Chemical Coding of Sensory Neurons Supplying the Hip Joint Capsule in the Sheep

Abstract

Immunohistochemical properties of nerve fibres supplying the joint capsule were previously described in many mammalian species, but the localization of sensory neurons supplying this structure was studied only in laboratory animals, the rat and rabbit. However, there is no comprehensive data on the chemical coding of sensory neurons projecting to the hip joint capsule (HJC). The aim of this study was to establish immunohistochemical properties of sensory neurons supplying HJC in the sheep. The study was carried out on 10 sheep, weighing about 30-40 kg. The animals were injected with a retrograde neural tracer Fast Blue (FB) into HJC. Sections of the spinal ganglia (SpG) with FB-positive (FB+) neurons were stained using antibodies against calcitonin gene-related peptide (CGRP) substance P (SP), pituitary adenylate cyclase-activating peptide (PACAP), nitric oxide synthase (n-NOS), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), Leu-5-enkephalin (Leu-Enk), galanin (GAL) and vesicular acetylcholine transporter (VACHT). The vast majority of FB+ neurons supplying HJC was found in the ganglia from the 5th lumbar to the 2nd sacral. Immunohistochemistry revealed that most of these neurons were immunoreactive to CGRP or SP (80.7 ± 8.0% or 56.4 ± 4.8%, respectively) and many of them stained for PACAP or GAL (52.9 ± 2.9% or 50.6 ± 19.7%, respectively). Other populations of FB+ neurons were those immunoreactive to n-NOS (37.8 ± 9.7%), NPY (34.6 ± 6.7%), VIP (28.7 ± 4.8%), Leu-Enk (27.1 ± 14.6) and VACHT (16.7 ± 9.6).

Peripheral mechanisms of arthritic pain: A proposal to leverage large animals for in vitro studies

“…For example, in human DRG neurons, the voltage-gated sodium channel (Na V ) 1.8 blocker A-803467 is much less effective at blocking Na V -mediated currents in human DRG neurons than in rat DRG neurons, suggesting that Na V blockers with efficacy in rodents might not translate to clinical pain relief in human diseases due to different expression levels ( Zhang, et al, 2017 ). The feasibility of obtaining DRG from large animals has been demonstrated in many species including horses ( Russo et al, 2010a ), sheep ( Deng et al, 2018 , Dudek et al, 2017 , Domenico Russo et al, 2010b ), pigs ( Jonas et al, 2015 , Klusch et al, 2018 , Kozłowska et al, 2017 , Obreja et al, 2008 , Sandercock et al, 2019 ) and dogs ( Ganchingco et al, 2019 , Schwarz et al, 2019 ), providing proof-of-concept that DRG neurons from large animals can be utilized as in vitro models for arthritis pain.…”