Neurotropin® ameliorates chronic pain associated with scar formation in a mouse model: A gene expression analysis of the inflammatory response.

Background: Scar formation after trauma and surgery involves an inflammatory response and can lead to the development of chronic pain. Neurotropin® (NTP) is a nonprotein extract of inflamed skin of rabbits inoculated with vaccinia virus. It has been widely used for the treatment of chronic pain. However, the in vivo effects of NTP on painful scar formation have not been determined. To investigate the molecular mechanisms underlying the effects of NTP on the inflammatory response, we evaluated gene expression in the scar tissues and dorsal root ganglions (DRGs) of mice administered NTP and control mice. Methods and results: Mice injected with saline or NTP were used as controls; other mice were subjected to surgery on the left hind paw to induce painful scar formation, and then injected with saline or NTP. Hind paw pain was evaluated by measuring the threshold for mechanical stimulation using the von Frey test. The paw withdrawal threshold gradually returned to pre-operative levels over 4 weeks post-operation; NTP-treated mice showed a significantly shortened recovery time of approximately 3 weeks, suggesting that NTP exerted an analgesic effect in this mouse model. Total RNA was extracted from the scarred hind paw tissues and DRGs were collected 1 week post-operation for a microarray analysis. Gene set enrichment analysis revealed that the expression of some gene sets related to inflammatory responses was activated or inhibited following surgery and NTP administration. Quantitative real-time reverse transcription-polymerase chain reaction analysis results for several genes were consistent with the microarray results. Conclusion: The administration of NTP to the hind paws of mice with painful scar formation following surgery diminished nociceptive pain and reduced the inflammatory response. NTP inhibited the expression of some genes involved in the response to surgery-induced inflammation. Therefore, NTP is a potential therapeutic option for painful scar associated with chronic pain.

Perioperative Analgesics and Anesthesia as Risk Factors for Postoperative Chronic Opioid Use in Patients Undergoing Total Knee Arthroplasty: A Retrospective Cohort Study Using Japanese Hospital Claims Data.

BACKGROUND: Patients with chronic postsurgical pain are commonly prescribed opioids chronically because of refractory pain although chronic opioid use can cause various severe problems. OBJECTIVE: We aimed to investigate postoperative chronic opioid use and its association with perioperative pain management in patients who underwent a total knee arthroplasty in a Japanese real-world clinical setting. METHODS: We conducted a retrospective cohort study using an administrative claims database. We used a multivariate logistic regression analysis to examine the association between perioperative analgesic and anesthesia prescriptions and postoperative chronic opioid use. We calculated all-cause medication and medical costs for each patient. RESULTS: Of the 23,537,431 patient records, 14,325 patients met the criteria and were included in the analyses. There were 5.4% of patients with postoperative chronic opioid use. Perioperative prescriptions of weak opioids, strong and weak opioids, and the α2δ ligand were significantly associated with postoperative chronic opioid use (adjusted odds ratio [95% confidence interval], 7.22 [3.89, 13.41], 7.97 [5.07, 12.50], and 1.45 [1.13, 1.88], respectively). Perioperative combined prescriptions of general and local anesthesia were also significantly associated with postoperative chronic opioid use (3.37 [2.23, 5.08]). These medications and local anesthesia were more commonly prescribed on the day following surgery, after routinely used medications and general anesthesia were prescribed. The median total direct costs were approximately 1.3-fold higher among patients with postoperative chronic opioid use than those without postoperative chronic opioid use. CONCLUSIONS: Patients who require supplementary prescription of analgesics for acute postsurgical pain are at high risk of postoperative chronic opioid use and these prescriptions should be given careful consideration to mitigate the patient burden.

Possible Repositioning of an Oral Anti-Osteoporotic Drug, Ipriflavone, for Treatment of Inflammatory Arthritis via Inhibitory Activity of KIAA1199, a Novel Potent Hyaluronidase.

KIAA1199 has a strong hyaluronidase activity in inflammatory arthritis. This study aimed to identify a drug that could reduce KIAA1199 activity and clarify its effects on inflammatory arthritis. Rat chondrosarcoma (RCS) cells were strongly stained with Alcian blue (AB). Its stainability was reduced in RCS cells, which were over-expressed with the KIAA1199 gene (RCS-KIAA). We screened the drugs that restore the AB stainability in RCS-KIAA. The effects of the drug were evaluated by particle exclusion assay, HA ELISA, RT-PCR, and Western blotting. We further evaluated the HA accumulation and the MMP1 and three expressions in fibroblast-like synoviocytes (FLS). In vivo, the effects of the drug on symptoms and serum concentration of HA in a collagen-induced arthritis mouse were evaluated. Ipriflavone was identified to restore AB stainability at 23%. Extracellular matrix formation was significantly increased in a dose-dependent manner (p = 0.006). Ipriflavone increased the HA accumulation and suppressed the MMP1 and MMP3 expression on TNF-α stimulated FLS. In vivo, Ipriflavone significantly improved the symptoms and reduced the serum concentrations of HA. Conclusions: We identified Ipriflavone, which has inhibitory effects on KIAA1199 activity. Ipriflavone may be a therapeutic candidate based on its reduction of KIAA1199 activity in inflammatory arthritis.

Efficacy and safety of magnetic resonance-guided focused ultrasound treatment for refractory chronic pain of medial knee osteoarthritis.

OBJECTIVE: To elucidate the efficacy and safety of MRgFUS in the treatment for refractory pain derived from medial knee OA. METHODS: Twenty patients with medial knee OA eligible for total knee arthroplasty were included in this prospective, non-controlled study (UMIN000010193). MRgFUS treatment was provided at the site of most severe tenderness around the medial femorotibial joint of each patient under real-time monitoring of temperature. The goal temperature of the targeted bone surface was 55 °C. Numerical rating scale (NRS) worst pain scores, Western Ontario and McMaster Universities osteoarthritis index (WOMAC) scores, EuroQol 5 dimensions index (EQ-5D) scores and pressure pain threshold (PPT) were evaluated before treatment (baseline) and at 1 week and 1, 3, 6, and 12 months post-treatment, respectively. Complications and adverse events were also assessed clinically and radiographically. RESULTS: Treatment response (a 50% or greater decrease in NRS score) was seen in 14 patients (14/19, 73.7%) at 12 months post-treatment. Mean NRS score rapidly decreased at 1 month after treatment and continued to decline through the following 12 months. At final follow-up, mean NRS score was 3.2 ± 1.9, significantly lower than at baseline (p = 0.0013). Mean WOMAC and EQ-5D scores also improved significantly from 1 month after treatment. Fifteen patients showed significant sustained increases in PPTs at the sites of most severe tenderness. No serious adverse events were observed during and after treatment. CONCLUSIONS: MRgFUS treatments were effective not only for managing refractory pain, but also for improving physical functions without adverse events in elderly patients with medial knee OA.

Bone marrow derived mast cells injected into the osteoarthritic knee joints of mice induced by sodium monoiodoacetate enhanced spontaneous pain through activation of PAR2 and action of extracellular ATP.

Conditions that resemble osteoarthritis (OA) were produced by injection of sodium monoiodoacetate (MIA) into the knee joints of mice. Bone marrow derived mast cells (BMMCs) injected into the OA knee joints enhanced spontaneous pain. Since no spontaneous pain was observed when BMMCs were injected into the knee joints of control mice that had not been treated with MIA, BMMCs should be activated within the OA knee joints and release some pain-inducible factors. Protease activated receptor-2 (PAR2) antagonist (FSLLRY-NH2) almost abolished the pain-enhancing effects of BMMCs injected into the OA knee joints, suggesting that tryptase, a mast cell protease that is capable of activating PAR2, should be released from the injected BMMCs and enhance pain through activation of PAR2. When PAR2 agonist (SLIGKV-NH2) instead of BMMCs was injected into the OA knee joints, it was also enhanced pain. Apyrase, an ATP degrading enzyme, injected into the OA knee joints before BMMCs suppressed the pain enhanced by BMMCs. We showed that purinoceptors (P2X4 and P2X7) were expressed in BMMCs and that extracellular ATP stimulated the release of tryptase from BMMCs. These observations suggest that ATP may stimulate degranulation of BMMCs and thereby enhanced pain. BMMCs injected into the OA knee joints stimulated expression of IL-1ß, IL-6, TNF-α, CCL2, and MMP9 genes in the infrapatellar fat pads, and PAR2 antagonist suppressed the stimulatory effects of BMMCs. Our study suggests that intermittent pain frequently observed in OA knee joints may be due, at least partly, to mast cells through activation of PAR2 and action of ATP, and that intraarticular injection of BMMCs into the OA knee joints may provide a useful experimental system for investigating molecular mechanisms by which pain is induced in OA knee joints.

Clipping Hind Paws Under Isoflurane Sedation as a Useful Tool for Evaluation of Chronic Pain in CCI Animals.

BACKGROUND: Several behavioral tests have been devised to assess pain in rodent models, one of which is the Chronic constriction injury (CCI) model of the sciatic nerve, including the sensitivity of the paw evaluated through reflex reactions to heat or mechanical stimuli. However, because of their high restless activity and responsiveness to humans, it is tough to give the moving animals consistent stimuli to get consistent and reliable reactions. METHODS: Experiments were performed on male C57BL/6J mice (aged eight weeks) and prairie voles (aged eight weeks). Sham animals (five mice and six prairie voles) and CCI animals (six mice and seven prairie voles) were tested before surgery, four days after, and seven days after surgery. Each animal was rated using a modified rating scale for the scoring of nociceptive behavior. The mechanical threshold test was administered by applying arterial clips to the base of toes under isoflurane-induced sedation. RESULTS: The right hind paw of the CCI administered side showed significant increases in the scores of nociceptive behavior on day 4 and day 7. The right hind paw of the CCI-administered side showed significant reductions in the mechanical threshold test on day 4 and day 7. CONCLUSIONS: The results of the mechanical threshold test were consistent with those of the scoring of nociceptive behavior in CCI model animals, and the method of using arterial clips under sedation was useful for the mechanical threshold test.

Association between Trunk Muscle Strength, Lumbar Spine Bone Mineral Density, Lumbar Scoliosis Angle, and Skeletal Muscle Volume and Locomotive Syndrome in Elderly Individuals: A Dual-Energy X-ray Absorptiometry Study.

INTRODUCTION: The present study aimed to investigate the association between trunk muscle strength, lumbar spine bone mineral density (BMD), lumbar scoliosis angle (LSA), and appendicular skeletal muscle mass index (ASMI) and the severity locomotive syndrome (LS) using dual-energy X-ray absorptiometry (DXA) technology in elderly individuals. METHODS: In this cross-sectional study, we enrolled 168 individuals aged >60 years. We measured their trunk muscle strength (flexion and extension) and BMD, LSA, and ASMI using DXA. We defined degenerative lumbar scoliosis (DLS) as LSA ≥ 10° by the Cobb method using the DXA image. The locomotor function was evaluated using the timed up-and-go (TUG) test and the 25-question Geriatric Locomotive Function Scale (GLFS-25) score. Normal locomotor function, LS-1, and LS-2 were defined as a GLFS-25 score of <7, ≥7 and <16, and ≥16, respectively. We compared the three groups, analyzing the associations between all variables and the locomotor function using univariate and multivariate analyses. RESULTS: Although there was no significant difference in sex ratio, BMD, ASMI, and trunk-flexor strength, significant differences were observed in age (p < 0.01), the prevalence of DLS (p = 0.02), trunk-extensor strength (p < 0.01), and trunk-extensor/flexor strength ratio (p < 0.01) among the three groups. In multiple regression analyses, the significant risk factors of the TUG test were age (ß = 0.26), body mass index (ß = 0.36), LSA (ß = 0.15), ASMI (ß = -0.30), and trunk-extensor strength (ß = -0.19), whereas the significant factor of the GLFS-25 score was trunk-extensor strength (ß = -0.31). CONCLUSIONS: The results indicate that it is clinically important for LS to pay careful attention not only to BMD but also to lumbar scoliosis when DXA examination of the lumbar spine is routinely conducted. Moreover, it is essential to note that trunk-extensor strength is more important than trunk-flexor strength in maintaining locomotor function in elderly individuals.

Forced expression of KIAA1199, a novel hyaluronidase, inhibits tumorigenicity of low-grade chondrosarcoma.

Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Chondrosarcoma, particularly when low-grade, is characterized by the formation of an extracellular matrix (ECM) containing abundant HA, and its drug/radiation resistance has become a clinically relevant problem. This study aimed to evaluate the effects of a novel hyaluronidase, KIAA1199, on ECM formation as well as antitumor effects on chondrosarcoma. To clarify the roles of KIAA1199 in chondrosarcoma, mouse KIAA1199 was stably transfected to Swarm rat chondrosarcoma (RCS) cells (histologically grade 1). We investigated the effects of KIAA1199 on RCS cells in vitro and an autografted model in vivo. HA binding protein (HABP) stainability and ECM formation in KIAA1199-RCS was markedly suppressed compared with that of control cells. No significant changes in messenger RNA expression of Has1, Has2, Has3, Hyal1, or Hyal2 were observed. KIAA1199 expression did not affect proliferation or apoptosis but inhibited migration and invasion of RCS cells. In contrast, the expression of KIAA1199 significantly inhibited the growth of grafted tumors and suppressed the stainability of alcian blue in tumor tissues. Although there was no direct inhibitory effect on proliferation in vitro, induction of KIAA1199 showed the antitumor effects in grafted tumor growth in vivo possibly due to changes in the tumor microenvironment such as inhibition of ECM formation. Forced expression of KIAA1199 exhibits antitumor effects on low-grade chondrosarcoma, which has chemo- and radio-therapy resistant features. Together, KIAA1199 could be a novel promising therapeutic tool for low-grade chondrosarcoma, mediated by the degradation of HA.

A Nationwide Survey of Spinal Cord-Related Pain Syndrome in Japan: Clinical Characteristics and Treatment.

INTRODUCTION: In this study, we defined chronic neuropathic pain (NeP) in patients with diseases associated with spinal cord damage, such as spinal cord-related pain syndrome, and performed a nationwide survey investigating the prevalence, actual status, and features of this syndrome in Japan in order to gather basic information needed for planning control measures. METHODS: In this nationwide epidemiologic survey, a mail-in questionnaire was sent to 3,206 institutions throughout Japan certified by the Japanese Orthopaedic Association (2,065 institutions) and the Japan Neurosurgical Society (1,141 institutions). The survey included the number of patients, frequency, and type of allodynia, concomitant diseases, and types of and responses to treatment. RESULTS: Valid responses were obtained from 552 institutions on 3,401 patients. Of these, 1,719 (50.5%) patients experienced no pain, and thus the study involved the analysis of data of the remaining 1,682 patients with pain. The most frequent underlying conditions were cervical spondylotic myelopathy (26.7%), spinal cord injury (17.4%), and ossification of the posterior longitudinal ligament (OPLL) of the cervical spine (14.1%). Among the 1,682 patients, 62.5% reported at-level pain, among which 43.0% presented with allodynia. On the other hand, 38.7% presented with below-level pain. The majority of patients (73.4%) used nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants (46.6%). The effectiveness of treatment was significantly higher in patients using anticonvulsants (31.1%) than in those using other medications. About a third of the patients stopped the treatment for either lack of effect or adverse effects. CONCLUSIONS: The characteristics of NeP in patients with spinal cord-related pain syndrome varied according to its level in relation to the affected spinal segment (at-level and/or below-level). Unfortunately, medications are sometimes ineffective and have potential adverse effects. Further classification of allodynia is needed for effective symptom-based treatment.

Effects of MRgFUS Treatment on Musculoskeletal Pain: Comparison between Bone Metastasis and Chronic Knee/Lumbar Osteoarthritis.

Local bone denervation by magnetic resonance-guided focused ultrasound (MRgFUS) is a promising tool for alleviation of pain in patients with painful bone metastasis (BM). Considering the underlying mechanism of pain alleviation, MRgFUS might be effective for various bone and joint diseases associated with local tenderness. This study was conducted to clarify the therapeutic effect of focused ultrasound in patients with various painful bone and joint diseases that are associated with local tenderness. Ten patients with BM, 11 patients with lumbar facet joint osteoarthritis (L-OA), and 19 patients with knee osteoarthritis (K-OA) were included. MRgFUS treatment was applied to the bone surface with real-time temperature monitoring at the target sites. Pain intensity was assessed using a 100 mm numerical rating scale (NRS) at various time points. Pressure pain threshold (PPT) was evaluated on the sonication area and control sites. Compared to baseline, the pain NRS scores significantly decreased in all groups 1 month after treatment, and PPT at the treated sites significantly increased in all groups 3 months after treatment. The percentage of patients who showed a ≥ 50% decrease in pain NRS scores at 1 month after treatment was 80% in BM, 64% in L-OA, and 78% in K-OA groups. PPTs were significantly higher after treatment at all evaluation time points. This study indicated that MRgFUS is effective in reducing pressure pain at the site of most severe tenderness in patients with painful bone and joint diseases. Treatment response was comparable between patients with BM, L-OA, and K-OA.

Lowering barometric pressure induces neuronal activation in the superior vestibular nucleus in mice.

Weather changes accompanied by decreases in barometric pressure are suggested to trigger meteoropathy, i.e., weather-related pain. We previously reported that neuropathic pain-related behavior in rats is aggravated by lowering barometric pressure, and that this effect is abolished by inner ear lesions. These results suggest that mechanisms that increase vestibular neuronal activity may parallel those that contribute to meteoropathy generation. However, it remains unknown whether changes in barometric pressure activate vestibular neuronal activity. To address this issue, we used expression of c-Fos protein as a marker for neural activation. Male and female mice were placed in a climatic chamber, and the barometric pressure was lowered by 40 hPa, from 1013 hPa, for 50 min (LP stimulation). The total number of c-Fos-positive cells in the vestibular nuclei was counted bilaterally after LP stimulation. We also video-recorded mouse behaviors and calculated the total activity score during the LP stimulation. LP stimulation resulted in significant c-Fos expression in the superior vestibular nucleus (SuVe) of male and female mice. There was no effect of LP stimulation on the total activity score. These data show that distinct neurons in the SuVe respond to LP stimulation. Similar mechanisms may contribute to the generation of meteoropathy in humans.

Pilot field testing of the chronic pain classification for ICD-11: the results of ecological coding.

BACKGROUND: A task force of the International Association for the Study of Pain (IASP) has developed a classification of chronic pain for the ICD-11 consisting of seven major categories. The objective was to test whether the proposed categories were exhaustive and mutually exclusive. In addition, the perceived utility of the diagnoses and the raters' subjective diagnostic certainty were to be assessed. METHODS: Five independent pain centers in three continents coded 507 consecutive patients. The raters received the definitions for the main diagnostic categories of the proposed classification and were asked to allocate diagnostic categories to each patient. In addition, they were asked to indicate how useful they judged the diagnosis to be from 0 (not at all) to 3 (completely) and how confident they were in their category allocation. RESULTS: The two largest groups of patients were coded as either chronic primary pain or chronic secondary musculoskeletal pain. Of the 507 patients coded, 3.0% had chronic pain not fitting any of the proposed categories (97% exhaustiveness), 20.1% received more than one diagnosis. After adjusting for double coding due to technical reasons, 2.0% of cases remained (98% uniqueness). The mean perceived utility was 1.9 ± 1.0, the mean diagnostic confidence was 2.0 ± 1.0. CONCLUSIONS: The categories proved exhaustive with few cases being classified as unspecified chronic pain, and they showed themselves to be mutually exclusive. The categories were regarded as useful with particularly high ratings for the newly introduced categories (chronic cancer-related pain among others). The confidence in allocating the diagnoses was good although no training regarding the ICD-11 categories had been possible at this stage of the development.

Suppression of hyaluronan synthesis attenuates the tumorigenicity of low-grade chondrosarcoma.

Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Chondrosarcoma, particularly when low-grade, is characterized by the formation of an extracellular matrix (ECM) containing abundant HA, and its drug/radiation resistance has become a clinically relevant problem. This study aimed to evaluate the effects of an HA synthesis inhibitor, 4-methylumbelliferone (MU), on ECM formation as well as antitumor effects in chondrosarcoma. We investigated the effects of MU on rat chondrosarcoma (RCS) cells with a grade I histological malignancy in vitro and in vivo grafted model. HA binding protein (HABP) stainability on and around the RCS cells was effectively reduced with treatment of MU. ECM formation was markedly suppressed by MU at a dose of 1.0 mM. Cell proliferation was significantly reduced by MU at 24 h. Cell motility and invasion were suppressed in a dose-dependent manner by MU. No significant changes in mRNA expression of Has1-3 were observed. Furthermore, MU inhibited the growth of grafted tumors in vivo. Histologically, chondrosarcoma cells of control tumors showed a cell-clustering structure. HABP stainability was markedly decreased in the MU-treated group. These results suggest that MU exhibits antitumor effects on low-grade chondrosarcoma, via inhibition of HA accumulation and ECM formation. MU, which is an approved drug in bile therapy, could be a new off-label medication for chondrosarcomas. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1573-1580, 2018.

Prevalence, characteristics, and burden of failed back surgery syndrome: the influence of various residual symptoms on patient satisfaction and quality of life as assessed by a nationwide Internet survey in Japan.

We conducted a cross-sectional, Internet-based survey with a nationally representative sample of Japanese adults to assess the prevalence and characteristics of failed back surgery syndrome (FBSS). Data regarding the residual symptoms and patient satisfaction from an online survey of 1842 lumbar surgery patients revealed the prevalence of FBSS to be 20.6% (95% confidence interval [CI], 18.8-22.6). The prevalence of low back pain, dull ache, numbness, cold sensations, and paresthesia after surgery was 94.0%, 71.1%, 69.8%, 43.3%, and 35.3%, respectively. With a logistic regression model, severe residual low back pain (numerical rating scale 8-10), higher pain intensity, and multiple low back surgeries were strongly associated with FBSS, with odds ratios of 15.21 (95% CI, 7.79-29.7), 1.40 (95% CI, 1.32-1.49), and 1.87 (95% CI, 1.25-2.81), respectively. Respondents with FBSS had significantly lower EuroQol-5D (P<0.001) values and significantly higher scores on the Kessler six-item psychological distress scale (P<0.001), compared with the non-FBSS group. Our findings indicate that residual sensations have a significant effect on patient quality of life, similar to that of chronic low back pain. Precise presurgical provision of prognoses based on comprehensive epidemiologic data, as well as scrupulous attention to patient satisfaction and clinical progress may help reduce the incidence of FBSS.

The Effect of Guidance regarding Home Exercise and ADL on Adolescent Females Suffering from Adverse Effects after HPV Vaccination in Japanese Multidisciplinary Pain Centers.

Background. Two prophylactic papillomavirus (HPV) vaccines have been available for primary prevention of cervical cancer. Although serious adverse effects (AE) were rare, more than 230 women have been suffering from severe AEs such as persistent pain and headache in Japan. Our research group started to treat adolescent females suffering from the AEs. Objective. To survey the characteristics of and the effects of cognitive behavioral therapy on adolescent female suffering from the AEs in Japanese multidisciplinary pain centers. Methods. One hundred and forty-five patients suffering from the AEs were reviewed retrospectively and 105 patients of them were provided guidance on home exercise and activities of daily living based partially on a cognitive-behavioral approach. The intensity of pain was rated by the patients using a numerical rating scale (NRS). Furthermore, the Hospital Anxiety and Depression Scale (HADS) and the Pain Catastrophizing Scale (PCS) were used. Results. Eighty out of the 105 patients who received the guidance were followed up, 10 displayed a marked improvement, and 43 showed some improvement. Conclusions. Guidance on home exercise and activities of daily living based on a cognitive-behavioral approach alleviated the AEs that women suffered from after HPV vaccination in Japan.

Fibromyalgia and Chronic Pain Syndromes: A White Paper Detailing Current Challenges in the Field.

This manuscript, developed by a group of chronic pain researchers and clinicians from around the world, aims to address the state of knowledge about fibromyalgia (FM) and identify ongoing challenges in the field of FM and other chronic pain syndromes that may be characterized by pain centralization/amplification/hypersensitivity. There have been many exciting developments in research studies of the pathophysiology and treatment of FM and related syndromes that have the potential to improve the recognition and management of patients with FM and other conditions with FM-like pain. However, much of the new information has not reached all clinicians, especially primary care clinicians, who have the greatest potential to use this new knowledge to positively impact their patients' lives. Furthermore, there are persistent misconceptions about FM and a lack of consensus regarding the diagnosis and treatment of FM. This paper presents a framework for future global efforts to improve the understanding and treatment of FM and other associated chronic pain syndromes, disseminate research findings, identify ways to enhance advocacy for these patients, and improve global efforts to collaborate and reach consensus about key issues related to FM and chronic pain in general.

Prevalence and Location of Neuropathic Pain in Lumbar Spinal Disorders: Analysis of 1804 Consecutive Patients With Primary Lower Back Pain.

STUDY DESIGN: A cross-sectional study of 1804 consecutive patients. OBJECTIVE: The aim of this study was to investigate the prevalence of pathological pain and its distribution features in patients with chronic lumbar spinal disorders. SUMMARY OF BACKGROUND DATA: Clinical spinal disorders can involve pathological neuropathic pain (NeP) as well as physiological nociceptive pain (NocP), as they have varied pathology, including spinal cord injury, stenosis, and compression. A study conducted by the Japanese Society for Spine Surgery and Related Research (JSSR) has determined a prevalence of 29.4% for NeP in patients with lumbar spinal disorder. However, the data did not include information on pain location. METHODS: Patients aged 20 to 79 years with chronic lower back pain (≥3 months, visual analog scale score ≥30) were recruited from 137 JSSR-related institutions. Patient data included an NeP screening questionnaire score and pain location (lower back, buttock, and legs). The association between the pain pathology and its location was analyzed statistically using the unpaired t test and Chi-square test followed by Fisher test. P < 0.05 was considered significant. RESULTS: Low back pain subjects showed 31.9% of NeP prevalence, and the pain distribution showed [NocP(%)/NeP(%)] low back pain only cases: 44/22, while low back pain with leg pain cases showed a prevalence of 56/78. This indicates that low back pain alone can significantly induce NocP rather than NeP (P < 0.01). Buttock pain was revealed to significantly induce both lower back pain and leg pain with NeP properties (P < 0.01). Leg pain was revealed to be predominantly neuropathic, especially when it included peripheral pain (P < 0.01). CONCLUSION: Low back pain with no buttock pain induces NocP rather than NeP. Buttock pain is significantly associated with NeP prevalence whether or not leg pain exists. Leg pain can increase the prevalence of NeP, especially when it contains a peripheral element. LEVEL OF EVIDENCE: 3.

Burdensome problems of chronic musculoskeletal pain and future prospects.

According to a recent survey, about 15 % of the Japanese population suffers from moderate-severe chronic musculoskeletal pain persisting for at least 6 months. Social factors and related psychological factors (including depression) thus appear to greatly affect chronic musculoskeletal pain. This suggests the need for measures that take these factors into account. Treatment for musculoskeletal pain at present is generally based on a biomedical model that has been used for many years in this field, and modern medical imaging technologies have been a high priority to support this model and treatment strategy. Under the concept of the biomedical model, nonsteroidal antiinflammatory drugs, channel blockers and opioid analgesics are generally used as pharmacotherapy to alleviate chronic pain. However, these drugs are commonly associated with problems such as adverse effects, drug dependency and drug abuse, and they must be used with care. Surgery may also be effective in treating certain diseases, but studies have shown that many patients suffer residual chronic pain even after such treatment. Besides, exercise therapy has been found to be effective in treating many different types of chronic pain. Lately, various countries have been launching interdisciplinary pain centers that use a multidisciplinary approach to treat chronic musculoskeletal pain. Treatment in these centers is provided by a team of specialists in anesthesiology, psychiatry and orthopedics as well as the relevant paramedical professionals. The therapeutic strategy is based on a cognitive-behavioral approach, and patients are taught about methods for restoring physical function and coping with pain, mostly with drugs and exercise therapy, so that any pain present does not impair function and the patient can reintegrate into society.

The dorsal pedis artery as a new distal landmark for extramedullary tibial alignment in total knee arthroplasty.

PURPOSE: It is better to use multiple anatomical landmarks to reduce errors in component alignment in total knee arthroplasty. Therefore, it is worthwhile to find a new landmark that can be used as an addition to conventional ones. Herein, we assessed the dorsal pedis artery as a new distal landmark for extramedullary tibial alignment. METHODS: Fifty-two ankles in patients undergoing total knee arthroplasty and 10 ankles in normal controls were included. Color Doppler ultrasonography was used to locate the dorsal pedis artery at the level of the ankle joint. Conventional landmarks, including the tibialis anterior tendon, the extensor hallucis longus tendon, the extensor digitorum longus tendon, and the malleolar centre, were also located on ultrasound images. The distances between the ankle centre and each landmark were measured and compared. RESULTS: The dorsal pedis artery was absent in 2 patients and impalpable but visible with ultrasonography in other 2 patients. The dorsal pedis artery was located anatomically closest to the ankle centre in patients (0.4 ± 3.4 mm lateral). Statistical analysis showed that the dorsal pedis artery, the extensor hallucis longus tendon, and the malleolar centre were located significantly closer to the ankle centre comparing with the extensor digitorum longus tendon and the tibialis anterior tendon in both patients and controls (p < 0.001). CONCLUSIONS: As long as the dorsal pedis artery exists, it can be used as an addition to the conventional landmarks in total knee arthroplasty. Using this new landmark will help reduce errors in coronal plane alignment of tibial component. LEVEL OF EVIDENCE: II.