Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.

The December 2014 Spine Roundup. 360 . looks at: surgeon outcomes;. complications and scoliosis surgery; is sequestrectomy enough in lumbar disc prolapse?; predicting outcomes in lumbar disc herniation; sympathectomy has a direct effect on the dorsal root ganglion; and distal extensions of fusion in adolescent idiopathic scoliosis

Objectives. In order to elucidate the influence of sympathetic nerves on lumbar radiculopathy, we investigated whether sympathectomy attenuated pain behaviour and altered the electrical properties of the dorsal root ganglion (DRG) neurons in a rat model of lumbar root constriction. Methods. Sprague-Dawley rats were divided into three experimental groups. In the root constriction group, the left L5 spinal nerve root was ligated proximal to the DRG as a lumbar radiculopathy model. In the root constriction + sympathectomy group, sympathectomy was performed after the root constriction procedure. In the control group, no procedures were performed. In order to evaluate the pain relief effect of sympathectomy, behavioural analysis using mechanical and thermal stimulation was performed. In order to evaluate the excitability of the DRG neurons, we recorded action potentials of the isolated single DRG neuron by the whole-cell patch-clamp method. Results. In behavioural analysis, sympathectomy attenuated the mechanical allodynia and thermal hyperalgesia caused by lumbar root constriction. In electrophysiological analysis, single isolated DRG neurons with root constriction exhibited lower threshold current, more depolarised resting membrane potential, prolonged action potential duration, and more depolarisation frequency. These hyperexcitable alterations caused by root constriction were significantly attenuated in rats treated with surgical sympathectomy. Conclusion. The present results suggest that sympathectomy attenuates lumbar radicular pain resulting from root constriction by altering the electrical property of the DRG neuron itself. Thus, the sympathetic nervous system was closely associated with lumbar radicular pain, and suppressing the activity of the sympathetic nervous system may therefore lead to pain relief

The outcomes of 261 nerve injuries in 100 patients were graded good in 173 cases (66%), fair in 70 (26.8%) and poor in 18 (6.9%) at the final review (median 28.4 months (1.3 to 64.2)). The initial grades for the 42 sutures and graft were 11 good, 14 fair and 17 poor. After subsequent revision repairs in seven, neurolyses in 11 and free vascularised fasciocutaneous flaps in 11, the final grades were 15 good, 18 fair and nine poor. Pain was relieved in 30 of 36 patients by nerve repair, revision of repair or neurolysis, and flaps when indicated. The difference in outcome between penetrating missile wounds and those caused by explosions was not statistically significant; in the latter group the onset of recovery from focal conduction block was delayed (mean 4.7 months (2.5 to 10.2) vs 3.8 months (0.6 to 6); p = 0.0001). A total of 42 patients (47 lower limbs) presented with an insensate foot. By final review (mean 27.4 months (20 to 36)) plantar sensation was good in 26 limbs (55%), fair in 16 (34%) and poor in five (11%). Nine patients returned to full military duties, 18 to restricted duties, 30 to sedentary work, and 43 were discharged from military service. Effective rehabilitation must be early, integrated and vigorous. The responsible surgeons must be firmly embedded in the process, at times exerting leadership.

We describe 261 peripheral nerve injuries sustained in war by 100 consecutive service men and women injured in Iraq and Afghanistan. Their mean age was 26.5 years (18.1 to 42.6), the median interval between injury and first review was 4.2 months (mean 8.4 months (0.36 to 48.49)) and median follow-up was 28.4 months (mean 20.5 months (1.3 to 64.2)). The nerve lesions were predominantly focal prolonged conduction block/neurapraxia in 116 (45%), axonotmesis in 92 (35%) and neurotmesis in 53 (20%) and were evenly distributed between the upper and the lower limbs. Explosions accounted for 164 (63%): 213 (82%) nerve injuries were associated with open wounds. Two or more main nerves were injured in 70 patients. The ulnar, common peroneal and tibial nerves were most commonly injured. In 69 patients there was a vascular injury, fracture, or both at the level of the nerve lesion. Major tissue loss was present in 50 patients: amputation of at least one limb was needed in 18. A total of 36 patients continued in severe neuropathic pain.

This paper outlines the methods used in the assessment of these injuries and provides information about the depth and distribution of the nerve lesions, their associated injuries and neuropathic pain syndromes.

The mammalian growth plate is a complex structure which is essential for the elongation of long bones. However, an understanding of how the growth plate functions at the cellular level is lacking. This review, summarises the factors involved in growth-plate regulation, its failure and the consequence of injury. We also describe some of the cellular mechanisms which underpin the increase in volume of the growth-plate chondrocyte which is the major determinant of the rate and extent of bone lengthening. We show how living in situ chondrocytes can be imaged using 2-photon laser scanning microscopy to provide a quantitative analysis of their volume. This approach should give better understanding of the cellular control of bone growth in both healthy and failed growth plates.

Most injuries to the femoral nerve are iatrogenic in origin and occur during resection of large retroperitoneal tumours. When the defect is considerable a nerve graft is mandatory to avoid tension across the suture line. We describe two cases of iatrogenic femoral nerve injury which recovered well after reconstruction with long sural nerve grafts.

The probable reasons for success were that we performed the grafting soon after the injury, the patients were not too old, the nerve repairs were reinforced with fibrin glue and electrical stimulation of the quadriceps was administered to prevent muscle atrophy. Good functional results may be obtained if these conditions are satisfied even if the length of a nerve graft is more than 10 cm.

A rat model of lumbar root constriction with an additional sympathectomy in some animals was used to assess whether the sympathetic nerves influenced radicular pain. Behavioural tests were undertaken before and after the operation. On the 28th post-operative day, both dorsal root ganglia and the spinal roots of L4 and L5 were removed, frozen and sectioned on a cryostat (8 μm to 10 μm). Immunostaining was then performed with antibodies to tyrosine hydroxylase (TH) according to the Avidin Biotin Complex method. In order to quantify the presence of sympathetic nerve fibres, we counted TH-immunoreactive fibres in the dorsal root ganglia using a light microscope equipped with a micrometer graticule (10 x 10 squares, 500 mm x 500 mm). We counted the squares of the graticule which contained TH-immunoreactive fibres for each of five randomly-selected sections of the dorsal root ganglia. The root constriction group showed mechanical allodynia and thermal hyperalgesia. In this group, TH-immunoreactive fibres were abundant in the ipsilateral dorsal root ganglia at L5 and L4 compared with the opposite side. In the sympathectomy group, mechanical hypersensitivity was attenuated significantly. We consider that the sympathetic nervous system plays an important role in the generation of radicular pain

This paper describes how we came to understand the pathophysiology of Volkmann’s ischaemic contracture with references to relevant papers in this Journal, and the investigation and management of acute compartment syndrome is briefly discussed.

The anatomical studies, basic to our understanding of lumbar spine innervation through the sinu-vertebral nerves, are reviewed. Research in the 1980s suggested that pain sensation was conducted in part via the sympathetic system. These sensory pathways have now been clarified using sophisticated experimental and histochemical techniques confirming a dual pattern. One route enters the adjacent dorsal root segmentally, whereas the other supply is non-segmental ascending through the paravertebral sympathetic chain with re-entry through the thoracolumbar white rami communicantes.

Sensory nerve endings in the degenerative lumbar disc penetrate deep into the disrupted nucleus pulposus, insensitive in the normal lumbar spine. Complex as well as free nerve endings would appear to contribute to pain transmission.

The nature and mechanism of discogenic pain is still speculative but there is growing evidence to support a ‘visceral pain’ hypothesis, unique in the muscloskeletal system. This mechanism is open to ‘peripheral sensitisation’ and possibly ‘central sensitisation’ as a potential cause of chronic back pain.

Complex regional pain syndrome is characterised by an exaggerated response to injury in a limb with intense prolonged pain, vasomotor disturbance, delayed functional recovery and trophic changes. This review describes the current knowledge of the condition and outlines the methods of treatment available with particular emphasis on the knee.

We describe two patients in whom poor healing after chemical ablation for ingrown toenails unmasked significant vascular disease of the lower extremities. We have found no similar reports in the English language literature.

Thirty-six patients with reflex sympathetic dystrophy primarily affecting the knee were reviewed. Injuries or operation about the patellofemoral joint triggered its onset in 64% of patients. Co-existent mechanical derangement of the knee was present in 64% of patients. Those patients who underwent sympathetic blockade or sympathectomy within one year of onset of symptoms had significantly better pain and function scores than those in whom intervention was later. Early diagnosis remains the key to successful management. Surgery for co-existent mechanical derangement in the affected knee should not be performed until the syndrome is controlled

1. An experimental study of the effects of nerve and muscle lesions upon the growth of bone has been made. In each case animals were subjected to unilateral lesions in the hind limb, the other limb serving as a control. The growth of the tibia was measured by calculating the difference between the length of the bone on a radiograph at the beginning of the experiment and the length of the dried bone after necropsy. The weights of the dried bones were compared. 2. In the young rabbit simple exposure of the common peroneal nerve, or division of the sural nerve, produced no change in the growth rate of the tibia. Division of both peroneal nerves, producing paralysis of the muscles below the knee, led to lengthening of the affected tibia, and this lengthening persisted until maturity several months later. A similar lengthening was seen after division of the tendons around the ankle. In spite of this lengthening the tibia on the side of the operation was almost always lighter than its fellow. 3. In the puppy division of the anterior nerve roots supplying the hind limb produced a significant lengthening of the tibia of the affected limb three months after operation. No significant changes in limb length occurred after lumbar sympathectomy in the puppy. 4. The significance of these experimental nerve lesions has been considered together with recent observations upon the growth of bone in the presence of lower motor neurone lesions in the child. From this analysis it is suggested that the initial effect of paralysis is to produce lengthening of the affected bone. This lengthening is probably due to the hyperaemia of disuse. In the presence of persistent paralysis the growth of the limb is ultimately depressed. This depression is rarely seen in the experimental animal because the growing period is relatively short. The possible causes of this secondary depression of bone growth have been considered

1. The history of the development of the operation of sympathetic ganglionectomy for vasospasm is related. 2. A simple classification is given of the common diseases of the peripheral arteries. 3. The symptoms of peripheral arterial disease are described. 4. The investigations are discussed. 5. The treatment, both conservative and surgical, is discussed, with comments on arterial grafts. 6. Special points are made regarding poliomyelitis, acrocyanosis, Bazin's disease, cervical rib, vascular injuries and crutch arteritis. 7. The long-term results of sympathectomy are reviewed

1. Forty-eight cases of causalgia are reviewed and the clinical features are briefly described. 2. Multiple nerve injuries are common and the pain is often associated with all the injured nerves. In the upper limb there was always an incomplete lesion of the lower trunk or medial cord of the brachial plexus, or of the median nerve. In the lower limb there was always an incomplete lesion of the medial popliteal division of the sciatic, the medial popliteal, or the posterior tibial nerve. These nerves carry most of the sympathetic fibres to the hand and foot. With two exceptions all the nerve lesions were at or above the level of the knee or elbow. 3. Sympathectomy gives marked relief of pain in most cases of causalgia. Prompt treatment is essential to prevent the crippling deformities which follow prolonged voluntary immobilisation of the painful limb. The results of preganglionic are superior to those of postganglionic sympathectomy. 4. The possible pain pathways are discussed, and an explanation is offered for the successful results of sympathectomy in the treatment of causalgia

1 . Twenty-four patients complaining of severe pain after nerve injuries have been considered from a diagnostic and therapeutic point of view. 2. The typical syndrome of causalgia develops only when the median or internal popliteal nerves are injured. It is doubtful whether pain associated with injury in the peripheral part of the limb, or of the brachial plexus, should be classed as causalgia. 3. The importance of novocaine block of the sympathetic ganglia as a diagnostic test is stressed, and its usefulness as a therapeutic measure is considered. 4. Sympathectomy is shown to be a reliable method of treatment in suitable cases. 5. The limited field of application of radiotherapy is also indicated

Ischaemia threatening an injured limb gives rise to the syndrome of pain, pallor, paralysis, and pulselessness. It is due to arterial injury by laceration, compression, intra-mural rupture or contusion, or to arterial spasm with or without demonstrable local arterial damage. The differentiation of spasm without local injury from organic obstruction is not possible by clinical methods. The suggested plan of treatment and of management is:. 1. General systemic investigation (blood-pressure, blood-count, coagulation time, etc.). 2. Removal of all external pressure. 3. Resuscitation. 4. Direct attempt to relieve the obstruction by operation. 5. Post-operative care. The operative procedure recommended is:. 1. Manipulative reduction of the fracture if possible. 2. Proximal control of the artery. 3. Arteriography. 4. Exposure of the occluded artery (unless contra-indicated by time factors and by the anatomy of the collateral circulation), liberation and mobilisation of the vessel, repair by suture where such is necessary and possible, and arterectomy only forirreparable local damage. 5. The provision of sympathetic block by injection or by sympathectomy. The important elements of post-operative care are:. 1. To maintain the blood-pressure while cooling the limb and heating the patient