Organization of pERK-immunoreactive cells in trigeminal spinal nucleus caudalis, upper cervical cord, NTS and Pa5 following capsaicin injection into masticatory and swallowing-related muscles in rats

Tsujimura, Takanori; Shinoda, Masamichi; Honda, Kuniya; Hitomi, Suzuro; Kiyomoto, Masaaki; Matsuura, S.; Katagiri, Ayano; Tsuji, Kojun; Inoue, Makoto; Shiga, Yoshi; Iwata, Koichi

doi:10.1016/j.brainres.2011.08.032

Cited by 10 publications

(9 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the distribution of pERK-IR cells was more widespread along the rostrocaudal dimension after capsaicin injection into the digastric and sternohyoideus muscle [21]. In this study, the largest number of pERK-IR cells was aggregated at the obex level and distributed within a quite narrow area (-720 μm to 720 μm from obex).…”

Section: Discussionmentioning

confidence: 66%

“…In the trigeminal system, ERK was found to be phosphorylated in many Vc and C1-C2 neurons within 5 min after capsaicin injection into various orofacial regions, and the number of pERK-IR cells increased following increases in the stimulus intensity [12,20,21,24]. These findings strongly suggest that ERK phosphorylation in Vc and C1-C2 neurons is a reliable marker of excitable neurons following noxious stimulation of the orofacial region.…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Metabotropic glutamate receptor 5 contributes to inflammatory tongue pain via extracellular signal-regulated kinase signaling in the trigeminal spinal subnucleus caudalis and upper cervical spinal cord

Liu

Matsuura

Shinoda

et al. 2012

J Neuroinflammation

Self Cite

View full text Add to dashboard Cite

BackgroundIn the orofacial region, limited information is available concerning pathological tongue pain, such as inflammatory pain or neuropathic pain occurring in the tongue. Here, we tried for the first time to establish a novel animal model of inflammatory tongue pain in rats and to investigate the roles of metabotropic glutamate receptor 5 (mGluR5)-extracellular signal-regulated kinase (ERK) signaling in this process.MethodsComplete Freund’s adjuvant (CFA) was submucosally injected into the tongue to induce the inflammatory pain phenotype that was confirmed by behavioral testing. Expression of phosphorylated ERK (pERK) and mGluR5 in the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were detected with immunohistochemical staining and Western blotting. pERK inhibitor, a selective mGluR5 antagonist or agonist was continuously administered for 7 days via an intrathecal (i.t.) route. Local inflammatory responses were verified by tongue histology.ResultsSubmucosal injection of CFA into the tongue produced a long-lasting mechanical allodynia and heat hyperalgesia at the inflamed site, concomitant with an increase in the pERK immunoreactivity in the Vc and C1-C2. The distribution of pERK-IR cells was laminar specific, ipsilaterally dominant, somatotopically relevant, and rostrocaudally restricted. Western blot analysis also showed an enhanced activation of ERK in the Vc and C1-C2 following CFA injection. Continuous i.t. administration of the pERK inhibitor and a selective mGluR5 antagonist significantly depressed the mechanical allodynia and heat hyperalgesia in the CFA-injected tongue. In addition, the number of pERK-IR cells in ipsilateral Vc and C1-C2 was also decreased by both drugs. Moreover, continuous i.t. administration of a selective mGluR5 agonist induced mechanical allodynia in naive rats.ConclusionsThe present study constructed a new animal model of inflammatory tongue pain in rodents, and demonstrated pivotal roles of the mGluR5-pERK signaling in the development of mechanical and heat hypersensitivity that evolved in the inflamed tongue. This tongue-inflamed model might be useful for future studies to further elucidate molecular and cellular mechanisms of pathological tongue pain such as burning mouth syndrome.

show abstract

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 95%

Metabotropic glutamate receptor 5 contributes to inflammatory tongue pain via extracellular signal-regulated kinase signaling in the trigeminal spinal subnucleus caudalis and upper cervical spinal cord

Liu

Matsuura

Shinoda

et al. 2012

J Neuroinflammation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Fig. 1 shows that brainstem sensory processing through the trigeminal system is complex, with multiple collaterals and connections to autonomic centers [3,6]. The afferents of this reflex response probably involve faster Aδ rather than C fibers, considering the fast response to cold water [4].…”

Section: Dear Sirsmentioning

confidence: 99%

“…The first has a short latency, is lancinating, sharp and well localized (mechanical Aδ mediation), whereas with temperatures 10°C below the threshold for the first, a second pain with longer latency starts (C fibers) [4]. Orofacial nociceptive afferents are processed at the trigeminal spinal subnucleus caudalis and upper cervical spinal cord (C1) neurons, but the nucleus tractus solitarii and paratrigeminal nucleus also receive noxious input from the orofacial regions [3,6]. We describe a previously undescribed form of brainstem sensory synesthesia triggered by cold stimulation of teeth.…”

Section: Dear Sirsmentioning

confidence: 99%

Generalized somatic dysesthesias induced by stimulation of teeth with cold water: An unreported form of brainstem integrative synesthesia

Gondim

Thomas

2014

Journal of the Neurological Sciences

View full text Add to dashboard Cite

“…Furthermore, injection of capsaicin into the whisker pad, masseter, sternohyoid, digastric, and lingual muscles have shown to result in a decreased number of reflexive swallows in rodents Tsujimura, Kondo, et al, 2009;Tsujimura et al, 2011). These changes suggest that injury or inflammatory signaling at the periphery likely affect swallowing motor outputs.…”

Section: Discussionmentioning

confidence: 99%

Swallow and breathing coordination following suprahyoid muscle injury.

Kimbel¹

View full text Add to dashboard Cite

DEDICATIONTo my wife, Kate, for all her support and patience. iv ACKNOWLEDGMENTS First, I would like to thank my thesis advisor at the University of Louisville. She provided invaluable input into the thesis process. Her knowledge base related to the scope of this paper was instrumental in its publication. Further, she was patient and forthright in her feedback. Under her tutelage, I fostered a newly found passion for research. Swallowing motility disorders (dysphagia) are a major complication following radiation treatment for head and neck cancer, affecting ~50% of those treated. One reason for this is that radiation causes muscle damage, provoking sensorimotor pathologies.Previous work has suggested that injury may cause discoordination between breathing and swallowing behaviors. We sought to determine if muscle injury provokes changes in this behavior. We hypothesized that acute suprahyoid muscle damage would alter crossbehavior excitability, causing destabilization of the respiratory-swallow pattern.Swallowing was evoked in anesthetized spontaneously breathing cats via injection of a 3cc bolus of water into the oropharyngeal cavity. A suprahyoid injury was induced unilaterally by applying a ~2mm cryoprobe to the belly of the mylohyoid muscle.Electromyography (EMG) activity (duration, amplitude) was measured concurrently in thyrohyoid, mylohyoid, thyropharyngeal, and diaphragm muscles. Swallow-breathing coordination (SBC) was measured by determining inspiration/expiration phase during the onset and offset of a swallowing event, based off the mylohyoid initiation and thyropharyngeal termination bursts, respectively. Results showed an injury-related effect in the mylohyoid muscle, as indicated by a significant decrease in the mean amplitude vi post-injury compared to pre-injury. During swallowing, the expiratory phase was found to predominate the respiratory cycle in both pre-and post-injury. No significant changes to the swallow-breathing coordination were found following injury. Results demonstrate that mylohyoid muscle injury does not appear to interfere with short-term changes in the respiratory-swallow pattern. Although deficits in muscle function were found immediately following injury, an extended time or more severe injury may be needed to adversely inhibit these behaviors. Thus, disrupting the stable coupling between respirations and swallowing, which has been found clinically, may not be apparent immediately after injury and require long-term changes in function.

show abstract

Organization of pERK-immunoreactive cells in trigeminal spinal nucleus caudalis, upper cervical cord, NTS and Pa5 following capsaicin injection into masticatory and swallowing-related muscles in rats

Cited by 10 publications

References 37 publications

Metabotropic glutamate receptor 5 contributes to inflammatory tongue pain via extracellular signal-regulated kinase signaling in the trigeminal spinal subnucleus caudalis and upper cervical spinal cord

Metabotropic glutamate receptor 5 contributes to inflammatory tongue pain via extracellular signal-regulated kinase signaling in the trigeminal spinal subnucleus caudalis and upper cervical spinal cord

Generalized somatic dysesthesias induced by stimulation of teeth with cold water: An unreported form of brainstem integrative synesthesia

Swallow and breathing coordination following suprahyoid muscle injury.

Contact Info

Product

Resources

About