This study examined the effects of immobilization and low–intensity isotonic muscle contraction exercise on swelling and pain threshold during the early stages of arthritis in rats.
   Twenty–one male Wistar rats (8 weeks old) were randomly divided into 4 groups: (1) arthritis group (n=5); (2) arthritis and immobilization group (immobilization group, n=5); (3) arthritis and exercise group (exercise group, n=6); and (4) sham arthritis control group (control group, n=5). Arthritis was induced by injecting a mixture of 3% kaolin and 3% carrageenan into the right knee joint. Plaster casts were used to immobilize the right knee joint of rats in the immobilization group. Low–intensity isotonic muscle contraction of the quadriceps was initiated the day after injection and induced by electric stimulation (frequency, 50 Hz; intensity, 2 – 3 mA) for 20 min/day, 6 days/week, over 4 weeks. Joint swelling was determined by measuring the width of the knee joint. The pressure withdrawal threshold (PWT) was measured in the area of the lateral knee joint using a strain gauge algometer. Mechanical hypersensitivity in the hind paw was evaluated using von Frey filaments.
   Joint swelling was significantly increased for 2 weeks after injection in the arthritis and exercise groups compared with that in the control group. In the immobilization group, joint swelling remained significantly increased for 4 weeks compared with that in the control group. The PWT was decreased from the first day after injection in the arthritis, immobilization, and exercise groups. In the exercise group, the PWT was significantly increased at 1 week after injection compared with that in the arthritis and immobilization groups, and did not differ from that in the control group at 3 weeks after injection. Mechanical hypersensitivity was observed from the first day after injection and lasted for 4 weeks in the arthritis and immobilization groups. In the immobilization group, the mechanical hypersensitivity was significantly increased at 4 weeks after injection compared with that in the arthritis group. In contrast, the mechanical hypersensitivity in the exercise group did not differ from that in the control group at 2 weeks after injection.
   We conclude that early initiation of low–intensity isotonic muscle contraction after the induction of joint inflammation can alleviate inflammatory symptoms and prevent the induction of chronic hyperalgesia outside of arthritic lesions.

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   Bladder pain is a most prominent feature of interstitial cystitis ⁄ painful bladder syndrome (IC ⁄ PBS), but unfortunately the efficacy of current analgesic­s was thought to be insufficient in many patients with IC. Despite the clinical significance of bladder pain, there have been only a few research efforts to elucidate the mechanisms of this chronic pain and its patho­physiology remains poorly understood. One of the reasons is the lack of well–characterized experimental animal models of bladder pain. Hence, the present study was conducted to establish a novel bladder pain model in mice and examined whether nerve growth factor (NGF), a major pain mediator, was involved in bladder pain. Repeated injections of cyclophosphamide (150 mg/kg) for 4 days induced persisting mechanical hypersensitivity in mouse abdomen, decreased the threshold gradually from day 1, peaked at day 4 and persisted for at least day 7 after the first injection. The treatments also altered the levels of bladder impairment markers such as heparin binding–epidermal growth factor–like growth factor and glycosaminoglycan without apparent inflammatory signs on day 4. Peroral administrations of amitriptyline (2.5 – 10 mg/kg) and gabapentin (10 and 30 mg/kg) suppressed the mechanical hypersensitivity on day 4 in these cystitis mice, but indometha­cin (10 and 30 mg/kg) did not affect it. Bladder NGF levels were significantly increased in these cystitis mice and an intravenous injection of anti–NGF serum reversed mechanical hypersensitivity. These results show that this chronic cystitis model induced by repeated cyclophosphamide treatments has less inflammatory elements and NGF–sensitive pain mechanism, which are similar to some features observed in IC patients. Recently, anti–NGF antibody tanezumab has been reported to show the signifi­cant efficacy in relieving bladder pain of IC patients and is now working on clinical stage. This model may be useful for not only the mechanism study of chronic bladder pain but also the development of novel therapies for IC patients.

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   Osteoarthritis (OA) of knee is a common disease in the elderly, and these patients have severe knee pain as chief complaints. OA pain reduces ADL and QOL in these patients. The degree of pain does not correlate with radio­graphic grades, and the strong wear of cartilage does not mean necessarily strong pain. However, the cellular mechanism of chronic pain in this disease has been unclear. Recently many reports have suggested that transient receptor potential vanilloid 1 (TRPV1) is involved in various kinds of persistent pain, including knee OA pain. In this study to clarify the mechanisms underlying knee OA pain, we analyzed the nociceptive signals from the knee joint by recording spontaneous excitatory postsynaptic currents (sEPSC) in spinal dorsal horn neurons by in vivo patch–clamp technique. In order to generate knee OA model, Monosodium Iodoacetate (MIA) was injected into the right knee joint of male adult Sprague–Dawley rats. Three weeks after the injection of MIA, we performed in vivo patch–clamp recording from substantia gelatinosa (SG) neurons containing the L3–5 dorsal root entry zone. The average frequency of sEPSC in OA model rats was significantly larger than that of normal rats (p<0.05). Moreover, we analyzed sEPSC at each spinal segment in normal and OA rats. At L3 and L4 level the average frequency of sEPSCs in OA rats was significantly larger than that of normal rats. Next, we analyzed the effects of a TRPV1 antagonist, capsaicin injection into right knee of normal or OA rats. The capsaicin–induced increases of the frequency and amplitude of sEPSC were weak and had ended instantly in normal rats. While in OA model rats sEPSC largely increased immediately after capsaicin injection and it had lasted for a long time. This capsaicin–induce sEPSC enhancement was significantly larger than those in normal. These results suggest that TRPV1 is an important contributor to OA pain enhancement. And TRPV1 could be the target of pain relief in the patients suffering from the persistent knee OA pain.

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   Many patients have neck and back pain, and their standing posture (spinal alignment) is sometimes considered to be one of the factors that contributes to such pain. Thus, it would be useful to evaluate spinal loads in that posture. A method to evaluate individual spinal loads using link segment models made from body mass distributions using DXA (dual–energy X–ray absorptiometry) was developed.
   An element was defined as 1.30 × 1.22 cm, and a detailed body mass distribution consisting of 7473 elements was constructed using DXA equipment (QDR4500). The subjects' bodies were divided into cervicofacial (vertex–C7 ⁄ T1), thoracic (C7 ⁄ T1 – T12 ⁄ L1), and lumbar (T12 ⁄ L1 – L4 ⁄ 5) segments. Each mass, M₁, M₂, and M₃, and the center of the masses were calculated. With these parameters and DXA images, each torque, T_C7/T1, T_T12/L1, and T_L4/5, was calculated from the following formulas: T_C7/T1 = M₁gr₁cosθ₁, T_T12/L1 = M₁g (l₂cosθ₂ + r₁cosθ₁) + M₂gr₂cosθ₂, and T_L4/5 = M₁g (l₃cosθ₃ + l₂cosθ₂ + r₁cosθ₁) + M₂g (l₃cosθ₃ + r₂cosθ₂) + M₃gr₃cosθ₃ (r₁, r₂, and r₃: lengths from the rotation center to each center of mass; l₂ and l₃: lengths of C7 ⁄ T1 – T12 ⁄ L1 and T12 ⁄ L1 – L4 ⁄ 5; θ₁, θ₂, and θ₃: angles formed between a horizontal line and r₁, r₂, and r₃). In order to reproduce the standing posture on DXA, the standing side was formed by a vacuum cushion for operative position in advance.
   The parameters from DXA in the lateral view were as follows. In case 1 (38–year–old man, healthy, 164.0 cm and 55.5 kg), they were M₁ = 4.50, M₂ = 13.24, M₃ = 6.92 kg, T_C7/T1 = –0.28, T_T12/L1 = –3.80, and T_L4/5 = –6.42 Nm (facing right, clockwise: positive). In case 2 (76–year–old man, lumbar spondylosis, 156.9 cm and 59.6 kg), they were M₁ = 4.83, M₂ = 14.27, M₃ = 10.34 kg, T_C7/T1 = –1.69, T_T12/L1 = –16.1, and T_L4/5 = –44.3 Nm. In case 3 (71–year–old woman, lumbar spondylosis, scoliosis, 147.2 cm and 49.0 kg), they were M₁ = 4.63, M₂ = 11.42, M₃ = 5.36 kg, T_C7/T1 = –2.53, T_T12/L1 = –16.0, and T_L4/5 = –27.0 Nm. Torques at L_4/5 were 6.9 and 4.2 times greater in cases 2 and 3 than in case 1. Total masses calculated from DXA were 54.5, 59.0, and 47.6 kg, and errors between these and actual weights were –1.8, –1.0, and –2.9％, respectively.
   A method for evaluating spinal loads as torques was developed using DXA. In the future, it will be possible to use this method to evaluate factors such as pain and the effect of rehabilitation. The relationships between torques and various scales (such as pain, depression, ADL, and QOL) need to be examined, taking into account age, sex, muscular strength, etc.

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