Histopathological analysis of the posterior cruciate ligament in primary osteoarthritis.

BACKGROUND: According to some authors, the indication of an arthroplasty maintaining the posterior cruciate ligament (PCL) demands adequate structural preservation and proprioceptive function of this ligament. The nervous fibers contained in the synovial neurovascular bundle (NVB) around the PCL are involved in proprioception. A study evaluating the grade of PCL and NVB degeneration by using clinical, radiological, and perioperative parameters in knee arthritis patients, in theory, could help surgeons in the decision of preserving or not preserving the PCL in a particular patient. QUESTIONS: (1) Can the degree of the PCL collagen fibers degeneration be predicted by clinical, radiographic, and perioperative parameters in knee arthritis patients? (2) Is the NVB histological degeneration status predictable using clinical, radiographic, and perioperative parameters in the same subset of patients? (3) Is there a correlation between the degree of the PCL collagen fibers degeneration and NVB status in knee arthritis patients? METHODS: Eighty-nine PCLs (85 patients) obtained from total knee replacement surgery were studied. The histologic degeneration of PCL collagen fibers and the NVB status (preserved, degenerated, not detected) were evaluated. These histological degeneration patterns were correlated with clinical and radiographic parameters and with anterior cruciate ligament (ACL) status. RESULTS: A small prevalence of preserved NVB was related to Grades IV and V of Ahlbäck's classification, ACL absence, and severe PCL degeneration. The clinical and radiological parameters studied were not able to predict the grade of histological degeneration of the PCL. CONCLUSIONS: Ahlbäck's classification and ACL status provided useful information about NVB integrity. LEVEL OF EVIDENCE: Basic Science Level IV.

Immunohistochemical analysis of the neural structures of the posterior cruciate ligament in osteoarthritis patients submitted to total knee arthroplasty: an analysis of thirty-four cases.

OBJECTIVES: Many authors recommend posterior cruciate ligament-retaining arthroplasty with the intention to maintain the proprioception properties of this ligament. Preservation of the neuroreceptors and nervous fibers may be essential for retaining the proprioception function of the posterior cruciate ligament. The present study was thus developed to evaluate the presence of neural structures in the posterior cruciate ligament resected during posterior stabilized arthroplasty in osteoarthritis patients. In particular, clinical, radiographic and histological parameters were correlated with the presence or absence of neural structures in the posterior cruciate ligament. METHODS: In total, 34 posterior cruciate ligament specimens were stained with hematoxylin-eosin and Gomori trichrome. An immunohistochemical analysis using antibodies against the S100 protein and neurofilaments was also performed. The presence of neural structures was correlated with parameters such as tibiofemoral angulation, histological degeneration of the posterior cruciate ligament, Ahlbäck radiological classification, age, gender and the histologic pattern of the synovial neurovascular bundle around the posterior cruciate ligament. RESULTS: In total, 67.5% of the cases presented neural structures in the posterior cruciate ligament. In 65% of the cases, the neurovascular bundle was degenerated. Nervous structures were more commonly detected in varus knees than in valgus knees (77% versus 50%). Additionally, severe histologic degeneration of the posterior cruciate ligament was related to neurovascular bundle degeneration. CONCLUSIONS: Severe posterior cruciate ligament degeneration was related to neurovascular bundle compromise. Neural structures were more commonly detected in varus knees. Intrinsic neural structures were detected in the majority of the posterior cruciate ligaments of patients submitted to knee arthroplasty for osteoarthritis.

Histological changes and neural elements in the posterior cruciate ligament in osteoarthritic knees.

PURPOSE: To evaluate histological changes and neural elements in 100 posterior cruciate ligaments (PCLs) in patients with osteoarthritis. METHODS: 100 PCLs were obtained from a consecutive series of 46 women and 16 men aged 49 to 91 (mean, 67) years who underwent primary PCL-retaining total knee replacement for osteoarthritis. Histology was examined using conventional light microscopy. The PCLs were graded histologically in terms of parallel orientation of collagen fibres, mucoid degeneration, inflammation, and haemosiderin deposition. Histological changes were graded as normal, mild degeneration, moderate degeneration, and severe degeneration. The neural elements were assessed using immunohistochemical staining for S100 protein and neurofilaments. The histopathologist was blinded to the age, gender, and clinical and radiological grades of osteoarthritis. RESULTS: One specimen was excluded from analysis owing to inadequate tissue. In the remaining 99 specimens, histology was normal in 72, mildly degenerative in 4, moderately degenerative in 4, and severely degenerative in 15. 76 specimens were positive for S100 protein or neurofilament or both by immunohistochemical staining, indicating the presence of neural elements. CONCLUSION: Most knees with osteoarthritis present with viable PCLs. Retaining the PCL in total knee replacement is a good option for better kinematics, stability, and proprioception.

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.

[Sensorimotor potential of the intact and injured anterior and posterior cruciate ligaments--a neurophysiological study in an animal model]. / Sensomotorisches Potenzial vom intakten und traumatisierten vorderen und hinteren Kreuzband -- eine tierexperimentelle, neurophysiologische Studie.

AIM: This neurophysiological study is intended to investigate the sensomotor potential of the anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL) which may provide joint stabilization via a ligamentomuscular reflex arch. In addition, the role of ligamentous injury on the sensomotor potential has been investigated. METHOD: The sensomotor potential was investigated using 24 knee joints in a sheep model under in-vivo conditions. The cruciate ligaments were mechanically loaded and the muscular activities of the hamstrings and the quadriceps were recorded simultaneously via electromyography. Injury to the ligaments was simulated by defined mechanical elongation of the ACL and PCL to failure. RESULTS: The results confirm the hypothesis of the existence of a ligamentomuscular reflex loop between ligamentary mechanoreceptors and the joint-stabilizing muscles. Mechanical loading of the ACL triggered mainly the activity of the hamstrings, whereas loading of the PCL led to the activation of the quadriceps. The rate of elongation which caused disturbances to the sensomotor potential was significantly smaller as compared to the elongation to failure. CONCLUSION: The cruciate ligaments provide dynamic joint stabilization via a ligamentomuscular reflex arch. It was demonstrated that the sensomotor potential of both structures is significantly more susceptible to ligament injury than the biomechanical potential.

Estudio anatomopatológico de los elementos neurales en el ligamento cruzado posterioren rodillas con gonartrosis / Histologic study of neural elements in the posterior cruciate ligament in osteoarthritic knees

El desarrollo de los diseños de los implantes de prótesis totales de rodilla ha ido acompañado de una controversia aún no solucionada sobre el papel y la función del ligamento cruzado posterior (LCP). Fundamentalmente se han realizado estudios y valoraciones de su papel biomecánico. Manteniéndose la discusión sobre el papel en la propiocepción de la rodilla artrósica del LCP, planteamos la realización del estudio histológico de las estructuras neurales en especímenes de LCP obtenidos en el momento de la cirugía protésica de la gonartrosis tricompartimental. Los resultados evidenciaron en 18 de las 23 muestras (78 por ciento) la existencia de filetes nerviosos periféricos con papel en la nocicepción articular. Según estos resultados la realización de las prótesis totales de rodilla con preservación del LCP permitiría un mejor funcionamiento y conservación del implante, aun cuando dicho LCP no fuese funcionante biomecánicamente (AU)

Proprioception of the cruciate ligaments: receptor mapping in an animal model.

Ten anterior and posterior cruciate ligaments (ACL and PCL) harvested from adult sheep were investigated under light microscopy for data on the frequency and localisation of neural structures. Serial sections of 25 microns thickness were stained with a modified gold chloride technique. Receptors were classified according to their histological structure. Topographic distribution and frequency within the ligament texture were determined with the help of computerized image analysis. Three distinct neural structures could be identified: Ruffini endings, Ruffini corpuscles of the Golgi tendon organ-like type and Pacinian corpuscles. Golgi tendon organs were not found. In total, 274 and 238 neural structures were present in the 10 ACL and 10 PCL, respectively. Pacinian receptors were the most common structures, with a mean frequency of 13.6 +/- 5.3 (ACL) and 12.4 +/- 5.1 (PCL), followed by Ruffini endings with 8.9 +/- 3.2 (ACL) and 7.8 +/- 2.9 (PCL), whereas Ruffini corpuscles had the lowest frequency with a mean value of 4.9 +/- 2.1 (ACL) and 3.4 +/- 1.1 (PCL). The majority of the neural structures were located in the subsynovial sheath or closely associated with endotenon structures. The tibial and femoral insertion areas had a significantly increased receptor density compared with the midpart of the ACL and PCL (P < 0.001), where only 19.3% and 23.7% of the receptors were located. These results emphasise the complex sensory structure of the cruciate ligaments and provide a valid morphological basis for further neurophysiological investigations.

Immunohistochemical analysis of mechanoreceptors in the human posterior cruciate ligament: a demonstration of its proprioceptive role and clinical relevance.

Although long-term studies report successful results with total knee arthroplasty (TKA), performed with or without posterior cruciate ligament (PCL) retention, controversy exists as to which is preferable in regard to patient outcome and satisfaction. The possible proprioceptive role of the PCL may account for a more normal feeling of the arthroplasty. Although the PCL has been examined using various histological techniques, immunohistochemical techniques are the most sensitive for neural elements. Therefore an immunohistochemical study was designed to determine the patterns of innervation, the morphological types of the proprioceptors, and their immunohistochemical profile. During TKA, samples were obtained from 22 osteoarthritic PCLs and subjected to immunohistochemical analysis with mouse monoclonal antibodies against neurofilament protein (NFP), S100 protein (S100P), epithelial membrane antigen (EMA), and vimentin (all present in neuromechanoreceptors). Three normal PCLs from cadaveric specimens were also obtained and analyzed for comparison. Five types of sensory corpuscles were observed in both the normal and the arthritic PCLs: simple lamellar, Pacini-like, Ruffini, Krause-like, and morphologically unclassified. Their structure included a central axon, inner core, and capsule in lamellar and Pacini corpuscles and variable intracorpuscular axons and periaxonal cells in the Ruffini and Krause-like corpuscles. The immunohistochemical profile showed the central axon to have NFP immunoreactivity, periaxonal cells to have S100P and vimentin immunoreactivity, and the capsule to have EMA and vimentin immunoreactivity. Nerve fibers and free nerve endings displayed NFP and S100P immunoreactivity. The immunohistochemical profile of the PCL sensory corpuscles is almost identical to that of cutaneous sensory corpuscles. Some prior histological studies of the PCL reported Golgi-like mechanoreceptors, and others found encapsulated corpuscles but no Golgi-like structures. This report determined the innervation of the PCL by the more sensitive immunohistochemical means, revealing four major types of encapsulated mechanoreceptors. The plentiful and varied types of encapsulated mechanoreceptors found in even the arthritic PCL suggests a rich proprioceptive role. It is controversial as to whether preservation of the PCL at TKA improves postoperative proprioception. Our findings tend to support those clinical reports of improved proprioception after PCL-retaining versus PCL-substituting TKAs. The presence of many and varied types of mechanoreceptors may account for the improved stair climbing reported in patients with PCL-retaining TKA and may contribute to patient satisfaction and a more normal feeling after TKA.

[The nerve supply of the knee joint]. / Die nervöse Versorgung der Kniegelenke.

The paper presents the present state of research on the most important receptors of joints and muscles with regard to occurrence, structure, and function. Proprioception relies on the nervous supply of the tissues in the knee joint, and on the surrounding muscles and tendons; it is the basis of coordination.

Neural system of the human posterior cruciate ligament in osteoarthritis.

The purpose of this study was to quantify the neural elements in a group of posterior cruciate ligaments from osteoarthritic patients in comparison with normal subjects. Nine ligaments obtained from total knee arthroplasty procedures and five control ligaments from amputated limbs or fresh cadavers were stained with gold chloride. The percentage area occupied by the receptors and the neural network was determined by means of a computer-assisted image analyzer. A significant reduction of the neural elements was observed in the group of ligaments from osteoarthritic patients (0.44 +/- 0.132 SEM vs 0.958 +/- 0.13 SEM, P = .001). The loss of mechanoceptors and the consequent reduction of neural afferences may reduce the functional stability of the joint, participating in the osteoarthritic degenerative process.

Innervation of the canine cruciate ligaments. A neurohistological study.

A search for mechanoreceptors within the substance of the cruciate ligaments was undertaken using the modified gold-chloride technique. Abundant Pacinian, Vater-Pacini, Ruffini end organs and Ruffini-type receptors were found within the substance of the anterior and posterior cruciates. The receptors were innervated by axons of 5 to 10 micrometers in diameter penetrating from the synovium investing the ligaments. The findings support the contention that the cruciate ligaments have important mechanoreceptive and proprioceptive functions.

A sensory role for the cruciate ligaments.

Morphologic, physiologic, and clinical evidence for the sensory role of the cruciate ligaments is reviewed. The cruciate ligaments accommodate morphologically different sensory nerve endings (Ruffini endings, Pacinian corpuscles, Golgi tendon organlike endings, and free nerve endings) with different capabilities of providing the central nervous system with information not only about noxious and chemical events but also about characteristics of movements and position-related stretches of these ligaments. A survey of available data reveals that low threshold joint-ligament receptor (i.e., mechanoreceptor) afferents evoke only weak and rare effects in skeletomotor neurons (alpha-motor neurons), while they frequently and powerfully influence fusimotor neurons (gamma-motor neurons). The effects on the gamma-muscle-spindle system in the muscles around the knee are so potent that even stretches of the cruciate ligaments at relatively moderate loads (not noxious) may induce major changes in responses of the muscle spindle afferents. As the activity in the primary muscle spindle afferents modifies the stiffness in the muscles, the cruciate ligament receptors, via the gamma-muscle-spindle system, may participate in the regulation and preprogramming of the muscular stiffness around the knee joint and thereby of the knee joint stiffness. Thus, the sensory system of the cruciate ligaments is able to significantly contribute to the functional stability of the knee joint.

Receptors in the knee joint ligaments and their role in the biomechanics of the joint.

The knee joint ligaments contain Ruffini, Pacinian, Golgi, and free-nerve endings with different capabilities of providing the CNS with information about movement and position as well as about noxious events. Skeletomotor neurons (alpha-motoneurons) are known to be influenced only very rarely and weakly from low-threshold mechanoreceptors in the ligaments, while the effects on the tau-muscle-spindle system in the muscles around the knee are so potent that even ligament stretches at very low loads may induce major changes in the responses of the muscle spindle afferents. Since the primary muscle spindle afferents participate in the regulation of muscular stiffness, the receptors in the knee joint ligaments probably contribute, via the tau-muscle-spindle system, to preparatory adjustment (pre-setting) of the stiffness of the muscles around the knee joint, and thereby to the joint stiffness and the functional joint stability.