Dorsal root ganglion neurones with dichotomising axons are present in several species and are considered to play a role in referred pain. Clinically, patients with lesions in the lower lumbar discs occasionally complain of pain in the groin. We investigated the existence of dichotomising afferent neurones projecting axons both to the lumbar disc and to the groin skin, using the double fluorescent-labelling technique in rats. We observed neurones labelled with a tracer applied at the ventral portion of the L5-L6 disc and another tracer placed on the groin skin in L1 and L2 dorsal root ganglia. Our results showed that the double-labelled neurones had peripheral axons which dichotomised into both the L5-L6 disc and the groin skin, indicating the convergence of afferent sensory information from the disc and groin skin. Our findings provide a possible neuroanatomical mechanism for referred groin pain in patients with disc lesions

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

We examined whether somatosensory evoked potentials (SEPs) were detectable after direct electrical stimulation of injured, reconstructed and normal anterior cruciate ligaments (ACL) during arthroscopy under general anaesthesia. We investigated the position sense of the knee before and after reconstruction and the correlation between the SEP and instability.

We found detectable SEPs in all ligaments which had been reconstructed with autogenous semitendinosus and gracilis tendons over the past 18 months as well as in all cases of the normal group. The SEP was detectable in only 15 out of 32 cases in the injured group, although the voltages in the injured group were significantly lower than those of the controls. This was not the case in the reconstructed group. The postoperative position sense in 17 knees improved significantly, but there was no correlation between it and the voltage. The voltage of stable knees was significantly higher than that of the unstable joints. Our findings showed that sensory reinnervation occurred in the reconstructed human ACL and was closely related to the function of the knee.

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

Using a rat model the characteristics of the sensory neurones of the dorsal-root ganglia (DRG) innervating the hip were investigated by retrograde neurotransport and immunohistochemistry. Fluoro-Gold solution (FG) was injected into the left hip of ten rats. Seven days later the DRG from both sides between T12 and L6 were harvested. The number of FG-labelled calcitonin gene-related peptide-immunoreactive or isolectin B4-binding neurones were counted. The FG-labelled neurones were distributed throughout the left DRGs between T13 and L5, primarily at L2, L3, and L4. Few FG-labelled isolectin B4-binding neurones were present in the DRGs of either side between T13 and L5, but calcitonin gene-related peptide-immunoreactive neurones made up 30% of all FG-labelled neurones. Our findings may explain the referral of pain from the hip to the thigh or lower leg corresponding to the L2, L3 and L4 levels. Since most neurones are calcitonin gene-related peptide-immunoreactive peptide-containing neurones, they may have a more significant role in the perception of pain in the hip as peptidergic DRG neurones

An 18-year-old man who presented with weakness in his lower limbs, had an upper motor neurone lesion at the D12-L1 level. At laminectomy two stone-like objects were found which proved to be bundles of tiny pieces of wood. They are thought to have entered the cord through an abdominal penetrating injury sustained six years previously

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The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold.

The physiological role of mechanoreceptors in the anterior cruciate ligament (ACL) was studied in unanaesthetised decerebrate-spinalised cats and dogs. Tonic activity in the quadriceps and the hamstring increased in response to physiological loading of the ACL. Evoked potentials in the posterior articular nerve (PAN) were elicited by electrical stimulation of the surface of the ligament. ACL loading also induced significant discharges from the PAN. The results suggest that ACL loading has an excitatory effect on the thigh muscles through a multimotor neurone output, and that the PAN is one of the afferent routes from the mechanoreceptors of the ACL. The ACL-muscle reflex may therefore play a physiological role in maintaining knee kinematics

1 . In the common type of Volkmann's ischaemic contracture affecting the forearm flexors, the infarct takes the form of an ellipsoid with its axis in the line of the anterior interosseous artery and with its central point a little above the middle of the forearm. The greatest damage is at the centre and usually falls most heavily on flexor digitorum profundus and flexor pollicis longus, which are often necrotic. Those muscles more superficially placed, and sometimes the deep extensors, are more likely to exhibit fibrosis. 2. The median nerve runs near the centre of the ellipsoid and may exhibit profound ischaemia. The ulnar nerve, lying at the edge of the ischaemic zone, tends to be less severely affected. 3. The treatment for this condition is excision of all tissues irreparably damaged by ischaemia. If this operation is performed within twelve months from the time of injury, correction of the contracture should be almost complete. The tendons of shortened but active muscles are lengthened or transplanted. 4. After such excision it is possible to carry out reconstructive procedures commonly used in the surgery of lower motor neurone disorders and of trauma. A wide variety of tendon transplantations is available. The median nerve may be repaired either by a free graft or, in cases where both nerves have been extensively damaged by ischaemia, by an ulnar to median nerve-pedicle graft

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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).

Introduction and Aims: It has been suggested that elderly patients have poorer outcomes following carpal tunnel decompression than younger patients, especially if there is severe compression. The purpose of this study was to determine the outcomes of carpal tunnel decompression in the elderly patient and whether the outcome could be predicted from pre-operative nerve conduction studies. Method: A retrospective study of all patients over 70 years who had a carpal tunnel release over a three-year period at Dunedin Hospital, with a minimum one-year follow-up. Pre-operative nerve conduction studies were graded from one to six according to severity. Patients were followed up by postal questionnaire (Boston carpal tunnel symptom severity score) and telephone follow-up. Results: 109 procedures were performed in 96 patients. Eight patients had died, two excluded (one with Motor Neurone disease and one acute CTS following fracture) and five were demented and unable to fill out the questionnaire. Eighty-one patients with 92 wrists were available for review. Mean age was 78.6 years. Eighty percent had marked to severe neurophysiological changes (Grade 4–6). Post-operatively, the median Boston score was 1.27 with 84% having a Boston score of < 2.0. Patients were satisfied with the result in 94.6% of procedures. There was a positive correlation between nerve conduction grade and post-operative Boston Score (p=0.042). Conclusion: Despite nerve conduction studies consistent with marked to severe compression, elderly patients have low symptom severity scores following carpal tunnel decompression and a high rate of satisfaction. Carpal tunnel release in patients over 70 years of age is justified and usually associated with a good outcome

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Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

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

Purpose and Background: We have previously reported our investigations of nerve ingrowth into intervertebral discs (IVD) from patients with mechanical low back pain. We have shown that in discs that are painful on discography (pain level discs) nerves actively grow into the deep annulus fibrosus and nucleus pulposus. Nerve ingrowth accompanies blood vessel ingrowth and advances into the nucleus pulposus from the end plate. The morphology and neurochemistry of these nerves indicate them to be nociceptive. The growth of non-myelinated pain fibres in other settings is regulated by the cytokine Nerve Growth Factor (NGF). In this study, we have investigated the production and distribution of NGF, or more particularly its active isoform – NGF-β, and its receptors, in diseased intervertebral discs in order to establish whether this cytokine might be responsible for the observed nerve ingrowth in this situation. Methods: Tissue sections of 21 pain level, 15 non-pain level diseased and 12 normal intervertebral discs, taken at the time of spinal surgery, and from cadavers, were probed by radioactive in situ hybridisation (ISH) for expression of NGF-β, and by immunohistochemistry (IHC) for its high and low affinity receptors (trk-A and p75 respectively). In addition, either serial sections were stained with cell specific markers (CD31 – endothelial cell, PGP9.5 – neurones, GAP43 – actively growing nerves) or sections were doubled stained (two antibodies or both ISH and IHC). Results: We have demonstrated that NGF-β is synthesised by the endothelial cells of blood vessels growing into the IVD from the end plate. The high affinity receptor is expressed by those small nerve fibres that accompany the vessels and in their offshoots in pain level discs that are growing from perivascular nerves into the disc. In addition to their expressing the nerve specific molecule PGP9.5, the trk-A positive cells also express the nerve growth associated protein GAP43. Conclusion: The data indicate that nerve ingrowth into IVD is regulated by NGF-β. We have localised this production to the endothelial cells of ingrowing blood vessels. NGF-β is a potential therapeutic target for the management of back pain

Study Design: To examine the innervation of the lumbar spine from patients with lower back pain, and spinal nerve roots from patients with traumatic brachial plexus injuries. Objectives: To demonstrate the presence of nerve fibres in lumbar spine structures and spinal nerve roots, and determine whether they express the sensory neuronespecific sodium channels SNS/PN3 and NaN/SNS2. Summary of background data: The anatomical and molecular basis of low back pain and sciatica is poorly understood. Previous studies have demonstrated sensory nerves in facet joint capsule and prolapsed intervertebral disc, but not in ligamentum flavum. The voltagegated sodium channels SNS/PN3 and NaN/SNS2 are expressed by sensory neurones which mediate pain, but their presence in the lumbar spine is unknown. Methods: Tissue samples (ligamentum flavum n=32; facet joint capsule n=20; intervertebral disc n=15; spinal roots n=8) were immunostained with specific antibodies to protein gene product (PGP) 9.5, a pan-neuronal marker, SNS/PN3 and NaN/SNS2. Results: PGP 9.5-immunoreactive nerve fibres were detected in 72% of ligamentum flavum and 70% of facet joint capsule but only 20% of intervertebral disc specimens. SNS/PN3-and NaN/SNS2-positive fibres were detected in 28% and 3% of ligamentum flavum and 25% and 15% of facet joint capsule specimens respectively. Numerous SNS/PN3 and NaN/SNS2-positive fibres were found in the acutely injured spinal roots, and some were still present in dorsal roots in the chronic state. Conclusions: SNS/PN3 and NaN/SNS2-immunoreactivity is present in a subset of nerve fibres in lumbar spine structures, including ligamentum flavum and injured spinal roots. This is the first time that sensory nerve fibres have been demonstrated in the ligamentum flavum, and this raises the possibility that, contrary to the conclusions of previous studies, this unique ligament may be capable of nociception. Selective SNS/PN3 and NaN/ SNS2 blocking agents may provide new effective therapy for back pain and sciatica, with fewer side effects. Other novel ion channels are being studied in these tissues

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Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are common orthopaedic procedures requiring postoperative radiographs to confirm implant positioning and identify complications. Artificial intelligence (AI)-based image analysis has the potential to automate this postoperative surveillance. The aim of this study was to prepare a scoping review to investigate how AI is being used in the analysis of radiographs following THA and TKA, and how accurate these tools are.

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MicroRNA-183 (miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms.

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This study used an artificial neural network (ANN) model to determine the most important pre- and perioperative variables to predict same-day discharge in patients undergoing total knee arthroplasty (TKA).