The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
A multi-target approach for pain treatment: dual inhibition of fatty acid amide hydrolase and TRPV1 in a rat model of osteoarthritis
Abstract
The pharmacological inhibition of anandamide (AEA) hydrolysis by fatty acid amide hydrolase (FAAH) attenuates pain in animal models of osteoarthritis (OA) but has failed in clinical trials. This may have occurred because AEA also activates transient receptor potential vanilloid type 1 (TRPV1), which contributes to pain development. Therefore, we investigated the effectiveness of the dual FAAH-TRPV1 blocker OMDM-198 in an MIA-model of osteoarthritic pain. We first investigated the MIA-induced model of OA by (1) characterizing the pain phenotype and degenerative changes within the joint using X-ray microtomography and (2) evaluating nerve injury and inflammation marker (ATF-3 and IL-6) expression in the lumbar dorsal root ganglia of osteoarthritic rats and differences in gene and protein expression of the cannabinoid CB1 receptors FAAH and TRPV1. Furthermore, we compared OMDM-198 with compounds acting exclusively on FAAH or TRPV1. Osteoarthritis was accompanied by the fragmentation of bone microstructure and destroyed cartilage. An increase of the mRNA levels of ATF3 and IL-6 and an upregulation of AEA receptors and FAAH in the dorsal root ganglia were observed. OMDM-198 showed antihyperalgesic effects in the OA model, which were comparable with those of a selective TRPV1 antagonist, SB-366,791, and a selective FAAH inhibitor, URB-597. The effect of OMDM-198 was attenuated by the CB1 receptor antagonist, AM-251, and by the nonpungent TRPV1 agonist, olvanil, suggesting its action as an "indirect" CB1 agonist and TRPV1 antagonist. These results suggest an innovative strategy for the treatment of OA, which may yield more satisfactory results than those obtained so far with selective FAAH inhibitors in human OA.
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In the citing paper
“Administration of MIA into the knee joint leads to upregulation of CB 2 and CB 1 receptor mRNA in the ipsilateral spinal cord of rats, suggesting that these receptors undergo compensatory changes in this osteoarthritis model, and may represent potential targets for novel osteoarthritis treatments (Burston et al, 2013;Malek et al, 2015).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Malek et al, 2015
In the citing paper
“suggesting that these receptors undergo compensatory changes in this osteoarthritis model, and may represent potential targets for novel osteoarthritis treatments (Burston et al, 2013;Malek et al, 2015).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Malek et al, 2015
In the citing paper
“OMDM-198, a combined FAAH inhibitor-TRPV1 antagonist, attenuates mechanical hyperalgesia elicited by MIA injection (Malek et al, 2015).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Malek et al, 2015
In the citing paper
“Furthermore, MIA administration leads to upregulation of FAAH and TRPV1 mRNA in the ipsilateral spinal cord (Malek et al, 2015).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Malek et al, 2015
In the citing paper
“The FAAH inhibitor URB597 reduces MIA-induced mechanical hyperalgesia and restores weight bearing on the arthritic limb (Malek et al, 2015;Schuelert et al, 2011).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Malek et al, 2015
Citations
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Donvito, G., Nass, S. R., Wilkerson, J. L., Curry, Z. A., Schurman, L. D., Kinsey, S. G., & Lichtman, A. H. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.204 · Cited by 301
Metadata
- Authors
- Malek, N., Mrugala, M., Makuch, W., Kolosowska, N., Przewlocka, B., Binkowski, M., Czaja, M., Morera, E., Di Marzo, V., & Starowicz, K.
- Affiliations
- University of Silesia in Katowice (PL)
- Sapienza University of Rome (IT)
- Corresponding author
- Starowicz, Katarzyna
- Venue
- Pain
- Published
- 2015-05
- Volume
- 156
- Issue
- 5
- Pages
- 890-903
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W1996295130
- Cited by
- 63
- References
- 70
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 9 · 2020: 9 · 2019: 2 · 2018: 10 · 2017: 9 · 2016: 7 · 2015: 1
- FWCI
- 6.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Keywords
- osteoarthritis pain, anandamide, fatty acid amide hydrolase, TRPV1, CB1 receptor, dorsal root ganglia, ATF3, interleukin-6, antihyperalgesia, AM251, olvanil, endocannabinoid system
- MeSH terms
- Fatty Acid Amide Hydrolases, Amidohydrolases, Anilides, Animals, Arachidonic Acids, Benzamides, Capsaicin, Carbamates, Cinnamates, Disease Models, Animal, Ganglia, Spinal, Hyperalgesia, Inflammation, Lumbar Vertebrae, Male, Osteoarthritis, Pain, Pain Measurement, Piperidines, Pyrazoles, Interleukin-6, Gene Expression, Rats, Wistar, Receptor, Cannabinoid, CB1, TRPV Cation Channels, Rats, Activating Transcription Factor 3, Polyunsaturated Alkamides, Pain Management, Endocannabinoids
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- CoChat. (2026). Citation check: A multi-target approach for pain treatment: dual inhibition of fatty acid amide hydrolase and TRPV1 in a rat model of osteoarthritis. https://app.cochat.ai/papers/10.1097/j.pain.0000000000000132
- The paper
- Malek, N., Mrugala, M., Makuch, W., Kolosowska, N., Przewlocka, B., Binkowski, M., Czaja, M., Morera, E., Di Marzo, V., & Starowicz, K. (2015). A multi-target approach for pain treatment: dual inhibition of fatty acid amide hydrolase and TRPV1 in a rat model of osteoarthritis. Pain. https://doi.org/10.1097/j.pain.0000000000000132
