Analysis of Mechanoreceptors and Free Nerve Endings of the Transverse Carpal Ligament

Background: The treatment of carpal tunnel syndrome (CTS) by sectioning the transverse carpal ligament (TCL) is not exempt from complications. Some nerve branches may be damaged by the incision. The aim of this study is to identify and map the TCL nerve endings, serving as a guide for sectioning this structure in a zone with less nerve ending density. Methods: Ten TCLs were obtained from fresh frozen cadavers. The TCLs were measured, divided into 3 equal bands (radial, central, and ulnar), and submitted to cryostat sectioning. The sections were subjected to immunofluorescence with the protein gene product (PGP) 9.5 and confocal microscopy analysis. Results: All the specimens contained type I and type IV mechanoreceptors. Neural elements occupied 0.695 ± 0.056% of the ligament area. The density of the neural elements was greater in the radial, followed by the ulnar and central bands, with 0.730 ± 0.083%, 0.686 ± 0.009%, and 0.669 ± 0.031%, respectively. Conclusion: The present findings suggest that the region with the least potential for neural element injury during TCL release is the central third near the transition with the ulnar third. When performed distally to proximally with a slight inclination from the radial to the ulnar, this release compromises the lowest nerve element density. Topographically, the proximal limit of the release is the distal wrist crease, while the distal limit is the intersection of Kaplan cardinal line and the axis of the third webspace.

Probing the multimodal fungiform papilla: complex peripheral nerve endings of chorda tympani taste and mechanosensitive fibers before and after Hedgehog pathway inhibition

The fungiform papilla (FP) is a gustatory and somatosensory structure incorporating chorda tympani (CT) nerve fibers that innervate taste buds (TB) and also contain somatosensory endings for touch and temperature. Hedgehog (HH) pathway inhibition eliminates TB, but CT innervation remains in the FP. Importantly, after HH inhibition, CT neurophysiological responses to taste stimuli are eliminated, but tactile responses remain. To examine CT fibers that respond to tactile stimuli in the absence of TB, we used Phox2b-Cre; Rosa26LSL−TdTomato reporter mice to selectively label CT fibers with TdTomato. Normally CT fibers project in a compact bundle directly into TB, but after HH pathway inhibition, CT fibers reorganize and expand just under the FP epithelium where TB were. This widened expanse of CT fibers coexpresses Synapsin-1, β-tubulin, S100, and neurofilaments. Further, GAP43 expression in these fibers suggests they are actively remodeling. Interestingly, CT fibers have complex terminals within the apical FP epithelium and in perigemmal locations in the FP apex. These extragemmal fibers remain after HH pathway inhibition. To identify tactile end organs in FP, we used a K20 antibody to label Merkel cells. In control mice, K20 was expressed in TB cells and at the base of epithelial ridges outside of FP. After HH pathway inhibition, K20 + cells remained in epithelial ridges but were eliminated in the apical FP without TB. These data suggest that the complex, extragemmal nerve endings within and disbursed under the apical FP are the mechanosensitive nerve endings of the CT that remain after HH pathway inhibition.

Angiotensin II and the Cardiac Parasympathetic Nervous System in Hypertension

The renin–angiotensin–aldosterone system (RAAS) impacts cardiovascular homeostasis via direct actions on peripheral blood vessels and via modulation of the autonomic nervous system. To date, research has primarily focused on the actions of the RAAS on the sympathetic nervous system. Here, we review the critical role of the RAAS on parasympathetic nerve function during normal physiology and its role in cardiovascular disease, focusing on hypertension. Angiotensin (Ang) II receptors are present throughout the parasympathetic nerves and can modulate vagal activity via actions at the level of the nerve endings as well as via the circumventricular organs and as a neuromodulator acting within brain regions. There is tonic inhibition of cardiac vagal tone by endogenous Ang II. We review the actions of Ang II via peripheral nerve endings as well as via central actions on brain regions. We review the evidence that Ang II modulates arterial baroreflex function and examine the pathways via which Ang II can modulate baroreflex control of cardiac vagal drive. Although there is evidence that Ang II can modulate parasympathetic activity and has the potential to contribute to impaired baseline levels and impaired baroreflex control during hypertension, the exact central regions where Ang II acts need further investigation. The beneficial actions of angiotensin receptor blockers in hypertension may be mediated in part via actions on the parasympathetic nervous system. We highlight important unknown questions about the interaction between the RAAS and the parasympathetic nervous system and conclude that this remains an important area where future research is needed.

The skin: largest organ of the body

This article concludes this series in the anatomy and physiology of the body systems. An overview of the skin is provided and the various and functions of this, the largest organ of the body, are described. The three layers of the skin are discussed, along with an overview of skin pigmentation. The skin would be unable to complete most of its functions without the help of its appendages. The subcutaneous glands, hair, nails and nerve endings (the appendages) that allow it to function efficiently are summarised briefly. One other function of the skin—vitamin D synthesis—is described. The article ends with a glossary of terms and a set of questions that are intended to assist with leaning.

Immunoelectron Microscopic Characterization of Vasopressin-Producing Neurons in the Hypothalamo-Pituitary Axis of Non-Human Primates by Use of Formaldehyde-Fixed Tissues Stored at –25 °C for Several Years

Translational research often requires the testing of experimental therapies in primates, but research in non-human primates is now stringently controlled by law around the world. Tissues fixed in formaldehyde without glutaraldehyde have been thought to be inappropriate for use in electron microscopic analysis, particularly those of the brain. Here we report the immunoelectron microscopic characterization of arginine vasopressin (AVP)-producing neurons in macaque hypothalamo-pituitary axis tissues fixed by perfusion with 4% formaldehyde and stored at –25 °C for several years (4–6 years). The size difference of dense-cored vesicles between magnocellular and parvocellular AVP neurons was detectable in their cell bodies and perivascular nerve endings located, respectively, in the posterior pituitary and median eminence. Furthermore, glutamate and the vesicular glutamate transporter 2 could be colocalized with AVP in perivascular nerve endings of both the posterior pituitary and the external layer of the median eminence, suggesting that both magnocellular and parvocellular AVP neurons are glutamatergic in primates. Both ultrastructure and immunoreactivity can therefore be sufficiently preserved in macaque brain tissues stored long-term, initially for light microscopy. Taken together, these results suggest that this methodology could be applied to the human post-mortem brain and be very useful in translational research.

Role of Neuroimmune Crosstalk in Mediating the Anti-inflammatory and Analgesic Effects of Acupuncture on Inflammatory Pain

Inflammatory pain is caused by peripheral tissue injury and inflammation. Inflammation leads to peripheral sensitization, which may further cause central sensitization, resulting in chronic pain and progressive functional disability. Neuroimmune crosstalk plays an essential role in the development and maintenance of inflammatory pain. Studies in recent years have shown that acupuncture can exert anti-inflammatory and analgesic effects by regulating peripheral (i.e., involving local acupoints and inflamed regions) and central neuroimmune interactions. At the local acupoints, acupuncture can activate the TRPV1 and TRPV2 channels of mast cells, thereby promoting degranulation and the release of histamine, adenosine, and other immune mediators, which interact with receptors on nerve endings and initiate neuroimmune regulation. At sites of inflammation, acupuncture enables the recruitment of immune cells, causing the release of opioid peptides, while also exerting direct analgesic effects via nerve endings. Furthermore, acupuncture promotes the balance of immune cells and regulates the release of inflammatory factors, thereby reducing the stimulation of nociceptive receptors in peripheral organs. Acupuncture also alleviates peripheral neurogenic inflammation by inhibiting the release of substance P (SP) and calcitonin gene-related peptide from the dorsal root ganglia. At the central nervous system level, acupuncture inhibits the crosstalk between glial cells and neurons by inhibiting the p38 MAPK, ERK, and JNK signaling pathways and regulating the release of inflammatory mediators. It also reduces the excitability of the pain pathway by reducing the release of excitatory neurotransmitters and promoting the release of inhibitory neurotransmitters from neurons and glial cells. In conclusion, the regulation of neuroimmune crosstalk at the peripheral and central levels mediates the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain in an integrated manner. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of inflammatory diseases.