through a separate incision in the patient’s abdomen, chest wall, flank, or in the case of smaller devices and larger patients, next to the stimulated area in the patient’s paraspinal region or the painful extremity.

Before the invention of implantable generators, there were radiofrequency-coupled systems that included an implanted antenna/receiver and an external power source. Such devices have not been used for several decades, but the concept was resurrected with more compact versions of either radiofrequency-coupled or direct current/induction-based devices. Finally, a new generation of these devices employs nanotechnology concepts to miniaturize the stimulator hardware and to power it via “wireless” approach. Examples of such new devices include StimRouter (Bioness), Reprieve (BlueWind Medical), and Freedom (StimWave) neurostimulators [14, 15]. Insertion of these new devices has become much less invasive, as they do not require tunneling and generator implantation.

Despite a 50-year clinical history of using PNS in a variety of pain syndromes, there is remarkably little evidence of its long-term effectiveness. In 1996, a prospective series by Hassenbusch et al. [5] documented good or fair pain relief in 63% (19/30) patients with reflex sympathetic dystrophy that were followed by 2–4 years. They also noted marked improvement in vasomotor tone chances and the patients’ activity levels, whereas improvement in motor weakness and trophic changes was less impressive.

A large multi-center nationwide study in Austria showed that subcutaneous targeted stimulation (frequently called peripheral nerve field stimulation) used in the treatment of focal non-cancer pain in 111 patients resulted in across-the-board improvement in pain intensity by more than 50% (from 8.2 to 4.0 in mean numeric rating scale measurements) [16]. These results were similar to an earlier US study of 20 patients with chronic back and leg pain, who were treated with a combination of spinal cord stimulation and peripheral nerve field stimulation [17]. Following these promising results, a prospective multi-center observational study in 11 centers across Austria and Switzerland analyzed 105 patients with chronic low back pain who were treated with peripheral nerve field stimulation. The analysis showed that all pain and quality-of-life measures (including pain intensity, depression, disability questionnaires, etc.) improved during the 6 months follow-up period in a statistically significant fashion; the review of medication usage showed highly significant reduction as well [18]. The most recent review of PNS in the treatment of back pain emphasized the importance of proper depth in the placement of stimulating electrodes. Specifically, a lead depth of 10–12 mm from the skin surface appeared to maximize target sensation that was mediated by fast-adapting A-beta fibers [19]. The authors from Australia came to this conclusion based upon analysis of published studies and their own extensive experience in the use of PNS for a variety of peripheral neuropathic conditions.