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Peripheral Nerve Stimulation for Neuropathic Pain

and when stimulation is applied, the paresthesias (pleasant sensation described as tingling or warmth) are felt in the distribution of sensory representation of the stimulated nerve.

In a similar fashion, modern applications of PNS in the treatment of pain produce paresthesias in the distal body regions that represent the sensory coverage of the nerve. The best examples of such a principle would be stimulation of the occipital nerves, when paresthesias are perceived all the way to the vertex of the skull or the frontal hairline while the electrode is located over the craniocervical junction, or infraorbital nerve stimulation, which produces paresthesias in the upper teeth and upper lip while the electrode is traveling next to the infraorbital foramen.

In contrast to true PNS, the more recently introduced concepts of subcutaneous neuromodulation,11 neurostimulation (SPNS),12

peripheral subcutaneous neurostimulation (PSNS),14 subcutaneous field stimulation (PSFS)15

peripheral nerve field stimulation (PNFS),13 and peripheral

refer to stimulation of smaller

nerves or even nerve endings and the paresthesias are felt in the vicinity of the electrode itself. Since these concepts (PNS and PNFS/SPNS/PSNS/PSFS) may overlap to some extent, and since none of them currently has regulatory approval in the US (European approval was obtained in 2010 by two different companies), there is a certain element of confusion in the literature regarding terminology. This issue has already been addressed in multiple publications16–18

but continues

to be a point of contention at professional conferences, as there is no universal agreement on where to draw the line (and whether the line has to be drawn) between these two approaches.

Mechanism of Action

Interestingly enough, despite a long history of clinical application of PNS, its mechanism of action remains rather unclear.19

An original explanation,

the cornerstone of the gate control theory of pain, postulated that antegrade (orthodromic) stimulation of non-nociceptive Aβ nerve fibers results in activation of the same interneurons in the superficial layers (Rexed laminae 2 and 3) of the dorsal horn of the spinal cord that are involved in processing and transmission of nociceptive information delivered by peripheral Aβ and C nerve fibers. Such non-painful stimulation provided by PNS inhibits the interneurons and interrupts or decreases transmission of pain signals.1

Additional modifications of the

half-century-old theory enhanced it by more complex excitatory and inhibitory interactions but the general principle remains the same.20

Another possible explanation combines electrical and neurohumoral effects of stimulation, as peripheral stimulation may be changing local concentrations of important chemicals, such as neurotransmitters and endorphins, and augments local blood flow that may be contributing to production of chronic pain.5,19

In addition to this, PNS may directly change the excitability of peripheral nerve fibers.21

A recent experimental study on human volunteers showed that direct stimulation of a peripheral nerve inhibits neurotransmission, as documented by elevated thresholds for nociceptive stimulation.22

The mechanism of pain suppression, however, is likely to be more complex than simple peripheral and spinal inhibition. Multiple neuroimaging studies


In treatment of chronic pain in the extremities, the open surgical approach remains the ‘gold standard’ in reaching the peripheral nerves, as evidenced by recently published large clinical series from Israel and Australia35,36

implanted in the 1980s in Belgium.39

and a uniquely long follow-up in a cohort of patients For this application, a percutaneous

approach is only starting to gain acceptance as evidenced by anecdotal reports using PNS in both upper40,41

and lower37,38,42 extremities.

Chronic neuropathic pain in the neck, chest, abdomen, lower back, and pelvis has been successfully treated with PNS and PNFS applications. There are published reports of PNS/PNFS use in localized neck pain;14,15 pain due to intercostal neuralgia43 scapular fracture,46

chest wall and thoracic myelopathy;47

and after sternotomy,44 abdominal13,48

thoracotomy,45 and inguinal49

pain; lower back pain—with the use of percutaneous electrodes implanted close to the area of pain,12,50

from each other (the so-called ‘cross-talk’ concept),51

percutaneous electrodes implanted far a combination of

145 subcutaneous peripheral

The original PNS use was aimed at patients with painful peripheral neuropathies in the extremities, mainly due to traumatic injury of the nerve that was subsequently chosen as a target for stimulation. This evolved to acceptance of PNS in the treatment of chronic pain due to post-surgical or entrapment neuropathy, as well as complex regional pain syndromes, both type 1 (formerly known as reflex sympathetic dystrophy) and 2 (causalgia).30–36

Chronicity and severity of pain, as well

as failure of less invasive approaches, have been established as necessary criteria in patient selection. It became clear early on that the best responders to PNS are those patients whose pain is mediated by primarily sensory nerves, since mixed and predominantly motor nerves do not tolerate PNS well, as motor phenomena due to stimulation prevent the increase in amplitude required for pain suppression.8

These major peripheral nerves traditionally had to be exposed surgically, not only because of their deep course within soft tissues, but also because of the frequent proximity of vascular structures. The issue of localization of the nerve trunks and delineation of adjacent vascular structures was resolved with the introduction of ultrasound guidance during percutaneous PNS electrode insertion.37,38

The rebirth of open surgery for very specific

cases of pain due to peripheral nerve injury—those caused by the presence of post-amputation neuromas—is expected with the development of a new dedicated PNS system with special cuff-like electrodes that is now undergoing clinical testing (unpublished data).

convincingly indicate the presence of central mechanisms of PNS action. These include both suppression of activity in pain-processing cerebral circuits and activation of those areas that are involved in the descending system of pain control and modulation.23

Common Indications

in the truncal area, including the lower back, abdomen, and inguinal region, in the chest wall anteriorly and posteriorly (post-sternotomy pain and intercostal neuralgias),25,26 craniofacial region.10,27–29

and in the

The simple fact that the peripheral nervous system supplies the entire human body translates into the applicability of the PNS approach to essentially every localized pain syndrome. Over the years, PNS has been successfully used in treatment of pain in both upper and lower extremities,24

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