Abstract
The neurophysiological mechanisms underlying NGF-induced masseter muscle sensitization and sex-related differences in its effect are not well understood in humans. Therefore, this longitudinal cohort study aimed to investigate the effect of NGF injection on the density and expression of substance P, NMDA-receptors and NGF by the nerve fibers in the human masseter muscle, to correlate expression with pain characteristics, and to determine any possible sex-related differences in these effects of NGF. The magnitude of NGF-induced mechanical sensitization and pain during oral function was significantly greater in women than in men (P < 0.050). Significant positive correlations were found between nerve fiber expression of NMDA-receptors and peak pain intensity (rs = 0.620, P = 0.048), and expression of NMDA-receptors by putative nociceptors and change in temporal summation pain after glutamate injection (rs = 0.561, P = 0.003). In women, there was a significant inverse relationship between the degree of NGF-induced mechanical sensitization and the change in nerve fiber expression of NMDA-receptors alone (rs = − 0.659, P = 0.013), and in combination with NGF (rs = − 0.764, P = 0.001). In conclusion, women displayed a greater magnitude of NGF-induced mechanical sensitization that also was associated with nerve fibers expression of NMDA-receptors, when compared to men. The present findings suggest that, in women, increased peripheral NMDA-receptor expression could be associated with masseter muscle pain sensitivity.
Highlights
The neurophysiological mechanisms underlying nerve growth factor (NGF)-induced masseter muscle sensitization and sexrelated differences in its effect are not well understood in humans
We tested the following hypotheses: [1] Injection of NGF into the masseter muscle increases the density of nerve fibers and increases the expression of NMDA receptor 2B (NR2B) and NGF; [2] the density and expressions differ in a sex-related manner; [3] the degree of mechanical sensitization induced by NGF injection is positively correlated to the expression of NR2B and NGF; and [4] the intensity of muscle pain and extent of mechanical sensitization evoked by glutamate injection into the masseter muscle is positively correlated with the expression of NR2B
The intramuscular injection of NGF on day 7 resulted in a significant decrease of pressure pain threshold (PPT) (P < 0.001) three days after injection when compared to baseline, with a mean percentage decrease of 59.1%
Summary
The neurophysiological mechanisms underlying NGF-induced masseter muscle sensitization and sexrelated differences in its effect are not well understood in humans This longitudinal cohort study aimed to investigate the effect of NGF injection on the density and expression of substance P, NMDA-receptors and NGF by the nerve fibers in the human masseter muscle, to correlate expression with pain characteristics, and to determine any possible sex-related differences in these effects of NGF. This study aimed to investigate the effect of NGF injection on the density of nerve fibers and the expression of substance P, NR2B and NGF by the nerve fibers in the human masseter muscle, to correlate expression with pain characteristics induced by either NGF or glutamate, and to determine any possible sex-related differences in these effects of NGF. We tested the following hypotheses: [1] Injection of NGF into the masseter muscle increases the density of nerve fibers and increases the expression of NR2B and NGF; [2] the density and expressions differ in a sex-related manner; [3] the degree of mechanical sensitization induced by NGF injection is positively correlated to the expression of NR2B and NGF; and [4] the intensity of muscle pain and extent of mechanical sensitization evoked by glutamate injection into the masseter muscle is positively correlated with the expression of NR2B
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