Role of tear size and tendon degeneration for development of pain in rat models of rotator cuff tear.

BACKGROUND: Rotator cuff tear (RCT) is a frequent etiology of shoulder pain and disability; however, the triggers for the onset and aggravation of pain remain obscure. In this study, we established novel rat RCT models to examine the impact of tear size and tendon degeneration on pain. METHODS: Fifty-five adult male Sprague-Dawley rats were allocated into 4 study groups: large tear (L group, n = 10), small tear (S group, n = 15), small tear with scratching (S+ group n = 15), and sham surgery (Sham group, n = 15). Pain-related behaviors were evaluated by weight distribution of forelimbs during a 5-minute free gait using a dynamic weight-bearing apparatus at 2, 4, 6, and 8 weeks. Calcitonin gene-related peptide (CGRP) expressions in ipsilateral dorsal root ganglion (DRG) neurons of C4, C5, and C6 were evaluated at 4 and 8 weeks. The area of scar tissues around the torn tendon, infiltration of inflammatory cells, and severity of tendon degeneration (modified Bonar score) were histologically assessed at 4 and 8 weeks. Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to evaluate the levels of cyclooxygenase-2 (COX-2) and nerve growth factor (NGF) expression in torn tendons and surrounding tissues at 4 weeks. RESULTS: The weight distribution ratio (ipsilateral and contralateral side) was significantly decreased in the L and S+ group compared with its baseline and Sham group (P < .05), but the S group showed no significant difference compared with the Sham. The ratio of CGRP-immunoreactive neurons in the DRGs was significantly higher in the L and S+ groups than in the S and Sham groups. The histologic assessment indicated that scar tissue formation was more extensive in the L group than in the S and S+ groups. Still, there was no significant difference between the S and S+ groups. The modified Bonar score was considerably higher in the S+ group than in the S group. Furthermore, ELISA analysis demonstrated no significant disparity in COX-2 levels between the groups; however, NGF levels were substantially higher in the S+ group than in the S and Sham groups. CONCLUSION: The present study provides compelling evidence that large RCT is strongly associated with heightened pain severity in a rat model. Nevertheless, even a small tear can significantly aggravate pain when the torn tendon is degenerated. CGRP upregulation driven by peripheral NGF possibly played a pivotal role in the genesis and exacerbation of pain in small RCT.

Assessment of multiple domains of pain following BNT162b2 mRNA COVID-19 vaccination.

Pain at the injection site is the most frequent reaction among COVID-19 vaccine recipients, but its characteristics were not fully described yet. The purpose of this study was to investigate multiple domains of pain following BNT162b2 mRNA vaccination. We included 107 subjects undergoing primary shot of the vaccination twice into deltoid muscle with a 3-week interval. They completed 6 sessions of pain assessments, one before the first and second dose (1-0, 2-0), and 1st/7th day after the first and second dose (1-1/1-7, 2-1/2-7). Pain visual analog scale (VAS), pain distribution, and pressure pain threshold (PPT) on deltoid muscle were evaluated in each session. The mean VAS (at rest/shoulder motion) was 6.0/27.6 mm at 1-1, and 12.8/34.0 mm at 2-1. Approximately, 90% of recipients showed localized pain within the upper arm. Percentage change of PPTs at 1-1 and 2-1 was bilaterally (ipsilateral/contralateral) decreased to 87.4/89.4% and 80.6/91.0%, which was recovered to the baseline level at 1-7 and 2-7. Temporary, mild-to-moderate intensity, localized distribution, concomitant with bilateral mechanical hyperalgesia on the deltoid muscle, were typical pain characteristics following this vaccination. These findings provide a rationale that will be informative for future recipients. J. Med. Invest. 70 : 355-360, August, 2023.

A Novel Rat Model to Study Postsurgical Pain After Joint Replacement Surgery.

Purpose: The mechanisms underlying chronic postsurgical pain after joint replacement (JR) are complex, and it has been suggested that chronic postsurgical pain can develop as a result of inadequate acute pain management. Few studies have addressed acute pain after JR using specific animal models. This study aimed to develop a novel JR model focused on postsurgical pain assessment and the time course of pain recovery. Materials and Methods: Rats were allocated to the following three groups: sham (joint exposure), joint destruction (JD; resection of the femoral head), and JR (femoral head replacement using an originally developed implant). The time course of postsurgical pain behavior was measured using a dynamic weight-bearing apparatus, along with radiological assessments. The expression of calcitonin gene-related peptide-immunoreactive (CGRP-IR) neurons in the dorsal root ganglion (DRG) was evaluated by immunohistochemistry on days 28 and 42. Results: The ratio of weight-bearing distribution in the JR group gradually recovered from day 14 and reached the same level as that in the sham group on day 42, which was significantly greater than that in the JD group after day 7 (p<0.05). Radiologically, no significant issues were found, except for transient central migration of the implant in the JR group. The percentage of CGRP-IR DRG neurons in the JR group was significantly lower than that in the JD group on day 28 (mean, 37.4 vs 58.1%, p<0.05) and day 42 (mean, 32.3 vs 50.0%, p<0.05). Conclusion: Our novel JR model presented acute postsurgical pain behavior that was successfully recovered to the baseline level at day 42 after surgery. Difference of the pain manifestation between the JR and JD groups could be supported by the expression of CGRP-IR in DRG neurons. This model is the first step toward understanding detailed mechanisms of post-JR pain.

Expression of Substance P and Nerve Growth Factor in Degenerative Long Head of Biceps Tendon in Patients with Painful Rotator Cuff Tear.

PURPOSE: Degenerative long head of biceps tendon (LHBT) has been recognized as a notable pain source in patients with rotator cuff tear (RCT). Tenotomy or tenodesis of LHBT is frequently indicated together with arthroscopic rotator cuff repair (ARCR) aiming for complete pain relief; however, it has not been fully investigated whether resected LHBT is really a source of pain. The purpose of this study was to investigate expression levels of pain-associated mediators in LHBT and its association with preoperative pain profiles. METHODS: Twenty-seven RCT patients who underwent ARCR with LHBT resection were included. Each LHBT was resected due to its abnormal arthroscopic findings including tenosynovitis, hypertrophy, and partial tear. Worst macroscopic lesion of the LHBT was obtained, and expression levels of substance P (SP) and nerve growth factor (NGF) were evaluated using enzyme-linked immunosorbent assay (ELISA). Ten healthy knee flexor tendons were analyzed as non-degenerative samples. Preoperatively, subjective shoulder pain VAS and pain duration were investigated. Conventional LHBT pain provocation tests (Speed, Yergason, O'Brien) were performed. Pressure pain threshold (PPT) of bilateral LHBT on the groove was recorded. RESULTS: Levels of SP and NGF expression were significantly higher compared with non-degenerative tendons (P<0.01). Shoulder pain VAS and pain duration were not directly associated with SP and NGF expression level. Patients with positive O'Brien test expressed greater SP than negative patients (P=0.001). Significant negative correlation between the PPT ratio (ipsilateral/contralateral) and SP expression level was observed (r=-0.453, P=0.034). CONCLUSION: Greater expression of SP and NGF in degenerative LHBT supported our hypothesis that it would be a pain source in RCT patients. SP was likely to be expressed highly in patients with localized pressure pain hypersensitivity and positive O'Brien test (ie, altered mechanistic pain profile of LHBT), which may help when considering simultaneous LHBT resection during ARCR. CLINICAL REGISTRATION: UMIN000023943.

Increased Calcitonin Gene-Related Peptide Expression in DRG and Nerve Fibers Proliferation Caused by Nonunion Fracture in Rats.

PURPOSE: Nonunion bone fracture can be a cause of persistent pain, but the pathophysiology remains largely unknown. The objective of this study was to identify how nonunion affect persistent pain after fracture. Specifically, we evaluated the association of neuropeptide change in dorsal root ganglia (DRG) and nerve proliferation at fracture sites with pain. METHODS: Rat union and nonunion fracture models were created. A piece of latex glove was placed at the fracture site to create a nonunion model. At 6 weeks after surgery, bone healing was assessed using radiography. In addition, the presence of calcitonin gene-related peptide-immunoreactive (CGRP-IR) DRG at the level of L3 and anti-growth associated protein 43-immunoreactive (GAP43-IR) nerve fibers in the scar tissue between the bone fragments were evaluated. Pain-related behavior was assessed using forced treadmill running. RESULTS: In radiological images at 6 weeks after surgery, callus formation was formed continuously between bone fragments in the union models. On the one hand, a clear gap was detected between fragments in nonunion models. The percentage of CGRP-IR DRG cells and the density of GAP43-IR nerve fibers in the scar tissue between the bone fragments in nonunion models was significantly higher than that in union models (p < 0.05). An increase in inflammatory cell infiltrate was observed in scar tissues in the nonunion models. During forced treadmill running, rats in the union model could run significantly longer than those in the nonunion models. CONCLUSION: Increased CGRP expression in DRG cells and abnormal nerve proliferation secondary to prolonged inflammation could lead to persistent pain after bone fracture. In clinical practice, early achievement of bone union may minimize the development of persistent pain after fractures.

Humeral Avulsion of the Lateral Collateral Ligament of the Elbow Concomitant with the Medial Epicondyle Fracture of a Child with General Joint Laxity.

Medial epicondyle fracture is a common elbow injury for children, and it was reported that 30-50% of this fracture was associated with elbow dislocation. However, dysfunction of the lateral collateral ligament (LCL) complex accompanied with the medial epicondyle fracture has rarely been reported. In this report, a 13-year-old girl who had a humeral avulsion of the LCL concomitant with a displaced medial epicondyle fracture was presented. Since her general joint laxity had been recognized from past medical history and the humeral avulsion of the LCL was clearly confirmed by ultrasonography, simultaneous surgical repair for the LCL avulsion and medial epicondyle fracture was conducted and satisfactory outcome was achieved. Although general joint laxity does not tend to receive attention in trauma as much as chronic conditions, it should be borne in mind to prevent overlooking important soft tissue damage coexisting with apparent fractures.

Primary cardiac chondrosarcoma with large cell pulmonary carcinoma.

A 55-year-old man was transferred to our hospital for removal of cardiac and pulmonary tumors. Transesophageal echocardiography demonstrated a large echogenic mass in the left ventricle. The mass was attached to the posterior wall of the left ventricle and the mitral valve. Chest computed tomography showed a solitary, well-defind nodular lesion in the right upper lung. We performed concomitant resection of cardiac and pulmonary tumors through a midline sternotomy. The pathological diagnosis was cardiac chondrosarcoma with pulmonary large cell carcinoma. Postoperatively pelvic computed tomography, bone and gallium scintigrams did not identify any other active lesion, hence the cardiac tumor was considered to be of cardiac origin. He is alive 20 months after the operation and findings from the cardiac and pulmonary examination are unremarkable. Primary cardiac chondrosarcoma is extremely rare, and to our knowledge, only 13 cases have been recorded. We summarize herein these 14 cases.

Forty-year survival with Smeloff-Cutter and Starr-Edwards prostheses.

This case study describes a 40-year follow-up of a man who had a double valve replacement with Smeloff-Cutter aortic (Cutter Laboratories, Berkeley, CA) and Starr-Edwards mitral prostheses (Edwards Laboratories, Santa Ana, CA) when he was 34 years old. Double valve replacement was performed for aortic and mitral valve stenosis and insufficiency. To date, no surgical treatment has been required except a pacemaker implantation. The patient presented with a New York Heart Association functional class of I to II. Echocardiography revealed intact prostheses.