Altered sodium channel expression in second-order spinal sensory neurons contributes to pain after peripheral nerve injury
- PMID: 15152043
- PMCID: PMC6729453
- DOI: 10.1523/JNEUROSCI.0300-04.2004
Altered sodium channel expression in second-order spinal sensory neurons contributes to pain after peripheral nerve injury
Abstract
Peripheral nerve injury is known to upregulate the rapidly repriming Na(v)1.3 sodium channel within first-order spinal sensory neurons. In this study, we hypothesized that (1) after peripheral nerve injury, second-order dorsal horn neurons abnormally express Na(v)1.3, which (2) contributes to the responsiveness of these dorsal horn neurons and to pain-related behaviors. To test these hypotheses, adult rats underwent chronic constriction injury (CCI) of the sciatic nerve. Ten days after CCI, allodynia and hyperalgesia were evident. In situ hybridization, quantitative reverse transcription-PCR, and immunocytochemical analysis revealed upregulation of Na(v)1.3 in dorsal horn nociceptive neurons but not in astrocytes or microglia, and unit recordings demonstrated hyperresponsiveness of dorsal horn sensory neurons. Intrathecal antisense oligodeoxynucleotides targeting Na(v)1.3 decreased the expression of Na(v)1.3 mRNA and protein, reduced the hyperresponsiveness of dorsal horn neurons, and attenuated pain-related behaviors after CCI, all of which returned after cessation of antisense delivery. These results demonstrate for the first time that sodium channel expression is altered within higher-order spinal sensory neurons after peripheral nerve injury and suggest a link between misexpression of the Na(v)1.3 sodium channel and central mechanisms that contribute to neuropathic pain after peripheral nerve injury.
Figures








Similar articles
-
Upregulation of sodium channel Nav1.3 and functional involvement in neuronal hyperexcitability associated with central neuropathic pain after spinal cord injury.J Neurosci. 2003 Oct 1;23(26):8881-92. doi: 10.1523/JNEUROSCI.23-26-08881.2003. J Neurosci. 2003. PMID: 14523090 Free PMC article.
-
Sodium channel expression in the ventral posterolateral nucleus of the thalamus after peripheral nerve injury.Mol Pain. 2006 Aug 17;2:27. doi: 10.1186/1744-8069-2-27. Mol Pain. 2006. PMID: 16916452 Free PMC article.
-
Expression of auxiliary beta subunits of sodium channels in primary afferent neurons and the effect of nerve injury.Neuroscience. 2003;121(2):441-50. doi: 10.1016/s0306-4522(03)00432-9. Neuroscience. 2003. PMID: 14522002
-
Distribution of the tetrodotoxin-resistant sodium channel PN3 in rat sensory neurons in normal and neuropathic conditions.J Neurosci. 1998 Mar 15;18(6):2174-87. doi: 10.1523/JNEUROSCI.18-06-02174.1998. J Neurosci. 1998. PMID: 9482802 Free PMC article. Review.
-
Fire and phantoms after spinal cord injury: Na+ channels and central pain.Trends Neurosci. 2006 Apr;29(4):207-15. doi: 10.1016/j.tins.2006.02.003. Epub 2006 Feb 21. Trends Neurosci. 2006. PMID: 16494954 Review.
Cited by
-
Exploring the Promise of Flavonoids to Combat Neuropathic Pain: From Molecular Mechanisms to Therapeutic Implications.Front Neurosci. 2020 Jun 9;14:478. doi: 10.3389/fnins.2020.00478. eCollection 2020. Front Neurosci. 2020. PMID: 32587501 Free PMC article. Review.
-
Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways.Toxins (Basel). 2019 Oct 29;11(11):626. doi: 10.3390/toxins11110626. Toxins (Basel). 2019. PMID: 31671792 Free PMC article. Review.
-
Identification of sodium channel isoforms that mediate action potential firing in lamina I/II spinal cord neurons.Mol Pain. 2011 Sep 12;7:67. doi: 10.1186/1744-8069-7-67. Mol Pain. 2011. PMID: 21910862 Free PMC article.
-
Corneal sensitivity and subjective complaints of ocular pain in patients with fibromyalgia.Eye (Lond). 2018 Apr;32(4):763-767. doi: 10.1038/eye.2017.275. Epub 2018 Jan 26. Eye (Lond). 2018. PMID: 29386615 Free PMC article.
-
Intercellular communication and ion channels in neuropathic pain chronicization.Inflamm Res. 2020 Sep;69(9):841-850. doi: 10.1007/s00011-020-01363-9. Epub 2020 Jun 12. Inflamm Res. 2020. PMID: 32533221 Review.
References
-
- Basbaum AI, Wall PD (1976) Chronic changes in the response of cells in adult cat dorsal horn following partial deafferentation: the appearance of responding cells in a previously non-responsive region. Brain Res 116: 181–204. - PubMed
-
- Bennett GJ, Xie YK (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33: 87–107. - PubMed
-
- Black JA, Dib-Hajj S, McNabola K, Jeste S, Rizzo MA, Kocsis JD, Waxman SG (1996) Spinal sensory neurons express multiple sodium channel alpha-subunit mRNAs. Res Mol Brain Res 43: 117–131. - PubMed
-
- Black JA, Langworthy K, Hinson AW, Dib-Hajj SD, Waxman SG (1997) NGF has opposing effects on Na+ channel III and SNS gene expression in spinal sensory neurons. NeuroReport 8: 2331–2335. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases