J Pharm Pharmacogn Res 2(Suppl. 1): S27, 2014
Special supplement with the abstract book of LATINFARMA 2013
C 007: PHENOTYPIC MODIFICATIONS OF PRIMARY AFFERENT NEURONS INNERVATING OSTEOARTHRITIC JOINTS
Castro-Lopes JM, Adães S, Ferreira-Gomes J.Department of Experimental Biology, Faculty of Medicine of the University of Porto and IBMC, Portugal.
Chronic pain associated with osteoarthritis (OA) is highly prevalent, but its mechanisms are not fully understood, and the pharmacological control of OA-associated pain is far from optimal. In an attempt to further clarify the neuronal mechanisms underlying nociception in OA, we have performed a series of studies on primary afferent neurons innervating OA joints, using the experimental model of intra-articular injection of mono-sodium iodoacetate (MIA) in the knee joint of adult rats, which causes a destruction of the articular cartilage.
By using the neuronal tracer Fluorogold (FG), we observed a decrease of 37% in the number of neurons innervating OA joints as compared to control animals, although there was no reduction in the total number of neurons in the dorsal root ganglia (DRGs). However, there was a decrease in the number of small neurons and a small increase of medium-large neurons in OA animals. Given that neurogenesis was not found in the DRGs of OA animals, those observations indicated a phenomenon of neuronal hypertrophy.
Regarding neurochemical markers for subpopulations of primary afferent neurons, there was an increase in the percentage of CGRP positive (peptidergic) neurons that innervate OA joints. Such increase occurred in small and large neurons. Since this peptide is usually not expressed in large neurons, our observation in OA animals points to a phenomenon of hypertrophy of medium-small neurons that normally express CGRP, or a phenotypic alteration of large neurons. No differences between OA and control animals were observed in what concerns labelling for IB4 or NF200 (labelling non-peptidergic or large non-nociceptive primary afferent neurons, respectively).
The changes described above could suggest the existence of damages in neurons that innervate OA joints. Therefore, we studied the expression of ATF-3 and NPY in the DRGs, since its expression has been associated with peripheral neuronal damage. Both markers were expressed in DRG neurons three days after injection of MIA, a very early stage in the development of experimental OA, decreased at day 14 of development of OA, and there was a second wave of expression later. We have also observed expression of GAP-43, a marker of neuronal regeneration, in ATF-3 positive cells.
Together, our results suggest that primary afferents that innervate MIA-induced OA joints are damaged, which may trigger the activation of neuronal regeneration mechanisms. Further studies are needed to clarify to which extent these phenomena contribute to pain associated with OA.