Abstract

Previous studies have shown that persistent limb immobilization using a cast increases nociceptive behavior to somatic stimuli in rats. However, the peripheral neural mechanisms of nociception remain unclear. Using single-fiber electrophysiological recordings in vitro, we examined the general characteristics of cutaneous C-fiber afferents in the saphenous nerve and their responsiveness to mechanical and heat stimuli in a rat model of immobilization-induced pain by subjecting the rats to hindlimb cast immobilization for 4 weeks. The mechanical response of C-fibers appeared to increase in the model; however, statistical analysis revealed that neither the response threshold nor the response magnitude was altered. The general characteristics and heat responses of the C-fibers were not altered. The number of microglia and cell diameters significantly increased in the superficial dorsal horn of the lumbar spinal cord. Thus, activated microglia-mediated spinal mechanisms are associated with the induction of nociceptive hypersensitivity in rats after persistent cast immobilization.

Highlights

  • Experimental cast immobilization of the wrist for 4 weeks led to the development of pain during movement in 90% of the participants [1]

  • Ohmichi et al demonstrated that cast immobilization from the pelvis to the middle of the hind paw for 2-week induced chronic widespread pain, and that the activation of microglia, followed by the activation of astrocytes in the spinal dorsal horn, was involved in the pathological mechanisms associated with immobilization [7, 15]

  • Pain‐related behaviors in an immobilization‐induced pain model Mechanical withdrawal thresholds measured with an electric von Frey apparatus significantly decreased on the ipsilateral side 4 weeks after cast immobilization (p = 0.0005, d = 5.957, Wilcoxon matched-pairs signed rank test, Fig. 1b)

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Summary

Introduction

Experimental cast immobilization of the wrist for 4 weeks led to the development of pain during movement in 90% of the participants [1]. Long-term cast immobilization of a limb following fracture and tissue injury leads to nociceptive hypersensitivity similar to that seen in patients with complex regional pain syndrome [2], muscular atrophy [3], osteoporosis [4], and joint contracture [5]. Ohmichi et al demonstrated that cast immobilization from the pelvis to the middle of the hind paw for 2-week induced chronic widespread pain, and that the activation of microglia, followed by the activation of astrocytes in the spinal dorsal horn, was involved in the pathological mechanisms associated with immobilization [7, 15]. The proportion of neurons in the cervical dorsal horn in response to wrist movement

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