Knee Pain and PNS
Knee pain: Definition, Mechanisms, and Clinical Spectrum
Knee pain is a common and complex clinical condition arising from the interaction of nociceptive, inflammatory, biomechanical, and neuropathic processes. Osteoarthritis (OA) remains the leading etiology worldwide and is driven by progressive cartilage loss, synovial inflammation, subchondral bone remodeling, and mechanical overload. These degenerative changes generate persistent nociceptive input and functional decline, affecting mobility, stair climbing, and weight-bearing capacity (Amirianfar et al., 2023). As the population ages and obesity rates rise, the prevalence of OA-related knee pain continues to increase, adding to the global burden of disability.
Post-surgical knee pain constitutes another major category, particularly following total knee arthroplasty (TKA). Although TKA is effective for most patients, 16–20% develop chronic postoperative pain that persists beyond the normal 3–6-month healing window (Früh et al., 2023). These patients often describe burning, stabbing, or electric sensations, reflecting underlying neuropathic mechanisms such as peripheral nerve irritation, neuroma formation, scar entrapment, or maladaptive central sensitization. Chronic post-TKA pain is further associated with decreased function, reduced walking tolerance, impaired sleep, and psychological distress (Vu et al., 2024).
Neuropathic components are increasingly recognized across both OA and post-surgical phenotypes. Features such as allodynia, paresthesia, and exaggerated pain responses indicate sensitization of Aδ and C fibers, as well as dorsal horn hyperexcitability (Zhu et al., 2023). These mechanisms often explain why many patients respond poorly to conventional analgesics, intra-articular injections, or radiofrequency ablation, which primarily target nociceptive pathways. Indeed, destructive procedures such as genicular nerve RFA frequently provide only temporary benefit, leaving many patients with refractory symptoms (Goree et al., 2024).
The clinical spectrum of knee pain therefore spans mechanical degeneration, inflammatory flares, postoperative neuropathic states, and mixed pain presentations. This heterogeneity underscores the need for individualized treatment strategies that address both peripheral and central contributors. As limitations of conservative and ablative therapies become more apparent, interest has grown in neuromodulatory approaches—particularly peripheral nerve stimulation—as a means to modulate aberrant pain signaling and improve functional outcomes in refractory knee pain populations (Hasoon et al., 2025).
Why Periphereal Nerve Stimulation for Knee pain
Understanding Knee Pain: Causes and Treatment Options
Peripheral nerve stimulation is increasingly recognized as a viable option for patients with chronic knee pain who have failed to achieve meaningful relief from conservative and minimally invasive therapies. Chronic knee pain often persists despite physical therapy, NSAIDs, steroid injections, or genicular radiofrequency ablation, and a substantial proportion of patients continue to suffer after total knee arthroplasty, with 16–20 percent experiencing long-term postoperative pain (Früh et al., 2023). These limitations underscore the need for interventions that can modulate pain without destroying neural tissue or requiring extensive surgery.
PNS offers a distinct advantage by targeting the sensory nerves responsible for transmitting knee pain, including branches of the saphenous, femoral, sciatic, and genicular nerves. By applying electrical stimulation to large-diameter afferent fibers, PNS reduces nociceptive transmission and dampens peripheral and central sensitization, a mechanism widely supported in neuromodulation research (Amirianfar et al., 2023). This selective neuromodulation allows for pain relief without motor impairment and avoids the risks associated with neurodestructive procedures.
Clinical evidence supports the role of PNS in both postoperative and nonoperative knee pain. A randomized controlled trial demonstrated that a 60-day percutaneous PNS protocol resulted in significantly higher responder rates and improved walking distance compared with placebo in patients with persistent post-TKA pain (Goree et al., 2024). Real-world data similarly show high responder rates, with 94 percent of patients achieving at least 50 percent pain reduction using short-term PNS systems (Hasoon et al., 2025). Additional case series report improvements in pain, sleep quality, and opioid reduction in patients undergoing saphenous or femoral nerve PNS (Zhu et al., 2023).
PNS is also minimally invasive and reversible, making it suitable for patients who are not candidates for further surgery or who prefer a nondestructive, nerve-preserving technique. Its ability to address both nociceptive and neuropathic pain components positions PNS as an attractive option for the heterogeneous population of individuals with refractory knee pain (Vu et al., 2024).
Periphereal Nerve Stimulation Procedure & Targets in Knee Pain
Peripheral nerve stimulation for knee pain involves a minimally invasive, image-guided technique designed to selectively activate large-diameter sensory fibers that modulate pathologic nociceptive signaling. The procedure is typically performed under ultrasound guidance to ensure precise visualization of peripheral nerves, minimize the risk of vascular or neural injury, and optimize lead positioning. After sterile preparation and local anesthesia, a fine-wire open-coil lead is inserted through an introducer needle and advanced to a position approximately one to three centimeters from the intended nerve. This distance allows recruitment of Aβ fibers while reducing the likelihood of motor activation or discomfort, a principle consistently emphasized across clinical reports (Zhu et al., 2023). Correct placement is verified when stimulation produces comfortable paresthesia or partial analgesia in the painful region without eliciting muscle contraction, confirming selective sensory engagement (Goree et al., 2024).
Multiple peripheral nerves are appropriate targets depending on the patient’s pain distribution and underlying etiology. One of the most frequently targeted nerves is the saphenous nerve, including its infrapatellar branch, which provides major sensory innervation to the anteromedial knee. Externally powered or permanent implants directed at saphenous branches have demonstrated substantial improvements in pain at rest and with motion, sleep quality, mood, and overall quality of life in chronic postoperative knee pain (Früh et al., 2023). The femoral nerve is another important target, particularly when pain radiates proximally or when suprapatellar or anterior thigh involvement is suspected. Temporary PNS of the femoral nerve has been effective in reducing pain and improving function among patients who are either candidates for arthroplasty or unwilling to undergo surgery (Zhu et al., 2023).
The sciatic nerve and its common peroneal branches may be targeted in cases of posterolateral, posterior, or diffuse knee pain. Randomized trial data confirm that combined femoral and sciatic stimulation provides significant analgesia and functional improvement in refractory post-TKA pain, demonstrating the utility of multinerve targeting in complex cases (Goree et al., 2024). Emerging evidence also supports PNS directed at genicular nerves, particularly in patients who have failed radiofrequency ablation. Case reports describe meaningful pain reduction and functional gains in patients treated with genicular PNS after exhausting conventional interventional options (Vu et al., 2024).
Overall, PNS implantation is flexible, individualized, and reversible, allowing clinicians to tailor therapy to the anatomical pain generators while avoiding destructive techniques. This adaptability makes PNS a valuable option for treating the heterogeneous and often neuropathic nature of chronic knee pain (Hasoon et al., 2025).
Clinical Outcomes & Long-Term Efficacy of PNS in Knee pain
Clinical outcomes across contemporary peripheral nerve stimulation studies consistently demonstrate that PNS offers substantial analgesia, functional improvement, and meaningful reductions in medication reliance for patients with refractory knee pain. Evidence spans randomized controlled trials, retrospective cohorts, and focused case series, capturing both postoperative and nonoperative phenotypes.
The highest level of evidence comes from a multicenter randomized, double-blind, placebo-controlled trial evaluating a 60-day percutaneous PNS protocol for persistent post-TKA pain. In this study, patients receiving active stimulation achieved significantly greater benefit, with sixty percent reporting at least fifty percent pain reduction compared with twenty-four percent in the placebo group (Goree et al., 2024). Functional gains paralleled analgesic outcomes, as demonstrated by a marked improvement in walking distance on the six minute walk test, in contrast to functional decline in the sham group. These results indicate that PNS provides efficacy exceeding placebo and improves not only pain intensity but also mobility, which is central to postoperative rehabilitation.
Real-world cohorts further reinforce these findings. A retrospective analysis of patients treated with a standardized 60-day PNS system reported that ninety-four percent achieved responder-level improvement, with an average pain reduction exceeding eighty percent among responders (Hasoon et al., 2025). Importantly, this cohort included mixed etiologies such as post-TKA pain and chronic knee pain linked to osteoarthritis, demonstrating that PNS retains effectiveness across varied diagnostic contexts. Improvements also extended to patient-reported functionality and daily activity levels.
In nonoperative knee osteoarthritis, PNS delivered through saphenous or femoral nerve targeting has demonstrated clinically meaningful pain relief. Case series have shown significant decreases in numerical pain scores, improved ambulation, and reductions in opioid consumption among patients unwilling or unable to undergo arthroplasty (Zhu et al., 2023). Externally powered implants targeting the saphenous nerve branches produced additional benefits, including improved sleep quality, mood, and health-related quality of life, highlighting multidimensional improvement beyond pain intensity alone (Früh et al., 2023).
Case-level evidence also supports PNS for highly complex postoperative presentations. Patients with combined post-TKA pain and structural complications, such as non-operable patella fractures, achieved substantial pain relief following genicular or saphenous nerve stimulation despite failure of nerve blocks, radiofrequency ablation, bracing, and multiple medications (Vu et al., 2024). This reinforces the value of PNS in patients with layered or refractory postoperative pathology.
Early long-term data suggest that improvements often persist after lead removal. Sustained benefit is hypothesized to arise from modulation of peripheral sensitization and durable central reorganization, as suggested by follow-up data in randomized and observational cohorts (Goree et al., 2024).
Overall, the totality of evidence indicates that PNS delivers robust, multidimensional, and potentially lasting improvement in chronic knee pain across diverse patient populations.
Side Effects & Safety Profile
Peripheral nerve stimulation is generally considered a safe and well-tolerated intervention for chronic knee pain, with most studies reporting low complication rates and predominantly minor, self-limited adverse events. In randomized and observational cohorts, no serious device-related complications were identified, and most side effects occurred during the lead-in or early stimulation period (Goree et al., 2024).
The most frequently reported issues include transient procedural discomfort, mild bruising, localized soreness, or temporary paresthesia near the lead insertion site. These events typically resolve without intervention. Lead migration is uncommon with modern fine-wire or externally powered systems, especially when placed under continuous ultrasound guidance. Short-term PNS systems also reduce the risk of long-term hardware complications, as leads are removed after the therapeutic window, eliminating concerns such as late erosion or chronic infection (Hasoon et al., 2025).
Infection rates remain low across clinical reports. In a large series of saphenous nerve implants, only a small number of patients required explantation due to superficial wound infection, and all cases resolved without long-term sequelae (Früh et al., 2023). Similarly, case series and postoperative applications reported no neurological injury, motor deficit, or permanent sensory impairment associated with stimulation (Zhu et al., 2023).
Overall, the safety profile of PNS is favorable compared with neurodestructive procedures such as radiofrequency ablation or with more invasive neuromodulation systems. Its reversibility, short-term lead duration, and low complication rate make PNS an attractive option for patients with refractory knee pain seeking a minimally invasive therapy (Vu et al., 2024).
What to Expect During Recovery and Follow-Up
Recovery after peripheral nerve stimulation for knee pain is typically smooth, gradual, and characterized by progressive improvement in pain, function, and mobility. Because PNS is a minimally invasive procedure performed under local anesthesia with percutaneous leads, most patients resume light daily activities immediately, with only mild soreness at the insertion site for the first one to two days. This early discomfort generally resolves without intervention and does not interfere with normal ambulation (Zhu et al., 2023).
During the active stimulation period, patients are instructed on how to use the external pulse generator and adjust stimulation intensity to achieve comfortable sensory activation without muscle contractions. This titration phase is important for optimizing analgesia and usually takes place over the first several days. Weekly or biweekly follow-up visits are common in research and clinical practice, allowing clinicians to verify lead position, review stimulation settings, assess analgesic response, and address any minor skin or dressing issues (Goree et al., 2024).
A hallmark of PNS recovery is the steady reduction in pain scores throughout the stimulation window. In randomized trials, meaningful pain reduction and functional gains often appear by weeks five to eight, with substantial improvements in walking distance and daily activity levels by the end of treatment (Goree et al., 2024). Real-world studies report similar trajectories, with most responders achieving noticeable benefit early in the course and sustaining improvement until the leads are removed at the end of the 60-day therapy (Hasoon et al., 2025).
After lead removal, patients typically continue their normal activities without restrictions. Importantly, many maintain pain relief well beyond the treatment period, a finding attributed to neuromodulatory changes that outlast peripheral stimulation. Observational data and postoperative case series report continued improvements in sleep, mood, and overall quality of life weeks to months after device removal (Früh et al., 2023, Zhu et al., 2023).
Overall, recovery and follow-up after PNS are marked by minimal downtime, low complication rates, structured monitoring, and the potential for durable improvements in pain and function. This predictable and patient-friendly recovery profile strengthens PNS as a favorable option for individuals with refractory knee pain seeking meaningful and sustained therapeutic benefit.
Predictors of Successful PNS Outcomes
Successful outcomes with peripheral nerve stimulation for knee pain depend on a combination of patient-specific, anatomical, and procedural factors that influence both neuromodulatory responsiveness and durability of analgesia. One of the strongest predictors is the presence of a neuropathic or mixed pain phenotype. Patients with burning, stabbing, or electric pain descriptors, as well as those exhibiting signs of peripheral or central sensitization, often respond more favorably because PNS directly modulates aberrant sensory signaling rather than relying solely on anti-inflammatory or structural interventions (Amirianfar et al., 2023). This pattern is particularly evident in chronic post-TKA pain, where neuropathic mechanisms frequently contribute to persistent symptoms and where PNS has consistently demonstrated robust analgesic benefit (Goree et al., 2024).
Another key predictor is refractoriness to, yet partial responsiveness from, prior peripheral nerve blocks. Patients who experience temporary relief from saphenous, femoral, or genicular nerve blocks often demonstrate a clear sensory-driven pain generator, making them more likely to benefit from sustained neuromodulation via PNS (Vu et al., 2024). This diagnostic insight helps distinguish patients with pain driven by nociceptive pathways from those whose symptoms may be mechanical or prosthetic in origin.
Precise lead placement is equally critical. Ultrasound-guided positioning one to three centimeters from the target nerve ensures selective activation of large-diameter fibers while avoiding motor recruitment. Studies show that optimal sensory mapping during implantation strongly correlates with long-term responder status, whereas suboptimal placement or inadequate paresthesia coverage may reduce clinical efficacy (Zhu et al., 2023). Consistency of stimulation throughout the 60-day therapy period also predicts stronger sustained outcomes, as continuous neuromodulation facilitates longer-lasting changes in sensory processing (Hasoon et al., 2025).
Psychological and functional factors play additional roles. Patients with realistic expectations, adherence to device use, and preserved mobility tend to experience greater improvements in pain and function during follow-up. Conversely, severe mood disturbance, opioid dependence, or untreated structural pathology may attenuate treatment response (Früh et al., 2023).
Overall, the most successful PNS outcomes occur in patients with neuropathic or mixed pain profiles, positive diagnostic block responses, accurate lead placement, and consistent engagement with therapy, highlighting the importance of individualized patient selection and technical precision in the procedure.
Summary
Peripheral nerve stimulation has become an increasingly promising therapy for patients with chronic knee pain who have insufficient response to conservative management, nerve blocks, or neurodestructive procedures. Across postoperative and nonoperative populations, evidence shows that PNS offers robust analgesia, functional improvement, and durable benefits that extend beyond the duration of stimulation. Chronic knee pain encompasses a heterogeneous set of mechanisms, including nociceptive input from osteoarthritis, neuropathic components following surgical procedures, and central sensitization that amplifies pain perception. This complexity partly explains why conventional therapies often fall short, leaving a significant proportion of patients with long-term disability, impaired mobility, and reduced quality of life.
The rationale for PNS is grounded in well-established neurophysiologic principles. By selectively activating large-diameter sensory fibers, PNS inhibits nociceptive transmission and modulates central processing of pain. This allows targeted treatment of pain-generating nerves such as the saphenous, femoral, sciatic, and genicular branches. Modern PNS systems enable precise lead placement under ultrasound guidance and allow patients to adjust stimulation to achieve comfortable sensory coverage without motor activation. These technological refinements have substantially improved safety and procedural reliability.
Clinical outcomes from randomized trials, retrospective cohorts, and case series consistently demonstrate meaningful pain reduction. In a multicenter randomized controlled trial, a 60-day percutaneous PNS protocol significantly outperformed placebo in both pain relief and functional measures, including improvements in walking distance (Goree et al., 2024). Real-world cohorts show similarly strong results, with responder rates exceeding ninety percent and substantial reductions in pain intensity, opioid use, and disability (Hasoon et al., 2025). Among patients with osteoarthritis who are unwilling or unable to undergo arthroplasty, temporary PNS of the femoral or saphenous nerve provides marked improvement in daily function and pain during motion and rest (Zhu et al., 2023). Externally powered PNS systems targeting saphenous nerve branches have also demonstrated enhancements in sleep quality, mood, and overall well-being (Früh et al., 2023).
The safety profile of PNS is favorable, with primarily minor and transient side effects such as mild soreness or skin irritation. Serious complications, including infection or lead migration, are rare and generally manageable without long-term consequences. Furthermore, many patients maintain benefit after lead removal, reflecting sustained neuromodulatory effects and reduced peripheral sensitization.
Overall, PNS stands out as a minimally invasive, reversible, and individualized intervention that addresses both nociceptive and neuropathic contributors to knee pain. Its strong efficacy, low complication rate, and suitability for complex clinical presentations position it as an important option within the modern management algorithm for chronic knee pain.
References
Amirianfar, E., Rosales, R., Logan, A., Doshi, T. L., Reynolds, J., & Price, C. (2023). Peripheral nerve stimulation for chronic knee pain following total knee arthroplasty: A systematic review. Pain Management, 13(11), 667–676. https://doi.org/10.2217/pmt-2023-0057
Früh, A., Sargut, T. A., Hussein, A., Muskala, B., Kuckuck, A., Brüßeler, M., Vajkoczy, P., & Bayerl, S. (2023). Peripheral nerve stimulation for the treatment of chronic knee pain. Scientific Reports, 13, 15543. https://doi.org/10.1038/s41598-023-42608-x
Goree, J. H., Grant, S. A., Dickerson, D. M., Ilfeld, B. M., Eshraghi, Y., Vaid, S., Valimahomed, A. K., Shah, J. R., Smith, G. L., Finneran, J. J., Shah, N. N., Guirguis, M. N., Eckmann, M. S., Antony, A. B., Ohlendorf, B. J., Gupta, M., Gilbert, J. E., Wongsarnpigoon, A., & Boggs, J. W. (2024). Randomized placebo-controlled trial of 60-day percutaneous peripheral nerve stimulation treatment indicates relief of persistent postoperative pain and improved function after knee replacement. Neuromodulation, 27, 847–861. https://doi.org/10.1016/j.neurom.2024.03.001
Hasoon, J., Rothkrug, A., Chen, G. H., Yong, R. J., & Robinson, C. L. (2025). Sixty-day peripheral nerve stimulation in chronic knee pain: A retrospective analysis. Orthopedic Reviews, 17. https://doi.org/10.52965/001c.143096
Vu, P. D., Gul, F., Robinson, C. L., Chen, G. H., & Hasoon, J. (2024). Peripheral nerve stimulation after total knee arthroplasty and non-operable patella fracture. Orthopedic Reviews, 16. https://doi.org/10.52965/001c.115599
Zhu, C., Gargya, A., & Haider, N. (2023). A case report of three patients who underwent temporary peripheral nerve stimulation for treatment of knee pain secondary to osteoarthritis. Cureus, 15(6), e40473. https://doi.org/10.7759/cureus.40473
Chitneni, A., Berger, A. A., Orhurhu, V., Kaye, A. D., & Hasoon, J. (2021). Peripheral nerve stimulation of the saphenous and superior lateral genicular nerves for chronic pain after knee surgery. Orthopedic Reviews, 13(1). https://doi.org/10.52965/001c.24435
Lin, C. P., Chang, K. V., Wu, W. T., & Özçakar, L. (2020). Ultrasound-guided peripheral nerve stimulation for knee pain: A mini-review of the neuroanatomy and the evidence from clinical studies. Pain Medicine, 21(Suppl 1), S56–S63. https://doi.org/10.1093/pm/pnz318