RT Journal Article
SR Electronic
T1 Acute inflammation sensitizes knee-innervating sensory neurons and decreases mouse digging behavior in a TRPV1-dependent manner
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 350637
DO 10.1101/350637
A1 Sampurna Chakrabarti
A1 Luke A. Pattison
A1 Kaajal Singhal
A1 James R.F. Hockley
A1 Gerard Callejo
A1 Ewan St. John Smith
YR 2018
UL http://biorxiv.org/content/early/2018/07/31/350637.abstract
AB Ongoing, spontaneous pain is characteristic of inflammatory joint pain and reduces an individual’s quality of life. To understand the neural basis of inflammatory joint pain, we made a unilateral knee injection of complete Freund’s adjuvant (CFA) in mice, which reduced their natural digging behavior. We hypothesized that sensitization of knee-innervating dorsal root ganglion (DRG) neurons underlies this altered behavior. To test this hypothesis, we performed electrophysiological recordings on retrograde labelled knee-innervating primary DRG neuron cultures and measured their responses to a number of electrical and chemical stimuli. We found that 24-hours after CFA-induced knee inflammation, knee neurons show a decreased action potential generation threshold, as well as increased GABA and capsaicin sensitivity, but have unaltered acid sensitivity. The inflammation-induced sensitization of knee neurons persisted for 24-hours in culture, but was not observed after 48-hours in culture. Through immunohistochemistry, we showed that the increased knee neuron capsaicin sensitivity correlated with enhanced expression of the capsaicin receptor, transient receptor potential vanilloid 1 (TRPV1) in knee-innervating neurons of the CFA-injected side. We also observed an increase in the co-expression of TRPV1 with tropomyosin receptor kinase A (TrkA), which is the receptor for nerve growth factor (NGF), suggesting that NGF partially induces the increased TRPV1 expression. Lastly, we found that systemic administration of the TRPV1 antagonist A-425619 reversed the decrease in digging behavior induced by CFA injection, further confirming the role of TRPV1, expressed by knee neurons, in acute inflammatory joint pain.