Mechanical allodynia in mice with tenascin-X deficiency associated with Ehlers-Danlos syndrome.

Abstract

Tenascin-X (TNX) is a member of the extracellular matrix glycoprotein tenascin family, and TNX deficiency leads to Ehlers-Danlos syndrome, a heritable human disorder characterized mostly by skin hyperextensibility, joint hypermobility, and easy bruising. TNX-deficient patients complain of chronic joint pain, myalgia, paresthesia, and axonal polyneuropathy. However, the molecular mechanisms by which TNX deficiency complicates pain are unknown. Here, we examined the nociceptive behavioral responses of TNX-deficient mice. Compared with wild-type mice, TNX-deficient mice exhibited mechanical allodynia but not thermal hyperalgesia. TNX deficiency also increased pain sensitivity to chemical stimuli and aggravated early inflammatory pain elicited by formalin. TNX-deficient mice were significantly hypersensitive to transcutaneous sine wave stimuli at frequencies of 250 Hz (Aδ fiber responses) and 2000 Hz (Aβ fiber responses), but not to stimuli at frequency of 5 Hz (C fiber responses). In addition, the phosphorylation levels of extracellular signal-related kinase, an active neuronal marker, and the activity of NADPH-diaphorase, a neuronal nitric oxide activation marker, were enhanced in the spinal dorsal horns of TNX-deficient mice. These results suggest that TNX deficiency contributes to the development of mechanical allodynia and hypersensitivity to chemical stimuli, and it induces hypersensitization of myelinated A fibers and activation of the spinal dorsal horn.

• Authors: Emiko Okuda-Ashitaka, Yuka Kakuchi, Hiroaki Kakumoto, Shota Yamanishi, Hiroki Kamada, Takafumi Yoshidu, Satoshi Matsukawa, Naoya Ogura, Sadahito Uto, Toshiaki Minami, Seiji Ito, Ken-Ichi Matsumoto
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 6569 (04 16 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32300146 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• RNA, Messenger
• Tenascin
• tenascin X
• Formaldehyde

Topics

• Analgesics (pharmacology, therapeutic use)
• Animals
• Ehlers-Danlos Syndrome (complications)
• Formaldehyde
• Hyperalgesia (complications, drug therapy, physiopathology)
• Male
• Mice, Inbred C57BL
• Pain (complications, pathology, physiopathology)
• RNA, Messenger (genetics, metabolism)
• Spinal Cord Dorsal Horn (drug effects, pathology, physiopathology)
• Tenascin (deficiency, genetics, metabolism)