Abstract
Arthritis, including osteoarthritis (OA) and other musculoskeletal-associated pain, is a worldwide problem, however, effective drug options are limited. Several receptors, neurotransmitters, and endogenous mediators have been identified in rodent models, but the relevance of these molecules in disease-associated pain is not always clear. Artemin, a neurotrophic factor, and its receptor, glial-derived neurotrophic factor (GDNF) family receptor alpha-3 (GFRα3), have been identified as involved in pain in rodents. Their role in OA-associated pain is unknown. To explore a possible association, we analyzed tissue from naturally occurring OA in dogs to characterize the correlation with chronic pain. We used behavioral assessment, objective measures of limb use, and molecular tools to identify whether artemin and GFRα3 might be associated with OA pain. Our results using banked tissue from well-phenotyped dogs indicates that artemin/GFRα3 may play an important, and hitherto unrecognized, role in chronic OA-associated pain. Elevated serum levels of artemin from osteoarthritic humans compared to healthy individuals suggest translational relevance. Our data provide compelling evidence that the artemin/GFRα3 signaling pathway may be important in OA pain in both non-humans and humans and may ultimately lead to novel therapeutics.
Highlights
A significant proportion of the economic burden of chronic pain is due to musculoskeletal pain, and yet treatment options remain limited and insufficient for the alleviation of osteoarthritis (OA)-associated pain, the major component of musculoskeletal pain (Burgess and Williams, 2010)
We evaluated dog DRG tissue for multiple receptors that we had found to be expressed on TRPV1expressing neurons in the dorsal root ganglia (DRG) in mice (Goswami et al, 2014)
Our results showed an approximately 4-fold increase in GFRα3 expression in ipsilateral DRG serving OA joints compared to those serving normal joints (Figure 1A) suggesting a role of GFRα3 in OA pain
Summary
A significant proportion of the economic burden of chronic pain is due to musculoskeletal pain, and yet treatment options remain limited and insufficient for the alleviation of osteoarthritis (OA)-associated pain, the major component of musculoskeletal pain (Burgess and Williams, 2010). Artemin signaling pathways have been shown to be involved in the pathogenesis of bone pain (Nencini et al, 2018) Another important role of artemin has been identified in the trigeminal ganglia (TG), where artemin regulates an inducible form of nitric oxide synthase (iNOS). Artemin exerts an antinociceptive effect on herpes-related pain by modulating the dynorphin levels in the central nervous system of HSV-inoculated mice (Asano et al, 2006). Based on this evidence, peripheral artemin is involved in generating pain signals in rodents
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
