GDNF induces mechanical hyperalgesia in muscle by reducing IBK in isolectin B4-positive nociceptors

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GDNF hyperalgesia is mediated by PLCgamma, MAPK/ERK, PI3K, CDK5 and Src family kinase signaling and dependent on the IB4-binding protein versican.

The function of the isolectin B4 (IB4+)-binding and GDNF-dependent Ret (Ret+)-expressing non-peptidergic subpopulation of nociceptors remain poorly understood. We demonstrate that acute administration of GDNF sensitizes nociceptors and produces mechanical hyperalgesia in the rat. Intrathecal IB4-saporin, a selective toxin for IB4+/Ret+-nociceptors, attenuates GDNF but not NGF hyperalgesia. Conv...

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Isolectin B(4)-positive and -negative nociceptors are functionally distinct.

Small-diameter sensory neurons that are primarily nociceptors can be divided neurochemically into two populations: isolectin B(4) (IB(4))-positive nonpeptidergic neurons, and IB(4)-negative peptidergic neurons. It has been shown that IB(4)-positive neurons depend on glial-derived neurotrophic factor (GDNF), whereas IB(4)-negative neurons depend on NGF for survival during postnatal development (...

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Nociceptors Mediate Persistent Muscle Pain Induced by GDNF

Title: IB4(+) Nociceptors Mediate Persistent Muscle Pain Induced by GDNF 1 2 Authors: Pedro Alvarez , Xiaojie Chen , Oliver Bogen , Paul G. Green 1,3 and 3 Jon D. Levine 1,2,3 4 5 Contributions: P.A., P.G.G. and J.D.L. designed experiments; P.A., X.J., O.B. and P.G.G. 6 performed experiments; P.A., X.J., and P.G.G. analyzed data and prepared 7 figures; P.A. and J.D.L. wrote the manuscript. 8 9 ...

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IB4(+) nociceptors mediate persistent muscle pain induced by GDNF.

Skeletal muscle is a well-known source of glial cell line-derived neurotrophic factor (GDNF), which can produce mechanical hyperalgesia. Since some neuromuscular diseases are associated with both increased release of GDNF and intense muscle pain, we explored the role of GDNF as an endogenous mediator in muscle pain. Intramuscularly injected GDNF induced a dose-dependent (0.1-10 ng/20 μl) persis...

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A-type voltage-gated K+ currents influence firing properties of isolectin B4-positive but not isolectin B4-negative primary sensory neurons.

Voltage-gated K+ channels (Kv) in primary sensory neurons are important for regulation of neuronal excitability. The dorsal root ganglion (DRG) neurons are heterogeneous, and the types of native Kv currents in different groups of nociceptive DRG neurons are not fully known. In this study, we determined the difference in the A-type Kv current and its influence on the firing properties between is...

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ژورنال

عنوان ژورنال: Neuroscience

سال: 2012

ISSN: 0306-4522

DOI: 10.1016/j.neuroscience.2012.06.011