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bioRxiv · 10.1101/350637

Acute inflammation sensitizes knee-innervating sensory neurons and decreases mouse digging behavior in a TRPV1-dependent manner.

Chakrabarti, S.·Pattison, L. A.·Singhal, K.·Hockley, J. R.·Callejo, G.·Smith, E. S. J.
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Abstract

Ongoing, spontaneous pain is characteristic of inflammatory joint pain and reduces an individuals quality of life. To understand the neural basis of inflammatory joint pain, we made a unilateral knee injection of complete Freunds 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.

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Chakrabarti, S., Pattison, L. A., Singhal, K., Hockley, J. R., Callejo, G., Smith, E. S. J.. 2018-06-19. Acute inflammation sensitizes knee-innervating sensory neurons and decreases mouse digging behavior in a TRPV1-dependent manner.. https://doi.org/10.1101/350637

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