Abstract:Background: Glutamate, as well as nerve growth factor (NGF), is involved in nociception from peripheral tissues, such as muscles. However, the potential interaction between glutamate and NGF still remains unclear. This study investigated the interaction between glutamate-induced masseter muscle pain and NGF-induced allodynia on pain perception and jaw function in healthy individuals, and any possible sex differences in the response.Materials and Methods: Thirty pain-free adult participants (15 men and 15 women… Show more
“…Injection of glutamate can also evoke masseter muscle sensitization through the activation of peripheral NMDA receptors 12 , 54 . Injection of glutamate into masseter muscles pretreated with NGF failed to cause an increase or decrease in PPT 15 , which could be an indication that glutamate and NGF can share a common pathway, thus preventing additional sensitization when these substances are used together 13 . It is also possible that a ceiling effect occurred by NGF on PPT and that additional sensitization by glutamate, thus was not possible.…”
Section: Discussionmentioning
confidence: 96%
“…1 a). The results from these examinations as well as DC/TMD results have been presented elsewhere 15 . Figure 1 Figure displaying the methodology of the study.…”
Section: Methodsmentioning
confidence: 99%
“…For TMD-myalgia, several exogenous experimental pain models that use injections of different substances such as glutamate, serotonin, acidic saline, hypertonic saline and nerve growth factors (NGF) have been proposed [8][9][10][11][12][13][14] . Both glutamate and NGF have advantages over other pain models where experimental injection of these substances alone or in combination into healthy human masseter muscle produced similar pain characteristics involved in TMD myalgia 7,15,16 . However, the cellular and molecular mechanisms involved in these models are still not well addressed in the literature, especially for humans.Substance P (SP) and NGF are important neurotransmitters/modulators that have been shown to mediate inflammatory hyperalgesia 17,18 .…”
Nocifensive behavior induced by injection of glutamate or nerve growth factor (NGF) into rats masseter muscle is mediated, in part, through the activation of peripheral NMDA receptors. However, information is lacking about the mechanism that contributes to pain and sensitization induced by these substances in humans. Immunohistochemical analysis of microbiopsies obtained from human masseter muscle was used to investigate if injection of glutamate into the NGF-sensitized masseter muscle alters the density or expression of the NMDA receptor subtype 2B (NR2B) or NGF by putative sensory afferent (that express SP) fibers. The relationship between expression and pain characteristics was also examined. NGF and glutamate administration increased the density and expression of NR2B and NGF by muscle putative sensory afferent fibers (P < 0.050). This increase in expression was greater in women than in men (P < 0.050). Expression of NR2B receptors by putative sensory afferent fibers was positively correlated with pain characteristics. Results suggest that increased expression of peripheral NMDA receptors partly contributes to the increased pain and sensitivity induced by intramuscular injection of NGF and glutamate in healthy humans; a model of myofascial temporomandibular disorder (TMD) pain. Whether a similar increase in peripheral NMDA expression occurs in patients with painful TMDs warrants further investigation.
“…Injection of glutamate can also evoke masseter muscle sensitization through the activation of peripheral NMDA receptors 12 , 54 . Injection of glutamate into masseter muscles pretreated with NGF failed to cause an increase or decrease in PPT 15 , which could be an indication that glutamate and NGF can share a common pathway, thus preventing additional sensitization when these substances are used together 13 . It is also possible that a ceiling effect occurred by NGF on PPT and that additional sensitization by glutamate, thus was not possible.…”
Section: Discussionmentioning
confidence: 96%
“…1 a). The results from these examinations as well as DC/TMD results have been presented elsewhere 15 . Figure 1 Figure displaying the methodology of the study.…”
Section: Methodsmentioning
confidence: 99%
“…For TMD-myalgia, several exogenous experimental pain models that use injections of different substances such as glutamate, serotonin, acidic saline, hypertonic saline and nerve growth factors (NGF) have been proposed [8][9][10][11][12][13][14] . Both glutamate and NGF have advantages over other pain models where experimental injection of these substances alone or in combination into healthy human masseter muscle produced similar pain characteristics involved in TMD myalgia 7,15,16 . However, the cellular and molecular mechanisms involved in these models are still not well addressed in the literature, especially for humans.Substance P (SP) and NGF are important neurotransmitters/modulators that have been shown to mediate inflammatory hyperalgesia 17,18 .…”
Nocifensive behavior induced by injection of glutamate or nerve growth factor (NGF) into rats masseter muscle is mediated, in part, through the activation of peripheral NMDA receptors. However, information is lacking about the mechanism that contributes to pain and sensitization induced by these substances in humans. Immunohistochemical analysis of microbiopsies obtained from human masseter muscle was used to investigate if injection of glutamate into the NGF-sensitized masseter muscle alters the density or expression of the NMDA receptor subtype 2B (NR2B) or NGF by putative sensory afferent (that express SP) fibers. The relationship between expression and pain characteristics was also examined. NGF and glutamate administration increased the density and expression of NR2B and NGF by muscle putative sensory afferent fibers (P < 0.050). This increase in expression was greater in women than in men (P < 0.050). Expression of NR2B receptors by putative sensory afferent fibers was positively correlated with pain characteristics. Results suggest that increased expression of peripheral NMDA receptors partly contributes to the increased pain and sensitivity induced by intramuscular injection of NGF and glutamate in healthy humans; a model of myofascial temporomandibular disorder (TMD) pain. Whether a similar increase in peripheral NMDA expression occurs in patients with painful TMDs warrants further investigation.
“…Temporal summation was assessed with 1.0 kg Palpeter (Sunstar Suisse SA, Etoy, Switzerland) 29 , by repeated applications of mechanical pressure for 1 second with a 2-second interval for ten times 30 .…”
Section: Temporal Summation and Chewing Testmentioning
confidence: 99%
“…During temporal summation and chewing test 30 , participants were asked to rate their pain level on a 0 -10 numerical rating scale (NRS) and their fatigue level on Borg's ratings of perceived exertion (RPE) scale (6 -20) 31 .…”
Section: Temporal Summation and Chewing Testmentioning
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 density and expression of substance P, NMDA-receptor 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 the oral function was significantly greater in women than in men (P<0.050). Significant positive correlations were found between nerve fibers 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 fibers 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.
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.
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