Augmented mechanical response of muscular thin‐fiber receptors in aged rats recorded in vitro

Abstract

Musculoskeletal pain deteriorates quality of life by disrupting daily activities and is a considerable economic burden to many countries because of the large number of patients. Little is known about the peripheral neural mechanisms of muscular nociception in the aged, although structural and functional changes in the muscle are apparent as a function of age. The aim of the present study was to investigate the activities of aged muscle nociceptors systematically to mechanical, chemical and thermal stimuli, and to compare with the data from young animals. Activities of single C-fibers were recorded from in vitro preparations of extensor digitorum longus muscle-nerve excised from hind legs of aged rats (125-133 weeks). Mechanical threshold measured by a ramp mechanical stimulus in the aged muscle (median; 45.2 mN (IQR; 38.1-59.1 mN), n=29) was significantly lower than that in the younger muscle (median; 65.4 mN (IQR; 46.6-122.0 mN), n=33, p<0.01, Mann-Whitney U-test) reported in our previous study (Taguchi et al., 2005). In addition, the magnitude of the mechanical response during the first 5s of the 10s stimulus was significantly greater in the aged muscle (11.0 spikes (IQR; 6.5-20.5 spikes)) than in the young (7.0 spikes (IQR; 4.0-11.5 spikes), p<0.05, Mann-Whitney U-test). In contrast, the numbers of discharges induced by chemical (pH 5.5, ATP and bradykinin) and thermal (cold and heat) stimuli were not different with the different ages. These results showed an augmented mechanical response in muscle C-afferents in the aged rats.

Peripheral and spinal mechanisms of nociception in a rat reserpine-induced pain model

“…Facilitated mechanical response was also observed in mechanoresponsive muscular C-fibers. This pattern of altered mechanical sensitivity combined with a reduced number of mechanoresponsive unmyelinated C-fibers is also observed in aging 28,29,51,53 and diabetic neuropathy, 18,36 and may also correspond with reports of small-fiber polyneuropathy in some patients diagnosed with fibromyalgia 32 and restless legs syndrome. 38 These changes seem to be related with decreased neurotrophic factors in primary sensory neurons, 3,18 however, in a reserpine-induced pain model, no apparent histological changes were detected in the sciatic nerve bundle and DRG by light microscopy, 27 which suggests that this paradoxical change in mechanical sensitivity likely results from reserpine-mediated functional alterations in the peripheral nervous system.…”

Alteration of Metabosensitive Afferent Response With Aging: Exercised versus Non-exercised Rats

“…In aged animals, because it was reported a concomitant decreased level of TRPV1 and GFRα3, and a decreased trophic support in the DRG ( Wang et al, 2006 ), we can assume that the decrease of growth factors with aging may reduce the number of TRPV1 in metabosensitive nerve endings and consequently their responses when stimulated by metabolic agents released by muscles. However, a study indicated that the numbers of discharges induced by low pH, ATP, bradykinin, cold and heat stimuli were not different with aging ( Taguchi and Mizumura, 2011 ).…”

An <em>In Vitro</em> Adult Mouse Muscle-nerve Preparation for Studying the Firing Properties of Muscle Afferents

“…Muscle length and force can be controlled and measured using commercially available systems. Similar in vitro preparations have been used in rodents to study Group III and IV muscle afferents in the rat EDL 11 , Group Ia and II spindle afferents in the rat fourth lumbrical toe muscle 12 and Group III and IV muscle afferents in the mouse plantar muscle 13 .…”