ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Deficient nonpeptidergic epidermis innervation and reduced inflammatory pain in glial cell line-derived neurotrophic factor family receptor alpha2 knock-out mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 77 citations in OpenAlex.
- Mechanisms, translational opportunities for diabetic polyneuropathy.Frontiers in endocrinology · 2026Review
- Peripheral neuronal sensitization and neurovascular remodelling in osteoarthritis pain.Nature reviews. Rheumatology · 2025Review
- Prolonged exposure to leisure screen time notably accelerates biological aging: Evidence from observational studies and genetic associations.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Observational
- Pain Hypersensitivity in SLURP1 and SLURP2 Knock-out Mouse Models of Hereditary Palmoplantar Keratoderma.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Skin Reinnervation by Collateral Sprouting Following Spared Nerve Injury in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Small fibre integrity and axonal pathology in the rat model of experimental autoimmune neuritis.Brain communications · 2024Article
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- Glial cell line-derived neurotrophic factors (GFLs) and small molecules targeting RET receptor for the treatment of pain and Parkinson's disease.Cell and tissue research · 2020Review
- Impaired mechanical, heat, and cold nociception in a murine model of genetic TACE/ADAM17 knockdown.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- GDNF, Neurturin, and Artemin Activate and Sensitize Bone Afferent Neurons and Contribute to Inflammatory Bone Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
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- p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by Potentiating Ret Signaling.Cell reports · 2017Article
- Liver X Receptor β Is Involved in Formalin-Induced Spontaneous Pain.Molecular neurobiology · 2017Article
- Cutaneous neurturin overexpression alters mechanical, thermal, and cold responsiveness in physiologically identified primary afferents.Journal of neurophysiology · 2017Article
- Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype.Frontiers in neurology · 2017Article
- Mitochondrial dysfunction in diabetic neuropathy: a series of unfortunate metabolic events.Current diabetes reports · 2015Review
- Limited changes in spinal lamina I dorsal horn neurons following the cytotoxic ablation of non-peptidergic C-fibers.Molecular pain · 2015Article
- A genome-wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain.European journal of pain (London, England) · 2015Article
- Vitamin D deficiency leads to sensory and sympathetic denervation of the rat synovium.Neuroscience · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most unmyelinated nociceptive neurons that mediate pain and temperature sensation from the skin bind isolectin B4 (IB4)-lectin and express Ret, the common signaling component of glial cell line-derived neurotrophic factor (GDNF) family. One of these factors, neurturin, is expressed in the epidermis, whereas its GDNF family receptor alpha2 (GFRalpha2) is expressed in the majority of unmyelinated Ret-positive sensory neurons. However, the physiological roles of endogenous neurturin signaling in primary sensory neurons are poorly understood. Here, we show that the vast majority (approximately 85%) of IB4 binding and P2X3 purinoreceptor-positive neurons, but virtually none of the calcitonin gene-related peptide (CGRP) or vanilloid receptor transient receptor potential vanilloid 1-positive neurons in mouse dorsal root ganglion (DRG) express GFRalpha2. In GFRalpha2 knock-out (KO) mice, the IB4-binding and P2X3-positive DRG neurons were present but reduced in size, consistent with normal number but reduced caliber of unmyelinated axons in a cutaneous nerve. Strikingly, nonpeptidergic (CGRP-negative) free nerve endings in footpad epidermis were >70% fewer in GFRalpha2-KO mice than in their wild-type littermates. In contrast, the density of CGRP-positive epidermal innervation remained unaffected. In the formalin test, the KO mice showed a normal acute response but a markedly attenuated persistent phase, indicating a deficit in inflammatory pain response. Behavioral responses of GFRalpha2-KO mice to innocuous warm and noxious heat were not blunted; the mice were actually markedly hypersensitive to noxious cold in tail immersion test. Overall, our results indicate a critical role for endogenous GFRalpha2 signaling in maintaining the size and terminal innervation of the nonpeptidergic class of cutaneous nociceptors in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.