Structural and molecular alterations of primary afferent fibres in the spinal dorsal horn in vincristine-induced neuropathy in rat
- PMID: 23975629
- DOI: 10.1007/s12031-013-0095-4
Structural and molecular alterations of primary afferent fibres in the spinal dorsal horn in vincristine-induced neuropathy in rat
Abstract
Vincristine is one of the most common anti-cancer drug therapies administered for the treatment of many types of cancer. Its dose-limiting side effect is the emergence of peripheral neuropathy, resulting in chronic neuropathic pain in many patients. This study sought to understand the mechanisms underlying the development of neuropathic pain by vincristine-induced neurotoxicity. We focused on signs of functional changes and revealed that deep layers of the spinal cord (III-IV) experience increased neuronal activity both in the absence of peripheral stimulation and, as a result of tactile mechanical stimulations. These laminae and superficial laminae I-II were also subject to structural changes as evidenced by an increase in immunoreactivity of Piccolo, a marker of active presynaptic elements. Further investigations performed, using DNA microarray technology, describe a large number of genes differentially expressed in dorsal root ganglions and in the spinal dorsal horn after vincristine treatment. Our study describes an important list of genes differentially regulated by vincristine treatment that will be useful for future studies and brings forward evidence for molecular and anatomical modifications of large diameter sensory neurons terminating in deep dorsal horn laminae, which could participate in the development of tactile allodynia.
Similar articles
-
Tissue plasminogen activator in primary afferents induces dorsal horn excitability and pain response after peripheral nerve injury.Eur J Neurosci. 2004 Jan;19(1):93-102. doi: 10.1046/j.1460-9568.2003.03080.x. Eur J Neurosci. 2004. PMID: 14750967
-
Vincristine increased spinal cord substance P levels in a peripheral neuropathy rat model.Drug Chem Toxicol. 2022 Jan;45(1):393-397. doi: 10.1080/01480545.2019.1706547. Epub 2020 Jan 3. Drug Chem Toxicol. 2022. PMID: 31899978
-
Spinal nerve ligation does not alter the expression or function of GABA(B) receptors in spinal cord and dorsal root ganglia of the rat.Neuroscience. 2006;138(4):1277-87. doi: 10.1016/j.neuroscience.2005.11.064. Epub 2006 Jan 20. Neuroscience. 2006. PMID: 16427742 Free PMC article.
-
Neuropathic pain is associated with alterations of nitric oxide synthase immunoreactivity and catalytic activity in dorsal root ganglia and spinal dorsal horn.Brain Res Bull. 2002 Jun;58(2):161-71. doi: 10.1016/s0361-9230(02)00761-x. Brain Res Bull. 2002. PMID: 12127013
-
Recent advances in our understanding of the organization of dorsal horn neuron populations and their contribution to cutaneous mechanical allodynia.J Neural Transm (Vienna). 2020 Apr;127(4):505-525. doi: 10.1007/s00702-020-02159-1. Epub 2020 Apr 2. J Neural Transm (Vienna). 2020. PMID: 32239353 Free PMC article. Review.
Cited by
-
Integrated Medicine for Chemotherapy-Induced Peripheral Neuropathy.Int J Mol Sci. 2021 Aug 26;22(17):9257. doi: 10.3390/ijms22179257. Int J Mol Sci. 2021. PMID: 34502166 Free PMC article. Review.
-
Chemotherapy-induced peripheral neuropathy: an update on the current understanding.F1000Res. 2016 Jun 22;5:F1000 Faculty Rev-1466. doi: 10.12688/f1000research.8053.1. eCollection 2016. F1000Res. 2016. PMID: 27408692 Free PMC article. Review.
-
Mechanism-based treatment for chemotherapy-induced peripheral neuropathic pain.Nat Rev Neurol. 2014 Dec;10(12):694-707. doi: 10.1038/nrneurol.2014.211. Epub 2014 Nov 4. Nat Rev Neurol. 2014. PMID: 25366108 Review.
-
Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.Pain. 2017 Sep;158(9):1647-1655. doi: 10.1097/j.pain.0000000000000953. Pain. 2017. PMID: 28722694 Free PMC article.
-
Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review.Front Pharmacol. 2017 Feb 24;8:86. doi: 10.3389/fphar.2017.00086. eCollection 2017. Front Pharmacol. 2017. PMID: 28286483 Free PMC article. Review.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources