Painful stimuli induce in vivo phosphorylation and membrane mobilization of mouse spinal cord NKCC1 co-transporter
- PMID: 15893647
- DOI: 10.1016/j.neuroscience.2005.02.025
Painful stimuli induce in vivo phosphorylation and membrane mobilization of mouse spinal cord NKCC1 co-transporter
Erratum in
- Neuroscience. 2005;135(2):655
Abstract
The Na+ --Cl- --K+ isoform 1 (NKCC1) is a co-transporter that increases the intracellular concentration of chloride. NKCC1 plays a critical role in neuronal excitability and it has been recently suggested that it can contribute to hyperalgesic states by modulating the chloride concentration inside nociceptive neurons. In the spinal cord, trafficking of neurotransmitter receptors from the cytosol to the plasma membrane has been demonstrated to contribute to the development of hyperalgesia. However, it is unknown if trafficking of co-transporters can also occur in the nervous system or if it can be induced by painful stimulation. In this study, we have induced referred mechanical hyperalgesia in vivo by intracolonic instillation of capsaicin in mice. Using subcellular fractionation of proteins and cross-linking of membrane proteins we have observed that intracolonic capsaicin induced a 50% increase in NKCC1 in the plasma membrane of lumbosacral spinal cord 90 and 180 min after instillation, in parallel with a similar decrease in the cytosolic fraction. These effects returned to basal levels 6 h after capsaicin treatment. Intracolonic capsaicin also evoked a rapid (10 min) and transient phosphorylation of NKCC1, however, intracolonic saline did not produce significant changes in either NKCC1 trafficking or phosphorylation and none of the treatments induced any alterations of NKCC1 in the thoracic spinal cord. These results suggest that phosphorylation and recruitment of NKCC1 might play a role in referred mechanical hyperalgesia evoked by a painful visceral stimulus. The time course of the effects observed suggests that phosphorylation could contribute to the initial generation of hyperalgesia whereas trafficking could participate in the maintenance of hyperalgesic states observed at longer time points.
Similar articles
-
The role of KCC2 and NKCC1 in spinal cord injury: From physiology to pathology.Front Physiol. 2022 Dec 15;13:1045520. doi: 10.3389/fphys.2022.1045520. eCollection 2022. Front Physiol. 2022. PMID: 36589461 Free PMC article. Review.
-
Stimulation of cutaneous low threshold mechanoreceptors in mice after intracolonic capsaicin increases spinal c-Fos labeling in an NKCC1-dependent fashion.J Pain. 2013 Jan;14(1):57-65. doi: 10.1016/j.jpain.2012.10.003. Epub 2012 Nov 27. J Pain. 2013. PMID: 23199419
-
Expression changes of K+-Cl- co-transporter 2 and Na+-K+-Cl- co-transporter1 in mouse trigeminal subnucleus caudalis following pulpal inflammation.Brain Res Bull. 2010 Apr 5;81(6):561-4. doi: 10.1016/j.brainresbull.2010.01.002. Epub 2010 Jan 11. Brain Res Bull. 2010. PMID: 20067823
-
Chloride regulation in the pain pathway.Brain Res Rev. 2009 Apr;60(1):149-70. doi: 10.1016/j.brainresrev.2008.12.015. Epub 2008 Dec 31. Brain Res Rev. 2009. PMID: 19167425 Free PMC article. Review.
-
Presynaptic inhibition and spinal pain processing in mice: a possible role of the NKCC1 cation-chloride co-transporter in hyperalgesia.Neurosci Lett. 2004 May 6;361(1-3):200-3. doi: 10.1016/j.neulet.2003.12.015. Neurosci Lett. 2004. PMID: 15135928
Cited by
-
Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain.Cells. 2022 Sep 17;11(18):2910. doi: 10.3390/cells11182910. Cells. 2022. PMID: 36139484 Free PMC article. Review.
-
Improving NKCC1 Function Increases the Excitability of DRG Neurons Exacerbating Pain Induced After TRPV1 Activation of Primary Sensory Neurons.Front Cell Neurosci. 2021 May 25;15:665596. doi: 10.3389/fncel.2021.665596. eCollection 2021. Front Cell Neurosci. 2021. PMID: 34113239 Free PMC article.
-
Presynaptic Inhibition of Pain and Touch in the Spinal Cord: From Receptors to Circuits.Int J Mol Sci. 2021 Jan 2;22(1):414. doi: 10.3390/ijms22010414. Int J Mol Sci. 2021. PMID: 33401784 Free PMC article. Review.
-
Differential expression of Na+/K+/Cl- cotransporter 1 in neurons and glial cells within the superficial spinal dorsal horn of rodents.Sci Rep. 2020 Jul 16;10(1):11715. doi: 10.1038/s41598-020-68638-3. Sci Rep. 2020. PMID: 32678166 Free PMC article.
-
Neuropathic pain after chronic nerve constriction may not correlate with chloride dysregulation in mouse trigeminal nucleus caudalis neurons.Pain. 2017 Jul;158(7):1366-1372. doi: 10.1097/j.pain.0000000000000926. Pain. 2017. PMID: 28426550 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical