Time course and localization of nerve growth factor expression and sensory nerve growth during progression of knee osteoarthritis in rats.

OBJECTIVES: Nerve growth factor (NGF) and sensory nerves are key factors in established osteoarthritis (OA) knee pain. We investigated the time course of NGF expression and sensory nerve growth across early and late stages of OA progression in rat knees. DESIGN: Knee OA was induced by medial meniscectomy in rats. OA histopathology, NGF expression, and calcitonin gene-related peptide immunoreactive (CGRP-IR) nerves were quantified pre-surgery and post-surgery at weeks 1, 2, 4 and 6. Pain-related behavior was evaluated using dynamic weight distribution and mechanical sensitivity of the hind paw. RESULTS: NGF expression in chondrocytes increased from week 1 and remained elevated until the advanced stage. In synovium, NGF expression increased only in early stages, whereas in osteochondral channels and bone marrow, NGF expression increased in the later stages of OA progression. CGRP-IR nerve density in suprapatellar pouch peaked at week 4 and decreased at week 6, whereas in osteochondral channels and bone marrow, CGRP-IR innervation increased through week 6. Percent ipsilateral weight-bearing decreased throughout the OA time course, whereas reduced paw withdrawal thresholds were observed only in later stages. CONCLUSION: During progression of knee OA, time-dependent alterations of NGF expression and CGRP-IR sensory innervation are knee tissue specific. NGF expression increased in early stages and decreased in advanced stage in the synovium but continued to increase in osteochondral channels and bone marrow. Increases in CGRP- IR sensory innervation followed increases in NGF expression, implicating that NGF is a key driver of articular nerve growth associated with OA pain.

Impact of Tongue Pressure and Peak Expiratory Flow Rate on Nutritional Status of Older Residents of Nursing Homes in Japan: A Cross-Sectional Study.

OBJECTIVES: Swallowing function is critical for continuing oral feeding to prevent frailty in older adults. In this study, we investigated the impact of tongue pressure and pulmonary function on the nutritional status of older adults. DESIGN, SETTING, PARTICIPANTS: This cross-sectional study was conducted in Kitakyushu, Japan from August 2017 to November 2018. Fifty-two residents aged >65 years of age from three nursing care insurance facilities in Kitakyushu City, Japan were recruited. MEASUREMENTS: Oral health status, swallowing function, nutritional status using a mini nutritional assessment short form (MNA-SF), cognitive function, activities of daily living, peak expiratory flow rate (PEFR) for pulmonary function, and tongue pressure were assessed. The associations between nutritional status and the above factors were analysed using a logistic regression model. RESULTS: Participants were divided into two groups: well-nourished group (MNA-SF ≤12) and undernutrition group (MNA-SF <12). Multivariate logistic regression analysis revealed that the correlations of PEFR [odds ratio (OR) = 0.23, 95% confidence interval (CI) = 0.23-0.89 p=0.033) and tongue pressure (OR = 0.88, 95% CI = 0.88-0.99, p=0.029) remained significant even after adjustment with possible confounders. CONCLUSION: Maximum tongue pressure and PEFR in older adults were significantly associated with their nutritional status. These findings suggest that maintaining oral and pulmonary function may be a preventive factor against a decrease in the nutritional status of older frail adults.

Impact of medial versus lateral knee pain on deep tissue hyperalgesia and muscle strength.

BACKGROUND: Accumulating evidence indicates that knee pain gives rise to sensory and motor alterations, however, whether different profile of knee pain causes different alterations has not been investigated. The purpose of this experimental study is to clarify characteristics of medial and lateral knee pain and its potential for modulating sensory and motor function in humans. METHODS: Fourteen healthy men were included. Medial knee pain (MP) was induced by injection of hypertonic saline (0.5 mL) into the tibial insertion of the medial collateral ligament. For comparison, lateral knee pain (LP) was induced by injection of hypertonic saline identically into the iliotibial tract. Isotonic saline was injected contralaterally as control. Pain intensity was assessed on a continuous electronic visual analogue scale (VAS). Before, during and after the painful state, pressure pain thresholds from the knee (PPTs), maximal isometric muscle strength of the quadriceps and grip power were assessed bilaterally. RESULTS: MP demonstrated significantly higher VAS scores than LP and compared with control. PPTs decreased on medial and lateral knee in MP but only on the lateral knee in LP. Quadriceps muscle strength and grip power reduced bilaterally in both models, however, MP caused significantly greater reduction of ipsilateral quadriceps strength compared with LP. CONCLUSION: Medial knee pain has a greater impact on deep tissue hyperalgesia and reduction of the muscle strength compared with lateral knee pain. This is a novel finding that should be taken into consideration in a treatment strategy for painful knee patients. SIGNIFICANCE: The experimental medial knee pain model demonstrated higher pain intensity, more localized pain distribution, widespread deep tissue hyperalgesia and more severe inhibition of muscle strength compared with the lateral knee pain model.

Endoscopic photodynamic therapy using talaporfin sodium for recurrent intranasal carcinomas after radiotherapy in three dogs.

Radiation is the treatment of choice for canine nasal tumours but, in almost all cases, there is local recurrence associated with poor prognosis. This report describes the effect of endoscopic photodynamic therapy using talaporfin sodium for canine intranasal carcinoma recurring after radiation therapy. Rhinoscopic photodynamic therapy was administered after radiation therapy in three dogs with recurrent intranasal carcinoma. Two to 24 illuminations of a 665-nm diode laser were performed two hours after intravenous bolus injection of 5·0 mg/kg of talaporfin sodium. Photodynamic therapy induced almost complete remission and prolonged survival time in all cases suggesting that it might be a useful treatment for intranasal carcinomas that recur after radiation.

Experimental pain in the groin may refer into the lower abdomen: Implications to clinical assessments.

OBJECTIVES: To investigate the effects of experimental adductor pain on the pain referral pattern, mechanical sensitivity and muscle activity during common clinical tests. DESIGN: Repeated-measures design. METHODS: In two separate sessions, 15 healthy males received a hypertonic (painful) and isotonic (control) saline injection to either the adductor longus (AL) tendon to produce experimental groin pain or into the rectus femoris (RF) tendon as a painful control. Pain intensity was recorded on a visual analogue scale (VAS) with pain distribution indicated on body maps. Pressure pain thresholds (PPT) were assessed bilaterally in the groin area. Electromyography (EMG) of relevant muscles was recorded during six provocation tests. PPT and EMG assessment were measured before, during and after experimental pain. RESULTS: Hypertonic saline induced higher VAS scores than isotonic saline (p<0.001), and a local pain distribution in 80% of participants. A proximal pain referral to the lower abdominal region in 33% (AL) and 7% (RF) of participants. Experimental pain (AL and RF) did not significantly alter PPT values or the EMG amplitude in groin or trunk muscles during provocation tests when forces were matched with baseline. CONCLUSIONS: This study demonstrates that AL tendon pain was distributed locally in the majority of participants but may refer to the lower abdomen. Experimental adductor pain did not significantly alter the mechanical sensitivity or muscle activity patterns.

Posterior teeth occlusion and dysphagia risk in older nursing home residents: a cross-sectional observational study.

The total number of natural teeth was related to swallowing function among older adults; however, limited information is available regarding the impact of occluding pairs of teeth on swallowing function. This study aimed to examine the association between posterior teeth occlusion and dysphagia risk in older nursing home residents. This cross-sectional study included 238 residents aged ≥60 years from eight nursing homes in Aso City, Japan. Swallowing function was evaluated using the modified water swallowing test (MWST); the primary outcome was dysphagia risk (MWST score ≤3). Posterior teeth occlusion was assessed using number of functional tooth units (FTUs), determined based on number and location of the remaining natural and artificial teeth on implant-supported, fixed or removable prostheses. Univariate and multivariate logistic regression analyses were performed to examine the association between posterior teeth occlusion and dysphagia risk, adjusted for the covariates of number of natural teeth, demographic characteristics, comorbidities, physical function, body mass index and cognitive function. Of the 238 subjects, 44 (18·5%) were determined to be at risk of dysphagia based on the MWST scores. The odds ratio (OR) of dysphagia risk decreased in subjects with higher total FTUs [OR = 0·92, 95% confidence interval (CI) 0·87-0·98]. After adjusting for covariates, this association remained significant (OR = 0·90, 95% CI 0·84-0·97). Loss of posterior teeth occlusion was independently associated with dysphagia risk in older nursing home residents. Maintaining and restoring posterior teeth occlusion may be an effective measure to prevent dysphagia.

User-independent assessment of conditioning pain modulation by cuff pressure algometry.

BACKGROUND: The use of conditioning pain modulation (CPM) is hampered by poor reproducibility and lack of user-independent paradigms. This study refined the CPM paradigm by applying user-independent cuff algometry. METHODS: In 20 subjects, the CPM effect of conditioning with cuff stimulation on the arm was investigated by pain test stimuli on the contralateral leg before and in parallel with different cuff conditionings (10, 30, 60 kPa/60 s; 30, 60 kPa/10 s). As test stimulus, another cuff was inflated (1 kPa/s) until the subjects detected the pain tolerance threshold (PTT) during which the pain detection threshold (PDT) and the pressure at a pain intensity of 6 cm on a 10-cm visual analogue scale (PVAS6) were extracted. For comparison, pressure pain thresholds (PPTs) as test stimuli were recorded by the user-dependent handheld pressure algometry. Combinations of cuff locations for conditioning (pain intensity standardized) and contralateral test stimuli were additionally evaluated (leg-arm, leg-leg, arm-thigh). The test-retest reliability in two sessions 1 month apart was assessed in five CPM protocols. RESULTS: In all protocols, the PDT, PVAS6 and PTT increased during conditioning compared with baseline (p < 0.05). The CPM effect (i.e. conditioning minus baseline) for PVAS6, PTT and PPT increased for increasing conditioning intensities (p < 0.05). The CPM effects were not significantly different for changes in conditioning durations or conditioning/test stimulus locations. In two sessions, the CPM effects for PVAS6 and PTT assessed after 60 s of conditioning on the leg/thigh showed the highest intra-class correlations (0.47-0.73), where they were 0.04-0.6 for PPTs. CONCLUSIONS: The user-independent cuff algometry is reliable for CPM assessment and for supra-pain threshold test stimuli better than the user-dependent technology. SIGNIFICANCE: A user-independent CPM technique where the conditioning is controlled by one cuff stimulation, and the test-stimulus is provided by another cuff stimulation. This study shows that cuff algometry is reliable for CPM assessment.

Effects of oral care with tongue cleaning on coughing ability in geriatric care facilities: a randomised controlled trial.

Methods for preventing aspiration pneumonia are needed soon in order to reduce mortality from aspiration pneumonia and promote the health of the elderly. The aim of this randomised controlled trial was to examine whether oral care with tongue cleaning improves coughing ability in elderly individuals living in geriatric care facilities. Participants comprised of 114 residents of 11 group homes and private nursing homes in Aso City in Kumamoto Prefecture. Participants were randomly assigned to either (i) a group that underwent routine oral care with tongue cleaning (intervention group; n = 58) or (ii) a group that underwent routine oral care alone (control group; n = 56). Coughing ability was evaluated by measuring peak expiratory flow (PEF) before and after 4 weeks of intervention. Before the intervention, PEF did not differ significantly between the intervention group (1·65 ± 1·11 L s-1 ) and control group (1·59 ± 1·05 L s-1 ; P = 0·658). However, on termination of the intervention, PEF was significantly higher in the intervention group (2·54 ± 1·42 L s-1 ) than in the control group (1·90 ± 1·20 L s-1 ; P = 0·014). After the intervention, PEF had increased significantly in both groups; however, this increase was significantly greater in the intervention group (0·90 ± 0·95 L s-1 ) than in the control group (0·31 ± 0·99 L s-1 ; P < 0·001). Oral care with tongue cleaning led to increased PEF, suggesting improved coughing ability. Oral care incorporating tongue cleaning appears to be important for preventing aspiration pneumonia.

Nociceptive phenotype alterations of dorsal root ganglia neurons innervating the subchondral bone in osteoarthritic rat knee joints.

OBJECTIVE: Subchondral bone plays a role in generating knee joint pain in osteoarthritis (OA). The objective of this study was to clarify nociceptive phenotype alterations of subchondral bone afferents of the distal femur in mono-iodoacetate (MIA)-induced OA rats. METHODS: OA was induced by intra-articular injection of MIA in rats. Two different retrograde tracers were separately injected into the knee joint cavity and the subchondral bone to identify joint and subchondral bone afferents. Immunohistochemistry was used at 2 weeks (early stage) and 6 weeks (advanced stage) after MIA injection to determine the expression of nociceptive markers (calcitonin gene-related peptide (CGRP) and tyrosine receptor kinase A (TrkA)) and the soma size distribution of CGRP-immunoreactive (IR) neurons. Histological subchondral bone and cartilage damage was scored according to the Osteoarthritis Research Society International grading system. Pain-related behavior was evaluated using weight distribution and mechanical sensitivity of the hind paw. RESULTS: OA caused an up-regulation of CGRP, TrkA and enlargement of soma size of CGRP-IR neurons in both joint and subchondral bone afferents. CGRP and TrkA expression in subchondral bone afferents gradually increased over 6 weeks. Furthermore, up-regulation of CGRP and TrkA in subchondral bone afferents displayed a strong correlation with the subchondral bone damage score. CONCLUSION: Up-regulation of nociceptive markers in subchondral bone afferents correlated with subchondral bone damage, suggesting that subchondral bone is a therapeutic target, especially in the case of advanced stage knee OA. In particular, CGRP and TrkA are potentially molecular therapeutic targets to treat joint pain associated with subchondral lesions.

Resisted adduction in hip neutral is a superior provocation test to assess adductor longus pain: An experimental pain study.

The criterion of long-standing groin pain diagnoses in athletes usually relies on palpation and clinical tests. An experimental pain model was developed to examine the clinical tests under standardized conditions. Pain was induced by hypertonic saline injected into the proximal adductor longus (AL) tendon or rectus femoris (RF) tendon in 15 healthy male participants. Isotonic saline was injected contralaterally as a control. Pain intensity was assessed on a visual analog scale (VAS). Resisted hip adduction at three different angles and trunk flexion were completed before, during, and after injections. Pain provocation in the presence of experimental pain was recorded as a true positive compared with pain provocation in the non-pain conditions. Similar peak VAS scores were found after hypertonic saline injections into the AL and RF and both induced higher VAS scores than isotonic saline (P < 0.01). Adduction at 0° had the greatest positive likelihood ratio (+LR = 2.8, 95%CI: 1.09-7.32) with 45° (-LR = 0.0, 95%CI: 0.00-1.90) and 90° (-LR = 0.0, 95%CI: 0.00-0.94) having the lowest negative LR. This study indicates that the 0° hip adduction test resisted at the ankles optimizes the diagnostic procedure without compromising diagnostic capacity to identify experimental groin pain. Validation in clinical populations is warranted.

Constipation is not associated with colonic diverticula: a multicenter study in Japan.

BACKGROUND: The association of diverticula with bowel habits is unclear. We therefore analyzed the association between diverticula and bowel habits in over 1000 Japanese individuals. METHODS: Japanese subjects who underwent total colonoscopies at seven centers in Japan from June to September 2013 were analyzed. Bowel habits were evaluated using the Gastrointestinal Symptom Rating Scale, and stool form was assessed using a part of the Bristol Scale and Rome ΙΙΙ criteria. Diverticula were diagnosed by colonoscopy with a transparent soft-short hood. KEY RESULTS: The study evaluated 1066 subjects, 648 males and 418 females (ratio, 1.55 : 1), of mean age 63.9 ± 13.0 years. After adjusting for age and sex, the presence of constipation was associated with a significantly reduced likelihood of diverticula (odds ratio [OR] = 0.70, 95% confidence interval [CI] 0.52-0.93). When assessed according to the location of diverticula, the presence of constipation was associated with a significantly decreased likelihood of left-sided (OR = 0.39, 95% CI 0.16-0.93), but not right-sided (OR = 1.10, 95% CI 0.48-2.53), diverticula. Furthermore, stool form was unrelated with the presence or absence of diverticula. CONCLUSIONS & INFERENCES: The wide-spread hypothesis that constipation was associated with colonic diverticula was not supported. Rather, we found that the absence of diverticula was associated with constipation, suggesting the need to reassess the etiology of colonic diverticula.

Repeated intra-articular injections of acidic saline produce long-lasting joint pain and widespread hyperalgesia.

BACKGROUND: Synovial fluid in inflamed joint shows a drop in pH, which activates proton-gated ion channels in nociceptors. No studies have ever tried to develop and characterize acid-induced joint pain. METHODS: Rats were injected intra-articularly with pH 4.0 acidic saline twice, 5 days apart. Pain-related behaviour tests including weight-bearing asymmetry, paw withdrawal threshold and knee compression threshold were conducted. To clarify the roles of proton-gated ion channels, rats were injected intra-articularly with selective antagonists for ASIC1a, ASIC3 and TRPV1 on day 5 (before the second injection) or on day 14. Underlying peripheral and central pain mechanisms were evaluated using joint histology, interleukin-1ß concentrations in the synovium, single-fibre recording of the knee afferent and expression of phosphorylated cyclic adenosine monophosphate-responsive element-binding protein (p-CREB) in the spinal dorsal horn. RESULTS: Repeated injections of acidic saline induced weight-bearing asymmetry, decrease in paw withdrawal threshold and knee compression threshold bilaterally, which lasted until day 28. Early administration of ASIC3 antagonist reduced the bilateral and long-lasting hyperalgesia. Neither articular degeneration nor synovial inflammation was observed. C-fibre of the knee afferent was activated by acidic saline, which was attenuated by pre-injection of ASIC3 antagonist. p-CREB expression was transiently up-regulated bilaterally on day 6, but not on day 14. CONCLUSION: We developed and characterized a model of acid-induced long-lasting bilateral joint pain. Peripheral ASIC3 and spinal p-CREB played important roles for the development of hyperalgesia. This animal model gives insights into the mechanisms of joint pain, which is helpful in developing better pain treatments.

Effects of intra-articular hyaluronic acid injection on immunohistochemical characterization of joint afferents in a rat model of knee osteoarthritis.

BACKGROUND: Intra-articular hyaluronic acid (HA) injection, known as viscosupplementation, is a widely used therapy for pain relief in knee osteoarthritis (OA). Long-term clinical efficacy of HA has been reported in spite of a relatively short residence time. Herein, we evaluated our hypothesis that intra-articular HA injection could reduce the OA-associated changes in joint afferents. METHODS: OA was induced by intra-articular injection of mono-iodoacetate in rats. Animals in the OA + HA group were given three weekly intra-articular HA injections. Pain-related behaviours, including weight-bearing asymmetry and mechanical hyperalgesia of the paw, knee joint histology and immunohistochemistry of joint afferents identified by retrograde labelling, were compared between groups (naïve, OA and OA + HA). RESULTS: OA rats showed pain-related behaviours and up-regulation of pain-related neurochemical markers [calcitonin gene-related peptide (CGRP), tyrosine receptor kinase A (TrkA) and acid-sensing ion channel 3 (ASIC3)] in joint afferents. HA injections reduced not only the severity of OA and pain behaviours but also OA-associated neurochemical changes in joint afferents. The differences between OA and OA + HA were statistically significant in CGRP (61 ± 10% vs. 51 ± 10%; p = 0.0406) but not significant in TrkA (62 ± 10% vs. 54 ± 9%; p = 0.0878) and ASIC3 (38 ± 9% vs. 32 ± 8%; p = 0.3681). CONCLUSION: Intra-articular HA injections reduced the severity of OA, decreased mechanical hyperalgesia of the paw, but not weight-bearing asymmetry, and attenuated OA-associated up-regulation of CGRP, but not TrkA and ASIC3, in joint afferents. The modulatory effects of HA on joint afferents is one of the underlying mechanisms of the gap between HA residence time and duration of clinical efficacy.

Effects of Janus kinase inhibitor tofacitinib on circulating serum amyloid A and interleukin-6 during treatment for rheumatoid arthritis.

The Janus kinase inhibitor tofacitinib is currently being investigated as a disease-modifying agent in rheumatoid arthritis (RA). We investigated the in-vivo effects of tofacitinib treatment for 4 weeks on elevated circulating acute-phase serum amyloid (SAA) levels in 14 Japanese patients with RA. SAA levels fell from 110·5 ± 118·5 µg/ml (mean ± standard deviation) at treatment initiation to 15·3 ± 13·3 µg/ml after 4 weeks treatment with tofacitinib. The reduction in SAA levels was greater in patients receiving tofacitinib plus methotrexate compared with those receiving tofacitinib monotherapy. Tofacitinib was also associated with reduced serum interleukin (IL)-6, but had no effect on serum levels of soluble IL-6 receptor. Patients were divided into groups with adequate (normalization) and inadequate SAA responses (without normalization). Serum IL-6 levels were reduced more in the group with adequate SAA response compared with those with inadequate SAA response. These results suggest that tofacitinib down-regulates the proinflammatory cytokine, IL-6, accompanied by reduced serum SAA levels in patients with active RA. The ability to regulate elevated serum IL-6 and SAA levels may explain the anti-inflammatory activity of tofacitinib.

Nociceptive phenotype of dorsal root ganglia neurons innervating the subchondral bone in rat knee joints.

BACKGROUND: The subchondral bone of the distal femur is a source of pain caused by osteoarthritis (OA) or spontaneous osteonecrosis of the knee. However, nociceptive phenotype of dorsal root ganglia (DRG) neurons innervating the subchondral bone in rat knee joints has not been clarified. METHODS: Retrograde labelling was used to identify afferents innervating the subchondral bone of the distal femur and the knee joint in rats. The nociceptive phenotype markers [calcitonin gene-related peptide (CGRP), tyrosine receptor kinase A (TrkA), neurofilament 200 (NF200) and isolectin B4 (IB4)], segmental distribution and the soma size of backlabelled DRG neurons were examined. Furthermore, we evaluated the differences in nociceptive phenotype between the subchondral bone and the knee joint afferents. RESULTS: The majority (60%) of the subchondral bone afferents were localized in L3 DRGs and fewer in L4 and L5, while the knee joint afferents were localized mainly in L3 and L4. The percentage of CGRP immunoreactive (IR), TrkA-IR, NF200-IR and IB4-binding neurons in the subchondral bone afferents were 50%, 65%, 35% and 0%, respectively. The percentage of CGRP-IR and TrkA-IR neurons in the subchondral bone afferents was significantly higher than that in the knee joint afferents, respectively (p < 0.05). CONCLUSION: The majority of sensory DRG neurons innervating the subchondral bone of the distal femur were CGRP-IR and TrkA-IR. It is expected that therapeutic approaches targeting CGRP and TrkA could be effective in attenuating pain from the subchondral bone in knee joints.

Inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway in rheumatoid synovial fibroblasts using small molecule compounds.

Janus kinase (JAK) inhibitors have been developed as anti-inflammatory agents and have demonstrated clinical efficacy in rheumatoid arthritis (RA). We investigated if JAK-3-selective inhibition alone could disrupt cytokine signalling in rheumatoid synovial fibroblasts. In-vitro studies were performed using synovial fibroblasts isolated from patients with RA. Levels of activated JAK and signal transducer and activator of transcription (STAT) proteins were detected by immunoblot analysis. Target-gene expression levels were measured by reverse transcription-polymerase chain reaction (RT-PCR) or real-time PCR. The JAK inhibitors CP-690,550 and INCB028050 both suppressed activation of JAK-1/-2/-3 and downstream STAT-1/-3/-5, as well as the expression levels of target proinflammatory genes (MCP-I, SAA1/2) in oncostatin-M (OSM)-stimulated rheumatoid synovial fibroblasts. In contrast, the JAK-3-selective inhibitor, PF-956980, suppressed STAT-1/-5 activation but did not affect STAT-3 activation in OSM-stimulated rheumatoid synovial fibroblasts. In addition, PF-956980 significantly suppressed MCP-1 gene expression, but did not block SAA1/2 gene expression in OSM-stimulated rheumatoid synovial fibroblasts. These data suggest that JAK-3-selective inhibition alone is insufficient to control STAT-3-dependent signalling in rheumatoid synovial fibroblasts, and inhibition of JAKs, including JAK-1/-2, is needed to control the proinflammatory cascade in RA.

Nociceptive sensory innervation of the posterior cruciate ligament in osteoarthritic knees.

INTRODUCTION: Although the posterior cruciate ligament (PCL) is considered to contain not only proprioceptive but also nociceptive sensory fibers, there is a lack of information about nociceptive sensory innervation of the PCL. We hypothesized that the PCL has constant nociceptive sensory innervation, suggesting the possible source of osteoarthritic (OA) knee pain. MATERIALS AND METHODS: Innervation of the PCL was examined by immunohistochemistry with particular reference to nociceptive nerve fibers in OA knees. Sensory nerve fibers were semi-quantitatively counted in the PCL of OA knees, comparing with non-OA knees. Protein gene product 9.5 (PGP9.5) as a general neuronal marker and calcitonin gene related peptide (CGRP) as a marker for nociceptive neuron were used. RESULTS: The PCLs had constant CGRP-immunoreactive (IR) nerve fibers in both OA and non-OA knees. The difference of the CGRP-IR nerve density between groups did not reach a statistical significance (p = 0.062). For PGP9.5-IR nerve fibers, however, the PCLs in OA knees were statistically less innervated than non-OA knees (p = 0.0009). CONCLUSIONS: Our results showed that, in spite of a significant decrease in total innervation in OA knees, the PCLs have constant nociceptive sensory innervation. Although the relationship between the decrease in total innervations in the PCL and OA pathophysiology is still unclear, the PCL is the possible source of OA knee pain. Our results should be taken into account when examining the pain source of the OA knees and handling the PCL during total knee arthroplasty.

The impact of childhood abuse history, domestic violence and mental health symptoms on parenting behaviour among mothers in Japan.

BACKGROUND: To assess the impact of childhood abuse history, domestic violence experiences and mental health symptoms on the parenting behaviour of mothers in Japan who have separated from violent husbands or partners. METHODS: A self-administered questionnaire survey was conducted on a sample of mothers (n = 304) and their children (n = 498) residing in 83 mother-child homes in Japan. The survey assessed the mothers' childhood abuse history (physical, psychological and sexual abuse and neglect history), domestic violence experiences, current mental health symptoms (dissociative, depressive and traumatic symptoms) and parenting behaviours after moving into the homes to separate from a violent husband or partner. RESULTS: The mothers' childhood abuse history and experience of domestic violence were not associated with their not playing with their children. In contrast, the mothers' dissociative and depressive symptoms were significantly associated with not playing with their children. Although there was no association between the mothers' total childhood abuse history and not praising their children, their childhood physical abuse history was significantly associated with their not praising their children. The dissociative and depressive symptoms were also associated with no praise. Interestingly, the experience of domestic violence showed an inverse association with no praise. CONCLUSIONS: Mental health symptoms, more specifically dissociative and depressive symptoms, are associated with a decrease in parenting quality. Mothers who were physically abused as children are less likely to praise their own children, independent of maternal mental health symptoms. In contrast, mothers who experienced domestic violence but subsequently separated from their violent husbands or partners are more likely to praise their children. The treatment of mental health symptoms, particularly dissociative and depressive symptoms, therapy for childhood abuse history and separation from violent husbands or partners might be effective ways to enhance the quality of parenting in Japan.