Role of Calcitonin Gene-Related Peptide in Bone Repair after Cyclic Fatigue Loading

Calcitonin gene related peptide (CGRP) is a neuropeptide that is abundant in the sensory neurons which innervate bone. The effects of CGRP on isolated bone cells have been widely studied, and CGRP is currently considered to be an osteoanabolic peptide that has effects on both osteoclasts and osteoblasts. However, relatively little is known about the physiological role of CGRP in-vivo in the skeletal responses to bone loading, particularly fatigue loading.We used the rat ulna end-loading model to induce fatigue damage in the ulna unilaterally during cyclic loading. We postulated that CGRP would influence skeletal responses to cyclic fatigue loading. Rats were fatigue loaded and groups of rats were infused systemically with 0.9% saline, CGRP, or the receptor antagonist, CGRP(8-37), for a 10 day study period. Ten days after fatigue loading, bone and serum CGRP concentrations, serum tartrate-resistant acid phosphatase 5b (TRAP5b) concentrations, and fatigue-induced skeletal responses were quantified. We found that cyclic fatigue loading led to increased CGRP concentrations in both loaded and contralateral ulnae. Administration of CGRP(8-37) was associated with increased targeted remodeling in the fatigue-loaded ulna. Administration of CGRP or CGRP(8-37) both increased reparative bone formation over the study period. Plasma concentration of TRAP5b was not significantly influenced by either CGRP or CGRP(8-37) administration.CGRP signaling modulates targeted remodeling of microdamage and reparative new bone formation after bone fatigue, and may be part of a neuronal signaling pathway which has regulatory effects on load-induced repair responses within the skeleton

Student perceptions of veterinary anatomy practical classes: a longitudinal study

Using cadaveric material to teach veterinary students poses many challenges. However, little research exists on the contribution of this traditional approach to student learning. This longitudinal study aimed to investigate student perceptions of cadaver-based anatomy classes in a vertically integrated veterinary curriculum at the University of Nottingham's School of Veterinary Medicine and Science. Likert-scale statements and free-text boxes were used in a questionnaire distributed to second-year veterinary students (response rate 59%, 61/103). The same questionnaire was subsequently distributed to the same cohort 2 years later, in the students' fourth year of study (response rate 68%, 67/98). Students agreed that cadaver-based activities aid their learning, and they particularly value opportunities to develop practical skills while learning anatomy. There are few changes in perception as undergraduates progress to clinical years of teaching. Students perceive anatomy to be important, and feel that their learning has prepared them for clinical placements. This study emphasizes the importance of using cadaveric materials effectively in anatomy teaching and, in particular, using clinical skills training to enhance the anatomy curriculum

Ultrasound-guided regional anesthesia: How much practice do novices require before achieving competency in ultrasound needle visualization using a cadaver model

Background and Objectives: Ultrasound needle visualization is a fundamental skill required for competency in ultrasound-guided regional anesthesia. The primary objective of this study using a cadaver model was to quantify the number of procedures that novices need to perform before competency, using a predefined dynamic scoring system was achieved in ultrasound needle visualization skills.Methods: Fifteen trainees, novices to ultrasound-guided regional anesthesia, performed 30 simulated sciatic nerve blocks in cadavers. After each procedure, a supervisor provided feedback regarding quality-compromising behaviors. Learning curves were constructed for each individual trainee by calculating cusum statistics. Trainees were categorized into those who were proficient, not proficient, and undetermined. A mathematical model predicted the number of procedures required before an acceptable success rate would be attained. Logistic regression was used to identify factors associated with success.Results: There was wide variability in individual cusum curves. The mean number of trials required to achieve competency in this cohort was 28. Trainees were categorized as proficient (n = 6), not proficient (n = 5), and undetermined (n = 4). With each subsequent procedure, there was a significant increase in the likelihood of success for trainees categorized as not proficient (P = 0.023) or undetermined (P = 0.024) but not for trainees categorized as proficient (P = 0.076). Participants recruited later in the study had an increased likelihood of success (P < 0.001).Conclusions: Trainees became competent in ultrasound needle visualization at a variable rate. This study estimates that novices would require approximately 28 supervised trials with feedback before competency in ultrasound needle visualization is achieved

Mechanosensory perception : are there contributions from bone-associated receptors

1. The identity of the receptors and afferent nerve fibres that mediate the sense of touch varies somewhat with body location. Those that have been most intensively characterized are associated with the distal glabrous skin of the limbs and, in primates, mediate the sense of touch in the fingertips and palms. In this glabrous skin region, there appear to be three or four principal classes of tactile sensory nerves that fall into two broad groups. One group, the so-called slowly adapting (SA) receptors and afferent fibres, is responsive to static mechanical displacement of skin tissues and is made up of two classes, the type I (SAI) fibres that innervate Merkel receptors and the type II (SAII) fibres that innervate Ruffini endings. The second broad group displays a pure dynamic sensitivity to tactile stimuli and also falls into two principal classes, the rapidly adapting (RA) tactile fibres that are associated with Meissner corpuscle receptors and the Pacinian corpuscle (PC)-associated class of tactile afferent fibres. 2. In other regions of the skin, such as the hairy skin of the arms, legs and trunk, there are similar functional classes of tactile sensory nerves, although the receptor endings differ somewhat from those of the glabrous skin. 3. Receptors in close association with the long bones of the limbs include groups of Pacinian corpuscles distributed along the interosseous membranes. These are highly sensitive to dynamic forms of mechanical stimuli, in particular vibrotactile disturbances. However, despite their close association with bone, these receptors probably cannot be legitimately considered 'osseoreceptors'. 4. Both the periosteum and the bone marrow are richly supplied by nerve fibres. However, much evidence indicates that these are largely or entirely in the fine-diameter category of nerve fibres, whose roles may be confined to either nociception or to the efferent autonomic regulation of bone-associated blood vessels. 5. In conclusion, it remains uncertain whether any aspects of our innocuous touch or kinaesthetic senses, in either the limbs or in orofacial regions, can be ascribed to 'osseoreceptors' located in the periosteum or within the bone marrow itself

Mechanisms of nerve growth factor signaling in bone nociceptors and in an animal model of inflammatory bone pain

Sequestration of nerve growth factor has been used successfully in the management of pain in animal models of bone disease and in human osteoarthritis. However, the mechanisms of nerve growth factor-induced bone pain and its role in modulating inflammatory bone pain remain to be determined. In this study, we show that nerve growth factor receptors (TrkA and p75) and some other nerve growth factor-signaling molecules (TRPV1 and Nav1.8, but not Nav1.9) are expressed in substantial proportions of rat bone nociceptors. We demonstrate that nerve growth factor injected directly into rat tibia rapidly activates and sensitizes bone nociceptors and produces acute behavioral responses with a similar time course. The nerve growth factor-induced changes in the activity and sensitivity of bone nociceptors we report are dependent on signaling through the TrkA receptor, but are not affected by mast cell stabilization. We failed to show evidence for longer term changes in expression of TrkA, TRPV1, Nav1.8 or Nav1.9 in the soma of bone nociceptors in a rat model of inflammatory bone pain. Thus, retrograde transport of NGF/TrkA and increased expression of some of the common nerve growth factor signaling molecules do not appear to be important for the maintenance of inflammatory bone pain. The findings are relevant to understand the basis of nerve growth factor sequestration and other therapies directed at nerve growth factor signaling, in managing pain in bone disease

Absence of large-diameter sensory fibres in a nerve to the cat humerus

A fine branch of the median nerve innervates the periosteum and medullary cavity of the cat humerus. After branching to innervate the periosteum on the medial surface of the humerus, the nerve enters and supplies the medullary cavity via a nutrient foramen, accompanied by a small artery and vein. The composition of the fibres in the nerve was examined using electron microscopy. Myelinated fibres with diameters of 0.8–6.6 µm and unmyelinated fibres with diameters of 0.1–1.4 µm were observed. These diameters indicate that afferent fibres of this nerve are confined within the Group III and IV categories, and may therefore be nociceptive or mechanoreceptive in function. In addition, autonomic efferent fibres may also be present in these fibre groups. As no fibre diameters greater than 7 µm were noted, it appears that Group I and II fibres are absent in this nerve. The fibre distribution suggests that the principal role of this nerve is to relay bone-related nociceptive or mechanoreceptive information to the central nervous system and to provide autonomic regulatory influences on the bone