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Yoshinori Terashima,1,2 Tsuneo Takebayashi,3 Shunsuke Jimbo,1 Izaya Ogon,1 Tatsuya Sato,2 Nobutoshi Ichise,2 Noritsugu Tohse,2 Toshihiko Yamashita1 1Department of Orthopaedic Surgery, School of Medicine, Sapporo Medical University, Sapporo 060-0061, Japan; 2Department of Cellular Physiology and Signal Transduction, School of Medicine, Sapporo Medical University, Sapporo 060-0061, Japan; 3Sapporo Maruyama Orthopaedic Hospital, Sapporo 060-0007, Japan Purpose: Radicular pain is a frequently observed symptom of lumbar disk herniation or lumbar spinal canal stenosis. Achieving radicular pain relief is difficult. This type of pain may progress to chronic neuropathic pain. Calcitonin (elcatonin [eCT]) has been used mainly for hypercalcemia and pain associated with osteoporosis. The purpose of this study was to investigate analgesic effects of repeated eCT administration on radicular pain in male rats and changes in mRNA-expression levels of voltage-dependent sodium channels in the dorsal root ganglion (DRG). Methods: Seventy male Sprague-Dawley rats were used. A right L5 hemilaminectomy and an L5–L6 partial facetectomy were performed to expose the right L5 nerve root. Under a microscope, the right L5 spinal nerve root was tightly ligated extradurally with 8-0 nylon suture proximally to the DRG to cause radicular pain in rats. Mechanical hyperalgesia, thermal hyperalgesia, and analgesic effects of eCT were compared among rats with radicular pain that received eCT, those that received the vehicle, and sham rats that received the vehicle. Real-time reverse-transcription PCR was performed to measure mRNA-expression levels of tetrodotoxin-sensitive (NaV1.3 and NaV1.6) and tetrodotoxin-resistant (NaV1.8 and NaV1.9) sodium channels in the DRG. Results: Mechanical and thermal hyperalgesic reactions occurring in rats with radicular pain significantly improved on days 5 and 9 of eCT administration, respectively. In rats with radicular pain, mRNA-expression levels of NaV1.3, NaV1.8, and NaV1.9 increased. After repeated eCT administration, mRNA-expression levels of these sodium channels in rats with radicular pain improved to the same levels as in sham rats. Conclusion: The present study demonstrated that repeated systemic eCT administration was effective for radicular pain. No serious side effects of eCT have been reported thus far. Therefore, calcitonin may be a preferred therapeutic option for patients with radicular pain or for those requiring long-term treatment. Keywords: radiculopathy, hyperalgesia, lumbar disk herniation, lumbar spinal canal stenosis, sodium channel, elcatonin

Shunsuke Jimbo,1 Yoshinori Terashima,1,2 Atsushi Teramoto,1 Tsuneo Takebayashi,3 Izaya Ogon,1 Kota Watanabe,4 Tatsuya Sato,2,5 Nobutoshi Ichise,2 Noritsugu Tohse,2 Toshihiko Yamashita1 1Department of Orthopaedic surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; 2Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; 3Sapporo Maruyama Orthopaedic Hospital, Sapporo 060-0007, Japan; 4Department of Second Division of Physical Therapy, Sapporo Medical University School of Health Sciences, Sapporo 060-8556, Japan; 5Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan Purpose: Ankle osteoarthritis (OA) causes significant pain and debilitation; yet, its underlying mechanisms remain unclear. Clinically, hyaluronic acid (HA) is widely used to treat OA. The present study aimed to investigate the roles of HA in pain-related behavior, joint function, swelling, and pathological changes in cartilage in a rat model of monoiodoacetate (MIA)-induced ankle OA. Materials and methods: Male Sprague Dawley rats were assigned to three experimental groups as follows: 1) MIA rats injected with 1 mg MIA in the right tibiotarsal joint for two consecutive days; 2) sham rats injected with saline instead of MIA; and 3) MIA-HA rats injected with HA in the tibiotarsal joint at 7, 14, and 21 days after MIA injection. Joint swelling, range of motion (ROM), and pain-related behavior were evaluated 1 day before and on the 7th, 14th, 21st, and 28th day after MIA or saline injection. Pathological changes in the ankle joint were assessed 28 days after MIA or saline injection. Results: No significant difference in the degree of ankle swelling or ROM reduction was observed between MIA rats and MIA-HA rats. However, compared with those in MIA rats, mechanical and thermal hypersensitivity was significantly reduced and stride length significantly improved in MIA-HA rats. Histologic analysis revealed that cartilage degeneration was significantly suppressed in MIA-HA rats compared with that in MIA rats, reflecting the chondroprotective effects of HA. Conclusion: HA improved pain-related behavior and stride length and suppressed MIA-induced cartilage degeneration. HA may thus inhibit OA progression and suppress peripheral and/or central sensitization. Keywords: ankle osteoarthritis, monoiodoacetate, osteoarthritis pain, hyaluronic acid

Sayuri Katano1, Yasuyuki Nakamura1,2, Aki Nakamura1, Yoshitaka Murakami3, Taichiro Tanaka4, Toru Takebayashi5, Akira Okayama6, Katsuyuki Miura2, Tomonori Okamura7, Hirotsugu Ueshima2, for HIPOP-OHP Research Group1Cardiovascular Epidemiology, Kyoto Women's University, Kyoto, Japan; 2Department of Health Science, Shiga University of Medical Science, Otsu, Japan; 3Department of Medical Statistics, Shiga University of Medical Science, Otsu, Japan; 4Department of Health Sciences, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Japan; 5Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan; 6The First Institute of Health Service, Japan Anti-Tuberculosis Association, Tokyo, Japan; 7Department of Preventive Cardiology, National Cardiovascular Center, Suita, JapanObjective: To examine the relation between sleep duration and metabolic syndrome (MetS).Methods: We examined the baseline data from 4356 healthy workers (3556 men and 800 women) aged 19–69 years. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). We defined four components of MetS diagnostic components in this study as follows: 1) high blood pressure (BP) systolic BP [SBP] ≥ 130 mmHg, or diastolic BP [DBP] ≥ 85 mmHg, or on medication; 2) dyslipidemia (high-density lipoprotein-cholesterol concentration ,40 mg/dL, or triglycerides concentration ≥150 mg/dL, or on medication; 3) impaired glucose tolerance (fasting blood sugar concentration ≥ 110 mg/dL, or if less than 8 hours after meals ≥ 140 mg/dL), or on medication; and 4) overweight (body mass index [BMI] ≥ 25 kg/m2), or obesity (BMI ≥ 30 kg/m2). There were 680 participants in the group, with sleep duration