SPRR1A expression in experimental Osteoarthritis. Is there a role in pain?
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1
Faculty of Medicine, University of Porto, Portugal
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2
Michigan State University, United States
Osteoarthritis (OA) is an articular disease characterized by the presence of chronic unbearable pain. In fact, pain control in OA patients remains the main clinical concern in its treatment. Studies from our group showed an increase in the number of primary afferent neurons expressing markers of neuronal damage and of GAP-43, a regeneration associated-gene (RAG), in ipsilateral dorsal root ganglia (DRG) of OA animals. Recently, small proline rich protein 1A (SPRR1A) was proposed to be also a RAG since it was highly expressed in DRG neurons after peripheral nerve injury.
Taking this into account, we investigated if SPRR1A is expressed in DRG neurons of collagenase-induced OA (OA-Coll) in the rats’s knee. Through RT-qPCR and Western Blot, we showed an increased SPRR1A expression in ipsilateral DRG neurons of OA-Coll animals regarding to control rats. To understand the role of SPRR1A in the nociceptive behaviour of OA animals, we overexpressed SPRR1A in OA-Coll rats, by injecting a viral vector engineered to express SPRR1A (AAV2/5-SPRR1A) in L4 and L5 ipsilateral DRG, 14 days after model induction. OA-Coll animals without intraganglionic injection served as controls. The establishment and evolution of the disease and the effect of SPRR1A on the nociceptive behaviour were monitored weekly. Coll+SPRR1A animals showed a tendency to have an attenuation of movement- and loading-induced nociceptive behaviours (Knee-Bend and CatWalk tests). RT-qPCR results confirmed SPRR1A was overexpressed in DRGs.
To confirm if this effect was not model-specific, we performed similar studies in another OA model, induced by Monoiodoacetate (MIA) injection in the knee. The von Frey test showed an attenuation of mechanical hypersensitivity throughout time after AAV2/5-SPRR1A delivery to OA-MIA rats; however, movement-induced allodynia (Knee-Bend) showed no differences between the OA-MIA and OA-MIA+SPRR1A groups. Data from the CatWalk and Rotarod tests seem to be related, since an increase in movement- and loading-induced nociceptive behaviour was accompanied by a lower motor coordination in OA-MIA+SPRR1A animals. RT-qPCR analyses confirmed also an SPRR1A increase in DRGs of OA-MIA+SPRR1A rats.
Data suggest SPRR1A is implicated in OA pain events at the DRG level. However, the underlying molecular mechanisms still need to be clarified.
Keywords:
Osteoathritis,
Pain,
Dorsal root ganglia (DRG),
Intraganglionic injection,
small proline rich protein 1A (SPRR1A)
Conference:
XVI Meeting of the Portuguese Society for Neuroscience (SPN2019), Lisboa, Portugal, 30 May - 1 Jun, 2019.
Presentation Type:
Poster presentation
Topic:
Cellular and Molecular Neurosciences
Citation:
Alonso
RN,
Neto
FM,
Gomes
JF,
Adães
S,
Lipton
J,
Kanaan
N and
Mota
BC
(2019). SPRR1A expression in experimental Osteoarthritis. Is there a role in pain?.
Front. Cell. Neurosci.
Conference Abstract:
XVI Meeting of the Portuguese Society for Neuroscience (SPN2019).
doi: 10.3389/conf.fncel.2019.01.00034
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Received:
27 Feb 2019;
Published Online:
27 Sep 2019.
*
Correspondence:
Miss. Raquel N Alonso, Faculty of Medicine, University of Porto, Porto, Portugal, raquel_mna@hotmail.com