Neurotrophins and hyperalgesia
Open accessAbstract
Nerve growth factor (NGF), a member of the neurotrophin family, is crucial for survival of nociceptive neurons during development. Recently, it has been shown to play an important role in nociceptive function in adults. NGF is up-regulated after inflammatory injury of the skin. Administration of exogenous NGF either systemically or in the skin causes thermal hyperalgesia within minutes. Mast cells are considered important components in the action of NGF, because prior degranulation abolishes the early NGF-induced component of hyperalgesia. Substances degranulated by mast cells include serotonin, histamine, and NGF. Blockade of histamine receptors does not prevent NGF-induced hyperalgesia. The effects of blocking serotonin receptors are complex and cannot be interpretable uniquely as NGF losing its ability to induce hyperalgesia. To determine whether NGF has a direct effect on dorsal root ganglion neurons, we have begun to investigate the acute effects of NGF on capsaicin responses of small-diameter dorsal root ganglion cells in culture. NGF acutely conditions the response to capsaicin, suggesting that NGF may be important in sensitizing the response of sensory neurons to heat (a process that is thought to operate via the capsaicin receptor VR1). We also have found that ligands for the trkB receptor (brain-derived neurotrophic factor and neurotrophin-4/5) acutely sensitize nociceptive afferents and elicit hyperalgesia. Because brain-derived neurotrophic factor is up-regulated in trkA positive cells after inflammatory injury and is transported anterogradely, we consider it to be a potentially important peripheral component involved in neurotrophin-induced hyperalgesia.
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- Authors
- Shu, X.-Q., & Mendell, L. M.
- Affiliations
- Stony Brook University (US)
- ORCID
- Mendell, L. M.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-07-06
- Volume
- 96
- Issue
- 14
- Pages
- 7693-7696
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC33603
- OpenAlex
- W2078828516
- Cited by
- 266
- References
- 40
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 8 · 2016: 6 · 2015: 9 · 2014: 10 · 2013: 9 · 2012: 8
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Regeneron Pharmaceuticals
- National Institutes of Health (2r01ns032264-06, 5p01ns014899-20)
- Genentech
- National Institute of Neurological Disorders and Stroke (NS 32264, NS16996, NS 14899, R01NS016996)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- nerve growth factor, neurotrophins, thermal hyperalgesia, mast cell degranulation, serotonin receptors, histamine receptors, dorsal root ganglion neurons, capsaicin response, TRPV1, TrkB receptor, brain-derived neurotrophic factor, neurotrophin-4/5, nociceptive sensitization, inflammatory pain, anterograde transport
- MeSH terms
- Adult, Animals, Capsaicin, Ganglia, Spinal, Humans, Hyperalgesia, Nerve Growth Factors, Neurons, Nociceptors, Proto-Oncogene Proteins, Receptors, Drug, Receptors, Nerve Growth Factor, Receptor Protein-Tyrosine Kinases, Receptor, Ciliary Neurotrophic Factor, Receptor, trkA
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