Abstract
Introduction
This study aimed to evaluate pain outcomes after Neurotropin initiation in individuals with chronic low back pain (CLBP) and to explore factors associated with treatment response.
Methods
This multicenter retrospective observational study included patients with CLBP (duration ≥3 months) who received oral Neurotropin therapy (4 tablets daily) from May 2024 to May 2025. The primary outcome was pain intensity, measured using a visual analog scale (VAS) at baseline and at 2, 4, 8, and 12 weeks. The secondary outcomes were patient characteristics, pain features, simplified Spine painDETECT questionnaire scores, and Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP) scores. Statistical analyses were conducted using paired t-tests with Bonferroni correction, repeated-measures analysis of variance, and multivariate regression.
Results
A total of 106 patients (46 males, 60 females; mean age: 66.5±15.8 years) were included. The baseline VAS score was 6.74±1.12. Neurotropin was associated with significant pain reduction over 12 weeks, with VAS scores decreasing to 5.40±1.42 at 2 weeks, 5.15±1.39 at 4 weeks, 4.95±1.38 at 8 weeks, and 4.73±1.48 at 12 weeks (p<0.01 for all). The mean VAS score improvement was 2.14 points (95% confidence interval: 1.76-2.52) at 12 weeks. The minimal clinically important difference (≥1.5 points) was achieved by 62.3% (66/106) of patients. A BS-POP score ≥11 (indicating psychiatric problems) was significantly associated with reduced treatment response (VAS score improvement: 1.45±1.22 vs. 2.38±1.18 points, p=0.001). Pain duration was negatively correlated with treatment response (r=-0.26, p=0.049). No adverse events were reported.
Conclusions
Neurotropin was associated with significant pain reduction in CLBP in this retrospective observational study, with an excellent safety profile. Psychiatric comorbidities and longer pain duration were associated with reduced treatment response. Neurotropin may be a beneficial therapeutic option for CLBP, particularly in patients considered unsuitable for long-term non-steroidal anti-inflammatory drug therapy, although these findings require confirmation in randomized controlled trials.
Keywords: chronic low back pain, Neurotropin, retrospective study, pain management, psychiatric factors
Introduction
Chronic low back pain (CLBP) is a highly prevalent condition worldwide. In particular, chronic musculoskeletal pain has been reported in approximately 15.4% of the Japanese population, of which low back pain is the most frequent1). The pathophysiology of CLBP is complex and multifactorial, involving not only tissue damage and inflammation but also psychosocial factors and neuropathic pain components2,3).
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed medications for CLBP; however, their efficacy is limited, with pain reduction averaging only 7 points on a 100-point visual analog scale (VAS) compared to placebo4,5). Additionally, long-term NSAID therapy carries significant risks of adverse gastrointestinal and cardiovascular events; thus, alternative therapeutic approaches are necessary.
NeurotropinⓇ, an extract derived from inflamed rabbit skin inoculated with vaccinia virus, has been used for chronic pain management in Japan for decades6). Unlike conventional NSAIDs, Neurotropin exerts its analgesic effect by activating the central monoaminergic descending pain inhibitory systems6). Because Neurotropin does not involve the prostaglandin synthesis pathways, it has fewer gastrointestinal side effects and can be safely administered in the long term, with demonstrated efficacy against pain threshold reduction states, including neuropathic pain. Nonetheless, the efficacy of Neurotropin considerably varies among individuals, and the factors influencing treatment outcomes remain poorly understood. In particular, the impact of psychiatric factors, fatigue accumulation, and neuropathic pain components on the therapeutic efficacy of Neurotropin has not been adequately investigated. Therefore, the current retrospective observational study aimed to evaluate pain outcomes after Neurotropin initiation in individuals with CLBP and to explore factors associated with treatment response.
Materials and Methods
Study design and participants
This multicenter retrospective observational study investigated the association between Neurotropin therapy and pain outcomes in patients with CLBP. This study was conducted at 5 institutions (1 university hospital and 4 affiliated hospitals). Patients were consecutively enrolled from electronic medical records during the study period. CLBP was defined as low back pain persisting for ≥3 months, localized to the region between the 12th rib and the gluteal fold. All patients underwent imaging evaluation (X-ray and magnetic resonance imaging [MRI]) to assess underlying structural pathology. The study population included patients who received oral Neurotropin therapy (4 tablets daily in two divided doses) from May 2024 to May 2025 and who had available pre- and post-treatment evaluation data in their medical records. Exclusion criteria were: (1) low back pain caused by red flags (fracture, infection, malignancy), (2) requirement for surgical intervention during the treatment period, (3) severe psychiatric disorders requiring specialized treatment, and (4) known allergy to Neurotropin. This study was approved by the ethics committee of the representative institution.
Outcome measures
The primary outcome was temporal changes in pain intensity measured using the VAS at baseline and at 2, 4, 8, and 12 weeks after the initiation of Neurotropin therapy7). The VAS was rated from 0 (no pain) to 10 (worst possible pain) based on patients' subjective assessment. Baseline assessments were performed on the day of Neurotropin initiation. The primary outcome focused on low back pain rather than leg pain because low back pain was the chief complaint in all enrolled patients, and Neurotropin's primary indication is for low back pain conditions.
The secondary outcomes were (1) patients' background factors; (2) pain features, including the presence of movement-related pain (pain exacerbation with movement, standing, or walking), fatigue-related pain exacerbation (pain worsening with prolonged work or maintenance of the same posture), leg pain (sciatic nerve-type radiating leg pain), or concurrent pain at other sites (neck, shoulder, or knee pain); (3) simplified Spine painDETECT questionnaire (SF-SPDQ) scores; and (4) Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP) scores. Underlying conditions were diagnosed based on clinical and imaging findings. Lumbar spinal stenosis, lumbar disc herniation, and lumbar spondylolisthesis were diagnosed according to MRI criteria. Myofascial low back pain was defined as cases without significant structural abnormalities on imaging, with paravertebral muscle tenderness on palpation, and predominantly movement-related pain.
The SF-SPDQ evaluated two items: “Do you experience sudden electric shock-like pain attacks?” and “Do you have numbness in the painful area?” Each item was scored from 0 (not at all) to 5 (very strong) on a 6-point scale. SF-SPDQ scores were calculated by multiplying each item score by weighting coefficients (electric shock-like pain: -1.9, numbness: +4.2), summing them, and subtracting the constant 7. SF-SPDQ scores ≥0 were considered to indicate possible neuropathic pain8).
Psychosocial factors were assessed using the physician version of the BS-POP. The BS-POP physician version is a simple psychological assessment scale based on a physician's clinical evaluation, in which eight questions are scored on a 3-point scale for a total of 8-24 points. BS-POP scores ≥11 were considered to indicate psychiatric problems9). The physician version was selected for its feasibility in busy orthopedic outpatient settings and its established use in previous Japanese orthopedic studies. A physician survey regarding the timing of the onset of analgesic effect was also conducted.
Statistical analysis
For the collected VAS data, the change from baseline at each time point was calculated, and significance testing was performed using paired t-tests with Bonferroni correction for multiple comparisons, with the significance level set at two-sided p<0.05. Temporal changes in the VAS scores were verified using repeated-measures analysis of variance (ANOVA). To compare the mean change in VAS scores among the three groups based on concomitant analgesic use (Naive, Tapered, Continued), Dunn's test with Bonferroni correction was performed as a post hoc analysis. Regarding the secondary outcomes, the influence of each patient background factor was evaluated using VAS score improvement at 12 weeks (baseline VAS−12-week VAS) as the dependent variable. Univariate analysis was performed using Pearson's correlation coefficients or Welch's t-test, and multivariate linear regression analysis was conducted for variables showing significant trends. To address potential confounding by concomitant analgesic use, concomitant medication status (naïve/tapered/continued) was included as a covariate in the multivariate model in addition to the original covariates. Statistical analyses were performed using JMP (version 18.0; SAS Institute Inc., Cary, NC, USA).
Results
Patient characteristics
A total of 106 patients with CLBP (mean age: 66.5±15.8 years, range: 26-90 years) were included in this study (Table 1), with males and females accounting for 43.4% (n=46) and 56.6% (n=60), respectively. Older adults were predominant. The most common underlying condition was lumbar spinal stenosis (n=51, 48.1%), followed by myofascial low back pain (n=18, 17.0%), lumbar spondylolisthesis (n=16, 15.1%), lumbar disc herniation (n=14, 13.2%), and other conditions (n=7, 6.6%).
Table 1.
Baseline Characteristics of Patients (n=106).
| Variable | Value |
|---|---|
| Age (years), mean±SD | 66.5±15.8 |
| Range | 26-90 |
| Sex, n (%) | |
| Male | 46 (43.4%) |
| Female | 60 (56.6%) |
| Pain duration (months), mean±SD | 5.2±3.3 |
| Underlying condition, n (%) | |
| Lumbar spinal stenosis | 51 (48.1%) |
| Myofascial low back pain | 18 (17.0%) |
| Lumbar spondylolisthesis | 16 (15.1%) |
| Lumbar disc herniation | 14 (13.2%) |
| Other | 7 (6.6%) |
| Symptom characteristics, n (%) | |
| Movement-related pain | 98 (92.5%) |
| Fatigue-related exacerbation | 104 (98.1%) |
| Leg pain | 71 (67.0%) |
| Concurrent pain at other sites | 52 (49.1%) |
| SF-SPDQ score, mean±SD | 1.29±0.88 |
| Suspected neuropathic pain (≥0), n (%) | 96 (90.6%) |
| BS-POP score, mean±SD | 9.92±2.94 |
| Range | 8-20 |
| Suspected psychiatric problems (≥11), n (%) | 22 (20.8%) |
| Baseline VAS score, mean±SD | 6.74±1.12 |
BS-POP: Brief Scale for Psychiatric Problems in Orthopedic Patients; SD: standard deviation; SF-SPDQ: simplified Spine painDETECT questionnaire; VAS: visual analog scale
With respect to symptom characteristics, movement-related pain and fatigue-related pain exacerbation occurred in 98 (92.5%) and 104 (98.1%) patients, respectively, suggesting that nearly all patients with CLBP experienced pain worsening with movement and fatigue. Concurrent leg pain was present in 71 patients (67.0%), whereas concurrent pain at other sites, including neck, shoulder, and knee pain, was reported by 52 patients (49.1%). SF-SPDQ evaluation revealed that 96 patients (90.6%) had suspected neuropathic pain (SF-SPDQ scores ≥0), indicating that most cases had suspected neuropathic pain components. The mean SF-SPDQ score was 1.29±0.88. The mean BS-POP score was 9.92±2.94 (range: 8-20), with 22 patients (20.8%) having BS-POP scores ≥11, suggesting psychiatric problems. Most patients (n=84, 79.2%) had BS-POP scores ≤10, suggesting minimal psychiatric involvement.
Previous medication use and concomitant drugs
Overall, 87% of patients (n=92) used some form of analgesic medication prior to the initiation of Neurotropin therapy. Among previous medications, oral NSAIDs were the most commonly used, reported in 73 (79.3%) of the 92 patients. Other medications included pregabalin (LyricaⓇ) in 38 patients (41.3%), mirogabalin (TarligeⓇ) in 25 patients (27.2%), acetaminophen in 23 patients (25.0%), tramadol/acetaminophen combination (TramcetⓇ) in 18 patients (19.6%), extended-release tramadol (OnetramⓇ and TwotramⓇ) in 14 patients (15.2%), and duloxetine (CymbaltaⓇ) in 4 patients (4.3%) (multiple responses allowed).
Regarding the continuation of previous medications, 52 patients (49.1%) continued previous analgesics concomitantly with Neurotropin, 29 patients (27.4%) discontinued previous medications at the time of Neurotropin initiation, and 25 patients (23.6%) used them concomitantly with gradual reduction. Thus, approximately half of the patients continued existing analgesics concomitantly, whereas the other half transitioned to Neurotropin monotherapy. Among the continued concomitant medications, NSAID continuation was the most common (n=28), followed by pregabalin continuation (n=21) and acetaminophen continuation (n=14).
VAS pain improvement
Temporal changes in mean values are shown in Figure 1. The mean baseline VAS score for low back pain was 6.74±1.12. After the initiation of Neurotropin therapy, pain intensity significantly decreased over time. The mean VAS scores were 5.40±1.42 at 2 weeks, 5.15±1.39 at 4 weeks, 4.95±1.38 at 8 weeks, and 4.73±1.48 at 12 weeks, representing approximately a 2-point improvement from baseline to 12 weeks.
Figure 1.
Temporal changes in VAS scores after Neurotropin administration. Changes from baseline (mean±95% CI) to 2, 4, 8, and 12 weeks: -1.34±0.28 points (p<0.01), 1.63±0.34 points (p<0.01), 1.79±0.31 points (p<0.01), and -2.14±0.38 points (p<0.01), respectively. Paired t-test with Bonferroni correction.
The VAS scores significantly decreased from baseline by 1.63 points at 4 weeks (95% confidence interval [CI]: 1.29-1.97, p<0.01) and 2.14 points at 12 weeks (95% CI: 1.76-2.52, p<0.01). Repeated-measures ANOVA for temporal changes in VAS scores showed significant main effects (F(4,420)=28.7, p<0.01). Multiple comparisons revealed significantly lower VAS scores at all time points from 2 weeks onward compared with baseline. The minimal clinically important difference (MCID) for VAS in CLBP is generally considered to be 1.5-2.0 points10). In this study, 66 patients (62.3%) achieved MCID (≥1.5 points improvement) at 12 weeks (Table 2).
Table 2.
MCID Achievement Rate at 12 Weeks.
| Outcome | n | % |
|---|---|---|
| MCID achieved (ΔVAS ≥1.5 points) | 66 | 62.3% |
| MCID not achieved (ΔVAS <1.5 points) | 40 | 37.7% |
| Total evaluable | 106 | 100% |
MCID: minimal clinically important difference
Patients were categorized into three groups according to the status of concomitant analgesic medications during the 12-week NeurotropinⓇ treatment period:
・Naive group: patients who received no concomitant analgesic medications.
・Tapered group: patients whose concomitant analgesics were gradually tapered off.
・Continued group: patients who continued concomitant analgesics without dose reduction.
A Kruskal–Wallis test was conducted to assess differences in the change in VAS score from baseline to week 12 (ΔVAS) among the three groups. The overall comparison showed a trend toward significance (H=4.69, p=0.096). Subsequent pairwise comparisons using Dunn's test with Bonferroni correction revealed no statistically significant differences between groups, although the Naive group tended to show greater improvement in VAS scores compared with the Continued group (adjusted p=0.294) (Table 3).
Table 3.
Pairwise Comparison of ΔVAS (0w-12w) between Groups Using Dunn’s Test.
| Comparison | Group 1 Mean±SD | Group 2 Mean±SD | Difference | Adjusted p-value |
|---|---|---|---|---|
| Naive vs tapered | 2.52±1.68 (n=29) | 1.82±1.59 (n=25) | 0.70 | 1 |
| Naive vs continued | 2.52±1.68 (n=29) | 1.93±1.54 (n=52) | 0.59 | 0.29 |
| Tapered vs continued | 1.82±1.59 (n=25) | 1.93±1.54 (n=52) | –0.11 | 0.92 |
SD: standard deviation; VAS: visual analog scale
Factors affecting pain improvement
The relationship between patient background factors and VAS score improvements is shown in Table 4. Patients with higher BS-POP scores (indicating greater psychosocial factor involvement) tended to exhibit poorer pain improvement (Table 5). Specifically, BS-POP scores showed a moderate negative correlation with VAS score improvement (baseline−12 weeks) (correlation coefficient r=-0.39, p=0.002), indicating that patients with higher psychological assessment scores (stronger psychogenic elements) had smaller pain reduction with Neurotropin.
Table 4.
Multivariate Analysis Results (with concomitant medication status as covariate).
| Variable | β (standardized) | B (unstandardized) | 95% CI | p-value |
|---|---|---|---|---|
| Age | –0.05 | –0.004 | –0.03 to 0.02 | 0.712 |
| Sex (male) | –0.08 | –0.28 | –0.89 to 0.33 | 0.364 |
| BS-POP score ≥11 | –0.32 | –1.12 | –1.92 to –0.32 | 0.006* |
| Disease duration (months) | –0.23 | –0.07 | –0.12 to –0.02 | 0.008* |
| SF-SPDQ score | 0.03 | 0.006 | –0.04 to 0.05 | 0.812 |
| Leg pain (present) | –0.02 | –0.06 | –0.67 to 0.55 | 0.846 |
| Concomitant medication status | ||||
| Tapered vs Naive | –0.08 | –0.31 | –1.21 to 0.59 | 0.548 |
| Continued vs Naive | –0.14 | –0.48 | –1.32 to 0.36 | 0.264 |
| R2 | 0.168 | |||
| Adjusted R2 | 0.091 |
*p<0.01.
Dependent variable: ΔVAS (baseline VAS − 12-week VAS)
BS-POP: Brief Scale for Psychiatric Problems in Orthopedic Patients; CI: confidence interval; SF-SPDQ: simplified Spine painDETECT questionnaire; VAS: visual analog scale
Table 5.
Comparison of VAS Score Improvement According to BS-POP Scores.
| BS-POP Score | n | ΔVAS (mean±SD) | p-value |
|---|---|---|---|
| ≤10 (No psychiatric problems) | 84 | 2.38±1.18 | |
| ≥11 (Suspected psychiatric problems) | 22 | 1.45±1.22 | 0.001 |
BS-POP: Brief Scale for Psychiatric Problems in Orthopedic Patients; VAS: visual analog scale
Furthermore, group analysis based on BS-POP scores revealed that the group with suspected psychiatric problems (BS-POP scores ≥11, n=22) showed a VAS score improvement of 1.45±1.22 points, whereas the group without suspected psychiatric problems (BS-POP scores ≤10, n=84) showed an improvement of 2.38±1.18 points, with a statistically significant difference (p=0.001).
Additionally, CLBP duration influenced treatment response, with longer pain duration tending to show somewhat smaller VAS score improvement (r=-0.26, p=0.049). Multivariate analysis, including concomitant medication status as a covariate, identified BS-POP scores ≥11 (presence of psychiatric problems) and disease duration as independent significant negative factors affecting VAS score improvement (each p<0.01). These associations remained consistent after adjustment for concomitant medication status.
Conversely, no significant associations were found between age, sex, underlying disease type, concomitant medication status, and VAS score improvement. In particular, there was no significant difference in the mean 12-week VAS score improvement between patients with leg pain (concurrent nerve root symptoms) and those with low back pain alone, indicating that the presence or absence of sciatica did not influence the pain reduction associated with Neurotropin. Similarly, no correlation was found between SF-SPDQ scores (indicating the likelihood of neuropathic pain) and VAS score improvement (r=+0.05, p=0.70).
Time course of pain improvement
Regarding the timing of the onset of Neurotropin's analgesic effect, physician survey responses indicated a mean of 3.2±2.8 weeks. Most patients experienced pain reduction within approximately 3-4 weeks, suggesting that the analgesic effect of Neurotropin tended to develop several weeks after initiation.
Adverse event profile
No adverse events were observed during Neurotropin administration, and no side effects were reported in any of the 106 patients. No life-threatening adverse events, such as shock or anaphylaxis, occurred, and no safety concerns were observed.
Discussion
This study retrospectively evaluated the association between Neurotropin therapy and pain outcomes in patients with CLBP and examined its clinical utility and limitations. The results indicated an approximately 2-point VAS score improvement over 12 weeks of Neurotropin administration, indicating a significant reduction in pain intensity. In particular, the pain reduction was observed within 2-4 weeks of the initial administration and subsequently persisted, suggesting both rapid onset and sustained symptom relief with continued Neurotropin therapy.
The observed VAS improvement of 2.14 points should be interpreted in the context of placebo effects reported in CLBP trials, which typically range from 0.5 to 1.5 points11). While these results appear numerically larger than reported placebo-arm improvements, direct comparison is not possible without a control group. The MCID achievement rate of 62.3% suggests that a substantial proportion of patients experienced clinically meaningful improvement, although this must be interpreted cautiously given the study design.
Notably, a significant negative correlation was found between psychosocial factor strength (BS-POP scores) and treatment response. Specifically, patients with greater psychological burden, such as depressive tendencies, anxiety, and stress, tended to experience less pain reduction with Neurotropin administration. In particular, the group with suspected psychiatric problems (BS-POP score ≥11) showed significantly smaller VAS score improvement compared with the group with scores ≤10 (1.45 vs. 2.38 points, p=0.001), demonstrating reduced treatment response to Neurotropin. This finding is consistent with previous reports showing that psychosocial factors influence CLBP treatment outcomes2,3) and reaffirms the importance of “yellow flags” (psychosocial risk factors) in chronic pain management. Importantly, these associations remained consistent after adjustment for concomitant medication status in the multivariate model, suggesting that the observed relationships are independent of concomitant analgesic use.
Conversely, neuropathic pain elements evaluated using the SF-SPDQ (presence of electric shock-like pain and numbness) did not show clear associations as predictive factors for Neurotropin response. No differences in pain reduction were observed based on the presence or absence of sciatica, suggesting that, within the scope of this study, Neurotropin was associated with consistent pain relief, even in CLBP with neuropathic pain components. This is consistent with the fact that while NSAIDs primarily reduce nociceptive pain and have limited efficacy against neuropathic pain4), Neurotropin has demonstrated efficacy in neuropathic pain animal models6).
Interestingly, the results of this study indicate that psychiatric factors and fatigue-related pain exacerbation influence treatment response, suggesting that factors determining CLBP treatment outcomes may be common, regardless of the drug mechanisms of action.
No adverse events occurred in this study, confirming good tolerability in all 106 patients. The high safety profile of Neurotropin is well established, and unlike NSAIDs, it does not typically cause peptic ulcers or renal dysfunction due to its mechanism of action, representing a significant clinical advantage for safe long-term administration, even in elderly patients.
This study had several limitations. First, as a retrospective observational study, it lacked a placebo control and double-blinding, potentially allowing placebo effects or natural remission over time in observed pain reduction. The observed change may reflect a combination of placebo effects, regression to the mean, natural history, and potential treatment-related effects; the relative contribution of each cannot be determined without a randomized controlled trial. Second, the limited sample size of 106 patients may have resulted in insufficient statistical power to detect significant differences in the subgroup analyses. Third, the evaluation was primarily VAS-centered, and improvements in function and quality of life were not adequately assessed. Fourth, this study did not include long-term follow-up data beyond 12 weeks, and the durability of the pain-relieving effect remains unknown. Fifth, only the physician version of the BS-POP was used, which may underestimate psychiatric comorbidities compared with the combined use of physician and patient versions. The physician version was selected for practical reasons in busy outpatient settings, but future studies should consider using both versions for more comprehensive assessment. Sixth, non-pharmacological treatments such as physical therapy and rehabilitation were not systematically recorded and could not be controlled for in the analysis. Seventh, although we included concomitant medication status as a covariate in the multivariate analysis to address potential confounding, the heterogeneity in concomitant analgesic use (continuation, tapering, or discontinuation) may still introduce residual confounding that cannot be fully controlled in an observational study.
Future research should include larger prospective randomized controlled studies and incorporate more comprehensive evaluation indices, including patient-reported outcomes. Interventional studies validating the potential benefits of individualized treatment approaches based on the predictive factors identified in this study would also be valuable.
In conclusion, this retrospective observational study of patients with CLBP found that Neurotropin therapy was associated with significant improvement in VAS pain over 12 weeks of administration, with early pain reduction observed within 4 weeks of initiation. No adverse events were observed, confirming the excellent safety and tolerability of Neurotropin in older patients. While patients with suspected psychiatric problems (BS-POP scores ≥11) showed significantly reduced treatment response, the presence of sciatica and other neuropathic pain components did not appear to affect response to Neurotropin, suggesting its potential utility as an analgesic option for CLBP, including cases with neurogenic pain. Based on these findings, Neurotropin may be a beneficial treatment option for cases in which long-term NSAID use is difficult or for refractory CLBP with insufficient response to NSAIDs and other analgesics, although these findings require confirmation in randomized controlled trials. However, for patients with psychiatric problems, combining psychological support with psychiatric interventions may enhance treatment outcomes.
Author Contributions: Designed research, analyzed and/or interpreted the data, K.I., Y.E., S.O., Y.S., and S.O.; performed experiments, K.I., G.K., N.T., H.T., T.M., N.S, M.S., Y.S., M.I., T.H., S.O., K.T., M.M., S.T., A.I., and Y.O.; wrote the article, and K.I., Y.E., S.O., Y.S., and S.O. gave critical comments on the draft of the manuscript. All authors read and approved the final version of the manuscript.
Conflicts of Interest: The authors declare that there are no relevant conflicts of interest.
Disclaimer: Sumihisa Orita is one of the Editors of Spine Surgery and Related Research and on the journal's Editorial Committee. He was not involved in the editorial evaluation or decision to accept this article for publication at all.
Ethical Approval: 2894 (School of Medicine, Chiba University)
Informed Consent: Opt-out method
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