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October 13, 2012
1:00:00 PM - 4:00:00 PM
Room Hall C-Area J
Spinal Dorsal Horn Neurons Responding to Mechanical Stimulation of Bone Marrow Characteristics of Spinal Dorsal Horn Neurons Responding to Mechanical Stimulation of Bone Marrow
Takashi Ishida, M.D., Satoshi Tanaka, M.D., Tomoyuki Kawamata, M.D., Mikito Kawamata, M.D.
Shinshu University of Medicine, Matumoto, Japan

Bone cancer pain is one of the most serious forms of cancer pain. In addition to the periosteum, bone pain originates from the bone marrow, which relay nociceptive signals to the brain. However, the mechanisms that generate pain in the bone marrow still remain to be elucidated. The purpose of this study was to investigate the profiles of spinal dorsal horn (SDH) neurons in response to a transient increase in the bone marrow pressure of the femur.


All of the protocols of this study were approved by the Animal Care and Use Committee of our institution. A balloon (2 x 15 mm) was chronically implanted in the medullary cavity of the femur of adult male Sprague-Dawley rats. After single SDH neuronal activity at the lumbar level was indentified, the neurons were then classified as wide-dynamic-range (WDR), high-threshold (HT) or low-threshold (LT) according to their responses to brushing the skin or pinching the skin. Non-noxious (brush and 4-g von Frey filament) and noxious (pinch) stimuli were then applied on the skin of the hindpaw, thigh and lumbar region of the rat. After the responses to such stimuli and receptive field of the neurons were recorded, changes in neuronal activity in response to balloon infiltration were recorded. Effects of spinal application of morphine on neuronal activity in response to such stimuli were also measured.


Forty three SDH neurons (32 WDR and 11 HT neurons) responded to balloon inflation in the medullary cavity. Most of the SDH neurons had the receptive field of the skin at the lumbar region and the lateral part of thigh (Figure 1). Spinally administered morphine (1 μg) did not suppress the responses of the SDH neurons to brush and 4-g von Frey filament but those to pinch and balloon inflation in the medullary cavity (Figure 2).


The results show that nerve fibers in the bone marrow of the femur sense noxious stimulation and send the signals to SDH. Bone marrow afferent input converges onto the SDH neurons responding to noxious mechanical stimuli . The results suggest the concept that activation of bone marrow afferent might lead to the production of referred pain in the skin.

Figure 1. Location of receptive field (RF) areas of the neurons.

Figure 2. Effects of spinal application of morphine (1 μg) on responses of the wide-dynamic-range (WDR) neurons. *P<0.05 vs. Pre.
Figure 1
Figure 2

Copyright © 2012 American Society of Anesthesiologists