TY  - JOUR
A1  - Kress, Michaela
A1  - Hüttenhofer, Alexander
A1  - Landry, Marc
A1  - Kuner, Rohini
A1  - Favereaux, Alexandre
A1  - Greenberg, David
A1  - Bednarik, Josef
A1  - Heppenstall, Paul
A1  - Kronenberg, Florian
A1  - Malcangio, Marzia
A1  - Rittner, Heike
A1  - Üçeyler, Nurcan
A1  - Trajanoski, Zlatko
A1  - Mouritzen, Peter
A1  - Birklein, Frank
A1  - Sommer, Claudia
A1  - Soreq, Hermona
T1  - microRNAs in nociceptive circuits as predictors of future clinical applications
JF  - Frontiers in Molecular Neuroscience
N2  - Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain, and non-coding RNAs – and microRNAs (miRNAs) in particular – regulate both immune and neuronal processes. Specifically, miRNAs control macromolecular complexes in neurons, glia and immune cells and regulate signals used for neuro-immune communication in the pain pathway. Therefore, miRNAs may be hypothesized as critically important master switches modulating chronic pain. In particular, understanding the concerted function of miRNA in the regulation of nociception and endogenous analgesia and defining the importance of miRNAs in the circuitries and cognitive, emotional and behavioral components involved in pain is expected to shed new light on the enigmatic pathophysiology of neuropathic pain, migraine and complex regional pain syndrome. Specific miRNAs may evolve as new druggable molecular targets for pain prevention and relief. Furthermore, predisposing miRNA expression patterns and inter-individual variations and polymorphisms in miRNAs and/or their binding sites may serve as biomarkers for pain and help to predict individual risks for certain types of pain and responsiveness to analgesic drugs. miRNA-based diagnostics are expected to develop into hands-on tools that allow better patient stratification, improved mechanism-based treatment, and targeted prevention strategies for high risk individuals.
KW  - chronic pain
KW  - biomarker
KW  - polymorphism
KW  - miRNA-based diagnostics
KW  - miRNA expression patterns
KW  - miRNA polymorphisms
KW  - antagomir
KW  - miRNA-based analgesic
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154597
VL  - 6
IS  - 33
ER  - 
TY  - JOUR
A1  - Reinhold, Ann Kristin
A1  - Krug, Susanne M.
A1  - Salvador, Ellaine
A1  - Sauer, Reine S.
A1  - Karl-Schöller, Franziska
A1  - Malcangio, Marzia
A1  - Sommer, Claudia
A1  - Rittner, Heike L.
T1  - MicroRNA-21-5p functions via RECK/MMP9 as a proalgesic regulator of the blood nerve barrier in nerve injury
JF  - Annals of the New York Academy of Sciences
N2  - Both nerve injury and complex regional pain syndrome (CRPS) can result in chronic pain. In traumatic neuropathy, the blood nerve barrier (BNB) shielding the nerve is impaired—partly due to dysregulated microRNAs (miRNAs). Upregulation of microRNA-21-5p (miR-21) has previously been documented in neuropathic pain, predominantly due to its proinflammatory features. However, little is known about other functions. Here, we characterized miR-21 in neuropathic pain and its impact on the BNB in a human-murine back translational approach. MiR-21 expression was elevated in plasma of patients with CRPS as well as in nerves of mice after transient and persistent nerve injury. Mice presented with BNB leakage, as well as loss of claudin-1 in both injured and spared nerves. Moreover, the putative miR-21 target RECK was decreased and downstream Mmp9 upregulated, as was Tgfb. In vitro experiments in human epithelial cells confirmed a downregulation of CLDN1 by miR-21 mimics via inhibition of the RECK/MMP9 pathway but not TGFB. Perineurial miR-21 mimic application in mice elicited mechanical hypersensitivity, while local inhibition of miR-21 after nerve injury reversed it. In summary, the data support a novel role for miR-21, independent of prior inflammation, in elicitation of pain and impairment of the BNB via RECK/MMP9.
KW  - claudin-1
KW  - RECK
KW  - MMP9
KW  - CRPS
KW  - microRNA
KW  - neuropathic pain
KW  - blood nerve barrier
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318226
VL  - 1515
IS  - 1
SP  - 184
EP  - 195
ER  -