Long-Term Implant Fracture Rates Following Silicone Metacarpophalangeal Joint Arthroplasty in Rheumatoid Arthritis.

PURPOSE: The primary objective of this study was to compare the long-term survival rates of silicone metacarpophalangeal (MCP) arthroplasties between two major implants in patients with rheumatoid arthritis, using implant fracture as an end point. We also evaluated the difference in postoperative function between patients with fractured and intact implants as a secondary objective. METHODS: A retrospective cohort study was conducted on 372 fingers of 133 hands that underwent silicone MCP arthroplasty between January 2000 and June 2019 (mean follow-up, 7.6 years). The survival rates of Swanson-type and Sutter-type implants were compared, using implant fracture as the end point after a radiographic evaluation. Clinical measures and upper limb functional assessments using the Disabilities of the Arm, Shoulder, and Hand (DASH) score were performed in the nested cohort. RESULTS: The 10.6-year survival rates for implant fracture of Swanson- and Sutter-type implants were 86.2% and 9.4%, respectively, with significantly higher survival noted for Swanson-type implants. The Sutter-type implant showed increased susceptibility to fracture in all four fingers compared to the Swanson-type implant. Implant fractures were primarily observed at the stem-hinge junction. There were no significant differences in upper limb function between the fractured and intact implant groups. CONCLUSIONS: Sutter-type implants were found to be more prone to fracture compared with Swanson-type implants. However, implant fractures did not significantly affect upper limb function. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognosis IV.

Using peer role-playing to improve students' clinical skills for musculoskeletal physical examinations.

BACKGROUND: The traditional curriculum for medical students in Japan does not include sufficient opportunities for students to develop their skills for musculoskeletal (MSK) examination and clinical reasoning and diagnosis. Therefore, an effective programme is required to help medical students and residents improve their clinical skills in MSK. This paper aims to assess the clinical skills of medical students who have participated in a peer role-playing simulation programme using a mini clinical evaluation exercise (mini-CEX). METHODS: Participants were 90 female medical students who were completing their first orthopaedic clinical clerkship. They were divided into two groups. The simulation group participated in a role-play focussed on MSK cases as low-fidelity simulation, a structured debriefing with the course supervisor, and a self-reflection on Day 1 (n = 64). The control group did not participate in the role-play due to randomised clerkship schedules (n = 26). On Day 2 of the intervention, we observed and assessed all participants' performances during MSK outpatient encounters using the mini-CEX. We compared the mini-CEX score between the simulation group and the control group; the Wilcoxon rank-sum test was used for statistical analysis. RESULTS: The mini-CEX scores for physical examination, clinical reasoning and diagnosis, and overall clinical competency were significantly higher in the simulation group than in the control group (p < .05, physical examination: p = .014, clinical reasoning: p = .042, overall: p = .016). These findings suggest that medical students who partake in a peer role-playing simulation programme could experience improved clinical skills for physical examination, clinical reasoning and diagnosis, and overall clinical competency in real-life MSK outpatient encounters. CONCLUSIONS: Through a mini-CEX assessment, our findings indicate that medical students who participated in our peer role-playing simulation programme have improved clinical skills. Peer role-playing as a low-fidelity simulation and practical educational opportunity will enable educators to polish the competency of medical students in musculoskeletal physical examinations and clinical reasoning and diagnosis in a clinical setting.

Influence of different energy patterns on efficacy of radial shock wave therapy.

BACKGROUND: One of the mechanisms of the efficacy of extracorporeal shock wave therapy (ESWT) for impaired muscle coordination of limbs is the destruction of Acetylcholine receptors (AChRs) at neuromuscular junction. The highly increased density of AChRs can change the acoustic impedance, and this change of the acoustic impedance can be the reason that radial shock wave (rESW) destroy AChRs selectively. However, the relationship between applied energy of rESWs and the therapeutic efficacy remains unclear, although some studies compared the clinical efficacy of rESWT between high- and low-energy applications. This study aimed to compare the CMAP change among different energy and pulses of rESW application. METHODS: Male Sprauger-Dawley rats were used. A device that generates radial shock waves pneumatically, was used to apply the following six patterns of radial extracorporeal shockwaves in different energy flux densities and pulses to the right calf of each rat: 1, 8000 pulses at 0.045 mJ/mm2; 2, 4000 pulses at 0.09 mJ/mm2; 3, 2000 pulses at 0.18 mJ/mm2; 4, 4000 pulses at 0.045 mJ/mm2; 5, 2000 pulses at 0.09 mJ/mm2; 6, 1000 pulses at 0.18 mJ/mm2. Left calf muscles were considered controls. RESULTS: There was a significant reduction in CMAP amplitude between control and rESW-exposed muscles in the group applied 4000 pulses with EFD at 0.09 mJ/mm2 and the group applied 2000 pulses with EFD at 0.18 mJ/mm2. However, the group applied 8000 pulses with EFD at 0.045 mJ/mm2 and all groups which was exposed to total 180 mJ rESW application did not show a significantly decreased CMAP amplitude compared with the untreated side. CONCLUSIONS: Total energy and energy flux density correlate with a decrease in CMAP amplitude by rESW application. These findings could be availed by clinicians in actual clinical setting for the proper application of rESW.

Treatment of Capitellum Fracture with Chronic Radial Head Dislocation.

We encountered a case of capitellum fracture with radial head dislocation in which it was challenging to diagnose whether the dislocation was coincident with the fracture or this was chronic dislocation that presented before the fracture. Chronic radial head dislocation may be congenital or could occur in patients with untreated post-traumatic dislocation, although diagnosis is particularly challenging if the radial head dislocation is unilateral. Classical capitellum fracture involves anterosuperior bone fragment dislocation. However, in the present case, the bone fragment was present beneath the radial head, which suggests chronic radial head dislocation. When the bone fragment appears in a different position than usual, every effort should be made to understand the pathophysiology by reviewing the mechanism of onset, disease history, and imaging.

Optimal Measurement Level and Ulnar Nerve Cross-Sectional Area Cutoff Threshold for Identifying Ulnar Neuropathy at the Elbow by MRI and Ultrasonography.

PURPOSE: Imaging criteria for diagnosing compressive ulnar neuropathy at the elbow (UNE) have recently been established as the maximum ulnar nerve cross-sectional area (UNCSA) upon magnetic resonance imaging (MRI) and/or ultrasonography (US). However, the levels of maximum UNCSA and diagnostic cutoff values have not yet been established. We therefore analyzed UNCSA by MRI and US in patients with UNE and in controls. METHODS: We measured UNCSA at 7 levels in 30 patients with UNE and 28 controls by MRI and at 15 levels in 12 patients with UNE and 24 controls by US. We compared UNCSA as determined by MRI or US and determined optimal diagnostic cutoff values based on receiver operating characteristic curve analysis. RESULTS: The UNCSA was significantly larger in the UNE group than in controls at 3, 2, 1, and 0 cm proximal and 1, 2, and 3 cm distal to the medial epicondyle for both modalities. The UNCSA was maximal at 1 cm proximal to the medial epicondyle for MRI (16.1 ± 3.5 mm2) as well as for US (17 ± 7 mm2). A cutoff value of 11.0 mm2 for MRI and US was found to be optimal for differentiating between patients with UNE and controls, with an area under the receiver operating characteristic curve of 0.95 for MRI and 0.96 for US. The UNCSA measured by MRI was not significantly different from that by US. Intra-rater and interrater reliabilities for UNCSA were all greater than 0.77. The UNCSA in the severe nerve dysfunction group of 18 patients was significantly larger than that in the mild nerve dysfunction group of 12 patients. CONCLUSIONS: By measuring UNCSA with MRI or US at 1 cm proximal to the ME, patients with and without UNE could be discriminated at a cutoff threshold of 11.0 mm2 with high sensitivity, specificity, and reliability. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.

Extracorporeal shock wave treatment can selectively destroy end plates in neuromuscular junctions.

INTRODUCTION: This study assesses the effect of radial extracorporeal shock wave (rESW) exposure on neuromuscular transmission and neuromuscular junction (NMJ) morphology. METHODS: We applied 2,000 rESWs at 0.18 mJ/mm2 and a frequency of 15 Hz to the right calf of male rats, measured the compound muscle action potential (CMAP), and examined NMJ morphology using electron microscopy. Left calf muscles were used as controls. RESULTS: rESW exposure significantly reduced CMAP amplitude without delayed latency in exposed muscles compared with controls. All rESW-exposed muscles exhibited NMJs with irregular end plates. Mean interjunctional fold interval was significantly increased compared with controls. However, axon terminals and muscle fibers surrounding NMJs with irregular end plates were unchanged. DISCUSSION: This localized destruction of end plates may be caused by differences in acoustic impedance induced by the density of acetylcholine receptors. These results provide a possible mechanism for the effectiveness of rESW treatment for spasticity and dystonia. Muscle Nerve 57: 466-472, 2018.

Vein wrapping for chronic nerve constriction injury in a rat model: study showing increases in VEGF and HGF production and prevention of pain-associated behaviors and nerve damage.

BACKGROUND: Although efficacious clinical results have been reported after vein wrapping for the treatment of recurrent compressive neuropathy, the mechanism of nerve protection remains uncertain. METHODS: Eight-week-old male Wistar rats (n = 90) were randomly divided into three groups: sham procedure, chronic constriction injury, and chronic constriction injury plus vein wrapping. Mechanical withdrawal thresholds and walking patterns were measured with use of von Frey filaments and the CatWalk system, respectively. We investigated L4-L5 dorsal root ganglia immunohistochemically at fourteen days postsurgery and sciatic nerves histologically at fourteen days and again five months postsurgery. Concentrations of several sciatic neurotrophic factors in the ligated sciatic nerves were quantified with use of ELISA (enzyme-linked immunosorbent assay). RESULTS: In behavioral tests, the rats in which the chronic constriction injury had been followed by vein wrapping displayed significantly greater pain responses than the sham group, and the group with untreated chronic constriction injury showed greater pain responses than the vein-wrapping group (both p < 0.05). Immunoreactive markers of inflammation and nerve damage, calcitonin gene-related peptide (CGRP) and activating transcription factor-3 (ATF3), were upregulated in dorsal root ganglion neurons in the constriction-injury and vein-wrapping groups compared with those in the sham group, with greater upregulation in the constriction-injury group than in the vein-wrapping group (both p < 0.01). Histologic observation showed marked nerve degeneration and scar tissue formation around the sciatic nerve in the constriction-injury group, but these effects were prevented to some extent in the vein-wrapping group. Vascular endothelial growth factor (VEGF) levels at one and three days postsurgery and hepatocyte growth factor (HGF) levels at three, seven, fourteen, and twenty-eight days postsurgery were significantly higher in the vein-wrapping group than in the other groups (p < 0.05). CONCLUSIONS: Vein wrapping decreased pain-associated behavior and nerve damage caused by chronic constriction injury. VEGF and HGF produced in response to vein grafts may play a mechanistic role. CLINICAL RELEVANCE: These findings may lead to development of new therapies employing growth factors, with or without other materials, that simulate vein wrapping.

Expression of activating transcription factor 3 (ATF3) in uninjured dorsal root ganglion neurons in a lower trunk avulsion pain model in rats.

PURPOSE: Clinically, neuropathic pain is frequent and intense following brachial plexus injury. It is thought that brachial plexus pain is not generated by avulsed roots, but rather by non-avulsed roots, since the avulsed root could not possibly transmit action potentials to central nerves. The aim of this study was to evaluate pain behavior and activation of sensory neurons in a brachial plexus avulsion (BPA) model in rats. METHODS: Fifteen male Wistar rats were used. In the BPA group, the C8-T1 roots were avulsed from the spinal cord with forceps at the lower trunk level (n = 5). In the naïve group, rats did not receive any procedures (n = 5). In the sham-operated group, the lower trunk was simply exposed (n = 5). Mechanical hyperalgesia of forelimbs corresponding to C6 and C7 dermatomes was measured using von Frey filaments every third day for 3 weeks. Activation of DRG neurons was immunohistochemically examined using anti-ATF3 (a marker for neuron activation) antibodies 21 days after surgery. Von Frey and immunohistochemical data between groups were analyzed using a Kruskal-Wallis test, followed by Mann-Whitney U tests. Bonferroni corrections were performed. RESULTS: Animals in the BPA group displayed significant mechanical hyperalgesia at the dermatome innervated by uninjured nerves continuing through day 21 compared with animals in the sham-operated group. ATF3-immunoreactive small and large DRG neurons were significantly activated in the BPA group (10.6 ± 9.5 and 5.2 ± 4.1 %, 39.7 ± 6.7 and 25.2 ± 10.3 %, 78.0 ± 9.1 and 53.7 ± 29.3 %) compared with the sham-operated group (0.7 ± 0.9 and 0 ± 0 %, 2.8 ± 2.0 and 1.0 ± 2.0 %, 3.9 ± 2.7 and 8.6 ± 10.1 %) at every level of C5, 6, and 7. In the naïve group, no DRG neurons were activated. ATF3-immunoreactive small and large DRG neurons were significantly activated at the level of C7 compared with C6 and C5, and significantly activated at the level of C6 compared with C5 in the BPA group. CONCLUSIONS: Expression of ATF3 in uninjured DRG neurons may contribute to pain following brachial plexus avulsion injury. Consequently, spared spinal sensory nerves may represent therapeutic targets for treatment of this pain.

Athletic ability of school-age children after satisfactory treatment of congenital clubfoot.

BACKGROUND: This is the first study to objectively assess the athletic ability of school-age congenital clubfoot patients. METHODS: Forty-six feet of 30 patients (18 boys, 12 girls) were evaluated in this study. Nine patients were treated conservatively, 8 patients underwent percutaneous tenotomy of the Achilles tendon, and 13 patients were treated with extensive soft-tissue release. The mean age at the investigation was 9.2±1.9 years, and the mean follow-up period was 8.3±2.9 years. Athletic ability was evaluated by calculating Z-scores for the patients' scores in 5 physical fitness tests routinely performed nationwide at elementary schools: 50-meter run; standing long jump; repetition side steps; 20-meter shuttle run; and sit-ups. The Z-scores were calculated based on data published as the nationwide standards. RESULTS: Of the 148 scores recorded for the 5 tests for the 30 clubfoot patients, 143 scores (96.6%) were higher than the -2 SD value. The mean Z-scores were as follows: -0.32 for 50-meter run; -0.16 for standing long jump; -0.24 for 20-meter shuttle run; 0.22 for repetition side steps; and 0.06 for sit-ups. None of the events showed any significant differences among the three treatment groups. CONCLUSIONS: Congenital clubfoot with satisfactory treatment did not significantly impair the athletic performance. LEVEL OF EVIDENCE: Prognostic level III.

The effect of Anti-NGF receptor (p75 Neurotrophin Receptor) antibodies on nociceptive behavior and activation of spinal microglia in the rat brachial plexus avulsion model.

STUDY DESIGN: We measured the response of the behavior and spinal glial activation to anti-nerve growth factor receptor (p75 neurotrophin receptor [p75NTR]) antibodies in the rat brachial plexus avulsion (BPA) model. OBJECTIVE: The aim of this study was to investigate the effect of anti-p75NTR antibodies on nociceptive behavior and activation of spinal microglia in the rat BPA model. SUMMARY OF BACKGROUND DATA: Tanezumab (anti-nerve growth factor antibody) treatment is associated with pain reduction and improvement in function, but with several complications. METHODS: Thirty male Wistar rats were used. In the BPA group, the C8-T1 roots were avulsed from the spinal cord with forceps at the lower trunk level and 10 µL of saline was applied locally (n = 10). In the anti-p75NTR group, the C8-T1 roots were avulsed and 10 µL of anti-p75NTR antibody was applied locally (n = 10). In a sham-operated group, the lower trunk was simply exposed (n = 10). Mechanical hyperalgesia and pain-induced walking patterns were measured using von Frey filaments (Stoelting, Wood Dale, IL) and the CatWalk gait analysis (Noldus Information Technology, the Netherlands) system every third day for 3 weeks. Activation of astrocytes and microglia was immunohistochemically examined in the spinal cord using anti-glial fibrillary acidic protein (GFAP) and anti-Iba1 antibodies both 7 and 21 days after surgery. RESULTS: Animals in the BPA group displayed significant mechanical hyperalgesia that continued through day 21 compared with animals in the sham-operated group, and mechanical hyperalgesia in the anti-p75NTR group was significantly improved 6 days after the operation. Regarding pain-induced gait analysis via CatWalk, animals in the BPA group displayed a significantly greater pain-like gait pattern than the p75 group for up to 3 weeks. Levels of GFAP-immunoreactive astrocytes and Iba1-immunoreactive microglia in the anti-p75NTR group were significantly reduced compared with the BPA group. CONCLUSION: Our results suggest that p75NTR contributes to neuropathic pain associated with BPA, and that inhibition of p75NTR reduces neuropathic pain. LEVEL OF EVIDENCE: N/A.

Degeneration and recovery of the neuromuscular junction after application of extracorporeal shock wave therapy.

It is known that free nerve endings are degenerated after application of shock waves. We therefore hypothesized that the application of shock waves to muscle induces dysfunction of neuromuscular transmission at neuromuscular junctions. We investigated changes in neuromuscular transmission in response to shock wave application. Sprague-Dawley rats were used in this study. Two thousand shock waves at an energy flux density of 0.18 mJ/mm(2) were applied to their right calf muscles. Neuromuscular junctions of gastrocnemius muscles were evaluated using rhodamine-α-bungarotoxin on the day of treatment (n = 5). Amplitude and latency of compound muscle action potentials were measured on the day of treatment and 1, 2, 4, 6, and 8 weeks after treatment (n = 10, each group). Degenerated acetylcholine receptors existed in all treated muscles. Although the action potential amplitude on the treated side was significantly less than on the control side from the day of treatment (25.1 ± 7.8 vs. 34.5 ± 9.1, p = 0.012) to 6 weeks (27.9 ± 7.2 vs. 34.5 ± 7.2, p = 0.037), there was no significant difference at 8 weeks. There was no significant difference in transmission latency between the groups. The application of shock waves to muscle induced a transient dysfunction of nerve conduction at neuromuscular junctions.

Investigation of dichotomizing sensory nerve fibers projecting to the lumbar multifidus muscles and intervertebral disc or facet joint or sacroiliac joint in rats.

STUDY DESIGN: Immunohistological analysis of dichotomizing sensory nerve fibers projecting to the lumbar multifidus muscles and intervertebral disc (IVD), facet joint (FJ), or sacroiliac joint (SIJ) in rats. OBJECTIVE: To elucidate dichotomizing sensory nerve fibers projecting to the lumbar multifidus muscles and to IVDs, FJs, or SIJs. SUMMARY OF BACKGROUND DATA: Clinically, the origin of low back pain remains unknown. Multiple studies have identified lumbar muscles, IVDs, FJs, and SIJs as sources of low back pain. Pain may originate directly from lumbar muscles or be referred from the spine, or both. Dorsal root ganglion (DRG) neurons with dichotomizing axons have been reported in several species and are thought to be related to referred pain. METHODS: We used 2 neurotracers, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) and fluorogold (FG), in this double-labeling study involving 30 Sprague Dawley rats. DiI was applied to lumbar multifidus muscles in all rats. Simultaneously, FG was applied to the anterior left portion of L5-L6 IVDs in the IVD group (n = 10), to the left L5-L6 FJs in the FJ group (n = 10), and to the left SIJs in the SIJ group (n = 10). Fourteen days after surgery, left DRGs from L1 to L6 were harvested, sectioned, and observed under a fluorescence microscope. RESULTS: We verified the existence of double-labeled DRG neurons (i.e., dichotomizing sensory nerve fibers) projecting to lumbar multifidus muscles and to IVDs, FJs, or SIJs, depending on the group. The proportion of double-labeled cells in all DiI-labeled DRG neurons was higher in the FJ group (6.8%) and SIJ group (7.1%) than in the IVD group (3.1%) (P < 0.05). CONCLUSION: Our results document the presence of dichotomizing sensory nerve fibers projecting to lumbar multifidus muscles and to IVDs, FJs, and SIJs. Referred low back muscle pain may reflect disorders of lumbar posterior structures, such as FJs and SIJs, rather than disorders of lumbar anterior structures, such as IVDs.

Single versus double end-to-side nerve grafts in rats.

PURPOSE: Although the end-to-side nerve repair technique has been used clinically, it has not yet produced consistent motor and sensory recovery in patients. The aim of this study was to investigate whether end-to-side double nerve grafts display more axonal regeneration compared with a single nerve graft in a rat lower limb preparation. METHODS: The lower limbs of 96 Wister rats were used in experiments comparing single and double end-to-side nerve grafts. Left peroneal nerves were harvested and grafted between the right peroneal and tibial nerves. A single graft was attached end-to-side to the peroneal and tibial nerves through an epineural window (single graft group, n = 24). Two grafts were performed in the same manner in the double graft group (n = 24). The peroneal nerve was exposed in positive controls (n = 24) and no graft was performed in negative controls (n = 24). We recorded action potentials and moist weights of the left tibialis anterior muscle at each time point. Fluoro-Gold-labeled (Fluorochrome, Denver, CO) dorsal root ganglion neurons from L1 to L6 were counted using fluorescence microscopy and compared among the 4 groups. RESULTS: In both single and double groups, the amplitude and the tibialis anterior muscle weight increased significantly compared with negative controls but remained lower than those measured in positive controls. There was no significant difference between single and double groups. In Fluoro-Gold-labeled neurons, there was also no significant difference between single and double groups. CONCLUSIONS: The study showed that regeneration of motor and sensory nerve fibers was possible using 2 end-to-side nerve grafts. However, there was no significant difference between single and double grafts. This might suggest a therapeutic limitation of nerve transplants using 2 end-to-side nerve grafts. CLINICAL RELEVANCE: Double end-to-side repair attracts both motor and sensory axons, and this results in a medium degree of recovery of function; however, double end-to-side nerve grafting does not appear to offer any advantage over a single end-to-side graft.

Evaluation of behavior and neuropeptide markers of pain in a simple, sciatic nerve-pinch pain model in rats.

Pathomechanisms of injured-nerve pain have not been fully elucidated. Radicular pain and chronic constriction injury models have been established; however, producing these models is complicated. A sciatic nerve-pinch injury is easy to produce but the reliability of this model for evaluating pain behavior has not been examined. The current study evaluated pain-related behavior and change in pain markers in the dorsal root ganglion (DRG) of rats in a simple, sciatic nerve-pinch injury model. In the model, the sciatic nerve was pinched for 2 s using forceps (n = 20), but not injured in sham-operated animals (n = 20). Mechanical and thermal hyperalgesia were measured every second day for 2 weeks using von Frey filaments and a Hargreaves device. Calcitonin gene-related peptide (CGRP), activating transcription factor-3 (ATF-3), phosphorylated p38 mitogen activated protein (Map) kinase (p-p38), and nuclear factor-kappa B (NF-κB; p65) expression in L5 DRGs were examined at 4 and 7 days after surgery using immunohistochemistry. The proportion of neurons immunoreactive for these markers was compared between the two groups. Mechanical (during 8 days) and thermal hyperalgesia (during 6 days) were found in the pinch group rats, but not in the sham-operated animals (p < 0.05); however, hyperalgesia was not significant from days 10 to 14. CGRP, ATF-3, p-p38, and NF-κB expression in L5 DRGs was upregulated in the nerve-injured rats compared with the sham-operated rats (p < 0.01). Our results indicate that a simple sciatic nerve pinch produced pain-related behavior. Upregulation of the pain-marker expression in the nerve-injury model suggested it could be used as a model of pain. However, it was not considered as suitable for long-term studies.

Role of low-affinity nerve growth factor receptor inhibitory antibody in reducing pain behavior and calcitonin gene-related Peptide expression in a rat model of wrist joint inflammatory pain.

PURPOSE: Nerve growth factor (NGF), via the high-affinity receptor, tyrosine kinase A, has been widely reported as a mediator of pain caused by inflammation. A clinical trial has suggested that anti-NGF antibody is effective for pain caused by osteoarthritis of the knee. However, adverse events such as headache (8.9%), upper respiratory tract infection (7.3%), and paresthesia (6.8%) were reported. We hypothesized that inhibition of the low-affinity NGF receptor, p75 neurotrophin receptor (p75NTR), is also effective for joint pain and may reduce side effects. This study examined suppression of pain behavior and expression of pain-inducing neuropeptides such as calcitonin gene-related peptide (CGRP) and p75NTR in dorsal root ganglia neurons by a p75NTR inhibitory antibody in a rat model of wrist joint inflammatory pain. METHODS: We injected complete Freund's adjuvant (CFA) into the wrist joint of rats and used this as a model of inflammatory pain. We applied 10 microL of saline (CFA + saline group; n = 20) or 1, 10, or 50 microL of a p75NTR inhibitory antibody (CFA + p75NTR inhibitory antibody group; n = 40) directly to the inflamed joint in the rats. Mechanical hyperalgesia was measured for 2 weeks using von Frey filaments. We assessed CGRP and p75NTR expression in C8 dorsal root ganglia immunochemically. Adverse events such as loss of weight and/or appetite, constipation, and infection were examined. RESULTS: p75NTR inhibitory antibody reduced mechanical hyperalgesia caused by CFA (p<.05 vs controls) in the rat model (p<.01 vs saline), without any adverse events. We found that 10 and 50 microL of a p75NTR inhibitory antibody were more effective for pain, without a significant difference between doses. CGRP and p75NTR immunoreactivity was upregulated in the CFA + saline groups compared with a control group (p<.01). However, direct p75NTR inhibitory antibody application decreased CGRP and p75NTR expression after wrist inflammation (p<.01). CONCLUSIONS: p75NTR inhibition may be a therapeutic target for inflamed joint pain treatment with reduced adverse events.