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Injection of nerve growth factor into a low back muscle induces long-lasting latent hypersensitivity in rat dorsal horn neurons

Hoheisel, Ulricha,*; Reuter, Ragnaa; de Freitas, Milena Fernandesb; Treede, Rolf-Detlefa; Mense, Siegfrieda

doi: 10.1016/j.pain.2013.05.006
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Summary Injection of nerve growth factor into a low back muscle induces a transient hyperalgesia followed by a latent sensitization of rat dorsal horn neurons.

Little is known about the central mechanisms underlying the transition from local or regional to widespread pain in low back pain patients. The aim of the study was to find out if muscle input induced by injection of nerve growth factor (NGF) can be used as an animal model for studying spinal mechanisms involved in widespread myofascial low back pain. Electrophysiological recordings from rat dorsal horn neurons were made in vivo to study alterations in their responsiveness caused by 2 injections of NGF into the multifidus muscle at an interval of 5 days. NGF is known to be closely associated with many painful muscle disorders. The results demonstrate that the 2 NGF injections—but not a single one—caused a significant hyperexcitability of spinal neurons. Five days after the first NGF injection, the neurons were not significantly sensitized but were easier to sensitize by a second injection. The state of the neurons resembles nociceptive priming. Important findings were that the proportion of neurons having multiple receptive fields (RFs) in various tissues was significantly higher after 2 NGF injections, and new RFs appeared on the distal hind limb. The new RFs were located not in the skin but in deep tissues (muscles, thoracolumbar fascia). If similar changes occur in patients, the data might explain the diffuse nature and spread of myofascial low back pain.

aDepartment of Neurophysiology, Centre for Biomedicine and Medical Technology Mannheim, Ruprecht-Karls-University Heidelberg, Ludolf-Krehl-Str. 13-17, 68167 Mannheim, Germany

bDepartment of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil

*Corresponding author. Tel.: +49 621 383 9637; fax: +49 621 383 9921.

E-mail: ulrich.hoheisel@medma.uni-heidelberg.de

Submitted December 21, 2012; revised April 25, 2013; accepted May 2, 2013.

© 2013 Lippincott Williams & Wilkins, Inc.
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