Brian L. O'Connor

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.

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.

Effects of diacerhein in an accelerated canine model of osteoarthritis.

OBJECT To determine whether diacerhein has a disease-modifying effect in an accelerated canine model of osteoarthritis. DESIGN Fourteen adult mongrel dogs underwent unilateral L4-S1 dorsal root ganglionectomy (DRG), followed 3 weeks later by ipsilateral anterior cruciate ligament transection. Seven dogs received diacerhein (15-20 mg/kg) daily throughout the interval between DRG and sacrifice, eight weeks after ligament transection. The other seven dogs served as OA controls. RESULTS The mean volume of synovial fluid obtained from the OA knee of the diacerhein-treated dogs was approximately 40% less than that from the OA knee of the controls. In addition, diacerhein appeared to reduce the severity of fibrillation (femoral condyle) and full-thickness ulceration (trochlear ridge) of the articular cartilage and the level of collagenase activity in extracts of the OA cartilage, and to increase net PG synthesis in the OA cartilage, although none of the above changes were statistically significant. CONCLUSION The differences between the diacerhein group and untreated OA controls, even though not statistically significant, suggest that diacerhein was active in this rapidly progressive model of OA. Because changes associated with initiation of OA may be different than those associated with progression, whether diacerhein has a disease-modifying effect should be examined in a less rapidly progressive model.

Reduced sensory and motor conduction velocity in 25-week-old diabetic [] mice

Abstract Motor and sensory conduction velocities were measured in sural and tibial nerves of 25-week-old genetically diabetic ( db db ) mice and their nondiabetic littermates. For motor conduction velocity determination, the sciatic nerve was stimulated at the hip and the tibial nerve subsequently stimulated at the ankle while recording interosseous muscle potentials from needle electrodes placed in the foot. Sensory conduction velocities were determined by recording compound action potentials directly from sural and tibial nerves at the ankle after sciatic nerve stimulation. Control and diabetic conduction velocities were compared by Students t test. The motor conduction velocity was reduced by approximately 20% from the control, and the distal motor latency was increased in db db mice by 22% more than the control latency. Conduction velocity was also reduced in some sensory fibers, an observation not previously reported in the db db mouse. Sensory fibers most severely affected were the faster-conducting fibers of the sural nerve, whose conduction velocity was decreased by 18% from the control. Slower-conducting sensory fibers in sural and tibial nerves were only midly affected, whereas fast-conducting sensory fibers of the tibial nerve appeared to remain normal. These data suggest that not all nerve fibers react alike to the diabetic state in the genetically diabetic ( db db ) mouse.

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.

Serial kinematic analysis of the canine hindlimb joints after deafferentation and anterior cruciate ligament transection

OBJECTIVE AND DESIGN Transection of the anterior cruciate ligament 2 weeks after ipsilateral hindlimb deafferentation leads to osteoarthritis of the knee joint within 3 weeks. We analyzed the gait of six dogs that underwent this procedure in order to identify kinematic changes that could account for this rapid joint degeneration. All animals were video taped, 1, 3, 6, 9 and 13 weeks after surgery while they trotted on a treadmill. RESULTS In each dog, extension of the hip, knee and ankle joints of the unstable limb was increased, and the yield phase of the unstable knee was delayed or attenuated. When killed, five of six dogs showed a large full-thickness cartilage ulcer on the distal and/or anterior surface of the medial femoral condyle of the unstable knee; in the sixth dog, a smaller ulcer was observed. However, the severity of pathology in each individual was not obviously related to difference among the dogs in postoperative joint kinematics. CONCLUSIONS These data, and results of prior studies in humans and dogs, suggest that knee hyperextension resulting from limb deafferentation, and knee instability resulting from anterior cruciate ligament transection, operate in concert to create a mechanical environment (i.e., increased tibiofemoral separation and changes in the loading of articular surfaces) that results in rapid joint breakdown.

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.

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.