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Busch, C.;  Smith, O.;  Weaver, T.;  Vallabh, J.;  Abd-Elsayed, A. Lower Extremity Peripheral Nerve Stimulation. Encyclopedia. Available online: https://encyclopedia.pub/entry/25577 (accessed on 18 June 2024).
Busch C,  Smith O,  Weaver T,  Vallabh J,  Abd-Elsayed A. Lower Extremity Peripheral Nerve Stimulation. Encyclopedia. Available at: https://encyclopedia.pub/entry/25577. Accessed June 18, 2024.
Busch, Clayton, Olivia Smith, Tristan Weaver, Jayesh Vallabh, Alaa Abd-Elsayed. "Lower Extremity Peripheral Nerve Stimulation" Encyclopedia, https://encyclopedia.pub/entry/25577 (accessed June 18, 2024).
Busch, C.,  Smith, O.,  Weaver, T.,  Vallabh, J., & Abd-Elsayed, A. (2022, July 27). Lower Extremity Peripheral Nerve Stimulation. In Encyclopedia. https://encyclopedia.pub/entry/25577
Busch, Clayton, et al. "Lower Extremity Peripheral Nerve Stimulation." Encyclopedia. Web. 27 July, 2022.
Lower Extremity Peripheral Nerve Stimulation
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Neuropathic pain is defined as “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage” by the International Association for the Study of Pain (IASP). Peripheral nerve stimulation (PNS) is rapidly increasing in use. This interventional pain treatment modality involves modulating peripheral nerves for a variety of chronic pain conditions. 

lower extremity pain PNS neuropathy

1. Etiology and Epidemiology of Lower Extremity Pain

The lower extremity is defined as the anatomy inferior to the iliac crests excluding the pelvis and perineal structures as well as the low back. Neuropathic pain is particularly common in the world of chronic pain, and this is no different for the lower extremity. The etiologies of lower extremity pain targeted by PNS may result from nerve damage associated with trauma, iatrogenic injury, nerve compression, and amputation (as seen in neuropathic pain); it may also be secondary nociceptive processes associated with tissue damage such as acute post-operative pain [1][2][3][4][5][6][7]. Exciting preclinical work continues to uncover the basic sciences of neuropathic pain [8][9][10]. The focus of this clinical review, however, will emphasize the application of an emerging technology specifically in the context of lower extremity pain.
According to the CDC, lower extremity pain is the second most common cause of pain, affecting nearly one-third of all patients [11]. Unfortunately, when left untreated, patients with lower extremity pain are at risk for musculoskeletal impairment, diminished quality of life, and increasing health care costs. Notably, these findings disproportionately affect individuals coming from lower socioeconomic backgrounds and adults older than 65 [11]. Thus, the development of effective treatment modalities for lower extremity pain is also a matter of healthcare equality.

2. Ilioinguinal Nerve

The ilioinguinal nerve originates from the spinal nerve of L1. It supplies sensory input to the inguinal region of the lower extremity [12]. Ilioinguinal neuropathy classically occurs as sequelae after lower abdominal surgery (inguinal hernia repair, appendectomy, or hysterectomy). Treatment starts with conservative management. If conservative management fails, then patients may elect for selective nerve blocks, radiofrequency therapies, or surgical excision. In a case series of three patients who underwent PNS therapy for ilioinguinal neuralgia refractory to pharmacological and surgical interventions, pain levels were reduced by greater than 50%. All patients also reported decreases in pain medicine requirements with PNS and two were able to resume working [13]. Evidence for PNS in the ilioinguinal nerve is summarized in Table 1.
Table 1. Individual nerves of the lower extremity described by level of evidence as well as a summary of findings.
Nerve Evidence Level Summary of Evidence
Ilioinguinal nerve Level V
Four patients decreased pain scores by 5–9 points, decreased pain medicine use, and improved functional ability [1][14].
Genitofemoral nerve Level V
Four patients reported 70–90% pain improvement, decreased opioid use, and improved functional ability [1][2][15].
Lateral femoral cutaneous nerve Level V
Total of 80–100% improvement in symptoms [1][16].
Femoral and sciatic nerves Level II
In an RCT PNS in PLP provided significantly improved benefit over placebo and reduced opioid use by 71% [17].
Sciatic and femoral nerve PNS may provide relief for acute post-operative pain [5][6][12][18].
Obturator nerve Level V
One case report with robust response. Prior to PNS the patient consumed 255mg of morphine daily but was able to discontinue analgesics after PNS [13].
Saphenous, infrapatellar saphenous, and genicular nerves Level V
Total of 90–100% improvement in knee pain in 2 case reports [1][19][20].
Decrease in VAS from 7.7 to 2.7 in another case report [1].
Peroneal nerve Level V
Total of 60–80% pain relief or more with PNS [1][21][22].
75% improvement in activity [1].
Posterior Tibial nerve Level V
Most patients report at least 50% improvement in pain after 6 sessions of PNS [23].
Sural nerve Level V
Total of 50–75% improvement in pain at 6 months [1][24].
60% improvement in activity [1].

3. Genitofemoral Nerve

The genitofemoral nerve originates from spinal nerves L1–L2 [12]. It provides sensory input to the groin and inner thigh. Discomfort with this neuropathy was described in terms of paresthesia, burning pain, and hypoalgesia [19]. The pathology of the condition may be secondary to surgical sequelae, trauma, vasculitis, or infectious processes [2]. Genitofemoral pain treated with PNS has level V evidence as detailed in Table 1. Reported evidence demonstrated a 70–90% reduction in pain. Additionally, patients have reported improved functional ability and decreased opioid usage [1][2][20].

4. Lateral Femoral Cutaneous Nerve

The lateral femoral cutaneous originates from spinal nerves L2–L3 and provides sensation to the anterior lateral thigh [21]. Mononeuropathy of the lateral femoral cutaneous nerve is known as meralgia paresthetica. The superficial course of the nerve exposes it to multiple neuropathic etiologies such as obesity, use of tight clothing or belts, and iatrogenic causes such as pelvic surgery [3]. The pain was described as a numb or burning sensation down the lateral thigh that worsens with prolonged standing [3]. For those who fail conservative measures such as weight loss, neuropathic pharmacotherapy, and steroid injections, PNS is used as an effective therapy. The strength of evidence is summarized in Table 1, but for now, evidence is limited to case studies. Specific examples include a case described by Dalal and colleagues where a meralgia paresthetica patient failed multiple therapies prior to PNS including narcotics and steroid injections [22]. A SPRINT PNS lead was placed resulting in an 80% improvement of symptoms at 60 days [22]. Specifically, there was a complete resolution of pain symptoms with improved sleep, decreased somnolence, and improved functional ability. The device was explanted at 60 days. Re-evaluation one year after device explanation still demonstrated complete resolution of symptoms [16]. Similar results were achieved with the Bioness Stimrouter system [1].

5. Femoral and Sciatic Nerves

The femoral nerve originates from spinal nerves L2–L4. The anterior divisions supply sensation to the anteromedial thigh through the anterior cutaneous branches. The posterior divisions of the femoral nerve provide sensation to the medial lower legs and feet through the saphenous nerve and infrapatellar branches of the knee. The sciatic nerve originates from spinal nerves L4–S3. The tibial and peroneal nerves provide sensation to the lower legs and feet [25]. Thus far, much of the literature assessing the effectiveness of PNS for pain in the distribution of the femoral and sciatic nerves was performed in the context of phantom limb pain (PLP). Current treatment for PLP is similar to other neuropathic disorders [4]; however, there has been recent exploration with percutaneous PNS. In a case series by Ruack and colleagues, PLP patients treated with PNS implanted on the femoral and sciatic nerves improved pain scores by 81%. They also had a reduced Pain Disability Index and reported improved quality of life [26]. Another case study observed veterans with PLP who underwent PNS of the sciatic and femoral nerves. The intervention yielded a 50% reduction in pain symptoms. Their relief was again reported at long-term follow-up [27]. Finally, in a larger randomized, double-blinded, placebo-controlled trial, Gilmore and colleagues studied 28 participants with PLP. One group received femoral and sciatic nerve PNS devices and the other received placebo PNS. Therapy for each group was provided for 4 weeks. It was found that patients who received PNS had a significantly greater reduction in pain when compared to the placebo group. Additionally, there was a 71% reduction in the use of opioids while using PNS [17].
PNS of the femoral and sciatic nerves were also studied for use in acute post-operative pain. Specifically, Ilfeld and colleagues studied pain in the foot and knee while identifying an FDA-approved device for this indication [5]. A randomized, double-masked proof of concept trial compared patients undergoing hallux valgus osteotomy surgery that were randomized into two groups: sciatic nerve PNS or sham therapy. After five minutes of stimulation, the PNS group had significantly better analgesia than the sham therapy cohort. PNS was also associated with reduced opioid utilization [18]. Femoral nerve PNS may also yield results in total knee arthroplasty (TKA) and anterior cruciate ligament (ACL) reconstruction [6][12]Table 1 summarizes the findings for PNS in these nerves for both PLP and acute post-operative pain.

6. Obturator Nerve

The obturator nerve originates from spinal nerves L2–L4. It functions primarily as a motor nerve, but it does provide a small field of sensory innervation to the medial thigh [25]. One case report (highlighted in Table 1), was identified with a young female suffering from chronic pelvic pain with pubic symphysis dysfunction. She had failed multiple prior treatments for her pain including failed ilioinguinal and iliohypogastric nerve blocks. An obturator nerve block was eventually successful in reducing her symptoms, and she was trialed as a candidate for PNS therapy. Prior to PNS, her pain was poorly controlled on a multimodal pharmacologic regimen inclusive of opioids. PNS leads were then placed laparoscopically. Six months post-implantation the patient was weaned off chronic opioids and at 23 months she described herself as pain-free no longer taking any analgesic medicines. A marked improvement in pain and activity was reported, and the patient was also able to stop taking her antidepressant medication [13].

7. Saphenous, Infrapatellar Saphenous, and Genicular Nerves

The saphenous nerve, a branch from the femoral, is one of the largest cutaneous branches [28]. The saphenous nerve courses along the medial leg with numerous terminal branches providing sensory input to the medial leg and the knee. Branches to the knee include the infrapatellar saphenous (IPS) nerve, the prepatellar nerve, and the infrapatellar genicular nerve. Pathology to any of these nerves can result in anterior knee pain. Literature on PNS for these nerves is limited to case studies. In one case study, a 58-year-old male with a history of chronic pain related to osteoarthritis received saphenous, IPS, and superior lateral genicular nerve received PNS to achieve pain relief in the lateral knee and reported almost 100% pain relief and improved function after PNS [19]. In another, a 73-year-old female with chronic knee pain refractory to medical management was assessed. The saphenous and superior lateral genicular nerves were targeted with PNS and improvements in pain scores and function were seen three days after the procedure. A 90% improvement in pain was reported after 2 months [20]. A case series reviewing PNS in three saphenous nerve patients reported a 5-point decrease in visual analog scale (VAS) reporting [1]. The findings are summarized in Table 1.

8. Peroneal Nerve

The common peroneal nerve is a branch of the sciatic nerve and provides sensation to the anterior and lateral parts of the leg and foot [25]. The nerve then branches to the superficial peroneal (SPN), which can be injured after ankle fractures and surgeries due to its superficial nature [29]. This superficial nature also makes it a desirable target for PNS therapy. Again, evidence is limited to case studies. In one case report, a patient with right lateral leg and dorsal foot pain underwent PNS, and two weeks after implantation their pain improved by >80% [21]. In another report, two patients were described that underwent peroneal nerve PNS. During the 3-to-7-day trial, one patient experienced 60% and the other experienced 70% pain relief. Both patients underwent permanent implantation of the stimulator and had sustained relief of symptoms one month and beyond [22]. Oswald and colleagues reported peroneal neuropathy improvements from VAS of 9.0 to 2.3 with an associated 75% improvement in activity [1]Table 1 represents key highlights on PNS for the peroneal nerve.

9. Posterior Tibial Nerve

Posterior tibial neuralgia, also known as tarsal tunnel syndrome, is a compression neuropathy that can result in significant foot pain when the tibial nerve and its branches are compressed by the flexor retinaculum [29]. Two studies describe improvement in this condition with PNS. First, in an open-label study, PNS significantly reduced pain in volunteers. Most patients reported a 50% improvement after the first of six sessions and a 99.2% reduction after the last sessions [23]. Another case report described a patient suffering from both posterior tibial nerve neuropathy and sural neuropathy reviewed in greater detail in the sural nerve discussion [24]. The above findings are summarized in Table 1.
Stimulation of the posterior tibial nerve is indicated in an overactive bladder [30]. While not the primary focus of this paper, stimulation of the posterior tibial nerve for overactive bladder is briefly described here for completeness’ sake. The tibial nerve is a branch of the sciatic nerve originating from L4–S3. This nerve is targeted in overactive bladder syndrome as a third-line treatment option [30][31]. Percutaneous stimulation of the posterior tibial nerve has shown efficacy when used alone to treat an overactive bladder. There is further improvement still when combined with anti-muscarinic therapy.

10. Sural Nerve

The sural nerve is formed by the branches of the tibial and common peroneal nerves [25]. The sural nerve provides sensation to the lateral posterior corner of the leg, lateral foot, and fifth toe. Sural neuralgias, similar to posterior neuralgia, have limited data on PNS. In one case report a 60-year-old man with a history of sural and posterior tibial neuropathy secondary to a motorcycle accident presented with significant pain with mild relief on high-dose opiate therapy. The patient reported a 75% improvement in pain at three months and a 50% improvement at 6 months. He also enjoyed improved mobility [24]. These findings were similar to the 75% pain improvement noted by Oswald when SCS was utilized peripherally for sural neuralgia [1]Table 1 summarizes these data for PNS in sural nerve pain. Of note, there is currently no gold-standard treatment for sural neuralgia. Treatment should start, as always, with conservative management including massage, rest, and pharmacologic interventions. When these conservative measures fail, PNS may be a suitable option for patients.

References

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  27. Cohen, S.P.; Gilmore, C.A.; Rauck, R.L.; Lester, D.D.; Trainer, R.J.; Phan, T.; Kapural, L.; North, J.M.; Crosby, N.D.; Boggs, J.W. Percutaneous Peripheral Nerve Stimulation for the Treatment of Chronic Pain Following Amputation. Mil. Med. 2019, 184, e267–e274.
  28. Hosahalli, G.; Sierakowski, A.; Venkatramani, H.; Sabapathy, S.R. Entrapment Neuropathy of the Infrapatellar Branch of the Saphenous Nerve: Treated by Partial Division of Sartorius. Indian J. Orthop. 2017, 51, 474–476.
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  30. Bhide, A.A.; Tailor, V.; Fernando, R.; Khullar, V.; Digesu, G.A. Posterior tibial nerve stimulation for overactive bladder-techniques and efficacy. Int. Urogynecol. J. 2020, 31, 865–870.
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