Journal article
Select Androgen Receptor Modulator Microparticle Formulation Reverses Muscle Hyperalgesia in Mouse Model of Widespread Muscle Pain
The journal of pain, Vol.23(5), pp.20-20
05/2022
DOI: 10.1016/j.jpain.2022.03.077
Abstract
There is a need for the generation of non-opioid analgesics for chronic pain. The analgesic effects of testosterone have been demonstrated in preclinical and clinical studies. However, treatment with testosterone is not clinically feasible due to adverse effects. Select androgen receptor modulators (SARMs) were developed to overcome adverse effects of testosterone by selectively activating androgen receptors associated with anabolic effects while minimizing activation of androgenic effects. The purpose of this study was to develop a SARM-loaded microparticle formulation with a long-term release profile and test its efficacy in a preclinical model of chronic muscle pain. Chronic muscle pain was induced by 2 intramuscular injections of acidic saline (20μl, pH 4.0±0.1) spaced 5 days apart were delivered into the left gastrocnemius muscle of C57/BL6J male and female mice. Muscle withdrawal thresholds (MWT) were assessed with force sensitive tweezers applied to the gastrocnemius muscle before and weekly for 4 weeks after induction of the model. Efficacy of SARM ((s)-3-(4-cyanophenoxy)-n-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-2-methylpropanamide) was tested through daily systemic injection of the drug (25mg/kg, s.c.) or two injections of SARM loaded poly(lactic-co-glycolic acid) (PLGA) microparticles (200mg, s.c.; 24hr, 1wk). Drug release profiles from the SARM microparticle formulation was assessed both in vitro and in vivo via HPLC-UV. Liver and cardiac toxicity was analyzed from serum samples from animals receiving SARM microparticles. Statistical analysis for MWT was performed with repeated measures ANOVA compared with vehicle treatment. Both daily administration of SARMs and two injections of SARM microparticles alleviated decreased MWT bilaterally in both sexes (p<0.01). In vitro and in vivo release studies showed SARM was steadily released from microparticles for 4 weeks. Toxicity panels revealed no adverse effects of SARM microparticle treatment. The current study shows SARMs can alleviate muscle pain and SARM loaded microparticles increase clinical utility of administration due to fewer injections and long-term release profiles. Grant support from NIH AR073187 and P30CA086862.
Details
- Title: Subtitle
- Select Androgen Receptor Modulator Microparticle Formulation Reverses Muscle Hyperalgesia in Mouse Model of Widespread Muscle Pain
- Creators
- Joseph Lesnak - University of IowaDavid Nakhla - University of IowaAliasger Salem - University of IowaKathleen A. Sluka - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The journal of pain, Vol.23(5), pp.20-20
- DOI
- 10.1016/j.jpain.2022.03.077
- ISSN
- 1526-5900
- eISSN
- 1528-8447
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 05/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9984256770802771
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