Viscerotopic localization of preganglionic parasympathetic cell bodies of origin of the anterior and posterior subdiaphragmatic vagus nerves.

Utilizing the retrograde HRP transport method, fibers from anterior and posterior subdiaphragmatic branches of the vagus nerve in the rat were traced to their cells of origin in the brainstem. Efferents to the gut supplied by the subdiaphragmatic vagus nerves derive from cell bodies organized in a viscerotopic, spindle-shaped longitudinal cell column throughout the longitudinal extent of the classically described dorsal nucleus of the vagus (DNV) and in regions of nucleus commissuralis (NC), caudal to the DNV. This entire longitudinal group of cells is called the DNV cell column. In the caudal one third of the DNV cell column, the cell bodies were found in the midline and paramedian posterior portion of the NC, and in the anterior portion of the caudal DNV, in a horizontally oriented cluster of cells when viewed in cross section. In the middle one third of the DNV cell column, the cell bodies moved laterally, but still maintained their anterior position in the nucleus. In the rostral one third of the cell column, the cell bodies were located at the lateral margin of the DNV. A few scattered cell bodies extended caudally from the DNV cell column into the dorsal region of lamina X of spinal cord, and reached as far caudal as the C5-C6 segments. The anterior subdiaphragmatic branch of the vagus contained axons whose cell bodies were mainly but not exclusively located in the ipsilateral (left) side of the medulla, while the posterior subdiaphragmatic branch of the vagus contained axons whose cell bodies were found bilaterally in the medulla, with a majority (approx. 60%) located on the ipsilateral (right) side, and approximately 40% located on the contralateral (left) side.

Neurogenic factors in the etiopathogenesis of osteoarthritis.

In this article we have tried to unify several different lines of evidence bearing on how neuromuscular mechanisms might contribute to the etiopathogenesis of OA. Several key points bear emphasis. (1) The neuromuscular system is both the greatest threat that the joint faces and the principal means by which joints are protected, because this system exercises the definitive influence on the spectrum of forces to which the joint is exposed. If muscle contraction is not properly coordinated, the joint will exceed its normal extreme of excursion and the loading of its cartilage will be excessive. This trauma will be manifest pathologically as OA. It follows that if the neuromuscular system cannot control the mechanical environment of the joint, the articular and periarticular tissues will break down even in the face of treatment with "chondroprotective" drugs. (2) Speculation about the role of sensation in joint protection is pointless unless sensory ablation influences the development of OA. (3) Only a small minority of patients with severe peripheral sensory neuropathy develop a Charcot joint, and a clear correlation between the development of a Charcot joint and the severity of the sensory neuropathy or the activity level of the patient has yet to be established. Until proved otherwise, it should not be assumed that ipsilateral sensation plays a role in protecting the stable joint from breakdown. (4) There have been surprisingly few animal experiments in which the effect of sensory nerve ablation on synovial joints has been examined. Although the results of the early studies are not entirely consistent, they suggest that extensive deafferentation of a limb does not necessarily lead to joint pathology in the absence of exogenous trauma or infection. Such studies should be repeated under carefully controlled conditions. (5) Recent work in dogs suggests that ipsilateral sensation is not important in protecting the stable joint from OA but is necessary to protect the unstable joint from rapid deterioration. Moreover, there is evidence that sensation is temporarily important in protecting the unstable joint but that the CNS eventually acquires the ability to protect the unstable joint even in the absence of ipsilateral sensory input.

Serial kinematic analysis of the unstable knee after transection of the anterior cruciate ligament: temporal and angular changes in a canine model of osteoarthritis.

Transection of the anterior cruciate ligament in the dog leads to osteoarthritis. This study defines the kinematic changes in the unstable knee after transection of the cruciate ligament (six dogs) and after a sham operation (four dogs). In the dogs that were anterior cruciate ligament-deficient (ACL-D), the duration of stance 1 week postoperatively decreased 38% from the preoperative value, but only a 4% decrease was seen at 6 weeks. The duration of double hindlimb support increased from 6 to 19% of the entire cycle 1 week after surgery but returned to the baseline value by 18 weeks. As the unstable limb contacted the treadmill belt, the initial flexion (yield) and subsequent extension (propulsive) phases were not evident or were markedly attenuated in every ACL-D dog throughout the 26-week period of observation. The angular velocity patterns were characterized by a slight extension velocity at touchdown (compared with a zero value preoperatively) and a decrease in the peak velocities (both flexion and extension) during the remainder of the stance phase. None of these changes was observed in the animals that had a sham operation. These data indicate that, in the dog, the nervous system compensates for instability of the knee by altering angular, but not temporal, parameters. The extension velocity at touchdown and the reduction in peak flexion velocity during the yield component of the stance phase may reduce the ability of the limb to absorb impact forces and lead to the development of osteoarthritis of the knee.(ABSTRACT TRUNCATED AT 250 WORDS)

A quantitative comparison of motor and sensory conduction velocities in short- and long-term streptozotocin- and alloxan-diabetic rats.

Motor and sensory conduction velocities were measured in the sural and tibial nerves of streptozotocin (stz)-diabetic, alloxan-diabetic, and age-matched control rats. Conduction velocity (CV) determinations were made 2 weeks and 2, 4, 8, and 12 months following the induction of diabetes. CVs of control, stz-diabetic, and alloxan-diabetic rats were compared at each time period by one way analysis of variance and when appropriate by the Newman-Keuls multiple range test for multiple comparisons. Reductions of 10-20% in CV of diabetic rats were observed in several classes of sensory and motor nerve fibers. Larger reductions (31 and 38%) were seen in 2 classes of sensory nerve fibers in 12 month stz-diabetic rats. Sensory CV was slowed earlier and more frequently than motor CV. Differential involvement was also seen among the several classes of sensory nerve fibers examined. Slower conducting sensory fibers appeared to be affected earlier and more frequently than faster conducting sensory fibers. Comparing alloxan-diabetic with stz-diabetic rats revealed significant differences in CV 8 months after the induction of diabetes. Motor and sensory CVs of the tibial nerve were slower in stz-diabetic rats than in alloxan-diabetic rats. In general, the neuropathy appeared to be less severe and to develop later in the alloxan-diabetic rats. These data suggest that the neuropathy of stz- and alloxan-diabetes is primarily sensory in nature, and that the neuropathy in these 2 widely used models of diabetes may not be entirely equivalent.

Glycogen accumulation in tibial nerves of experimentally diabetic and aging control rats.

Tibial nerves of streptozotocin-diabetic, alloxan-diabetic, and age-matched control rats were examined at 2 weeks and 2, 4, 8, and 12 months following the induction of diabetes. Glycogen-like granules accumulated within perineurial and Schwann cells of only the diabetic animals. This accumulation may reflect a metabolic abnormality in these cells which could account for the reduced conduction velocities seen in the peripheral nerves of these same diabetic rats (Moore et al. 1980a). Glycogen-like granules were also present and increased with age in myelinated axons of both diabetic and control rats. Quantitative data suggest that axonal accumulation of glycogen-like granules is related to aging or injury related phenomena to which diabetic axons may be more susceptible.

Ultrastructural axonal pathology in experimentally diabetic and aging control rats.

Electron microscopic examination of tibial nerves from streptozotocin-diabetic, alloxan-diabetic and age-matched control rats was undertaken at two weeks and two, four, eight, and twelve months following the induction of diabetes. Many myelinated axons of both diabetic and control rats contained glycogen-like granules, axon-Schwann cell networks and fingerlike intrusions of myelin. These axonal changes were observed more frequently with advancing age and duration of diabetes, suggesting that they are related to aging or repeated injury. A larger proportion of diabetic axons than control axons were affected at early time periods, but by eight and twelve months the control axons were as frequently (or more frequently) involved as diabetic axons. Thus, experimental diabetes may confer upon peripheral myelinated axons an increased susceptability to aging or repeated injury. Specific morphologic abnormalities in peripheral myelinated axons associated uniquely with streptozotocin or alloxan diabetes in the rat were not noted.

Neurogenic acceleration of degenerative joint lesions.

A severe form of degenerative joint lesion (neuropathic arthropathy) is known to complicate a variety of diseases that are associated with sensory abnormalities. We studied the relationship between sensory deficits and the development of degenerative joint lesions in dogs in two complementary experiments. In Experiment 1, dogs that were subjected to unilateral dorsal-root ganglionectomy (fourth lumbar to first sacral vertebra) failed to show biochemical, gross, or histological evidence of degenerative joint lesions in ipsilateral femoral condylar cartilage after sixteen months. In Experiment 2, five of six dogs that were subjected to transection of the anterior cruciate ligament two weeks after deafferentation of the ipsilateral limb showed striking gross or histological lesions, or both, of the femoral condylar cartilage three weeks after ligament transection (five weeks after ganglionectomy). We concluded that the neuromuscular mechanisms that protect normal joints from damage are inadequate to protect unstable joints from becoming rapidly and severely damaged.

Neurogenic acceleration of osteoarthrosis. The effects of previous neurectomy of the articular nerves on the development of osteoarthrosis after transection of the anterior cruciate ligament in dogs.

The development of osteoarthrosis in unstable knee joints of dogs after transection of the anterior cruciate ligament is greatly accelerated when the afferent nerve fibers from the ipsilateral hindlimb have been interrupted by dorsal root ganglionectomy before transection. The purpose of the current study was to determine whether partial loss of the afferent fibers from the knee joints of dogs, accomplished by neurectomy of the primary articular nerves before transection of the ligament, also accelerates the development of osteoarthrosis. Osteoarthrosis did not develop in dogs that had had transection of the medial, posterior, and lateral articular nerves to the left knee joint but had an intact anterior cruciate ligament. Osteoarthrosis developed in all dogs that had had transection of the anterior cruciate ligament. However, the osteoarthrotic lesions, as gauged by histological and macroscopic criteria, were more frequent and severe in dogs that had had neurectomy before transection than in those that had intact sensory nerves and an unstable joint (p less than or equal to 0.05). A subchondral fracture occurred in three dogs that had had neurectomy and had an unstable joint but in none of the dogs that had intact sensory nerves and an unstable joint.

Serial kinematic analysis of the trunk and limb joints after anterior cruciate ligament transection: Temporal, spatial, and angular changes in a canine model of osteoarthritis.

To help elucidate how sensation-mediated kinematics modulate the rate of development of osteoarthritis in the unstable knee, we have examined the serial kinematic changes in hind- and forelimb joints, and alterations in vertical movement of the rump, in six dogs followed for 26 weeks after unilateral anterior curciate ligament transection. Although marked changes in the temporal parameters occurred in treadmill gait acutely in all four limbs, by the sixth postoperative week the stance and swing durations had returned to within ±10% of the baseline values, where they remained until sacrifice. As the cruciate-deficient limb contacted the treadmill surface, the amount of flexion (yield) of the unstable knee and ipsilateral ankle was reduced 10-20° (P < 0.05). In contrast, flexion of the contralateral ankle and knee increased about 10° during yield (P < 0.05), which was associated with a 100% increase in the extent of vertical movement of the rump (P < 0.05). Hip extension in the unstable limb increased about 10° during stance (P < 0.05), which moved the support provided by this limb away from the dog's centre of gravity. Kinematic changes in the forelimb joints were only transient, and less extensive than those in the hind limb. Before ligament transection, the joint angles of comparable joints of the different dogs were remarkably similar at touchdown. After ligament transection, the variability of the ipsilateral hip and knee joints was initially markedly increased. However, by 26 weeks after surgery the ipsilateral hip and knee touchdown joint angles of all the cruciate-deficient dogs were again similar to one another. Thus, after a period of 'trial and error', the dogs responded similarly to unilateral cruciate deficiency. This response was probably modulated by sensory nerves and reduced the trauma to the unstable knee during locomotion. Presumably, this facilitated effective, but suboptimal locomotion, while slowing the rate of progression of osteoarthritis in the unstable joint compared to dogs with a deafferented hind limb and unstable joint.

Serial kinematic analysis of canine hind limb joints after unilateral L4-S1 dorsal root ganglionectomy: Insights into locomotor control mechanisms.

Following unilateral L4-S1 dorsal root ganglionectomy to deafferent the hind limb, each of six dogs showed increased extension of the ipsilateral hip, knee and ankle joints during most of the gait cycle throughout a 26-week period of observation. The contralateral hind limb joints initially exhibited increased flexion during gait (which presumably compensated for the increased extension of the deafferented limb), but over time contralateral joint extension gradually increased, i.e. the movement of the joints of the contralateral limb progressively began to resemble that of the ipsilateral joints. We suggest that the long-term kinematic changes in both limbs (increased extension) occurred because of neurological changes in spinal cord structure, associated with death of sensory neurons and an associated increase in the influence of descending systems (e.g. vestibulospinal) on motoneurons. These results emphasize the importance of long-term observation of kinematic patterns after experimental induction of neural lesions and indicate that the contralateral limb should not, a priori, be considered a valid control in such studies.

Sacroiliac joint innervation and pain.

The present paper reviews current knowledge on the innervation of the human sacroiliac joint (SIJ). We conclude, based on a recent anatomic study on adult cadavers, with fetal correlation, that the joint is predominantly, if not entirely, innervated by sacral dorsal rami. This conclusion is in agreement with patterns of referred pain reported by asymptomatic volunteers upon direct SIJ capsular stimulation and with a reduction in pain in patients treated for (presumptive) SIJ pain by injection of an anesthetic into the SIJ. We also present preliminary data suggesting that the periarticular tissues of the SIJ, like those of other synovial joints, contain mechanoreceptors and nociceptors that function to inform the central nervous system about the state of the joint.

The functional morphology of the cercopithecoid wrist and inferior radioulnar joints, and their bearing on some problems in the evolution of the Hominoidea.

The cercopithecoid wrist joint differs from the wrist joints of hominoids in several ways. The distal ulna, the distal radius, the pisiform, the triquetrum, the hamate, and the base of the fifth metacarpal are on the one hand remarkably alike among cercopithecoid genera, and on the other remarkably distinct from homologous bones in the Hominoidea. Functionally, the triquetrum and the pisiform, in conjuction with the ulnar styloid process, check the proximal carpal row during ulnar deviation, and are possibly important in stabilizing the wrist during dorsiflexion as well. The head of the ulna almost certainly betokens a range of radioulnar supination in cercopithecoids that is substantially less than is to be found in any of the hominoid genera. The articulation between the hamate bone and the base of the fifth metacarpal allows for considerable dorsiflexion in the Cercopithecoidea; this potential was not evidenct in any of the hominoids examined. Behaviorally, the cercopithecoid wrist can most profitably be viewed as an adaptation for a quadrupedal life style involving dorsiflexion of the wrist and palmigrade/digitigrade substrate contact. The hominoid wrist joint is not adapted for such a behavioral potential.

The mechanoreceptor innervation of the posterior attachments of the lateral meniscus of the dog knee joint.

The posterior attachments of the dog knee joint lateral menisci have been studied to identify and characterize their mechanoreceptor innervation. Two basic types of mechanoreceptor were identified that appeared to be similar to the Type III and Type II endings described by Freeman & Wyke (1967) in cat knee periarticular tissues. Significantly, two distinct forms of Type II corpuscles were identified in this study, referred to as Types IIa and IIb, respectively. Endings were usually identified either at the point where the posterior meniscotibial ligament merged with the main body of the meniscus and the meniscofemoral ligament, or within the inner aspect of the meniscofemoral ligament where it joined the meniscal 'body'. The presence of encapsulated mechanoreceptors within the attachments of dog knee lateral menisci means that the central nervous system is being appraised of the mechanical state of these structures. A mechanism is suggested by which the tension of meniscal attachments could be varied according to knee joint position. A possible relationship between the morphology of the receptors identified in this study and the physiological responses of similar cat knee joint receptors is discussed.

The histological structure of dog knee menisci with comments on its possible significance.

Knee-joint menisci are poorly understood terminologically, structurally and functionally in spite of their almost universal occurrence in mammals and their considerable clinical significance in man. A study was therefore undertaken of dog knee menisci utilizing several histological techniques. Terminologically, it is proposed that the part of the meniscus extending between the anterior and posterior horns and exclusive of them be called the meniscal "body." Structurally, the horns and body differ in anumber of ways. The horns are oval in cross section, the body triangular. Hyalinized areas are much more frequent in the body than in the horns. The collagen of the horns is organized into discrete bundles that are separated from one another by loose connective tissue septa, while that of the body is arranged in a "herringbone" pattern; no septa are present in the body. Finally, the meniscal horns are richly supplied with blood vessels are nerves (including large myelinated fibers which apparently terminate in the horns) while the body is almost completely devoid of blood vessels and nerves. Functionally, it is hypothesized that knee-joint menisci may serve important sensory functions.

The structure and innervation of cat knee menisci, and their relation to a "sensory hypothesis" of meniscal function.

Previous work on dog knee menisci demonstrated structural differences between the meniscal horns and the meniscal bodies (O'Connor, '76). Of particular interest was the observation that the meniscal horns possessed an abundant blood and nerve supply, while the meniscal bodies did not. The presence of nerves in the meniscal horns prompted the speculation that menisci might perform a sensory function. The present study was undertaken in order to establish whether or not similar regional differences existed in cat knee menisci, structures previously believed to lack a corpuscular mechanoreceptor system (Freeman and Wyke, '67). Differences between the meniscal horns and meniscal bodies similar to those reported in the dog were found to characterize cat knee menisci. In particular, the meniscal horns possessed a rich neurovascular supply, while the meniscal bodies did not. Most important, at least two morphologically different mechano-receptors were identified in the meniscal horns, but none were identified in the meniscal bodies.

The composition of the medial articular nerve to the knee in the dog.

Light and electron microscopy were used to characterise the medial articular nerve to the knee in the dog, in terms of the total number of myelinated axons, the frequencies of different diameters of myelinated axons, the number of unmyelinated axons, and the ratios of unmyelinated to myelinated axons. Approximately 70% of all myelinated axons were of less than 5 micron diameter and, with the exception of two of sixteen nerves examined by light microscopy, all distributions were unimodal. The distributions of the two nerves of other than unimodal distribution were each characterised by a second, small peak of axon diameters ranging between 9 and 14 microns. Unmyelinated axons counted in five nerves suggested that approximately 72% of all axons of a given nerve were unmyelinated, giving a ratio of about 2.5 unmyelinated to 1.0 myelinated axon.

Low dose prednisone treatment does not reduce the severity of osteoarthritis in dogs after anterior cruciate ligament transection.

It was reported recently that oral administration of prednisone, 0.3 mg/kg/day, decreased osteophyte size and cartilage ulceration in dogs with osteoarthritis (OA) produced by "stab" transection of the anterior cruciate ligament. Since this dose would be equivalent to 17 mg/day for a 70-kg human, our study was performed to determine whether a lower, clinically more realistic, dose of prednisone also had ameliorating effects on OA in the canine model. Following arthrotomy and transection of the anterior cruciate ligament 10 adult mongrel dogs were each given prednisone, 0.1 mg/kg/day, begun either 0, 2, or 4 weeks after arthrotomy and continued until sacrifice 12 weeks after surgery; 7 others underwent the identical surgical procedure but received no prednisone and served as OA controls. No differences were noted between dogs treated with prednisone and the controls with respect to size or extent of osteophytes, severity of synovial inflammation, morphologic changes of OA in articular cartilage, or in vitro synthesis of glycosaminoglycans. Increases in cartilage thickness in the OA knee were similar in the 2 groups, as were increases in H2O content and uronic acid concentration. Regardless of the interval between arthrotomy and start of treatment, the low dose of prednisone used here did not reduce the severity of OA in this model.

Effects of surgically induced instability on rat knee articular cartilage.

Degenerative lesions in the articular cartilage were present following transection of the anterior cruciate ligament in the rat. These lesions included surface disruptions, a reduction in matrix proteoglycans, and cellular changes and therefore were similar to lesions seen in dogs following transection of the anterior cruciate ligament as well as lesions seen in other mechanical derangement models. Lesions were more frequently encountered in animals that had been exercised on a treadmill. This suggests that the rat knee joint may be a useful small animal model in studying the effect of mechanical derangement on articular tissues.