Tags

Type your tag names separated by a space and hit enter

Hyperalgesia and sensitization of dorsal horn neurons following activation of NK-1 receptors in the rostral ventromedial medulla.
J Neurophysiol. 2017 11 01; 118(5):2727-2744.JN

Abstract

Neurons in the rostral ventromedial medulla (RVM) project to the spinal cord and are involved in descending modulation of pain. Several studies have shown that activation of neurokinin-1 (NK-1) receptors in the RVM produces hyperalgesia, although the underlying mechanisms are not clear. In parallel studies, we compared behavioral measures of hyperalgesia to electrophysiological responses of nociceptive dorsal horn neurons produced by activation of NK-1 receptors in the RVM. Injection of the selective NK-1 receptor agonist Sar9,Met(O2)11-substance P (SSP) into the RVM produced dose-dependent mechanical and heat hyperalgesia that was blocked by coadministration of the selective NK-1 receptor antagonist L-733,060. In electrophysiological studies, responses evoked by mechanical and heat stimuli were obtained from identified high-threshold (HT) and wide dynamic range (WDR) neurons. Injection of SSP into the RVM enhanced responses of WDR neurons, including identified neurons that project to the parabrachial area, to mechanical and heat stimuli. Since intraplantar injection of capsaicin produces robust hyperalgesia and sensitization of nociceptive spinal neurons, we examined whether this sensitization was dependent on NK-1 receptors in the RVM. Pretreatment with L-733,060 into the RVM blocked the sensitization of dorsal horn neurons produced by capsaicin. c-Fos labeling was used to determine the spatial distribution of dorsal horn neurons that were sensitized by NK-1 receptor activation in the RVM. Consistent with our electrophysiological results, administration of SSP into the RVM increased pinch-evoked c-Fos expression in the dorsal horn. It is suggested that targeting this descending pathway may be effective in reducing persistent pain.NEW & NOTEWORTHY It is known that activation of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM), a main output area for descending modulation of pain, produces hyperalgesia. Here we show that activation of NK-1 receptors produces hyperalgesia by sensitizing nociceptive dorsal horn neurons. Targeting this pathway at its origin or in the spinal cord may be an effective approach for pain management.

Authors+Show Affiliations

Department of Diagnostic and Biological Sciences, University of Minnesota, School of Dentistry, Minneapolis, Minnesota; and.Department of Diagnostic and Biological Sciences, University of Minnesota, School of Dentistry, Minneapolis, Minnesota; and.Department of Diagnostic and Biological Sciences, University of Minnesota, School of Dentistry, Minneapolis, Minnesota; and.Department of Diagnostic and Biological Sciences, University of Minnesota, School of Dentistry, Minneapolis, Minnesota; and.Department of Neuroscience, University of Minnesota, School of Medicine, Minneapolis, Minnesota.Department of Diagnostic and Biological Sciences, University of Minnesota, School of Dentistry, Minneapolis, Minnesota; and simon003@umn.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28794197

Citation

Khasabov, Sergey G., et al. "Hyperalgesia and Sensitization of Dorsal Horn Neurons Following Activation of NK-1 Receptors in the Rostral Ventromedial Medulla." Journal of Neurophysiology, vol. 118, no. 5, 2017, pp. 2727-2744.
Khasabov SG, Malecha P, Noack J, et al. Hyperalgesia and sensitization of dorsal horn neurons following activation of NK-1 receptors in the rostral ventromedial medulla. J Neurophysiol. 2017;118(5):2727-2744.
Khasabov, S. G., Malecha, P., Noack, J., Tabakov, J., Giesler, G. J., & Simone, D. A. (2017). Hyperalgesia and sensitization of dorsal horn neurons following activation of NK-1 receptors in the rostral ventromedial medulla. Journal of Neurophysiology, 118(5), 2727-2744. https://doi.org/10.1152/jn.00478.2017
Khasabov SG, et al. Hyperalgesia and Sensitization of Dorsal Horn Neurons Following Activation of NK-1 Receptors in the Rostral Ventromedial Medulla. J Neurophysiol. 2017 11 1;118(5):2727-2744. PubMed PMID: 28794197.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hyperalgesia and sensitization of dorsal horn neurons following activation of NK-1 receptors in the rostral ventromedial medulla. AU - Khasabov,Sergey G, AU - Malecha,Patrick, AU - Noack,Joseph, AU - Tabakov,Janneta, AU - Giesler,Glenn J,Jr AU - Simone,Donald A, Y1 - 2017/08/09/ PY - 2017/06/26/received PY - 2017/08/04/revised PY - 2017/08/06/accepted PY - 2017/8/11/pubmed PY - 2018/6/22/medline PY - 2017/8/11/entrez KW - descending facilitation KW - electrophysiology KW - pain KW - spinal cord SP - 2727 EP - 2744 JF - Journal of neurophysiology JO - J Neurophysiol VL - 118 IS - 5 N2 - Neurons in the rostral ventromedial medulla (RVM) project to the spinal cord and are involved in descending modulation of pain. Several studies have shown that activation of neurokinin-1 (NK-1) receptors in the RVM produces hyperalgesia, although the underlying mechanisms are not clear. In parallel studies, we compared behavioral measures of hyperalgesia to electrophysiological responses of nociceptive dorsal horn neurons produced by activation of NK-1 receptors in the RVM. Injection of the selective NK-1 receptor agonist Sar9,Met(O2)11-substance P (SSP) into the RVM produced dose-dependent mechanical and heat hyperalgesia that was blocked by coadministration of the selective NK-1 receptor antagonist L-733,060. In electrophysiological studies, responses evoked by mechanical and heat stimuli were obtained from identified high-threshold (HT) and wide dynamic range (WDR) neurons. Injection of SSP into the RVM enhanced responses of WDR neurons, including identified neurons that project to the parabrachial area, to mechanical and heat stimuli. Since intraplantar injection of capsaicin produces robust hyperalgesia and sensitization of nociceptive spinal neurons, we examined whether this sensitization was dependent on NK-1 receptors in the RVM. Pretreatment with L-733,060 into the RVM blocked the sensitization of dorsal horn neurons produced by capsaicin. c-Fos labeling was used to determine the spatial distribution of dorsal horn neurons that were sensitized by NK-1 receptor activation in the RVM. Consistent with our electrophysiological results, administration of SSP into the RVM increased pinch-evoked c-Fos expression in the dorsal horn. It is suggested that targeting this descending pathway may be effective in reducing persistent pain.NEW & NOTEWORTHY It is known that activation of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM), a main output area for descending modulation of pain, produces hyperalgesia. Here we show that activation of NK-1 receptors produces hyperalgesia by sensitizing nociceptive dorsal horn neurons. Targeting this pathway at its origin or in the spinal cord may be an effective approach for pain management. SN - 1522-1598 UR - https://www.unboundmedicine.com/medline/citation/28794197/Hyperalgesia_and_sensitization_of_dorsal_horn_neurons_following_activation_of_NK_1_receptors_in_the_rostral_ventromedial_medulla_ L2 - https://journals.physiology.org/doi/10.1152/jn.00478.2017?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -