Peripheral AMPA receptors contribute to muscle nociception and c-fos activation

Chun, Yang‐Hyun; Frank, Dorie; Lee, Jong-Seok; Zhang, Youping; Auh, Q‐Schick; Ro, Jin Y.

doi:10.1016/j.neures.2008.06.007

Cited by 18 publications

(11 citation statements)

References 45 publications

(57 reference statements)

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“…It was interesting to note that MPEP had little effect on the capsaicin-induced resting discharge, data suggesting that acute nociception following capsaicin stimulation may not involve mGluR5. The blockade of NMDA and AMPA receptors has been shown to effectively attenuate acute nocifensive behaviors [5,16]. …”

Section: Discussionmentioning

confidence: 99%

Electrophysiological characterization of the rat trigeminal caudalis (Vc) neurons following intramuscular injection of capsaicin

Chun

2010

Neuroscience Letters

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Extracellular single unit recording experiments were performed to examine response characteristics of wide dynamic range neurons in the Vc that receive masseter afferent input in Sprague Dawley rats. Capsaicin, or its vehicle, was directly administered into the masseter muscle and changes in resting discharge, responses to mechanical stimulation on the cutaneous receptive field and the electrical threshold for masseter nerve stimulation were assessed. Intramuscular capsaicin induced significant increase in the background discharge and mechanical hypersensitivity to the cutaneous stimulation and lowered the threshold masseter nerve stimulation evoked responses in the majority of neurons. The capsaicin-induced increase in evoked responses, but not the resting discharge, was partially attenuated when the muscle was pretreated with a mGluR antagonist. The present study suggests that injury or inflammation in the masseter muscle induce generalized hyperexcitability of central trigeminal neurons and that the blockade of peripherally localized mGluR5 can effectively attenuate muscular hypersensitivity.

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Section: Discussionmentioning

confidence: 99%

Electrophysiological characterization of the rat trigeminal caudalis (Vc) neurons following intramuscular injection of capsaicin

Chun

2010

Neuroscience Letters

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“…The percentages of masseter afferents labeled with TRPV1 and/or P2X 3 were calculated and presented as mean ± standard error of the mean (SE). P2X 3 /TRPV1/FB positive cells were also categorized according to size (small <400µm 2 , medium 400–1000 µm 2 , and large >1000 µm 2 )(Chun et al, 2008). …”

Section: Methodsmentioning

confidence: 99%

P2X3 and TRPV1 functionally interact and mediate sensitization of trigeminal sensory neurons

Saloman

Chung

2013

Neuroscience

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Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) affect a large percentage of the population. Identifying mechanisms underlying hyperalgesia could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. In this study, we provide evidence of functional interactions between two ligand-gated channels, P2X3 and TRPV1, in trigeminal sensory neurons, and propose that the interactions serve as an underlying mechanism for the development of mechanical hyperalgesia. Mechanical sensitivity of the masseter muscle was assessed in lightly anesthetized rats via an electronic anesthesiometer (Ro et al., 2009). Direct intramuscular injection of a selective P2X3 agonist, αβmeATP, induced a dose- and time-dependent hyperalgesia. Mechanical sensitivity in the contralateral muscle was unaffected suggesting local P2X3 mediate the hyperalgesia. Anesthetizing the overlying skin had no effect on αβmeATP-induced hyperalgesia confirming the contribution of P2X3 from muscle. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810. P2X3 was co-expressed with TRPV1 in masseter muscle afferents confirming the possibility for intracellular interactions. Additionally, in a subpopulation of P2X3/TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly amplified following P2X3 activation. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal ganglia cultures. Significant phosphorylation was observed at 15 min, the time point at which behavioral hyperalgesia was prominent. Previously, activation of either P2X3 or TRPV1 had been independently implicated in the development of mechanical hyperalgesia. Our data propose P2X3 and TRPV1 interact in a facilitatory manner, which could contribute to the peripheral sensitization known to underlie masseter hyperalgesia.

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“…Hypertonic saline infusion or 20% MO injection into the rat masseter muscle causes an increase in Fos-ir in the superficial dorsal horn of the caudal spinal trigeminal nucleus. Intramuscular pretreatment with MK-801 (0.1, 0.3 mg/kg) or NBQX (1–100 nmol/10 μl) blocks or reduces this increase in Fos-ir (Ro et al, 2004, 2007; Chun et al, 2008). Some EAAR antagonists are administered peripherally, e.g., intraper-itoneal (i.p.…”

Section: Peripheral Effects Of Glutamate: Biophysicalmentioning

confidence: 99%

Glutamate pharmacology and metabolism in peripheral primary afferents: Physiological and pathophysiological mechanisms

Miller

Hoffman

Sutharshan

et al. 2011

Pharmacology & Therapeutics

121

129

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In addition to using glutamate as a neurotransmitter at central synapses, many primary sensory neurons release glutamate from peripheral terminals. Primary sensory neurons with cell bodies in dorsal root or trigeminal ganglia produce glutaminase, the synthetic enzyme for glutamate, and transport the enzyme in mitochondria to peripheral terminals. Vesicular glutamate transporters fill neurotransmitter vesicles with glutamate and they are shipped to peripheral terminals. Intense noxious stimuli or tissue damage causes glutamate to be released from peripheral afferent nerve terminals and augmented release occurs during acute and chronic inflammation. The site of action for glutamate can be at the autologous or nearby nerve terminals. Peripheral nerve terminals contain both ionotropic and metabotropic excitatory amino acid receptors (EAARs) and activation of these receptors can lower the activation threshold and increase the excitability of primary afferents. Antagonism of EAARs can reduce excitability of activated afferents and produce antinociception in many animal models of acute and chronic pain. Glutamate injected into human skin and muscle causes acute pain. Trauma in humans, such as arthritis, myalgia, and tendonitis, elevates glutamate levels in affected tissues. There is evidence that EAAR antagonism at peripheral sites can provide relief in some chronic pain sufferers.

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Peripheral AMPA receptors contribute to muscle nociception and c-fos activation

Cited by 18 publications

References 45 publications

Electrophysiological characterization of the rat trigeminal caudalis (Vc) neurons following intramuscular injection of capsaicin

Electrophysiological characterization of the rat trigeminal caudalis (Vc) neurons following intramuscular injection of capsaicin

P2X3 and TRPV1 functionally interact and mediate sensitization of trigeminal sensory neurons

Glutamate pharmacology and metabolism in peripheral primary afferents: Physiological and pathophysiological mechanisms

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