Movement-evoked Pain versus Pain at Rest in Postsurgical Clinical Trials and in Meta-analyses: An Updated Systematic Review.

BACKGROUND: Given the widespread recognition that postsurgical movement-evoked pain is generally more intense, and more functionally relevant, than pain at rest, the authors conducted an update to a previous 2011 review to re-evaluate the assessment of pain at rest and movement-evoked pain in more recent postsurgical analgesic clinical trials. METHODS: The authors searched MEDLINE and Embase for postsurgical pain randomized controlled trials and meta-analyses published between 2014 and 2023 in the setting of thoracotomy, knee arthroplasty, and hysterectomy using methods consistent with the original 2011 review. Included trials and meta-analyses were characterized according to whether they acknowledged the distinction between pain at rest and movement-evoked pain and whether they included pain at rest and/or movement-evoked pain as a pain outcome. For trials measuring movement-evoked pain, pain-evoking maneuvers used to assess movement-evoked pain were tabulated. RESULTS: Among the 944 included trials, 504 (53%) did not measure movement-evoked pain (vs. 61% in 2011), and 428 (45%) did not distinguish between pain at rest and movement-evoked pain when defining the pain outcome (vs. 52% in 2011). Among the 439 trials that measured movement-evoked pain, selection of pain-evoking maneuver was highly variable and, notably, was not even described in 139 (32%) trials (vs. 38% in 2011). Among the 186 included meta-analyses, 94 (51%) did not distinguish between pain at rest and movement-evoked pain (vs. 71% in 2011). CONCLUSIONS: This updated review demonstrates a persistent limited proportion of trials including movement-evoked pain as a pain outcome, a substantial proportion of trials failing to distinguish between pain at rest and movement-evoked pain, and a lack of consistency in the use of pain-evoking maneuvers for movement-evoked pain assessment. Future postsurgical trials need to (1) use common terminology surrounding pain at rest and movement-evoked pain, (2) assess movement-evoked pain in virtually every trial if not contraindicated, and (3) standardize movement-evoked pain assessment with common, procedure-specific pain-evoking maneuvers. More widespread knowledge translation and mobilization are required in order to disseminate this message to current and future investigators.

AAAPT Diagnostic Criteria for Acute Thoracic Surgery Pain.

Patients undergoing thoracic surgery experience particular challenges for acute pain management. Availability of standardized diagnostic criteria for identification of acute pain after thoracotomy and video assisted thoracic surgery (VATS) would provide a foundation for evidence-based management and facilitate future research. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the United States Food and Drug Administration, the American Pain Society (APS), and the American Academy of Pain Medicine (AAPM) formed the ACTTION-APS-AAPM Pain Taxonomy (AAAPT) initiative to address absence of acute pain diagnostic criteria. A multidisciplinary working group of pain experts was invited to develop diagnostic criteria for acute thoracotomy and VATS pain. The working group used available studies and expert opinion to characterize acute pain after thoracotomy and VATS using the 5-dimension taxonomical structure proposed by AAAPT (i.e., core diagnostic criteria, common features, modulating factors, impact/functional consequences, and putative mechanisms). The resulting diagnostic criteria will serve as the starting point for subsequent empirically validated criteria. PERSPECTIVE ITEM: This article characterizes acute pain after thoracotomy and VATS using the 5-dimension taxonomical structure proposed by AAAPT (ie, core diagnostic criteria, common features, modulating factors, impact and/or functional consequences, and putative mechanisms).

Preoperative Patient Expectations of Postoperative Pain Are Associated with Moderate to Severe Acute Pain After VATS.

OBJECTIVE: The goal of this post hoc analysis of subjects from a prospective observational study was to identify the predictors of patients developing moderate to severe acute pain (mean numerical rating scale [NRS] ≥4, 0-10) during the first three days after video-assisted thoracoscopic surgery (VATS) from a comprehensive evaluation of demographic, psychosocial, and surgical factors. METHODS: Results from 82 patients who were enrolled one week before VATS and evaluated during the first three postoperative days are presented. The primary outcome variable of the current study was the presence of moderate to severe acute pain after VATS. RESULTS: Fifty-nine percent (95% confidence interval, 47-69%) of study subjects developed moderate to severe acute pain after VATS. Factors univariately associated with the presence of moderate to severe acute pain were greater average expected postoperative pain, greater pain to a suprathreshold cold stimulus, and longer durations of surgery and hospital stay (P < 0.05). When considered in the multiple logistic regression models, the patients' preoperative average intensity of expected postoperative pain (NRS, 0-10) was the only measure associated with the moderate to severe acute pain. Average intensity of postoperative pain expected by patients when questioned preoperatively mediated the effect of reported intensity of pain to the suprathreshold cold stimulus for moderate to severe acute pain levels. Preoperative patient expectations had greater predictive value than other assessed variables including psychosocial factors such as catastrophizing or anxiety assessed one week before surgery. CONCLUSIONS: None of the preoperative psychosocial measures were associated with the moderate to severe acute pain after VATS. Average expected postoperative pain was the only measure associated with the development of moderate to severe acute pain after VATS.

Deep Tissue Incision Enhances Spinal Dorsal Horn Neuron Activity During Static Isometric Muscle Contraction in Rats.

Translational correlates to pain with activities after deep tissue injury have been rarely studied. We hypothesized that deep tissue incision causes greater activation of nociception-transmitting neurons evoked by muscle contraction. In vivo neuronal activity was recorded in 203 dorsal horn neurons (DHNs) from 97 rats after sham, skin-only, or skin + deep muscle incision. We evaluated DHN responses to static, isometric muscle contractions induced by direct electrical stimulation of the muscle. The effect of pancuronium on DHN response to contractions was also examined. Approximately 50% of DHNs with receptive fields in the hindpaw were excited during muscle contraction. One-second .5- and 1.0-g muscle contractions produced greater DHN activity after skin + deep muscle incision (median [interquartile range], 32 [5-39] impulses, P = .021; and 36 [26-46] impulses, P = .006, respectively) than after sham (6 [0-21] and 15 [8-32] impulses, respectively). Neuromuscular blockade with pancuronium inhibited the muscle contractions and DHN activation during electrical stimulation, demonstrating contraction-induced activation. The greater response of spinal DHNs to static muscle contraction after skin + deep muscle incision may model and inform mechanisms of dynamic pain after surgery. PERSPECTIVE: Completion of various activities is an important milestone for recovery and hospital discharge after surgery. Skin + deep muscle incision caused greater activation of nociception-transmitting DHNs evoked by muscle contraction compared with skin-only incision. This result suggests an important contribution of deep muscle injury to activity-evoked hyperalgesia after surgery.

Effect of Thoracic Epidural Anesthesia in a Rat Model of Phrenic Motor Inhibition after Upper Abdominal Surgery.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: One important example of impaired motor function after surgery is diaphragmatic dysfunction after upper abdominal surgery. In this study, the authors directly recorded efferent phrenic nerve activity and determined the effect of the upper abdominal incision. The authors hypothesized that phrenic motor output would be decreased after the upper abdominal incision; it was also hypothesized that blocking sensory input from the incision using thoracic epidural anesthesia would diminish this incision-induced change in phrenic motor activity. METHODS: Efferent phrenic activity was recorded 1 h to 10 days after upper abdominal incision in urethane-anesthetized rats. Ventilatory parameters were measured in unanesthetized rats using whole-body plethysmography at multiple time points after incision. The authors then determined the effect of thoracic epidural anesthesia on phrenic nerve activity and ventilatory parameters after incision. RESULTS: Phrenic motor output remained reduced by approximately 40% 1 h and 1 day after incision, but was not different from the sham group by postoperative day 10. One day after incision (n = 9), compared to sham-operated animals (n = 7), there was a significant decrease in spike frequency area-under-the-curve (median [interquartile range]: 54.0 [48.7 to 84.4] vs. 97.8 [88.7 to 130.3]; P = 0.0184), central respiratory rate (0.71 [0.63 to 0.79] vs. 0.86 [0.82 to 0.93]/s; P = 0.0460), and inspiratory-to-expiratory duration ratio (0.46 [0.44 to 0.55] vs. 0.78 [0.72 to 0.93]; P = 0.0023). Unlike humans, a decrease, not an increase, in breathing frequency has been observed after the abdominal incision in whole-body plethysmography. Thoracic epidural anesthesia attenuated the incision-induced changes in phrenic motor output and ventilatory parameters. CONCLUSIONS: Upper abdominal incision decreased phrenic motor output and ventilatory parameters, and this incision-induced impairment was attenuated by thoracic epidural anesthesia. The authors' results provide direct evidence that afferent inputs from the upper abdominal incision induce reflex inhibition of phrenic motor activity.

Ovine model of neuropathic pain for assessing mechanisms of spinal cord stimulation therapy via dorsal horn recordings, von Frey filaments, and gait analysis.

BACKGROUND: It is becoming increasingly important to understand the mechanisms of spinal cord stimulation (SCS) in alleviating neuropathic pain as novel stimulation paradigms arise. PURPOSE: Additionally, the small anatomic scale of current SCS animal models is a barrier to more translational research. METHODS: Using chronic constriction injury (CCI) of the common peroneal nerve (CPN) in sheep (ovine), we have created a chronic model of neuropathic pain that avoids motor deficits present in prior large animal models. This large animal model has allowed us to implant clinical grade SCS hardware, which enables both acute and chronic testing using von Frey filament thresholds and gait analysis. Furthermore, the larger anatomic scale of the sheep allows for simultaneous single-unit recordings from the dorsal horn and SCS with minimal electrical artifact. RESULTS: Detectable tactile hypersensitivity occurred 21 days after nerve injury, with preliminary indications that chronic SCS may reverse it in the painful limb. Gait analysis revealed no hoof drop in the CCI model. Single neurons were identified and discriminated in the dorsal horn, and their activity was modulated via SCS. Unlike previous large animal models that employed a complete transection of the nerve, no motor deficit was observed in the sheep with CCI. CONCLUSION: To our knowledge, this is the first reported large animal model of chronic neuropathic pain which facilitates the study of both acute and chronic SCS using complementary behavioral and electrophysiologic measures. As demonstrated by our successful establishment of these techniques, an ovine model of neuropathic pain is suitable for testing the mechanisms of SCS.

Hydrogen Peroxide Induces Muscle Nociception via Transient Receptor Potential Ankyrin 1 Receptors.

BACKGROUND: H2O2 has a variety of actions in skin wounds but has been rarely studied in deep muscle tissue. Based on response to the transient receptor potential ankyrin 1 antagonists after plantar incision, we hypothesized that H2O2 exerts nociceptive effects via the transient receptor potential ankyrin 1 in muscle. METHODS: Nociceptive behaviors in rats (n = 269) and mice (n = 16) were evaluated after various concentrations and volumes of H2O2 were injected into the gastrocnemius muscle or subcutaneous tissue. The effects of H2O2 on in vivo spinal dorsal horn neuronal activity and lumbar dorsal root ganglia neurons in vitro were evaluated from 26 rats and 6 mice. RESULTS: Intramuscular (mean ± SD: 1,436 ± 513 s) but not subcutaneous (40 ± 58 s) injection of H2O2 (100 mM, 0.6 ml) increased nociceptive time. Conditioned place aversion was evident after intramuscular (-143 ± 81 s) but not subcutaneous (-2 ± 111 s) injection of H2O2. These H2O2-induced behaviors were blocked by transient receptor potential ankyrin 1 antagonists. Intramuscular injection of H2O2 caused sustained in vivo activity of dorsal horn neurons, and H2O2 activated a subset of dorsal root ganglia neurons in vitro. Capsaicin nerve block decreased guarding after plantar incision and reduced nociceptive time after intramuscular H2O2. Nociceptive time after intramuscular H2O2 in transient receptor potential ankyrin 1 knockout mice was shorter (173 ± 156 s) compared with wild-type mice (931 ± 629 s). CONCLUSIONS: The greater response of muscle tissue to H2O2 may help explain why incision that includes deep muscle but not skin incision alone produces spontaneous activity in nociceptive pathways.

The ACTTION-APS-AAPM Pain Taxonomy (AAAPT) Multidimensional Approach to Classifying Acute Pain Conditions.

Objective: With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (e.g., pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain. Setting: Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM). Methods: As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions. Perspective: The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Conclusions: Significant numbers of patients still suffer from significant acute pain, despite the advent of modern multimodal analgesic strategies. Mismanaged acute pain has a broad societal impact as significant numbers of patients may progress to suffer from chronic pain. An acute pain taxonomy provides a much-needed standardization of clinical diagnostic criteria, which benefits clinical care, research, education, and public policy. For the purposes of the present taxonomy, acute pain is considered to last up to seven days, with prolongation to 30 days being common. The current understanding of acute pain mechanisms poorly differentiates between acute and chronic pain and is often insufficient to distinguish among many types of acute pain conditions. Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook a similar approach to organizing various acute pain conditions.

The ACTTION-APS-AAPM Pain Taxonomy (AAAPT) Multidimensional Approach to Classifying Acute Pain Conditions.

OBJECTIVE: With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (eg, pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain. SETTING: Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM). METHODS: As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions. PERSPECTIVE: The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. CONCLUSIONS: Significant numbers of patients still suffer from significant acute pain, despite the advent of modern multimodal analgesic strategies. Mismanaged acute pain has a broad societal impact as significant numbers of patients may progress to suffer from chronic pain. An acute pain taxonomy provides a much-needed standardization of clinical diagnostic criteria, which benefits clinical care, research, education, and public policy. For the purposes of the present taxonomy, acute pain is considered to last up to seven days, with prolongation to 30 days being common. The current understanding of acute pain mechanisms poorly differentiates between acute and chronic pain and is often insufficient to distinguish among many types of acute pain conditions. Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook a similar approach to organizing various acute pain conditions.

A Prospective Study of Chronic Pain after Thoracic Surgery.

BACKGROUND: The goal of this study was to detect the predictors of chronic pain at 6 months after thoracic surgery from a comprehensive evaluation of demographic, psychosocial, and surgical factors. METHODS: Thoracic surgery patients were enrolled 1 week before surgery and followed up 6 months postsurgery in this prospective, observational study. Comprehensive psychosocial measurements were assessed before surgery. The presence and severity of pain were assessed at 3 and 6 months after surgery. One hundred seven patients were assessed during the first 3 days after surgery, and 99 (30 thoracotomy and 69 video-assisted thoracoscopic surgery, thoracoscopy) patients completed the 6-month follow-up. Patients with versus without chronic pain related to thoracic surgery at 6 months were compared. RESULTS: Both incidence (P = 0.37) and severity (P = 0.97) of surgery-related chronic pain at 6 months were similar after thoracotomy (33%; 95% CI, 17 to 53%; 3.3 ± 2.1) and thoracoscopy (25%; 95% CI, 15 to 36%; 3.3 ± 1.7). Both frequentist and Bayesian multivariate models revealed that the severity of acute pain (numerical rating scale, 0 to 10) is the measure associated with chronic pain related to thoracic surgery. Psychosocial factors and quantitative sensory testing were not predictive. CONCLUSIONS: There was no difference in the incidence and severity of chronic pain at 6 months in patients undergoing thoracotomy versus thoracoscopy. Unlike other postsurgical pain conditions, none of the preoperative psychosocial measurements were associated with chronic pain after thoracic surgery.

Pain-Related Limitations in Daily Activities Following Thoracic Surgery in a United States Population.

BACKGROUND: Ringsted et al created a statistically validated questionnaire to assess pain-related limitations in daily activities following thoracic surgery and translated it to English. We utilized the questionnaire to assess the impact of pain impairing certain daily activities in a United States thoracic surgery population. OBJECTIVES: Examine if the questionnaire developed and translated to English by Ringsted et al to assess the effects of chronic pain after thoracic surgery on daily activities would be applicable in a sample of thoracic surgery patients in the United States. STUDY DESIGN: Cross-sectional study by mailed questionnaire. SETTING: All patients who had thoracic surgery between 6 months and 3 years ago at a university hospital. METHODS: We sent questionnaires to patients who had undergone thoracic surgery between 6 months and 3 years ago, yielding a sample of 349 eligible patients. Questionnaire results were statistically assessed for item fit, dimensionality, and internal reliability. RESULTS: The response rate was 26.4%. Of the responders, 36% (95% CI: 26.1% to 46.5%) identified themselves as having chronic pain related to their thoracic surgery. Activities such as lying on the operated side, coughing, and carrying groceries were impaired in more than 50% of the patients who had thoracic surgery related pain (P < 0.05). Patients with chronic pain were more likely to report pain in other body locations. Few activities were limited in the patients identifying themselves as not having chronic pain. Statistical measures indicate high internal reliability. LIMITATIONS: This was a retrospective questionnaire with 26.4% response rate. CONCLUSIONS: Pain continues to impair the daily activities of a significant proportion of patients after thoracic surgery in a sample from the United States. Despite cultural differences, the Danish procedure-specific questionnaire provides an applicable and similar assessment of functional impairment after thoracic surgery in American patients.Key words: Thoracic surgery, chronic pain, impairment, daily life, questionnaire.

Muscle Reactive Oxygen Species (ROS) Contribute to Post-Incisional Guarding via the TRPA1 Receptor.

BACKGROUND: Deep tissues and their afferents have unique responses to various stimuli and respond to injury distinctively. However, the types of receptors and endogenous ligands that have a key role in pain after deep tissue incision are unknown. TRPA1 has been shown to mediate pain-related responses in inflammation- and nerve injury-induced pain models. We hypothesized that TRPA1 has an important role in pain behaviors after deep tissue incision. METHODS: The effect of various doses of intraperitoneal (i.p.) TRPA1 antagonist, HC-030031, on pain behaviors after skin + deep tissue incision of the rat hind paw was measured. In vivo reactive oxygen species (ROS)-imaging and hydrogen peroxide (H2O2) levels after incision were also evaluated. Separate groups of rats were examined for H2O2-evoked pain-related behaviors after injections into the deep tissue or the subcutaneous tissue. RESULTS: Guarding pain behavior after skin + deep tissue incision was decreased by i.p. HC-030031. However, HC-030031 did not affect mechanical or heat responses after incision. Treatment either before or after incision was effective against incision-induced guarding behavior. ROS increased after skin + deep tissue incision in both the incised muscle and the skin. Tissue H2O2 also increased in both skin and muscle after incision. H2O2 injection produced pain behaviors when injected into muscle but not after subcutaneous injection. CONCLUSIONS: This study demonstrates that TRPA1 antagonist HC-030031 reduced spontaneous guarding pain behavior after skin + deep tissue incision. These data indicate that TRPA1 receptors on nociceptors are active in incised fascia and muscle but this is not evident in incised skin. Even though endogenous TRPA1 agonists like ROS and H2O2 were increased in both incised skin and muscle, those in skin do not contribute to nociceptive behaviors. This study suggests that endogenous TRPA1 ligands and the TRPA1 receptor are important targets for acute pain from deep tissue injury.

Research Gaps in Practice Guidelines for Acute Postoperative Pain Management in Adults: Findings From a Review of the Evidence for an American Pain Society Clinical Practice Guideline.

UNLABELLED: Acute postoperative pain is a common clinical condition that, when poorly controlled, can result in a number of significant negative consequences. The American Pain Society commissioned an evidence-based guideline on the management of postoperative pain to promote evidence-based, safe, and effective perioperative pain management. An interdisciplinary panel developed 31 key questions and inclusion criteria to guide the evidence review. Investigators reviewed 6556 abstracts from multiple electronic databases up to November 2012, an updated evidence review to October 2014, and key references suggested by expert reviewers. More than 800 primary studies not included in a systematic review and 107 systematic reviews were included. Despite a large body of evidence, a number of critical research gaps were identified where only low-quality or insufficient evidence was found to help guide clinical practice recommendations. This report identifies evidence gaps including optimal methods and timing of perioperative patient education, nonpharmacological modalities, combinations of analgesic techniques, monitoring of patient response to treatment, techniques for neuraxial and regional analgesia, and organizational care delivery models. Recommendations to help guide the design of future perioperative studies are offered. PERSPECTIVE: Acute postoperative pain is a common clinical condition requiring an evidence-based, planned, and multimodal approach. Despite the plethora of published evidence, much of it is weak and key questions remain unanswered. Researchers are encouraged to work together to produce strong evidence to help guide clinical decisions in perioperative pain management.

Comparison of Conventional and Kilohertz Frequency Epidural Stimulation in Patients Undergoing Trialing for Spinal Cord Stimulation: Clinical Considerations.

OBJECTIVE: Compare therapeutic response of patients to conventional versus high-frequency spinal cord stimulation (SCS). METHODS: Twelve patients with back and leg pain who met standard clinical criteria for a trial of conventional SCS (low-frequency stimulation [LFS]) participated in a half-day session of high-frequency stimulation (HFS) during their weeklong conventional trial. HFS consisted of frequencies ranging from 50 Hz to 4 kHz, or 100 Hz to10 kHz, at constant voltage settings increasing from 0.5 V to 10 V. Visual Analog Scale scores from 0 to10 were recorded, along with notes of any clinical discomfort and open patient comments. RESULTS: Two of 12 patients had no benefit from either LFS or HFS. In the remaining 10 patients, paresthesias were significantly altered by HFS, and four experienced complete elimination of paresthesias. Five patients preferred HFS to LFS, with an additional three preferring both equally. Abrupt sensation to the onset of HFS was described in six patients, and in ten patients, HFS allowed maximum voltage stimulation of 10 V without discomfort. The four patients who did not have a successful trial of stimulation had significantly longer duration of pain compared to the eight patients who went on to permanent implant (11.2 vs. 4.3 years, P = 0.04). CONCLUSIONS: HFS significantly altered the feeling of paresthesias in the majority of patients (ten of 12), was preferred to LFS in five of 12 patients, and non-inferior to LFS in eight of 12 patients. Both 4 kHz and 10 kHz stimulation allowed patients to benefit from HFS. HFS allowed maximum voltage stimulation without discomfort.