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Updated: Apr 23, 2026
Spontaneous and Evoked Measures of Pain in Murine Models of Monoarticular Knee Pain
Published on: February 22, 2019
Changes in rat spinal cord gene expression after inflammatory hyperalgesia of the joint and manual therapy
Rachel L Ruhlen1, Vineet K Singh2, Vanessa K Pazdernik2
1From the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri (Drs Snider, Sargentini, and Degenhardt); the departments of microbiology /immunology (Drs Singh and Sargentini), anatomy (Dr Towns), and osteopathic manipulative medicine (Dr Snider) at A.T. Still University-Kirksville College of Osteopathic Medicine in Missouri; and Research Support at A.T. Still University in Mesa, Arizona (Ms Pazdernik). Dr Ruhlen was affiliated with the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri, at the time of this study rachel@ruhlendavis.org.
Context:
Mobilization of a joint affects local tissue directly but may also have other effects that are mediated through the central nervous system.
Objective:
To identify differential gene expression in the spinal cords of rats with or without inflammatory joint injury after manual therapy or no treatment.
Methods:
Rats were randomly assigned to 1 of 4 treatment groups: no injury and no touch (NI/NT), injury and no touch (I/NT), no injury and manual therapy (NI/MT), and injury and manual therapy (I/MT). We induced acute inflammatory joint injury in the rats by injecting carrageenan into an ankle. Rats in the no-injury groups did not receive carrageenan injection. One day after injury, rats received manual therapy to the knee of the injured limb. Rats in the no-touch groups were anesthetized without receiving manual therapy. Spinal cords were harvested 30 minutes after therapy or no touch, and spinal cord gene expression was analyzed by microarray for 3 comparisons: NI/NT vs I/NT, I/MT vs I/NT, and NI/NT vs NI/MT.
Results:
Three rats were assigned to each group. Of 38,875 expressed sequence tags, 755 were differentially expressed in the NI/NT vs I/NT comparison. For the other comparisons, no expressed sequence tags were differentially expressed. Cluster analysis revealed that the differentially expressed sequence tags were over-represented in several categories, including ion homeostasis (enrichment score, 2.29), transmembrane (enrichment score, 1.55), and disulfide bond (enrichment score, 2.04).
Conclusions:
An inflammatory injury to the ankle of rats caused differential expression of genes in the spinal cord. Consistent with other studies, genes involved in ion transport were among those affected. However, manual therapy to the knees of injured limbs or to rats without injury did not alter gene expression in the spinal cord. Thus, evidence for central nervous system mediation of manual therapy was not observed.
