title: Sensory hyperinnervation and increase in NGF, TRPV1 and P2X3 expression in the epidermis following cast immobilization in rats.
abstract: BACKGROUND
  Cast immobilization is known to induce pain in humans and experimental animal models; however, the detailed mechanisms underlying this pain have yet to be elucidated. Recently, several lines of evidence have indicated that morphological changes in sensory innervation and changes in the expression of pain-related molecules in the epidermis are related to certain painful conditions. The aim of the present study was to temporally investigate the histological changes in the glabrous skin of the rat hind paw after 1, 2 and 4 weeks of ankle joint immobilization by casting.
  
  
  METHODS
  The von Frey test and the plantar test were performed to examine noxious sensitivity of the skin. Immunohistochemical methods were used to assess sensory nerve fibre profiles and to examine the expression of the nerve growth factor (NGF), transient receptor potential vanilloid 1 (TRPV1) and P2X3 in the epidermis.
  
  
  RESULTS
  Cast immobilization produced a time-dependent increase in mechanical and thermal sensitivity. In the plantar skin of immobilized rats, both myelinated A fibres and unmyelinated C fibres were increased. NGF, TRPV1 and P2X3 expression levels in the epidermis were also increased. Although the level of NGF expression did not display a meaningful change throughout the immobilization period, other changes became remarkable, depending on the period of immobilization.
  
  
  CONCLUSIONS
  The time course of the increase in peripheral nerve fibres and in the expression of TRPV1 and P2X3 paralleled the development of hypersensitivity, which suggests that histological changes of the skin following cast immobilization may have some relation to the resulting hypersensitivity.
authors.affiliation: Department of Locomotive Rehabilitation Science, Unit of Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sekino
authors.forename: J
authors.initials: J
authors.lastname: Nakano
authors.forename: Y
authors.initials: Y
authors.lastname: Hamaue
authors.forename: S
authors.initials: S
authors.lastname: Chuganji
authors.forename: J
authors.initials: J
authors.lastname: Sakamoto
authors.forename: T
authors.initials: T
authors.lastname: Yoshimura
authors.forename: T
authors.initials: T
authors.lastname: Origuchi
authors.forename: M
authors.initials: M
authors.lastname: Okita
mesh_terms: D000818:Animals; D004817:Epidermis / Q000294:innervation / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism / Q000523:psychology; D007103:Immobilization; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D058477:Receptors, Purinergic P2X3 / Q000096:biosynthesis*; D011984:Sensory Receptor Cells / Q000502:physiology*; D050916:TRPV Cation Channels / Q000096:biosynthesis*
chemical_list: D009414:Nerve Growth Factors; D058477:Receptors, Purinergic P2X3; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat