Peripheral nerve stimulation

General principles of PNS for treatment of pain

There are several main paradigms that are routinely used in PNS to treat pain. The first one involves production of painless paresthesias—this usually happens with continuous tonic stimulation at relatively low frequencies of 15–150 Hz [ , ]; the second involves complete interruption of neural transmission, in essence producing a reversible nerve block, usually at frequencies above 1000 Hz [ , ]; the third one involves central processing of information, either at the level of trigemino-cervical complex as in use of occipital and trigeminal PNS for treatment of migraines and cluster headaches [ ], or at the supraspinal levels as postulated to be the case in the use of PNS for fibromyalgia [ ]; the fourth one involves local normalization of muscle tone as a result of stimulation of intramuscular nerves and translates into lasting pain relief due to restoration of movements [ , ]; and the fifth paradigm which includes either high frequency [ ] or burst-type stimulation [ ] and provides pain relief without paresthesias and without nerve block and is likely explained by central effects of stimulation at spinal and supraspinal levels. In addition, there may be very different mechanisms of PNS when applied transcutaneously or via electroacupuncture. It is very possible that each clinical application of PNS involves more than one paradigm or that there are some other paradigms with mechanisms of action yet to be determined.

The basis of conventional PNS therapy is considered a reversible suppression of pain due to production of concordant paresthesias. Similar to SCS, this effect may be supported by the abovementioned “gate-control” theory of pain. PNS does not alter sensation in the zone supplied by the stimulated nerve—but it usually does not work when such sensation is already altered or absent, meaning that it is pretty much impossible to obtain pain-relieving effects in areas of complete numbness, such as in extreme cases of diabetic neuropathy or true anesthesia dolorosa.

There are two distinct technical modes of PNS use—and they dictate choice of equipment and surgical approach. Both of them follow the same goal of delivering repetitive electrical stimulation to the nerve that is involved in pain production or transmission. For therapy to be successful, one has to know which nerve or nerves are involved in generating pain for that particular patient, and the best way to confirm PNS usefulness is to perform a trial of stimulation. Although nerve blocks and transcutaneous electrical nerve stimulation were considered as possible predictors of PNS success, their effects have not been shown to correlate with PNS results (refs?).

For the first PNS approach, the nerve in question is surgically exposed and the electrode is placed directly over or under it (or around it—in the case of “wrap-around” or coiled electrodes). This open exposure for electrode placement is an older technique, with the first clinical series of the successful application of this approach published in the early 1970s [ , , ]. The use of flat (paddle-type) electrodes [ ] allowed eliminating some concerns of nerve injury from the scar around the electrode, and subsequent suggestion of putting a thin layer of fascia between the electrode contacts and the nerve itself was aimed at further reduction in nerve irritation from the presence of a large electrode nearby. Right around that time, a special electrode was developed and approved for use in PNS—a paddle electrode with a mesh attached to it (OnPoint, Medtronic, Minneapolis, MN). In addition, though not a single implantable pulse generator (IPG) is officially approved in the US for PNS, the radiofrequency-coupled systems that were at some point manufactured by Medtronic and Advanced Neuromodulation Systems (subsequently—St. Jude Medical; currently—Abbott, Chicago, IL) had PNS among their approved uses. The use of paddle-type electrodes for PNS continues to be an accepted means of PNS delivery—and multiple recent reports continue to document its success and reliability in a variety of clinical settings [ ]. Among currently approved devices, the Freedom four stimulator (Stimwave, Pompano Beach, FL) may be implanted via open exposure of the stimulated nerve, and the Altius device that is currently being investigated in multicenter studies (Neuros, Willoughby, OH) requires surgical exposure of the stimulated nerve so the electrode can be wrapped around it proximal to an amputation neuroma.

The second way of PNS application involves percutaneous insertion of stimulating electrodes. Initial technique of percutaneously inserted PNS devices was used to prove the concept when Wall and Sweet stimulated their own infraorbital nerves to confirm development of analgesia during the stimulation [ ]. This approach, however, was not used clinically until the mid-1990s when Weiner and Reed described their technique of percutaneous insertion of PNS electrodes for treatment of occipital neuralgia [ ]. Since then, this approach has been successfully used in many anatomical locations and for different clinical conditions. Although associated with a high rate of complications and frequent need for surgical revisions [ ], the percutaneous PNS approach is very appealing due to its technical ease and low invasiveness. A recent suggestion to use ultrasound guidance to localize the nerve to be stimulated [ ] now allows implanters to target many peripheral nerves along their subfascial or epifascial course. This includes occipital nerves and nerves in the trunk and extremities [ ].

Somewhat similar to the percutaneous PNS approach is so-called peripheral nerve field stimulation (PNFS). The difference in PNS and PNFS is the substrate of stimulation [ ]. Although both modalities definitely stimulate the nerve fibers that carry nociceptive information from the periphery to the central processing areas, PNS works with visible and identifiable nerves, usually named nerves, whereas PNFS works on unnamed, frequently multiple, smaller nerves that are hard to identify within subcutaneous tissues.

Most currently approved PNS and PNFS devices are intended for percutaneous insertion—these include StimRouter (Bioness, Valencia, CA), Freedom 4 (Stimwave), and SPRINT PNS (SPR Therapeutics, Cleveland, OH), all of which are approved by the US FDA [ ]. Similarly, the LightPulse family of devices with Lightline, Fixline, T-line, and Surline electrodes (Neurimpulse, Rubano, Italy) have CE Mark for PNS applications and are intended for percutaneous electrode insertion [ ].

Overall, however, all these approaches are quite similar to each other. The goal of stimulation in most cases remains the same as it is necessary to produce nonpainful sensation—paresthesias—in the area of pain, and maintain these paresthesias, usually on a continuous basis, for pain to subside.

From a technical point of view, traditional PNS implantation somewhat resembles SCS procedures as it is usually performed in stages. During the first stage, the electrodes are implanted for trialing purposes. If the plan is to keep the trialing electrode in place for subsequent permanent use, the electrode has to be anchored and connected to a temporary extension cable that is then tunneled away from the insertion point. Care should be taken to avoid damaging the nerve during electrode insertion. If the electrode is inserted with an open technique, the nerve is identified and dissected so that the electrode can be placed in its immediate vicinity. The anatomical location of a stimulation site should take into consideration the size of the electrode and the room for anchors, connectors, and extensions. There is usually no need for any adjunctive imaging technique as the large nerves are easily identifiable in their expected anatomical locations.

With the use of a percutaneous technique, the trial electrodes are frequently discarded upon completion of the trial. Different, new electrodes are then implanted during a subsequent second-stage PNS procedure. Here, there is no need to visualize the stimulated nerve directly. Instead, one may use standard anatomical landmarks trusting limited variability in the nerve course and an ability to capture the nerve with multiple contacts of the stimulating electrode, particularly if the electrode is placed perpendicular to the course of the nerve. In addition to this, both fluoroscopy and ultrasound have been used intraoperatively to check the position of the nerves (ultrasound) and direction of the electrode path (fluoroscopy).

Following the trial electrode insertion, the patient goes through a testing period that varies from 2 to 3 days to a week or even longer. During this time, the patient is encouraged to evaluate the effectiveness of PNS in terms of pain suppression, and to note any of the side effects that PNS may produce (pain, discomfort, spasms, etc.) so the decision can be made on whether overall benefits of PNS justify the trauma and expense associated with permanent implantation.

At the time of permanent implantation, an IPG is implanted away from the area of stimulation, and the electrode(s) may be either directly connected to the IPG or connected to it via extension cables of appropriate length. As opposed to SCS where electrodes are almost uniformly inserted into the posterior epidural space, PNS electrodes may be implanted anywhere in the body (face, head, neck, trunk, and extremities) and therefore one has to be creative in choosing the IPG site and the path for the electrodes and/or extension cables in order to minimize the chance of hardware migration (if the anchors are loose) or fracture (if the anchors are too tight) whenever excessive mobility is encountered. The thickness of tissues overlying the electrodes, anchors, connectors, and generators should also be taken into consideration so erosion and infections are more likely avoided, and easy charging for rechargeable IPG is feasible.

Some of the newer devices do not have implantable power sources—the energy is delivered from an external pulse generator (EPG) via microwave-based coupling (Freedom 4) [ , ], direct current from an external device that is taped over the implant (StimRouter) [ ], or direct attachment of the electrodes to an EPG for the entire duration of stimulation treatment (approved for a period of up to 60 days, SPRINT) [ ].

Since the decision on PNS effectiveness and side effects may only be made by the patient, it is important to go through all logistics of appropriate patient selection. In addition to confirmation of severity and chronicity of the pain, it is important to check whether less invasive modalities have already been tried, and whether a patient's psychological condition makes him/her an appropriate surgical candidate. The importance of psychological evaluation has been shown since the very beginning of PNS use [ , ] as those with untreated depression, psychosis, major secondary gains, and somatization disorder have had overall unsatisfactory results in the long term. As well, similar to all other neuromodulation applications, it is important to set realistic expectations as PNS does not cure underlying pain syndromes and rarely eliminates pain completely. With appropriate use in selected patients, it decreases pain levels and improves or normalizes patient functionality. Patients also should be prepared for a high chance of needing some kind of reoperation during the follow-up. Statistics shows that although most PNS complications are minor, they appear to be much more common compared to using other neuromodulation procedures.