稲毛 一秀

STUDY DESIGN: Retrospective study. PURPOSE: To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. OVERVIEW OF LITERATURE: Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. METHODS: Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. RESULTS: No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (p<0.001). CONCLUSIONS: Low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy might decrease the incidence of adverse events and prevent the transition of acute low back pain to chronic low back pain.

腰痛の診療にあたるうえで必要となる最低限の知識および解剖学的要素について概観した。腰痛は国民愁訴のなかでも最多と位置づけられているが、その原因は多岐にわたることも多く、また画像所見がすべて症状に直結するわけではないため、患者の主訴と身体所見を基に十分な考察を加えていくことが重要である。この際に必要となるのが疼痛の正確な知識(急性・慢性疼痛や侵害受容性疼痛、神経障害性疼痛など)や腰痛に関連する解剖学的知識(椎間板・椎体の神経支配や椎間関節における連結、矢状面アライメントなど)である。これらの事項を念頭に詳細な腰痛診断と評価を行い、患者の状況を把握することが医師、看護師や理学療法士を含むすべての腰痛診療に従事する医療スタッフにおいて重要である。また、近年では精神科医や臨床心理士など多職種のスタッフによる腰痛へのリエゾン療法の確立が求められつつある。(著者抄録)

腰痛はいうまでもなく国民病の一つであり、84%の人が一生のうちに一度は経験する。慢性腰痛は発症からの期間が3ヵ月以上と定義される。腰痛の原因は、脊椎由来、神経由来、内臓由来、血管由来、心因性の五つに大別される。腰痛の85%は診察および画像所見において明らかな器質的要因が認められない腰痛(非特異的腰痛)である。腰痛診断のポイントは、(1)危険信号(red flag)を有する腰痛、(2)神経症状を伴う腰痛、(3)非特異的腰痛の診断学的トリアージを十分に行うことである。慢性腰痛の治療には薬物療法、物理・装具療法、運動療法、手術療法などがある。慢性腰痛の治療のうち単独で有効性が確認されている治療法は少なく、それぞれの治療法を複合的に実施していくことが重要である。(著者抄録)

BACKGROUND: Far-out syndrome was reported by Wiltse et al. in 1984, which is a condition characterized by L5 spinal nerve radiculopathy due to nerve compression between the L5 transverse process and sacral alar. Although many cases of far-out syndrome have been reported, to our knowledge, the present case firstly showed far-out syndrome due to assimilated L4 hemivertebra and L5 vertebra through which abnormal nerve root passed. CASE PRESENTATION: A 71-year-old man presented with left lower back pain and intermittent claudication accompanied by severe left buttock pain. Radiological examination showed assimilation between the L4 hemivertebra and L5 vertebra, which had two pedicles on the right side, with no canal stenosis. However, computed tomography and magnetic resonance imaging of coronal sections showed extraforaminal stenosis between the L5 transverse process and sacral alar, whereby the L5 spinal nerve was pinched ("far-out lesion"), and an abnormal nerve root passage in the assimilated vertebral corpus. We performed transforaminal lumbar interbody fusion, then resected the L5 transverse process to decompress the extraforaminal stenosis, and finally installed pedicle screws, but not at the one of pedicles of the assimilated vertebra in order to prevent nerve injury. Postoperatively, the patient had no symptoms up to 1.5 years after the surgery. CONCLUSION: The current case suggests the importance of detailed preoperative examination of patients with anatomical abnormalities such as assimilated vertebrae, which may result in incorrect diagnosis and failed surgery.

慢性腰痛患者へのブロック注射から得られた知見からは、疼痛発生部位の可能性として、椎間板39〜41%、椎間関節15〜32%、仙腸関節13〜18.5%と報告された。椎間板性腰痛の症状として、前屈時の腰痛増強がその指標とされる。当院において椎間板性腰痛と診断され、固定術を施行された87名を対象とし、その術前の症状を検討した結果、前屈時増強65%、後屈時増強35%であり多彩な症状を呈することが判明した。椎間板造影は一般的に用いられる診断方法であるが、患者の心理社会的背景により陽性率が高くなる。われわれは椎間板造影による疼痛再現と、椎間板ブロックによる除痛による診断を行い、有意に手術成績を高めることができることを報告した。椎間板性腰痛に対する治療は未だ結論が無い。数個のrandomized control trialが存在する。保存療法と手術療法を比較し、その結果は相反するものであった。手術方法としては、椎間板性腰痛に対し、後方固定術、前後合併等の手術を比較した結果、椎間板操作をしなくても、いずれの手術方法も腰痛を軽減させ、有意差がないことが報告された。われわれも、椎間板性腰痛に運動療法、前方法、後側方固定術の比較を行った。前方固定術が僅かながらに有意に優れていたが、後側方固定術も成績が良好であった。(著者抄録)

抗RANKL(Receptor Activator of Nuclear factor Kappa-B Ligand)抗体を投与した閉経後骨粗鬆症患者40例(平均72.7±9.5歳)を対象として、骨代謝マーカーの経時的変化および椎体骨の力学的変化について検討した。投与前後の骨吸収マーカー、骨形成マーカー、腰椎YAM(Young Adult Mean)値と第1腰椎において1要素が圧迫破壊される応力(平均骨折荷重値)を測定した結果、投与後1ヵ月では骨吸収マーカーの有意低下を認めたにもかかわらず、骨形成マーカーは比較的保たれており、投与後6ヵ月ではカップリング効果が生じたものの骨密度の有意な増加と骨強度の有意上昇がみられた。抗RANKL抗体は良好な骨代謝環境調整作用を示すとともに、骨密度と骨強度の増加をもたらし、さらなる骨折予防に有効であることが示唆された。

STUDY DESIGN: Retrospective case series. PURPOSE: To determine whether symptoms predict surgical outcomes for patients with discogenic low back pain (DLBP). OVERVIEW OF LITERATURE: Specific diagnosis of DLBP remains difficult. Worsening of pain on flexion is a reported symptom of DLBP. This study sought to determine whether symptoms predict surgical outcomes for patients with DLBP. METHODS: We investigated 127 patients with low back pain (LBP) and no dominant radicular pain. Magnetic resonance imaging was used to select patients with disc degeneration at only one level. If pain was provoked during discography, we performed fusion surgery (87 patients). Visual analogue scale score and responses to a questionnaire regarding symptoms including worsening of pain on flexion or extension were assessed. Symptom sites before surgery were categorized into LBP alone, or LBP plus referred inguinal or leg pain. We followed 77 patients (average 3.0 years) and compared symptoms before surgery with surgical outcome. RESULTS: Sixty-three patients with a good outcome showed postsurgical pain relief (≥60% pain relief) and 14 patients with a poor outcome did not (<60% pain relief). In patients with good outcomes, worsening of LBP was evident in 65% of cases on flexion and in 35% on extension. However, these findings were not significantly different from those in patients with poor outcomes. The percentage of patients with LBP alone was significantly lower and the percentage of patients with LBP plus referred inguinal or leg pain was significantly higher in the group with good surgical outcome compared with patients in the group with poor surgical outcome (p<0.05). CONCLUSIONS: Worsening of pain on extension may be a symptom of DLBP. Surgical outcomes were superior in patients with both LBP and either referred inguinal or leg pain compared with those having LBP alone.

STUDY DESIGN: Retrospective case series. PURPOSE: To classify back muscle degeneration using magnetic resonance imaging (MRI) and investigate its relationship with back pain after surgery. OVERVIEW OF LITERATURE: Back muscle injury and degeneration often occurs after posterior lumbar surgery, and the degeneration may be a cause of back pain. However, the relationship between back muscle degeneration and back pain remains controversial. METHODS: A total of 84 patients (average age, 65.1 years; 38 men, 46 women) with lumbar spinal stenosis underwent posterior decompression surgery alone. MRI (1.5 tesla) was evaluated before and more than a year after surgery in all patients. Muscle on MRI was classified into three categories: low intensity in T1-weighted imaging, high intensity in T2-weighted imaging (type 1), high intensity in both T1- and T2-weighted images (type 2), and low intensity in both T1- and T2-weighted imaging (type 3). The prevalence of the types and their relationship with back pain (determined on a visual analog scale) were evaluated. RESULTS: MRI revealed muscle degeneration in all patients after surgery (type 1, 6%; type 2, 82%; and type 3, 12%). Type 2 was significantly more frequent compared with types 1 and 3 (p<0.01). Low back pain was significantly improved after surgery (p<0.01). Low back pain was not associated with any MRI type of muscle degeneration after surgery (p>0.05). CONCLUSIONS: Various pathologies of back muscle degeneration after posterior lumbar surgery were revealed. Type 2 (fatty) change was most frequent, and other patients had type 3 (scar) or type 1 (inflammation or water-like) changes. According to the Modic classification of bone marrow changes, Modic type 1 change is associated with inflammation and back pain. However, no particular type of back muscle degeneration was correlated with back pain after surgery.

近年、低侵襲前方固定として、Extreme lateral interbody fusion(XLIF)、Oblique lateral interbody fusion(OLIF)法が導入された。これらは大きな矯正力をもち、(1)間接除圧による手術、(2)脊柱変形に対する手術に対して有効な手術方法であるが、前方固定特有の合併症がある。XLIFは完全側臥位にて腸腰筋の真横からアプローチする方法で、OLIFはやや斜め前方から侵入する方法である。両者の共通の合併症としてケージのsubsidence、椎体終板損傷、術後大腿部の痺れ、違和感、分節動脈損傷がある。XLIFの方が頻度の高いものとして、脊髄神経損傷、下行結腸傷害、逆にOLIFの方が頻度の高いものとして、尿管損傷、腹膜損傷、逆行性射精がある。これらは術中に対応可能な場合と、不可能な場合がある。本稿ではOLIFにおける合併症の頻度、実際、その対策、予後について記載したい。(著者抄録)

PURPOSE: The pathophysiology of discogenic low back pain is not fully understood. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are associated with primary sensory nerve transmission, and the NaV1.7 channel has emerged as an analgesic target. Previously, we found increased NaV1.7 expression in dorsal root ganglion (DRG) neurons innervating injured discs. This study aimed to examine the effect of blocking NaV1.7 on sensory nerves after disc injury. MATERIALS AND METHODS: Rat DRG neurons innervating the L5/6 disc were labeled with Fluoro-Gold (FG) neurotracer. Twenty-four rats underwent intervertebral disc puncture (puncture group) and 12 rats underwent sham surgery (non-puncture group). The injury group was divided into a saline infusion group (puncture+saline group) and a NaV1.7 inhibition group, injected with anti-NaV1.7 antibody (puncture+anti-NaV1.7 group); n=12 per group. Seven and 14 days post-surgery, L1 to L6 DRGs were harvested and immunostained for calcitonin gene-related peptide (CGRP) (an inflammatory pain marker), and the proportion of CGRP-immunoreactive (IR) DRG neurons of all FG-positive neurons was evaluated. RESULTS: The ratio of CGRP-IR DRG neurons to total FG-labeled neurons in the puncture+saline group significantly increased at 7 and 14 days, compared with the non-puncture group, respectively (p<0.05). Application of anti-NaV1.7 into the disc significantly decreased the ratio of CGRP-IR DRG neurons to total FG-labeled neurons after disc puncture at 7 and 14 days (40% and 37%, respectively; p<0.05). CONCLUSION: NaV1.7 antibody suppressed CGRP expression in disc DRG neurons. Anti-NaV1.7 antibody is a potential therapeutic target for pain control in patients with lumbar disc degeneration.

Transforaminal lumbar interbody fusion (TLIF) is a popular posterior spinal fusion technique, but sometimes require salvage surgery when implant failure occurs, which involves possible neural damage due to postoperative adhesion. The current report deals with successful anterior transperitoneal salvage surgery for failed L5-S TLIF with less neural invasiveness.

INTRODUCTION: Although muscle injury is a common source of pain, the mechanism causing such pain is not completely known. We have previously reported nerve growth factor (NGF) as a proinflammatory mediator involved in acute pain, and clinical trials have shown the effectiveness of anti-NGF antibodies for management of low back pain. Here, we aim to examine the effects of anti-NGF antibodies on muscle-derived pain by studying their effects on sensory innervation in a rat muscle injury model. METHODS: A nervous system tracer, Fluoro-Gold, was applied to both gastrocnemius muscles of 24 male Sprague Dawley rats to stain the sensory nerves. Then, the drop-mass method was used to damage the right gastrocnemius muscle of the posterior limb. Anti-NGF antibodies (50μL) were injected into the injured muscles in 12 rats. Tissues were evaluated 1, 3, and 7 days post-injury by performing haematoxylin-and-eosin (HE) staining. The percentage of the total number of FG-positive cells that were also positive for a pain-related neuropeptide, calcitonin gene-related peptide (CGRP), was determined for the bilateral dorsal root ganglia from L1 to L6 7 days post-injury. RESULTS: HE staining showed active inflammation, indicated by increased basophil and eosinophil accumulation, at the injury site 1 and 3 days post-injury, as well as scar tissue formation 7 days post-injury. Injection of anti-NGF reduced muscle necrosis 1 and 3 days post-injury, and resulted in replacement of granulation tissue and muscle fibre regeneration 7 days post-injury. Anti-NGF also significantly inhibited CGRP among FG-positive cells (treatment group 38.2%, control group 49.6%; P<0.05). DISCUSSION: This study found active inflammation induced by NGF, which may contribute to pain after muscle injury. Anti-NGF antibodies successfully suppressed the pain mediator NGF and inhibited inflammation, suggesting NGF as a target for control in pain management.

ビスホスホネートによる骨粗鬆症に対する治療効果と除痛効果との関連について検討した。対象は腰痛を呈するも骨折のない骨粗鬆症患者113例(男性9例、女性104例、平均年齢73.8±8.0歳)で、ミノドロン酸水和物50mgを平均5.6ヵ月間投与した。その結果、1)痛みに関する経時的評価では腰痛平均NRSは安静時では開始前2.85±2.10、1ヵ月後2.64±2.31、2ヵ月後2.30±2.14、3ヵ月2.02±2.11、4〜6ヵ月後2.20±2.11と、投与2ヵ月後で開始時と比較し有意な低下が認められた。2)体動時腰痛NRSでは開始時4.67±2.84、1ヵ月後4.22±2.67、2ヵ月4.13±2.64、3ヵ月3.94±2.74、4〜6ヵ月3.81±2.71と経時的に軽減し、投与1ヵ月で開始時に比較し有意な低下がみられた。3)骨粗鬆症の治療効果に関する経時的評価では腰椎平均骨密度は開始時0.62±0.20g/cm2、4〜6ヵ月後0.64±0.20g/cm2と有意差は認められなかった。4)骨代謝マーカーの経時的変化では平均TRACP-5b値は開始時504.2±218.5から1ヵ月後306.0±135.7mu/dlと有意に低下(平均改善率36.5%)した。5)安静時NRS改善率とTRACP-5b改善率は有意な正の相関が認められたものの、体動時NRS改善率とTRACP-5b改善率は有意な相関はみられなかった。

【はじめに，目的】我が国では今日，超高齢社会を迎え，高齢者のQOL（quality of life）の向上は，必須の課題と考える。近年では，高齢者におけるQOL低下を招く原因として，サルコペニアによる筋量減少と骨粗鬆症による骨密度低下が注目されている。また，サルコペニアによる筋量減少は転倒などのリスクを増大させ，骨粗鬆症では骨折などのリスクを増大させることで，QOLの低下の原因になると考える。骨粗鬆症とサルコペニアにおいて様々な研究がなされているが，年代別にみた研究は数少ない。そこで本研究では，対象者全体と年代別にみた骨密度と筋量の関係について明らかにすることを目的とした。【方法】対象は2015年4月15日から10月2日までに当院に来院した60歳以上で椎体骨折，側弯変形，卵巣摘出手術など骨密度に影響を与えない，閉経女性394例（年齢74±7.09，身長158±5.85cm，体重51±9.44kg）とした。そのうち，60代121例（年齢65±2.74歳，身長154±5.33cm，体重52±10.76kg），70代187例（年齢75±2.90歳，身長151±5.13cm，体重51±9.20kg），80代86例（年齢83±2.60歳，身長148±6.04cm，体重49±7.31kg）と3群に群分けを行った。骨密度は，DXA法（GE社製DPX-BRAV）を用い，腰椎・大腿骨全体・大腿骨頸部の各骨密度を測定した。筋量は，インピーダンス法（InBody720，BIOSPACE社製）を用い，両上肢・両下肢の骨格筋量を体重比で正規化した骨格筋量指標（skeletal muscle mass index以下，SMI）を算出した。統計学的分析として，それぞれ年代別の腰椎・大腿骨全体・大腿骨頚部の各骨密度とSMIの相関にはspearmanの順位相関係数を用い，有意水準は1％未満とした。【結果】対象全体での骨密度とSMIは，各測定部位ともに正の相関関係を示した（相関係数：腰椎0.29，大腿骨全体0.39，大腿骨頸部0.40，すべてP＜0.01）。年代別（60代→70代→80代）にみると，加齢とともに全ての測定部位において相関係数は低下していた（相関係数：腰椎0.49→0.30→0.18，大腿骨全体0.46→0.40→0.29，大腿骨頸部0.41→0.40→0.15，80代の腰椎，大腿骨頸部のみP＞0.01，他はすべてP＜0.01）。DXA測定部位別にみると，大腿骨全体のみ全年代にわたり有意な相関関係を示していた（P＜0.01）。【結論】本研究では，対象全体での骨密度とSMIは相関するという結果を得た。すなわち，筋量の増加が骨密度の維持に繋がる可能性が示唆された。一方で，各年代別にみると加齢とともに，骨密度とSMIの相関度は低下していた。このことは，高齢になればなるほど，様々な運動器疾患（変形性膝関節症や変形性脊椎症など）が合併する頻度が高まるためと推測された。そのため，80歳以前の骨粗鬆症，サルコペニアの早期治療が必要である可能性も考えられる。今後は，骨粗鬆症，サルコペニアに対して，運動療法の介入方法を検討し，治療・予防効果を明確にしていく。

OBJECTIVE: To examine the analgesic effect of intradiscal administration of a tumor necrosis factor-αα (TNF-α) inhibitor in patients with discogenic low back pain (LBP). DESIGN: Prospective, randomized study. SETTING: Department of Orthopaedic Surgery, Chiba (Japan) University Hospital. SUBJECTS: Seventy-seven patients diagnosed with discogenic LBP. METHODS: Discogenic LBP patients were randomly assigned to the etanercept (n = 38; bupivacaine [2 mL] with etanercept [10 mg]) or control (n = 39; bupivacaine [2 mL]) groups. Patients received a single intradiscal injection. Numerical rating scale (NRS) scores for LBP at baseline, 1 day, and 1, 2, 4, and 8 weeks after the injection were recorded. The Oswestry disability index (ODI) scores at baseline and at 4 and 8 weeks after injection were evaluated. Postinjection complications were recorded and evaluated. RESULTS: In the etanercept group, the NRS scores were significantly lower than in the control group at every time point after the injection for 8 weeks (P < 0.05). Similarly, 4 weeks after the injection, the ODI score was lower in the etanercept group than in the control group (P < 0.05). However, the ODI scores were not significantly different at 8 weeks. Complications were not observed. CONCLUSIONS: Single intradiscal administration of a TNF-α inhibitor can alleviate intractable discogenic LBP for up to 8 weeks. TNF-α may be involved in discogenic pain pathogenesis. This procedure is a novel potential treatment; longer-term effectiveness trials are required in the future.

BACKGROUND: Inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, are gaining attention as important etiologic factors associated with discogenic low back pain. We conducted a prospective cohort study to evaluate the efficacy and safety of intradiscal injection of the interleukin-6 receptor antibody tocilizumab in patients with discogenic low back pain. METHODS: Thirty-two consecutive patients were intradiscally injected with 2 mL of 0.5% bupivacaine (control group). Another 31 consecutive patients were intradiscally injected with 40 mg tocilizumab and 1-2 mL of 0.5% bupivacaine (tocilizumab group) at the same time. Prior to treatment, the vertebral origin of low back pain was confirmed in all patients based on pain provocation during discography and pain relief with 1 mL of 1% xylocaine. Numeric rating scale and Oswestry disability index scores were used to evaluate pain level before and after treatment between the 2 groups. The association between pain relief with tocilizumab and intervertebral disc degeneration grade was also determined. RESULTS: At the end of the study (8 weeks after treatment), 30 patients in each group were evaluable. In the tocilizumab group, numeric rating scale and Oswestry disability index scores improved significantly at 2 and 4 weeks after treatment, respectively. Intervertebral disc degeneration was not associated with improvement of numeric rating scale score in the tocilizumab group. Local infection (i.e., discitis) was observed in 1 patient in the tocilizumab group. CONCLUSIONS: The results demonstrate the clinical relevance of interleukin-6 in discogenic low back pain. Intradiscal tocilizumab injection was shown to exert a short-term analgesic effect in patients with discogenic low back pain. Further research is required to determine the long-term effects of intradiscal tocilizumab therapy in patients with discogenic low back pain.