Background

For almost 40 years stimulation of peripheral nerves has been used for the control of neuropathic pain. Like spinal cord stimulation (SCS), the mechanism of peripheral nerve stimulation (PNS) is believed to have its basis in the gate control theory of pain.¹ Although PNS and SCS have been accepted techniques for the treatment of neuropathic pain, SCS has become more widely used. A number of factors have prevented the evolution of PNS, not least of which is a perception that PNS is an orphan modality. This has resulted in PNS never receiving the medical attention that it deserves from either manufacturers of implantable devices or implanting surgeons. Unfortunately, appropriate investigation of its scope and application remains latent.

Open surgical implantation of PNS electrodes, which was described between the early 1970s and 1990s, presaged the ongoing interest at selected centers in the United States and elsewhere to manage peripheral neuropathic pain by PNS.^2–13

Another handicap for the development of PNS is the lack of any coordinated effort by the implanting physicians who have a vested interest in furthering the scope of PNS to engage in a dialog with the U.S. Food and Drug Administration (FDA). For example, a dialog to extend the current approval for the radiofrequency (RF) interface to include approval for an implantable power source implantable pulse generator (IPG) is wanting. Only one manufacturer, Medtronic (Minneapolis, Minn), has FDA approval to provide an electrode in conjunction with an RF external generator for PNS. All IPGs, whether Medtronic, Advanced Neuromodulation Systems (ANS, Plano, Tex), or Boston Scientific (Valencia, Calif), that are used in conjunction with PNS are considered “off-label” indications. The PNS (On-Point) electrode itself was originally developed as a quadripolar electrode for use in SCS. Recently PNS has received a boost through the efforts to develop occipital nerve stimulation.^14,15

Definition

“Neuropathic pain is pain initiated or caused by a primary lesion, dysfunction, or transitory perturbation in the central or peripheral nervous system.”¹⁶

Indications

PNS is indicated for the treatment of neuropathic pain in the distribution of a peripheral nerve or nerve trunk that is chronic and unresponsive to conventional medical management (CMM). Loss of function, an inability to participate in exercise therapy, and the nonresponse to local anesthetic or sympathetic blocks are considerations for PNS. Cases of neuropathic pain arising from a plexus injury or mononeuropathies from various causes may have in addition a partial or complete sensory loss that is within a particular nerve distribution. Common indications for open PNS are shown in Table 17-1.

Table 17-1 Indications for Open (Surgical) PNS Implant Using the FDA-Approved On-Point (Paddle) Electrode

FDA, Food and Drug Administration; PNS, Peripheral nerve stimulation.

A number of conditions amenable to PNS are as follows: occipital neuralgia;^17,18 postherpetic neuralgia;^19,20 postherniorrhaphy pain;²¹ complex regional pain syndrome (CRPS);²² cluster headache;^23–26 chronic daily headache;^18,27 coccygodynia;²⁸ fibromyalgia;²⁹ cervicogenic pain;^30,31 and migraine.³² Neurogenic pain following surgery for tarsal or carpel tunnel and postherpetic pain in a peripheral nerve distribution on the face, trunk, or limb are obvious indications for PNS. As a consequence of the foregoing indications, the contemporary unavailability of dedicated electrode designs should stimulate the engineering of nerve-specific electrode interfaces. Other potential sites for PNS are the sphenopalatine ganglion (SPG)²⁶ and other autonomic nervous system targets.

As is customary in every prospective case of SCS, it is essential to obtain a psychological evaluation for all potential PNS patients. This has been summarized by Doleys.³³

Although a trial of neurostimulation always precedes implantation of an SCS, in the case of open PNS the success and stability of this technique in most cases does not warrant the risk of infection from having an externalized connection to a pulse generator for 48 to 72 hours. In addition, the high success rate of the modality precludes this initial step. This approach does not apply to percutaneous applications, in which case a trial is always mandated.

Contraindications

PNS is not associated with many contraindications other than the aspects that apply to all surgeries. Patients with bleeding diatheses or those in whom the discontinuation of anticoagulants is contraindicated are obviously excluded from PNS. Active infection, particularly in cases in which the possibility of bacteremia is high, and patients whose medical condition or malignancy may require serial magnetic resonance imaging (MRI) studies would preclude PNS at the present time.

Neuroanatomy

The axon is the functional unit of a peripheral nerve. Both afferent and efferent axons with their Schwann cells are enclosed in a delicate layer of endoneurial tissue (endoneurium). This is connective tissue that allows the free diffusion of fluids to and from neural structures. Each bundle of axons is enclosed by the perineurium. Cell bodies in the dorsal root ganglion are the source of an axon with a long branch that extends to its peripheral functional source and a shorter branch that passes from its cell body to the spinal cord. Sensory axons are unipolar and transmit sensory information from receptors in the periphery to second-order neurons in the spinal cord. On the other hand, motor neurons arise from the cell bodies in the ventral horn of the spinal cord and in contrast are multipolar with many dendrites. In addition, an axon carries impulses peripherally to activate their specific effector organs. Both dendrites and cell bodies of these neurons are highly specialized to integrate postsynaptic currents that modulate effector organs.

Myelinated nerve fibers have many concentric laminae that form from a single Schwann cell. The nodes of Ranvier are interruptions in the myelin sheath where the inward currents during depolarization are regenerated. An axon of a sensory neuron varies in diameter from as little as 2 µm to 11.75 µm.^34,35 To facilitate regional distribution and therefore sensory coverage, nerve fibers divide into many branches, thereby allowing the innervation of a significant tissue mass by a single neuron. Clinically this results in referred pain that may originate in a single neuron being transmitted by branches to other tissues in the same region. The axon reflex is another mechanism that allows pain to be felt in undisturbed tissue. In this case antidromic transmission passes to other adjacent tissue, causing an expansion of the painful area. Table 17-2 lists the diameters of nerve fibers and their conduction velocities and function. The fascicular anatomy within nerve trunks is shown in Fig. 17-1. Figs. 17-1 and 17-2 show nerve fibers grouped within a thin laminated sheet (epineurium) that covers the axons.

Fig. 17-1 Plexiform pattern of fascicular anatomy in a peripheral nerve. The dots demonstrate the expanding distribution of nerve fibers with distal projection.

Fig. 17-2 A, Transverse section of median nerve at the elbow. B, Groups of fasciculi are shown as circles. Letters AMPL reflect orientation. The letters within each fascicle are abbreviations of the distal motor and sensory nerves in the arm and forearm.

A collection of nerve fibers (axon bundles) are known as fascicles. Each fascicle containing many axons is encased by a connective tissue layer and perineurium. The entire nerve is contained within a loose outer covering, the epineurium. Although fascicles vary in size from 0.04 to 4 mm, the majority are found between 0.04 and 2 mm in diameter. As nerves proceed distally, their fascicles begin to divide into smaller and smaller units and become more numerous. In addition, this organization takes on a topographically discrete nature, particularly in mixed (motor and sensory) nerves, and is responsible for providing an intimate view of the fascicular architecture.^36–39 For example, in the ulnar nerve behind the medial epicondyle many nerve fibers are grouped into a single fascicle. A similar arrangement is found in the radial nerve in the spinal groove, the axillary nerve behind the humerus, and the common peroneal nerve in the lower thigh.

The histology of nerve fibers has considerable bearing on the ability to selectively stimulate the sensory or motor nerve fibers. The cross sectional area of a nerve trunk is comprised of 25% to 75% epineurial tissue, the highest amount being in the sciatic nerve in the gluteal region and the lowest in the ulnar nerve at the medial epicondyle. This characteristic influences the effect of neurostimulation. The greater the thickness (higher impedance), the greater is the attenuation of the electric field. In a similar manner, this effects the diffusion of local anesthetics and therefore the amount necessary to achieve their mechanism of action at the axon.