Does peripheral knee joint inflammation increase neurogenesis in the Spinal Cord and Hippocampus?

Abstract

Background: Osteoarthritis is a degenerative joint disease that involves swelling and damage of the affected joints causing pain, and hypersensitivity to mechanical and thermal stimulation. Peripheral and central neuronal sensitization, including the up-regulation of many excitatory postsynaptic receptors, ion channels and astrocytic proliferation, have provided a mechanistic explanation for the heat hyperalgesia and mechanical allodynia that develop post inflammation. Along with nociceptive behaviors associated with peripheral inflammation, the body also learns to adjust certain behaviors in response to altered environmental demands, such as guarding the inflamed site and changing gait patterns. Learning to adjust requires the hippocampus, and leads to neuroplasticity and neurogenesis in this area. Though it is well established that neurogenesis occurs in the hippocampus, new studies have recently shown that under normal conditions, adult spinal cord neurons can also undergo neurogenesis at a constant rate, and the newly born cells migrate to the superficial dorsal horn. However, whether this rate changes under pathological conditions is still not yet confirmed. Hypothesis and Aim: In light of these findings, we hypothesize that the observed central neuronal sensitization associated with peripheral inflammation, might be attributed to increased cellular proliferation that lead to reorganization of nociceptive neuronal circuits in the dorsal horn of the spinal cord as well as neurons in higher brain areas, particularly those involved in memory and learning. The aim of the present study is to examine whether knee joint inflammation, using an animal model of osteoarthritis, promotes cellular proliferation in the spinal cord as well as the dentate gyrus (DG) of the hippocampal region. Methods: Adult Male Sprague-Dawley rats were used in this study. To induce knee joint inflammation, a mixture of 3percent kaolin and carrageenan (K-C; 0.1ml) was injected in the synovial cavity of the left knee joint. A group of rats recei