1 . Voluntary activity of any given muscle in the hand is not an absolute indication of the state of the nerve which usually supplies it. 2. Significant variations in the standard pattern of innervation have been found in 20 per cent of 226 cases studied. 3. The pattern of innervation described in standard text-books occurred in only 33 per cent. of cases. 4. A striking variation is the supply of every thenar muscle by the ulnar nerve. In other cases the first dorsal interosseous muscle may be supplied by the median nerve. 5. In order to arrive at an accurate diagnosis when anomalous innervation is suspected, nerve blocks at appropriate levels are required. 6. Great care must be taken during operations to avoid damage to connections between the ulnar and the median nerves, especially in patients with anomalous innervation of the hand muscles

1. Pain and pressure sensibility has been studied in the fibrous articular ligament and synovial membrane of the knee joint in normal human subjects and in patients subjected to arthrotomy under local anaesthesia. 2. The fibrous ligament was found to be a highly sensitive structure, containing many spots which give rise to sensations of pain or pressure when stimulated mechanically or chemically. Synovial membrane was found to be a relatively insensitive structure which only occasionally contains pain-sensitive spots. 3. Histological examination of articular capsule from the knee joints of normal and sympathectomised cats shows that articular ligaments have a rich nerve plexus and a variety of specialised and unspecialised nerve endings, most of which are somatic in origin. Synovial membrane contains a more delicate nerve network and also a variety of nerve endings, the majority of which are autonomic in origin. But a substantial number of somatic nerves enter the synovial membrane, some of which terminate in nerve loops, globular endings or simple unspecialised endings. 4. Histological examination of normal human articular capsule shows that its innervation closely resembles that of the cat, but no sympathectomised human material was examined. 5. The bearing of these findings on the symptomatology of joint disease is discussed briefly

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.

Our understanding of the origin of hip pain in degenerative disorders of the hip, including primary osteoarthritis, avascular necrosis and femoroacetabular impingement (FAI), is limited. We undertook a histological investigation of the nociceptive innervation of the acetabular labrum, ligamentum teres and capsule of the hip, in order to prove pain- and proprioceptive-associated marker expression. These structures were isolated from 57 patients who had undergone elective hip surgery (44 labral samples, 33 ligamentum teres specimens, 34 capsular samples; in 19 patients all three structures were harvested). A total of 15 000 histological sections were prepared that were investigated immunohistochemically for the presence of protein S-100, 68 kDa neurofilament, neuropeptide Y, nociceptin and substance P. The tissues were evaluated in six representative areas.

Within the labrum, pain-associated free nerve ending expression was located predominantly at its base, decreasing in the periphery. In contrast, the distribution within the ligamentum teres showed a high local concentration in the centre. The hip capsule had an almost homogeneous marker expression in all investigated areas.

This study showed characteristic distribution profiles of nociceptive and pain-related nerve fibres, which may help in understanding the origin of hip pain.

Cite this article: Bone Joint J 2013;95-B:770–6.

We obtained intervertebral discs with cartilage endplates and underlying cancellous bone at operation from patients with degenerative disc disease and then used immunohistochemical techniques to localise the nerves and nerve endings in the specimens. We used antibodies for the ubiquitous neuronal protein gene product 9.5 (PGP 9.5). Immunoreactivity to neuropeptide Y was used to identify autonomic nerves and calcitonin gene-related peptide (CGRP) and substance P to identify sensory nerves. Blood vessels were identified by immunoreactivity with platelet-endothelial cell-adhesion molecule (CD31; PECAM).

In a control group with no known history of chronic back pain, nerve fibres immunoreactive to PGP 9.5 and neuropeptide Y were most closely related to blood vessels, with occasional substance P and CGRP immunoreactivity. In patients with severe back pain and markedly reduced disc height, proliferation of blood vessels and accompanying nerve fibres was observed in the endplate region and underlying vertebral bodies. Many of these nerves were immunoreactive to substance P or CGRP, and in addition, substance P- and CGRP-immunoreactive nociceptors were seen unrelated to blood vessels. Quantification by image analysis showed a marked increase in CGRP-containing sensory nerve fibres compared with normal control subjects.

We speculate that a chemotactic response to products of disc breakdown is responsible for the proliferation of vascularity and CGRP-containing sensory nerves found in the endplate region and vertebral body adjacent to degenerate discs. The neuropeptides substance P and CGRP have potent vasodilatory as well as pain-transmitting effects. The increase in sensory nerve endings suggests increase in blood flow, perhaps as an attempt to augment the nutrition of the degenerate disc. The increase in the density of sensory nerves, and the presence of endplate cartilage defects, strongly suggest that the endplates and vertebral bodies are sources of pain; this may explain the severe pain on movement experienced by some patients with degenerative disc disease.

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

This study was designed to test the hypothesis that the sensory innervation of bone might play an important role in sensing and responding to low-intensity pulsed ultrasound and explain its effect in promoting fracture healing. In 112 rats a standardised mid-shaft tibial fracture was created, supported with an intramedullary needle and divided into four groups of 28. These either had a sciatic neurectomy or a patellar tendon resection as control, and received the ultrasound or not as a sham treatment. Fracture union, callus mineralisation and remodelling were assessed using plain radiography, peripheral quantitative computed tomography and histomorphology. Daily ultrasound treatment significantly increased the rate of union and the volumetric bone mineral density in the fracture callus in the neurally intact rats (p = 0.025), but this stimulating effect was absent in the rats with sciatic neurectomy. Histomorphology demonstrated faster maturation of the callus in the group treated with ultrasound when compared with the control group. The results supported the hypothesis that intact innervation plays an important role in allowing low-intensity pulsed ultrasound to promote fracture healing

The aim of this study was to evaluate the feasibility of using the intact S1 nerve root as a donor nerve to repair an avulsion of the contralateral lumbosacral plexus. Two cohorts of patients were recruited. In cohort 1, the L4–S4 nerve roots of 15 patients with a unilateral fracture of the sacrum and sacral nerve injury were stimulated during surgery to establish the precise functional distribution of the S1 nerve root and its proportional contribution to individual muscles. In cohort 2, the contralateral uninjured S1 nerve root of six patients with a unilateral lumbosacral plexus avulsion was transected extradurally and used with a 25 cm segment of the common peroneal nerve from the injured leg to reconstruct the avulsed plexus. The results from cohort 1 showed that the innervation of S1 in each muscle can be compensated for by L4, L5, S2 and S3. Numbness in the toes and a reduction in strength were found after surgery in cohort 2, but these symptoms gradually disappeared and strength recovered. The results of electrophysiological studies of the donor limb were generally normal. . Severing the S1 nerve root does not appear to damage the healthy limb as far as clinical assessment and electrophysiological testing can determine. Consequently, the S1 nerve can be considered to be a suitable donor nerve for reconstruction of an avulsed contralateral lumbosacral plexus. Cite this article: Bone Joint J 2015; 97-B:358–65

In order to determine the potential for an internervous safe zone, 20 hips from human cadavers were dissected to map out the precise pattern of innervation of the hip capsule. The results were illustrated in the form of a clock face. The reference point for measurement was the inferior acetabular notch, representing six o’clock. Capsular branches from between five and seven nerves contributed to each hip joint, and were found to innervate the capsule in a relatively constant pattern. An internervous safe zone was identified anterosuperiorly in an arc of 45° between the positions of one o’clock and half past two. Our study shows that there is an internervous zone that could be safely used in a capsule-retaining anterior, anterolateral or lateral approach to the hip, or during portal placement in hip arthroscopy

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

Discogenic low back pain is a common cause of disability, but its pathogenesis is poorly understood. We collected 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, 12 from physiologically ageing discs and ten from normal control discs. We investigated the histological features and assessed the immunoreactive activity of neurofilament (NF200) and neuropeptides such as substance P (SP) and vasoactive-intestinal peptide (VIP) in the nerve fibres. The distinct histological characteristic of the painful disc was the formation of a zone of vascularised granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus along the edges of the fissures. SP-, NF- and VIP-immunoreactive nerve fibres in the painful discs were more extensive than in the control discs. Growth of nerves deep into the annulus fibrosus and nucleus pulposus was observed mainly along the zone of granulation tissue in the painful discs. This suggests that the zone of granulation tissue with extensive innervation along the tears in the posterior part of the painful disc may be responsible for causing the pain of discography and of discogenic low back pain

The pathogenesis of longitudinal reduction deformities of the limbs, or dysmelia, is still a matter of debate. Their morphological pattern was defined from a large collection of radiographs of children with dysmelia following the thalidomide disaster. We compared radiographs of 378 of these limbs with the sclerotomes which are areas of segmental sensory innervation of the limb skeleton defined by the radiation of referred pain. The pattern of dysmelia matched the sclerotomes closely in 279 limbs (73.5%). The principles of skeletal reduction in dysmelia are explained by the arrangement of the sclerotomes. The congruence between two separate and independent data sets shows that both patterns are expressions of the underlying segmental sensory innervation of the skeleton, and that the sensory nervous system is involved in the process of limb morphogenesis and teratogenesis

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

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors.

Cite this article: Bone Joint Res 2022;11(8):561–574.

Aims

Frozen shoulder is a common, painful condition that results in impairment of function. Corticosteroid injections are commonly used for frozen shoulder and can be given as glenohumeral joint (GHJ) injection or suprascapular nerve block (SSNB). Both injection types have been shown to significantly improve shoulder pain and range of motion. It is not currently known which is superior in terms of relieving patients’ symptoms. This is the protocol for a randomized clinical trial to investigate the clinical effectiveness of corticosteroid injection given as either a GHJ injection or SSNB.

Aims

Lateral femoral cutaneous nerve (LFCN) injury is a potential complication after the direct anterior approach for total hip arthroplasty (DAA-THA). The aim of this study was to determine how the location of the fasciotomy in DAA-THA affects LFCN injury.