Key points

Introduction

Chronic neuropathic pain syndromes are frequently very difficult to treat. Various surgical, medical, and physical therapy modalities have been used to relieve such pain. One of the surgical options is direct electrical stimulation of the affected nerve by placing a stimulating electrode over the nerve or under the skin in the area of pain. Peripheral nerve stimulation (PNS) or peripheral nerve/field stimulation (PNFS), as such subcutaneous stimulation has been called in the literature, has been used for the treatment of chronic neuropathic pain for many years. The practice of using electrical stimulation for pain control has ancient roots. In the modern era, Wall and Sweet first demonstrated the use of peripheral electrical stimulation for the abolition of pain. In later years, better understanding of the physiology and anatomy of pain and pain pathways allowed for the development of multiple therapeutic options. The improvement in the tools, techniques, and paradigms of neuromodulation in recent years has resulted in a resurgence of interest in this surgical modality. PNS remains an attractive option because of its minimally invasive nature and an ability to provide focal neuromodulation. PNFS is a surgical intervention whereby procedural pain is minimal, and the area of stimulation and area of pain converge without the need for any complex programming. It provides an excellent modality for the treatment of various neuropathic and musculoskeletal and, at times, intractable visceral pain conditions. It may be used to complement other electrical neuromodulation procedures such as spinal cord stimulation (SCS) whereby a hybrid of PNFS and SCS can be used. It may also be used in place of other neuromodulation procedures such as SCS when the pain is focal or predominantly truncal or axial. Although the mechanisms of action of PNFS are not clear, it is thought to have a somewhat peripheral action, similar to that of SCS, based on the gate-control theory of pain. In addition, it probably works by a more central neuromodulation of medial pain pathways or by inhibiting the central nociceptive processing of painful stimuli.

Despite its proven efficacy in multiple indications, PNS/PNFS is still considered novel or experimental. However, this is far from the truth. Although a resurgence of this technique has been witnessed in the last few years, the use of electroanalgesia is many decades old. When in 1967 Wall and Sweet tried to find a new approach to suppress neuropathic pain, they inserted an electrode first into their own infraorbital foramina and then implanted devices in the extremities of 8 patients. The stimulation resulted in temporary pain suppression lasting half an hour after a stimulation period of 2 minutes. In a later larger series of 69 patients studied by Sweet, 17 had permanent relief and 13 had temporary but sustained relief. In the subsequent 5 decades, multiple reports have been published expanding the indications, refining the techniques, and consistently showing increased efficacy of this modality.

In recent years, the focus of stimulation has moved from identifying individual nerves and stimulating them directly to placing an electrode under the skin in the area of pain for certain indications. In addition, a discussion has started on whether to name the technique subcutaneous field stimulation, or continue with the term peripheral nerve stimulation. PNFS seems an acceptable intermediate option.

Introduction

Chronic neuropathic pain syndromes are frequently very difficult to treat. Various surgical, medical, and physical therapy modalities have been used to relieve such pain. One of the surgical options is direct electrical stimulation of the affected nerve by placing a stimulating electrode over the nerve or under the skin in the area of pain. Peripheral nerve stimulation (PNS) or peripheral nerve/field stimulation (PNFS), as such subcutaneous stimulation has been called in the literature, has been used for the treatment of chronic neuropathic pain for many years. The practice of using electrical stimulation for pain control has ancient roots. In the modern era, Wall and Sweet first demonstrated the use of peripheral electrical stimulation for the abolition of pain. In later years, better understanding of the physiology and anatomy of pain and pain pathways allowed for the development of multiple therapeutic options. The improvement in the tools, techniques, and paradigms of neuromodulation in recent years has resulted in a resurgence of interest in this surgical modality. PNS remains an attractive option because of its minimally invasive nature and an ability to provide focal neuromodulation. PNFS is a surgical intervention whereby procedural pain is minimal, and the area of stimulation and area of pain converge without the need for any complex programming. It provides an excellent modality for the treatment of various neuropathic and musculoskeletal and, at times, intractable visceral pain conditions. It may be used to complement other electrical neuromodulation procedures such as spinal cord stimulation (SCS) whereby a hybrid of PNFS and SCS can be used. It may also be used in place of other neuromodulation procedures such as SCS when the pain is focal or predominantly truncal or axial. Although the mechanisms of action of PNFS are not clear, it is thought to have a somewhat peripheral action, similar to that of SCS, based on the gate-control theory of pain. In addition, it probably works by a more central neuromodulation of medial pain pathways or by inhibiting the central nociceptive processing of painful stimuli.

Despite its proven efficacy in multiple indications, PNS/PNFS is still considered novel or experimental. However, this is far from the truth. Although a resurgence of this technique has been witnessed in the last few years, the use of electroanalgesia is many decades old. When in 1967 Wall and Sweet tried to find a new approach to suppress neuropathic pain, they inserted an electrode first into their own infraorbital foramina and then implanted devices in the extremities of 8 patients. The stimulation resulted in temporary pain suppression lasting half an hour after a stimulation period of 2 minutes. In a later larger series of 69 patients studied by Sweet, 17 had permanent relief and 13 had temporary but sustained relief. In the subsequent 5 decades, multiple reports have been published expanding the indications, refining the techniques, and consistently showing increased efficacy of this modality.

In recent years, the focus of stimulation has moved from identifying individual nerves and stimulating them directly to placing an electrode under the skin in the area of pain for certain indications. In addition, a discussion has started on whether to name the technique subcutaneous field stimulation, or continue with the term peripheral nerve stimulation. PNFS seems an acceptable intermediate option.

Indications and patient selection

The common indications of PNFS can be classified based on the pain type and pain location. However, certain common factors underlie all of these indications. Whatever the type or location of pain may be, the pain has to be chronic, severe, negatively affecting the patient’s functionality, and refractory to the usual medical treatments, including opioid and nonopioid medications, physical therapy, trigger-point injections, injections of botulinum toxin, application of transcutaneous electrical nerve stimulation (TENS), and somatic and sympathetic nerve blocks.

There are 4 main pillars of patient selection for PNFS that are almost universally accepted.

• 1.
  

  Intractable pain. As already described, the pain has to be treatment-resistant and disabling. It is important to make sure that the patient has tried all other noninvasive methods of pain control, and has either failed or had only transient or partial benefit.

  
  
• 2.
  

  Distribution of pain. Extent of the area of pain is an important factor in deciding on which neuromodulation approach will work better. For PNS, the pain must be in the distribution of a single nerve, whereas for PNFS it is more important for the pain to be in an area that can be covered by the commercially available length of electrodes. Larger areas of pain can be better treated by other neuromodulation modalities such as SCS, targeted brain stimulation (such as deep brain stimulation or motor cortex stimulation), or intrathecal drug-delivery systems.

  
  
• 3.
  

  Pain psychology testing. This factor is borrowed from the standard approach when using neuromodulation procedures such as SCS. Psychological characteristics play an important role in shaping responses to any neuromodulation approach in chronic pain including PNS, PNFS, and SCS, in addition to a variety of other pain treatments. In SCS, the influence of psychological evaluation on outcomes has been noted by various groups. The same holds true for PNFS. All patients must undergo pain psychology testing and should be treated adequately for any underlying or unresolved anxiety, depression, or other psychiatric disorders.

  
  
• 4.
  

  Successful trial. Again this is similar to the SCS procedure. All patients need to undergo an externalized trial whereby the electrodes are placed percutaneously and are connected to an external stimulation generator. It is done exclusively on an outpatient basis. The length of the trial varies from 2 to 10 days. In most patients the response is seen within the first 48 hours. Some patients need outpatient reprogramming during the trial. A cutoff of 50% improvement in pain and concordant improvement in quality of life is generally accepted as a successful trial.

In addition to these criteria, some minor factors play a role in patient selection. These factors are PNFS specific and vary according to centers, but are generally agreed on by most implanters.

• 1.
  

  Sensory loss. Partial or complete sensory loss in the area of pain increases the chances of a failed trial, especially when performing field stimulation. For activation of the gait-control mechanism of pain suppression, at least partially functioning vibrotactile inflow is necessary. Even in patients with postlaminectomy syndromes with truncal or axial pain, electrodes placed very close to the scar of previous spinal surgery tend to fail to give as much benefit as electrodes placed farther away from the scar.

  
  
• 2.
  

  Allodynia. Severe allodynia changes the strategy of implantation. An electrode underlying a patch of allodynia can sometimes aggravate the pain. It is better to bracket a patch of allodynia with electrodes placed on either side of it rather than directly in it while performing field stimulation.

  
  
• 3.
  

  Predictive value of TENS. Failure of TENS does not have any negative predictive value. If a patient fails to improve with TENS, it should not stand in the way of trying PNFS for pain control. On the other hand, if TENS provides improvement in pain, the location of the effective TENS electrodes can help guide the placement of PNFS electrodes. However, by no means should the use of TENS be considered as a trial for PNFS.

  
  
• 4.
  

  Diagnostic nerve blocks. Apart from patients with injury to specific nerves in whom a nerve block can delineate the extent of area covered by that specific nerve, the usefulness of nerve blocks as a predictive tool is doubtful. Most notably, in patients with cephalgias and occipital neuralgia (ON), nerve blocks have no predictive value.

As in any surgical procedure, PNFS would be contraindicated in patients with bleeding disorders and those on anticoagulation that cannot be withheld in the perioperative period. Patients with severe immunosuppression or active infection are not candidates for any implantable device including PNFS. Patients with major cognitive impairment or untreated psychiatric conditions are not candidates for PNFS. Some centers will not offer neuromodulation for pain in patients who have ongoing litigation related to the cause of their pain. Patients who need routine magnetic resonance imaging (MRI) in conditions such as multiple sclerosis or metastatic disease have not been candidates for PNFS, as to date the implants have not been MRI compatible. Even with the recent introduction of MRI-compatible (conditionally safe) devices, MRI safety is only guaranteed for SCS applications and does not cover the use of PNFS.

Indications for PNFS have dramatically expanded in recent years. Ability to provide focused neuromodulation with minimal intervention has led to the more aggressive use of PNFS in various chronic pain conditions. Initially, neuropathic pain disorders along with complex regional pain syndrome (CRPS) were considered as some of the main indications for PNFS ; this was the followed by various cephalalgias and complex craniofacial pain. Axial and appendicular musculoskeletal pain then became an indication for PNFS. Recently, intractable visceral pain has also been treated by PNFS.

Indications of PNFS can be broadly classified as follows:

• 1.
  

  Neuropathic pain disorders. These pain disorders develop secondary to trauma, inflammation, neuropathy, or postintervention changes in a nerve. Sometimes, as in many cases of ON, this pain develops without obvious reasons (idiopathic). The specific neuropathic pain disorders that respond to PNFS are the following:

  
  
  
  
  • a.
    

    Post-herpetic neuralgias (PHN). PHN patients have been treated by electrical neurostimulation from as early as 1974. PNFS has been used with varying degrees of success for treating truncal and ophthalmic/trigeminal PHN.

    
    
  • b.
    

    Posttraumatic neuralgias. Pain related to the nerve trauma resulting from either injury or intervention causing neuropathic pain also seems to reliably respond to PNFS.

    
    
  • c.
    

    Complex craniofacial neuralgias. These neuralgias include trigeminal neuropathic pain, atypical face pain, supraorbital, infraorbital, or mandibular neuralgias, or a combination of these. These neuralgias may be secondary to repeated sinus or dental surgeries, or following interventions for trigeminal neuralgia, trauma, or facial fractures. Most of these neuralgias respond to very well to PNFS.

    
    
  • d.
    

    Occipital neuralgia. One of the most common neuralgias, this has been successfully treated by PNS/PNFS using a variety of leads and approaches.

    
    
  • e.
    

    Inguinal neuralgias. Ilioinguinal and genitofemoral neuralgias are an established indication for the use of PNFS. Most commonly, ilioinguinal neuralgia is seen after hernia repair, whereas genitofemoral neuralgias are generally a result of retroperitoneal or uterine and ovarian surgeries; both may be successfully treated with PNFS.

    
    
  • f.
    

    Other neuralgias. These neuralgias include suprascapular neuralgia, meralgia paresthetica, neuropathic pain in limbs following trauma, or nerve entrapment decompression surgeries. In the authors’ experience, all of these may be successfully treated with PNFS in well-selected patients.

  
  
  
  
• 2.
  

  CRPS. CRPS can be treated by various neuromodulation modalities such as SCS, intrathecal drug delivery, or PNS/PNFS. Well-localized CRPS secondary to a nerve injury (type II) can be treated by PNFS, with excellent results.

  
  
• 3.
  

  Cephalgias. A variety of headache syndromes can be successfully treated by PNFS :

  
  
  
  
  • a.
    

    Classic migraine, transformed migraine

    
    
  • b.
    

    Hemicrania continua

    
    
  • c.
    

    Occipital headaches

    
    
  • d.
    

    Cervicogenic headaches

    
    
  • e.
    

    Cluster headaches

    
    
  • f.
    

    Chronic daily headaches

  
  

A recent review summarized all of these indications in a systematic fashion.

• 4.
  

  Axial pain syndromes. Axial pain in the neck and middle and low back is difficult to control with SCS. PNFS alone or in combination with SCS has shown promise in treating this type of pain. Isolated PNFS has shown improvement in axial low back and neck pain in various retrospective studies. A recently published prospective, randomized, controlled, crossover study showed safety and effectiveness of PNFS as an aid in the management of chronic, localized back pain. The study design consisted of 2 phases. During phase I, patients were divided into 4 stimulation groups (minimal, subthreshold, low frequency, and standard stimulation). Responders, classified as those who had a 50% reduction in pain during any of the 3 active stimulation groups, proceeded with phase II, which began with the implantation of the permanent system and lasted 52 weeks. The primary end point was the reduction in pain, assessed by the visual analog scale (VAS). During phase I, there were significant differences in mean VAS scores between minimal stimulation and subthreshold stimulation ( P = .003), low-frequency stimulation ( P <.001), and standard stimulation ( P <.001). Twenty-four patients were classified as responders to the therapy, and 23 patients out of 44 trailed underwent permanent implant. Significant differences in VAS scores were observed between baseline and all follow-up visits during phase II ( P <.001). In addition, the combination of PNFS and SCS has been used in several studies.

  
  
• 5.
  

  Musculoskeletal pain. This pain is one of the emerging indications for PNFS. PNFS applied directly to an affected knee was found to be extremely effective for the relief of knee pain. In the authors’ experience, this also holds true for shoulder and elbow pain.

  
  
• 6.
  

  Other emerging indications. Fibromyalgia is a condition marked by widespread chronic pain, accompanied by a variety of other symptoms, including sleep and fatigue disorders, headaches, disorders of the autonomic nervous system, and cognitive and psychiatric symptoms. Recent literature shows that PNFS is effective in treating fibromyalgia.