Effect of capsaicin-sensitive sensory neurons on bone architecture and mechanical properties in the rat hindlimb suspension model

Abstract

SummaryBackground/ObjectiveThe participation of sensory neural regulation in bone metabolism has been widely studied. However, the physiological role of sensory neural regulation in the functional adaptation to weight bearing is not clear. This study was conducted to investigate the effect of capsaicin-induced sensory neuron lesions on cancellous architecture properties in a hindlimb suspension (HLS) model.MethodsThirty-two female rats were randomly assigned to four groups. Groups b and d underwent systemic capsaicin treatment, whereas Groups a and c were treated with vehicle. Then, Groups c and d were subjected to HLS, whereas Groups a and b were allowed hindlimbs full loading. The proximal trabecular and mid-shaft cortical bone structure were evaluated via microcomputed tomography, and the biomechanical properties of the tibial mid-shaft were assessed using the four-point bending test.ResultsThe trabecular bone volume was reduced by 40% and 50% in Groups b and c, respectively, and was also reduced significantly in Group d. Trabecular thickness and trabecular separation in Group b were not significantly different from those of Group a. The cortical bone area fraction showed no significant difference among all groups. Compared with Group a, the ultimate strength in Group b decreased by 20.3%, whereas it did not change significantly in Group c.ConclusionThe results suggest that capsaicin-sensitive sensory neurons play an important role in bone modelling. The effect of capsaicin is similar to HLS. However, HLS has no add-on effect to capsaicin in the reduction of bone density and mechanical properties.Translational potential of this article: This study gives clues to the function of sensory neurons in bone modelling.

The Role of Nerves in Skeletal Development, Adaptation, and Aging

“…Altogether, these data suggest that peripheral nerve activity may modulate the bone resorption response during disuse. A study of hindlimb unloading-induced bone loss in capsaicin-treated rats showed that both capsaicin treatment and 4 weeks of hindlimb unloading resulted in considerable loss of trabecular bone at the proximal tibia, but that hindlimb unloading of capsaicin-treated rats did not promote further bone loss ( 99 ). Altogether, these data suggest that diminished sensory nerve function diminishes bone volume but may make the bone less sensitive to the mechanical environment.…”

Effects of capsaicin-induced sensory denervation on early implant osseointegration in adult rats

“…However, another study showed that low-dose (37.5 mg kg −1 ) capsaicin had no influence on bone remodelling. High-dose capsaicin (150 mg kg −1 ) significantly increased the level of tartrate-resistant acid phosphatase form 5b (TRAP 5b) in the plasma but had no influence on the plasma osteocalcin concentration, suggesting that sensory nerve innervation contributed to the maintenance of trabecular bone mass and its mechanical properties by inhibiting bone resorption [7,21]. Similar to our research, these results indicated that the sensory nerve played an important role in the maintenance of trabecular bone mass.…”

“…It might be that the bone matrix secreted by osteoblasts gathers and adheres to the implant surface, which would be beneficial to the formation of bone on the surface of the implant in the early stage. In the repair process, the osteogenesis on the surface of the implant, also known as the BIC, was decreased significantly because sensory denervation could decrease the activity of osteoblasts and bone formation [7,21]. The results of the micro-CT evaluation also revealed the adverse effects of sensory denervation on implant osseointegration.…”

“…In the neurons of the dorsal root ganglion [19], high doses of capsaicin could lead to a loss of the immunoreactivities of CGRP and SP [20,21]. Systemic capsaicin treatment exerted a long-term blocking action against the sensory receptor, which could be used in the investigation of the function of afferent neurons [7].…”

Innervation of bones: Why it should not be neglected?

“…It is evident that sensory and sympathetic neurotransmitters and neuropeptides have trophic effects that are critical for joint and bone homeostasis (25). For instance, using capsaicin in an experimental study to selectively destroy unmyelinated sensory neurons in rats, led to depletion of substance P and CGRP in bone and caused significant loss of trabecular bone, suggesting that capsaicin-sensitive sensory nerves contribute to trabecular bone integrity (26,27). Obviously, CGRP and SP that are released from the peripheral terminals of sensory neurons are important local mediators ensuring maintenance of normal bone balance.…”