NGF-induced mechanical sensitization of the masseter muscle is mediated through peripheral NMDA receptors

Wong, Hayes; Kang, Isabell; Dong, Xu-Dong; Christidis, Nikolaos; Ernberg, Malin; Svensson, Peter; Cairns, Brian E.

doi:10.1016/j.neuroscience.2014.03.054

Cited by 56 publications

(107 citation statements)

References 45 publications

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“…Injection of NGF into the masseter muscle of healthy subjects resulted in a local mechanical sensitization that lasted for 1-3 wk, with a greater magnitude in women than men (Svensson et al 2003(Svensson et al , 2008a. In a previous study, we demonstrated that injection of NGF into the rat masseter muscle induced a prolonged local mechanical sensitization, which was also greater in female rats than male rats (Wong et al 2014). The duration of this sensitization was associated with an increased expression of NMDA receptors in masseter muscle afferent fibers, suggesting that NGF-induced sensitization may be maintained by increased peripheral NMDA receptor expression.…”

mentioning

confidence: 84%

“…The masseter muscle region was shaved before injection, and the injection site was marked with a permanent marker for subsequent identification. The concentration of NGF was selected based on the concentration used in previous human experimental pain studies and acute experiments in rats (Mann et al 2006;Svensson et al 2003Svensson et al , 2008aWong et al 2014). Injections of NGF or saline were made 3 days before electrophysiological recording experiments in anesthetized rats.…”

Section: Animalsmentioning

confidence: 99%

“…In vivo extracellular singleunit recording was performed 3 days after NGF injection, which was previously found to be the time of peak NGF-induced NMDA receptor upregulation (Wong et al 2014). Extracellular action potentials of masseter ganglion neurons were recorded with a parylene-coated tungsten microelectrode (0.10 in., 2 M⍀; A-M Systems, Carlsborg, WA).…”

Section: Animalsmentioning

confidence: 99%

“…In Fig. 2, the lines represent masseter mechanical withdrawal thresholds determined from an earlier behavioral study in male and female rats at 3 days after intramuscular injections of vehicle or NGF into the masseter muscle (Wong et al 2014). The injection procedure (vehicle, NGF concentration, and injection volume) in that study was identical to the one in this study.…”

Section: Mtmentioning

confidence: 99%

“…Evidence suggests that it may also play a role in peripheral nociception (Carlton et al 1995;Haas et al 2010;Lam et al 2005;Miller et al 2011). Glutamate and its receptors are found in trigeminal and dorsal root ganglion neurons and at their central and peripheral terminals (Cairns et al 2003a;Dong et al 2007;Li et al 2004;Wong et al 2014). Peripheral glutamate levels are elevated during cutaneous or deep tissue inflammation, produced by a variety of nonneuronal cells such as mast cells and macrophages (Newsholme and Calder 1997).…”

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confidence: 99%

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Nerve growth factor alters the sensitivity of rat masseter muscle mechanoreceptors to NMDA receptor activation

Wong

Dong

Cairns

2014

Journal of Neurophysiology

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Intramuscular injection of nerve growth factor (NGF) into rat masseter muscle induces a local mechanical sensitization that is greater in female than in male rats. The duration of NGF-induced sensitization in male and female rats was associated with an increase in peripheral N-methyl-d-aspartate (NMDA) receptor expression by masseter muscle afferent fibers that began 3 days postinjection. Here, we investigated the functional consequences of increased NMDA expression on the response properties of masseter muscle mechanoreceptors. In vivo extracellular single-unit electrophysiological recordings of trigeminal ganglion neurons innervating the masseter muscle were performed in anesthetized rats 3 days after NGF injection (25 μg/ml, 10 μl) into the masseter muscle. Mechanical activation threshold was assessed before and after intramuscular injection of NMDA. NMDA injection induced mechanical sensitization in both sexes that was increased significantly following NGF injection in the male rats but not in the female rats. However, in female but not male rats, further examination found that preadministration of NGF induced a greater sensitization in slow Aδ-fibers (2-7 m/s) than fast Aδ-fibers (7-12 m/s). This suggests that preadministration of NGF had a different effect on slowly conducting mechanoreceptors in the female rats compared with the male rats. Although previous studies have found an association between estrogenic tone and NMDA activity, no correlation was observed between NMDA-evoked mechanical sensitization and plasma estrogen level. This study suggests NGF alters NMDA-induced mechanical sensitization in the peripheral endings of masseter mechanoreceptors in a sexually dimorphic manner.

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mentioning

confidence: 84%

Section: Animalsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: Mtmentioning

confidence: 99%

mentioning

confidence: 99%

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Nerve growth factor alters the sensitivity of rat masseter muscle mechanoreceptors to NMDA receptor activation

Wong

Dong

Cairns

2014

Journal of Neurophysiology

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Delta‐9‐tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation

Wong

Hossain

Cairns

2017

European Journal of Pain

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Background: This study investigated whether intramuscular injection of delta-9-tetrahydrocannabinol (THC), by acting on peripheral cannabinoid (CB) receptors, could decrease nerve growth factor (NGF)-induced sensitization in female rat masseter muscle; a model which mimics the symptoms of myofascial temporomandibular disorders. Methods: Immunohistochemistry was used to explore the peripheral expression of cannabinoid receptors in the masseter muscle while behavioural and electrophysiology experiments were employed to assess the functional effects of intramuscular injection of THC. Results: It was found that CB1 and CB2 receptors are expressed by trigeminal ganglion neurons that innervate the masseter muscle and also on their peripheral endings. Their expression was greater in TRPV1-positive ganglion neurons. Three days after intramuscular injection of NGF, ganglion neuron expression of CB1 and CB2, but not TPRV1, was decreased. In behavioural experiments, intramuscular injection (10 lL) of THC (1 mg/mL) attenuated NGF-induced mechanical sensitization. No change in mechanical threshold was observed in the contralateral masseter muscles and no impairment of motor function was found after intramuscular injections of THC. In anaesthetized rats, the same concentration of THC increased the mechanical thresholds of masseter muscle mechanoreceptors. Co-administration of the CB1 antagonist AM251 blocked the effect of THC on masseter muscle mechanoreceptors while the CB2 antagonist AM630 had no effect. Conclusions: These results suggest that reduced inhibitory input from the peripheral cannabinoid system may contribute to NGF-induced local myofascial sensitization of mechanoreceptors. Peripheral application of THC may counter this effect by activating the CB1 receptors on masseter muscle mechanoreceptors to provide analgesic relief without central side effects. Significance: Our results suggest THC could reduce masticatory muscle pain through activating peripheral CB1 receptors. Peripheral application of cannabinoids could be a novel approach to provide analgesic relief without central side effects.

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Minocycline reduces experimental muscle hyperalgesia induced by repeated nerve growth factor injections in humans: A placebo‐controlled double‐blind drug‐crossover study

Dunn

Nagi

Mahns

2020

European Journal of Pain

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Background Hyperalgesia is a heightened pain response to a noxious stimulus and is a hallmark of many common neuropathic and chronic pain conditions. In a double‐blind placebo‐controlled drug‐crossover trial, the effects of concomitant and delayed minocycline treatment on the initiation and resolution of muscle hyperalgesia were tested. Methods An initial cohort (n = 10) received repeated injections (5 µg: days 0, 2 and 4) of nerve growth factor (NGF) in the flexor carpi ulnaris muscle of the forearm and pressure pain thresholds were collected at day 0 (control), day 7 (peak) and day 14 (recovery). A second cohort (n = 18) underwent an identical procedure, however, half received a placebo between days 0 and 7 before switching to minocycline from days 7 to 14 (P1/M2), while the remaining subjects received minocycline (day 0: 200mg then 100mg b.i.d. for 7 days) before switching to placebo (M1/P2). Results The initial cohort exhibited a diffuse muscular pain hypersensitivity with a decrease in pressure pain thresholds at day 7 before a partial return to normalcy at day 14. The P1/M2 treatment group exhibited an identical peak in hypersensitivity at day 7, however, after switching to minocycline in week 2 showed a significant reduction in muscle hyperalgesia compared with the initial cohort at day 14. The M1/P2 treatment group had significantly less (~43%) hyperalgesia at day 7 compared with the other groups. Conclusions The study indicates that the administration of minocycline can reduce experimentally induced muscle pain regardless of the time of administration. Significance In a double‐blind placebo‐controlled drug‐crossover study, the common antibiotic minocycline was found to reduce the muscle hyperalgesia induced by intramuscular injection of nerve growth factor. The results of the study showed that both concomitant (pre‐emptive) and delayed administration of minocycline can ameliorate the onset and facilitate the resolution of experimentally induced muscle hyperalgesia.

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NGF-induced mechanical sensitization of the masseter muscle is mediated through peripheral NMDA receptors

Cited by 56 publications

References 45 publications

Nerve growth factor alters the sensitivity of rat masseter muscle mechanoreceptors to NMDA receptor activation

Nerve growth factor alters the sensitivity of rat masseter muscle mechanoreceptors to NMDA receptor activation

Delta‐9‐tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation

Minocycline reduces experimental muscle hyperalgesia induced by repeated nerve growth factor injections in humans: A placebo‐controlled double‐blind drug‐crossover study

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