Functional and anatomical deficits in visceral nociception with age: a mechanism of silent appendicitis in the elderly?

The ability to sense visceral pain during appendicitis is diminished with age leading to delay in seeking health care and poorer clinical outcomes. To understand the mechanistic basis of this phenomenon, we examined visceral nociception in aged mouse and human tissue. Inflamed and noninflamed appendixes were collected from consenting patients undergoing surgery for the treatment of appendicitis or bowel cancer. Supernatants were generated by incubating samples in buffer and used to stimulate multiunit activity in intestinal preparations, or single-unit activity from teased fibres in colonic preparations, of young and old mice. Changes in afferent innervation with age were determined by measuring the density of calcitonin gene-related peptide-positive afferent fibres and by counting dorsal root ganglia back-labelled by injection of tracer dye into the wall of the colon. Finally, the effect of age on nociceptor function was studied in mouse and human colon. Afferent responses to appendicitis supernatants were greatly impaired in old mice. Further investigation revealed this was due to a marked reduction in the afferent innervation of the bowel and a substantial impairment in the ability of the remaining afferent fibres to transduce noxious stimuli. Translational studies in human tissue demonstrated a significant reduction in the multiunit but not the single-unit colonic mesenteric nerve response to capsaicin with age, indicative of a loss of nociceptor innervation. Our data demonstrate that anatomical and functional deficits in nociception occur with age, underpinning the atypical or silent presentation of appendicitis in the elderly

The psychoneuroimmunological effects of music:a systematic review and a new model

There has been a growing interest over the past decade into the health benefits of music, in particular examining its psychological and neurological effects. Yet this is the first attempt to systematically review publications on the psychoneuroimmunology of music. Of the selected sixty-three studies published over the past 22 years, a range of effects of music on neurotransmitters, hormones, cytokines, lymphocytes, vital signs and immunoglobulins as well as psychological assessments are cataloged. Research so far points to the pivotal role of stress pathways in linking music to an immune response. However, several challenges to this research are noted: (1) there is very little discussion on the possible mechanisms by which music is achieving its neurological and immunological impact; (2) the studies tend to examine biomarkers in isolation, without taking into consideration the interaction of the biomarkers in question with other physiological or metabolic activities of the body, leading to an unclear understanding of the impact that music may be having; (3) terms are not being defined clearly enough, such as distinctions not being made between different kinds of stress and ‘music’ being used to encompass a broad spectrum of activities without determining which aspects of musical engagement are responsible for alterations in biomarkers. In light of this, a new model is presented which provides a framework for developing a taxonomy of musical and stress-related variables in research design, and tracing the broad pathways that are involved in its influence on the body

The vulnerability of the human taenia coli to alterations in total collagen within the colon of the elderly

The structure of the colonic wall relies on collagen, distributed within the submucosa and the muscularis externa. A recent analysis of total collagen in human ascending colon (AC) suggests that the muscularis externa is more susceptible to age-related increases in collagen among the elderly. However, it is not clear if this change also occurs in the descending colon (DC) or if the circular and longitudinal muscle layers are similarly affected in either region of colon. The aim of this study is to determine the total collagen content in the DC and its distribution between the circular muscle (CM) and taenia coli (TC) of the AC and DC of adults and compare the same with tissue from the elderly. Masson's trichrome and Picrosirius red were used to assess total collagen content in the AC and DC; aged 22 - 91 years. Macroscopically normal AC from 22 patients (adults: 22-60 years; 6 male, 6 female; elderly: 70 - 91 years; 6 male, 4 female) and DC from 23 patients (adults: 23-63 years; 6 male, 7 female; elderly: 66 - 88 years; 6 male, 4 female) were obtained following surgery for non-obstructed bowel cancer. The total hydroxyproline content in DC samples was also evaluated. In the DC, tinctorial staining demonstrated an increased occurrence of total collagen fibres in the submucosa of the elderly (159.8 ± 9.6 in elderly vs. 126.9 ± 6.1 in the adults; p 0.05) and in the muscularis externa (respectively 37.4 ± 4.1 vs. 18.8 ± 2.4; p 0.01). In the adult AC and DC, there were no statistically significant differences in the amount of collagen within the CM and TC. In the elderly, the total collagen fibres within the TC was greater in the AC (mean grey intensity: 63.4 ± 3.9% in the elderly vs. 36.6 ± 1.6% in adults; p 0.05) and DC (mean grey intensity: respectively, 59.82 ± 2.4 vs. 40.2 ± 0.9%; p 0.05). In both AC and DC of the elderly samples, several thickened collagen fibrils were microscopically identified within the TC infiltrating to the myenteric plexus. In the TC of the elderly AC, the total collagen fibres were increased by approximately 4% compared to that of the DC. The total collagen concentration in the elderly DC assessed by hydroxyproline assay was increased by approximately 15% compared to the adult. Sex related differences were not found when data combined. We concluded that the total collagen content in the muscularis externa particularly of the TC of human colon increases with age. The subtle change in collagen distribution with age between AC and DC may differentially affect the tensile strength of the colon

Total collagen content and distribution is increased in human colon during advancing age

BACKGROUND: The effect of ageing on total collagen content of human colon has been poorly investigated. The aim of this study was to determine if ageing altered total collagen content and distribution in the human colon. METHODS: Macroscopically normal ascending colon was obtained at surgery from cancer patients (n = 31) without diagnosis of diverticular disease or inflammatory bowel disease. Masson’s trichrome and Picrosirius red stains were employed to identify the total collagen content and distribution within the sublayers of the colonic wall for adult (22–60 years; 6 males, 6 females) and elderly (70 – 91years; 6 males, 4 female) patients. A hydroxyproline assay evaluated the total collagen concentration for adult (30–64 years; 9 male, 6 female) and elderly (66–91 years; 8 male, 8 female) patients. KEY RESULTS: Histological studies showed that the percentage mean intensity of total collagen staining in the mucosa, submucosa and muscularis externa was, respectively, 14(1.9) %, 74(3.2) % and 12(1.5) % in the adult ascending colon. Compared with the adults, the total collagen fibres content was increased in the submucosa (mean intensity; 163.1 ± 11.1 vs. 124.5 ± 7.8; P < 0.05) and muscularis externa (42.5 ± 8.0 vs. 20.6 ± 2.8; P < 0.01) of the elderly patients. There was no change in collagen content of the mucosa. The total collagen concentration was increased in the elderly by 16%. Sex-related differences were not found, and data were combined for analysis. CONCLUSIONS: Greater total collagen content was found in the submucosa and muscularis externa of the elderly human male and female colon. These changes may contribute to a possible loss of function with ageing