Aims

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

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.

Aims

We aimed to evaluate the temperature around the nerve root during drilling of the lamina and to determine whether irrigation during drilling can reduce the chance of nerve root injury.

Aims

The aim of this study was to evaluate the time course of changes in parameters of diffusion tensor imaging (DTI) such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in patients with symptomatic lumbar disc herniation. We also investigated the correlation between the severity of neurological symptoms and these parameters.

The purpose of this study was to evaluate the expression of acid-sensing ion channels (ASICs) in the capsule and synovial fluid of patients with frozen shoulder. Capsular tissue and synovial fluid were obtained from 18 patients with idiopathic frozen shoulder (FS group) and 18 patients with instability of the shoulder (control group). The expressions of ASIC1, ASIC2, and ASIC3 in the capsule were determined using the reverse transcriptase-polymerase chain reaction, immunoblot analysis, and immunohistochemistry (IHC). The concentrations in synovial fluid were evaluated using an enzyme-linked immunosorbent assay.

The mRNA expression of ASIC1, ASIC2 and ASIC3 in the capsule were significantly increased in the FS group compared with the control group. The protein levels of these three ASICs were also increased. The increased expressions were confirmed by IHC. Of the ASICs, ASIC3 showed the greatest increase in both mRNA and levels of expression compared with the control group. The levels of ASIC1 and ASIC3 in synovial fluid were significantly increased in the FS group.

This study suggests that ASICs may play a role as mediators of inflammatory pain and be involved in the pathogenesis of frozen shoulder.

Cite this article: Bone Joint J 2015;97-B:824–9.

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

Introduction. In degenerative disorders of the spine such as disc herniation, intervertebral discs can affect neural tissue, which may result in pain as demonstrated in both basic science and clinical investigations. Previous in vitro and in vivo studies have shown that notochordal cells and chondrocyte-like cells in nucleus pulposus affect nervous tissue differently. The aim of the present study was to evaluate the morphology of spinal neural tissue in an in vivo rat model following application of cells derived from nucleus pulposus. Material and method. A disc herniation model in rats (n=58) was used. The L4 nerve root was exposed to a) nucleus pulposus (3mg), b) notochordal cells (25,000 cells) or c) chondrocyte-like cells (25,000 cells). Four control groups were included: 1) application of nucleus pulposus (3 mg) and mechanical displacement of the spinal nerve complex, 2) sham operated animals, 3) application of cell diluent (50 μl) and 4) naïve animals. Seven days after surgery the L4 nerve roots with their dorsal root ganglion were harvested and prepared for blinded neuropathological examinations using light microscopy. Results. Damage and loss of myelinated nerve fibers as well as epineural granulation tissue were most pronounced in the group that had been subjected to nerve root displacement and application of nucleus pulposus. There was significantly less nerve fiber damage in all other groups. The number of myelinated nerve fibers with enlarged outer Schwann cell compartment was significantly higher in all experimental groups as compared to naïve animals, except for animals in which the nerve root complex had been exposed to cell diluent, notochordal cells and chondrocyte-like cells. Discussion and Conclusion. This is the first examination nerve root and dorsal root ganglion morphology after exposure to notochordal cells and chondrocyte-like cells in an in vivo model. The results indicate that application of notochordal cells and chondrocyte-like cells, per se, do not structurally affect the myelinated nerve fibers compared to naïve animals. However, one cannot exclude that there may be physiological effects of notochordal cells and chondrocyte-like cells on nerve tissue in vivo although no morphological differences were observed with the present method. The findings in the present study support previous observations that mechanical nerve tissue displacement and application of nucleus pulposus can induce pronounced morphological nerve tissue changes. However, the combination of mechanical nerve tissue displacement and application of notochordal cells and/or chondrocyte-like cells was not tested. In conclusion, the present study suggests that mechanical nerve tissue displacement is a prerequisite for the induction of morphological changes following application of disc tissue and its components on neural tissue. Summary. The effects of notochordal cells and chondrocyte-like cells on spinal nerve tissue might be dependent on concurrent mechanical nerve tissue deformation

Summary Statement. TRPA1 antagonist reduced spontaneous excitatory postsynaptic currents of substantia gelatinosa neuron in spinal cord dorsal horn by in vivo patch-clamp analysis. TRPA1 may act as a mediator of excitatory synaptic transmission. Introduction. Little is known about the pathophysiological mechanisms of radicular pain. The substantia gelatinosa (SG) in the spinal cord dorsal horn receives primary afferent inputs, which predominantly convey nociceptive sensations. Nociceptive information is modified and integrated in the SG, suggesting that the SG may be a therapeutic target for treating radicular pain. Electrophysiological study using in vivo patch-clamp recording from SG neurons is a useful method to analyze functional properties in synaptic transmission. Transient receptor potential ankyrin 1 (TRPA1) has been widely identified in the central and peripheral nervous system such as peripheral nociceptor, dorsal root ganglion (DRG), and spinal cord dorsal horn, and is considered that they are involved in synaptic transmission of pain. However, it is still unknown about its functional role and mechanism of pain transmission in spinal cord dorsal horn. The purpose of this study is to investigate changes in excitatory synaptic transmission of SG neurons with TRPA1 antagonist and to clarify the potential role of TRPA1 in the rat spinal cord dorsal horn using in vivo patch-clamp analysis. Methods. Male Sprague-Dawley rat were divided into three experimental groups. In the root constriction (RC) group, the right L5 spinal root was ligated proximal to the DRG. The root was exposed only in the sham operation group, and no procedure was performed in the control group. In order to evaluate the excitability of the substantia gelatinosa neuron in the dorsal horn, we recorded excitatory postsynaptic currents (EPSCs) using in vivo whole-cell patch-clamp methods in each groups. Also, to clarify the function of TRPA1, we observed the change of EPSCs with application of TRPA1 antagonist (HC030031). Statistical significance was determined as P < 0.05 using Student's paired t test and one-way analysis of variance (ANOVA) followed by a Tukey–Kramer test. Results. Spontaneous EPSCs (sEPSCs) were increased in the RC group more than in the sham and control group. With application of HC030031, the frequency and amplitude of sEPSCs were significantly reduced in all three groups. The relative frequency and the relative amplitude were 81% and 89% in the RC group, 81% and 94% in the control group, 70% and 88% in the sham group, respectively. There was no statistical significant difference among the three groups. Discussion. The mechanism of synaptic transmission via TRPA1 in the spinal cord dorsal horn is considered that activated TRPA1 cause Ca. 2+. influx into presynaptic terminal and glutamate release from synaptic vesicle onto SG neuron. In the present study, sEPSCs were significantly reduced by TRPA1 antagonist not only in the RC group but also in the control group and sham group, which indicating that some TRPA1 were activated consistently in the rat spinal cord dorsal horn. It is considered that TRPA1 act as a mediator of excitatory transmission, thus, suppressing the activity of TRPA1 may lead to pain relief

Background. Foraminal stenosis is often encountered in patients undergoing decompression for spinal stenosis. Given the increased resection of facets and the presence of the more sensitive dorsal root ganglion, it is hypothesized that patients with foraminal stenosis have poorer postoperative outcomes. Methods. Thirty-one patients undergoing decompression without fusion for lumbar spinal stenosis were evaluated. The degree of foraminal stenosis was determined by 2 independent reviewers for absence of fat around the nerve roots. ImageJ digital imaging software was also used to evaluate the foraminal area. Patients with foraminal stenosis were compared with those without using the Oswestry Disability Index (ODI) and a numerical pain scale for back and leg pain at a minimum of 1 year follow-up. Results. Twenty patients in the foraminal stenosis group were compared with 11 without foraminal stenosis. There were no significant differences between the 2 groups regarding age, sex, comorbidities, number of levels operated on, preoperative ODI, back pain or leg pain scores. The foraminal area was significantly smaller in the foraminal stenosis group. Patients without foraminal stenosis reported significant improvements in ODI (mean 26.0), back pain (mean 3.1) and leg pain scores (mean 5.5). Patients with foraminal stenosis reported significant improvements in ODI (mean 18.8) and leg pain (mean 2.5) but not in back pain (mean 0.3). Comparing the 2 groups, the patients with foraminal stenosis had significantly less improvement in back pain (p = 0.02) and leg pain (p = 0.02). Conclusion. The results of this study suggest that presence of foraminal stenosis is a negative predictor for successful outcome following decompression surgery. This may be related to the increased instability that occurs when a foraminotomy is required. Spinal fusion may reduce this effect, and further study is required. NO DISCLOSURES

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.

The June 2012 Research Roundup³⁶⁰ looks at: platelet-rich plasma; ageing, bone and mesenchymal stem cells; cytokines and the herniated intervertebral disc; ulcerative colitis, Crohn’s disease and anti-inflammatories; the effect of NSAIDs on bone healing; osteoporosis of the fractured hip; herbal medicine and recovery after acute muscle injury; and ultrasound and the time to fracture union.

The June 2012 Spine Roundup³⁶⁰ looks at: back pain; spinal fusion for tuberculosis; anatomical course of the recurrent laryngeal nerve; groin pain with normal imaging; the herniated intervertebral disc; obesity’s effect on the spine; the medicolegal risks of cauda equina syndrome; and intravenous lidocaine use and failed back surgery syndrome.

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.

Purpose: Upper cervical spine stabilization in children can be challenging due to anatomic abnormalities such as incomplete posterior elements, vertebral artery variability and small patient size. Several techniques have been described for stabilization of the upper cervical spine, each with its own advantages and disadvantages. Since the introduction of the technique by Harms, many authors have shown C1 lateral mass screws to be safe and effective in the stabilization of the upper cervical spine in adults. No large series of paediatric C1 lateral mass screw fixation has been reported in the literature. The purpose of this study was to describe the indications, technique, and outcomes of C1 lateral mass screw fixation in a consecutive series of 11 paediatric patients. Method: A database generated retrospective review of all patients who underwent C1 lateral mass screw fixation as part of an upper cervical spine stabilization construct was performed. In all patients the C2 dorsal root ganglion was sacrificed. Patient demographics and clinical outcomes were obtained through chart review. Radiographs immediately post-operatively, at six-weeks, three-months, and final follow-up were reviewed. Results: Eleven consecutive paediatric patients underwent bilateral C1 lateral mass screw fixation for a variety of conditions including C1-C2 instability, deformity, congenital malformation, trauma, as well as revision surgery. The average age was 10 years (range 4 to 16 years) with a mean follow-up of 11 months (range 6 – 18 months). There were no iatrogenic vertebral artery, hypoglossal nerve or spinal cord injuries. All 11 patients had solid fusion clinically and radiographically, with no loss of fixation. The C2 dorsal root ganglion was sacrificed in all patients with resulting minor occipital parasthaesia that progressively diminished in severity. Conclusion: This is the largest series of consecutive patients reported in the literature to date showing that the technique is safe and effective, with acceptable morbidity when applied to the paediatric population. We believe that C1 lateral mass screws offer significant advantages over traditional fixation techniques when the C1 vertebra is to be included in an upper cervical instrumented construct

The nervous system is known to be involved in inflammation and repair. We aimed to determine the effect of physical activity on the healing of a muscle injury and to examine the pattern of innervation. Using a drop-ball technique, a contusion was produced in the gastrocnemius in 20 rats. In ten the limb was immobilised in a plaster cast and the remaining ten had mobilisation on a running wheel. The muscle and the corresponding dorsal-root ganglia were studied by histological and immunohistochemical methods.

In the mobilisation group, there was a significant reduction in lymphocytes (p = 0.016), macrophages (p = 0.008) and myotubules (p = 0.008) between three and 21 days. The formation of myotubules and the density of nerve fibres was significantly higher (both p = 0.016) compared with those in the immobilisation group at three days, while the density of CGRP-positive fibres was significantly lower (p = 0.016) after 21 days.

Mobilisation after contusional injury to the muscle resulted in early and increased formation of myotubules, early nerve regeneration and progressive reduction in inflammation, suggesting that it promoted a better healing response.

Restoration of hand function is rarely achieved after a complete closed traction lesion of the supraclavicular brachial plexus. We describe the injury, treatment, rehabilitation and long-term results of two patients who regained good function of the upper limb and useful function in the hand after such an injury. Successful repairs were performed within six days of injury. Tinel’s sign proved accurate in predicting the ruptures and the distribution of pain was accurate in predicting avulsion. The severe pain that began on the day of injury resolved with the onset of muscle function.

Recovery of muscle function preceded recovery of sensation. Recovery of the function of C and Aδ fibres was the slowest of all.

Introduction: C1-2 polyaxial screw-rod fixation is a relatively new technique. While recognising the potential for inadvertent vertebral artery injury there have been few reports in the literature outlining all the possible complications. Aim:To review all cases of C1 lateral mass screw insertion with emphasis on the evaluation of the potential structures at risk during the procedure. Methods: We retrospectively reviewed all patients in our unit who has C1 lateral mass screw insertion over a 2 year period. The C1 lateral mass screw was inserted as part of an atlantoaxial stabilisation or incorporated into a modular occiput/subaxial construct. Outcome measures included clinical and radiological parameters. Clinical indicators included age, gender, neurologic status, surgical indication and the number of levels stabilised. Intraoperative complications including blood loss, vertebral artery injury or dural tears were recorded. Radiological indicators included post-operative plain radiographs to assess sagittal alignment and to check for screw malposition or construct failure. Results: A total of 18 C1 lateral mass screws were implanted in 9 patients. There were 3 male and 6 female patients who had C1 lateral mass screws inserted in this tertiary referral centre. Two patients had atlantoaxial stabilisation of a C2 odontoid fracture. There were 4 patients with rheumatoid arthritis whose C1 lateral mass screws were inserted as part of an occipitocervical or subaxial cervical stabilisation. The other pathologies included trauma and spinal tumours. There was no vertebral artery injury and no cerebrospinal fluid leak. Three patients developed post operative occipital neuralgia. This neuralgia was transient in one of the patients having settled at 6-week follow up. In the other 2 patients the neuralgia was unresolved at the time of latest follow up but was adequately controlled with appropriate pain management. Post operatively no patient had radiographic evidence of construct failure and all demostrated excellent sagittal alignment. Conclusion: It has been reported that the absence of threads on the upper portion of the long shank screw may protect against neural irritation. However insertion of the C1 lateral mass screw necessitates careful caudal retraction of the C2 dorsal root ganglion. The insertion point for the C1 lateral mass screw is at the junction of the C1 posterior arch and the midpoint of the posterior inferior part of the C1 lateral mass. Two patients in our series suffered occipital neuralgia post insertion of the C1 lateral mass screws. This highlights the potential for C2 nerve root irritation during and after the insertion of the C1 lateral mass screw

The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries.

This review supports the theory that degeneration of the disc has a complex multifactorial aetiology. Which factors initiate the events in the degenerative cascade is a question that remains unanswered, but most evidence points to an age-related process influenced primarily by mechanical and genetic factors.

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.