Capsaicin-sensitive sensory nerves exert complex regulatory functions in the serum-transfer mouse model of autoimmune arthritis

Brain Behav Immun. 2015 Mar;45:50-9. doi: 10.1016/j.bbi.2014.12.012. Epub 2014 Dec 15.


Objective: The K/BxN serum-transfer arthritis is a widely-used translational mouse model of rheumatoid arthritis, in which the immunological components have thoroughly been investigated. In contrast, little is known about the role of sensory neural factors and the complexity of neuro-immune interactions. Therefore, we analyzed the involvement of capsaicin-sensitive peptidergic sensory nerves in autoantibody-induced arthritis with integrative methodology.

Methods: Arthritogenic K/BxN or control serum was injected to non-pretreated mice or resiniferatoxin (RTX)-pretreated animals where capsaicin-sensitive nerves were inactivated. Edema, touch sensitivity, noxious heat threshold, joint function, body weight and clinical arthritis severity scores were determined repeatedly throughout two weeks. Micro-CT and in vivo optical imaging to determine matrix-metalloproteinase (MMP) and neutrophil-derived myeloperoxidase (MPO) activities, semiquantitative histopathological scoring and radioimmunoassay to measure somatostatin in the joint homogenates were also performed.

Results: In RTX-pretreated mice, the autoantibody-induced joint swelling, arthritis severity score, MMP and MPO activities, as well as histopathological alterations were significantly greater compared to non-pretreated animals. Self-control quantification of the bone mass revealed decreased values in intact female mice, but significantly greater arthritis-induced pathological bone formation after RTX-pretreatment. In contrast, mechanical hyperalgesia from day 10 was smaller after inactivating capsaicin-sensitive afferents. Although thermal hyperalgesia did not develop, noxious heat threshold was significantly higher following RTX pretreatment. Somatostatin-like immunoreactivity elevated in the tibiotarsal joints in non-pretreated, which was significantly less in RTX-pretreated mice.

Conclusions: Although capsaicin-sensitive sensory nerves mediate mechanical hyperalgesia in the later phase of autoantibody-induced chronic arthritis, they play important anti-inflammatory roles at least partially through somatostatin release.

Keywords: Capsaicin-sensitive sensory nerves; Inflammation; Matrix-metalloproteinase; Pain; Somatostatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental*
  • Arthritis, Rheumatoid*
  • Capsaicin / pharmacology
  • Disease Models, Animal
  • Diterpenes / pharmacology*
  • Edema
  • Hindlimb
  • Hyperalgesia*
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nociceptors / drug effects*
  • Nociceptors / physiology
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Peroxidase / metabolism
  • Reactive Oxygen Species
  • Sensory System Agents / pharmacology
  • Somatostatin / metabolism
  • TRPV Cation Channels / agonists
  • Tarsus, Animal / diagnostic imaging
  • Tarsus, Animal / metabolism
  • Tarsus, Animal / pathology
  • X-Ray Microtomography


  • Diterpenes
  • Reactive Oxygen Species
  • Sensory System Agents
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Somatostatin
  • resiniferatoxin
  • Peroxidase
  • Matrix Metalloproteinases
  • Capsaicin