Effect of chronic intermittent hypoxia on ocular and intraoral mechanical allodynia mediated via the calcitonin gene-related peptide in a rat.

STUDY OBJECTIVES: Obstructive sleep apnea, a significant hypoxic condition, may exacerbate several orofacial pain conditions. The study aims to define the involvement of calcitonin gene-related peptide (CGRP) in peripheral and central sensitization and in evoking orofacial mechanical allodynia under chronic intermittent hypoxia (CIH). METHODS: Male rats were exposed to CIH. Orofacial mechanical allodynia was assessed using the eyeblink test and the two-bottle preference drinking test. The CGRP-immunoreactive neurons in the trigeminal ganglion (TG), CGRP-positive primary afferents projecting to laminae I-II of the trigeminal spinal subnucleus caudalis (Vc), and neural responses in the second-order neurons of the Vc were determined by immunohistochemistry. CGRP receptor antagonist was administrated in the TG. RESULTS: CIH-induced ocular and intraoral mechanical allodynia. CGRP-immunoreactive neurons and activated satellite glial cells (SGCs) were significantly increased in the TG and the number of cFos-immunoreactive cells in laminae I-II of the Vc were significantly higher in CIH rats compared to normoxic rats. Local administration of the CGRP receptor antagonist in the TG of CIH rats attenuated orofacial mechanical allodynia; the number of CGRP-immunoreactive neurons and activated SGCs in the TG, and the density of CGRP-positive primary afferent terminals and the number of cFos-immunoreactive cells in laminae I-II of the Vc were significantly lower compared to vehicle-administrated CIH rats. CONCLUSIONS: An increase in CGRP in the TG induced by CIH, as well as orofacial mechanical allodynia and central sensitization of second-order neurons in the Vc, supported the notion that CGRP plays a critical role in CIH-induced orofacial mechanical allodynia.

Anti-Inflammatory Effects of ß-Cryptoxanthin on 5-Fluorouracil-Induced Cytokine Expression in Human Oral Mucosal Keratinocytes.

Oral mucositis is a typical adverse effect of chemotherapy, causing oral pain that significantly reduces the patient's quality of life. ß-cryptoxanthin (ß-cry) is a carotenoid abundant in citrus fruits with antioxidant and anti-inflammatory effects. However, the ß-cry effect on oral mucositis remains unclear. We investigated the effects of 5-fluorouracil (5-FU) and ß-cry on human normal oral mucosal keratinocytes (hOMK). hOMK was seeded on a culture plate and cultured with 5-FU and ß-cry. The cell number, mRNA expression of inflammatory cytokines and matrix metalloproteinases (MMPs), and production of inflammatory cytokines in hOMK were evaluated. Additionally, the cell count and inflammatory cytokine production were analyzed when hOMK was co-stimulated with Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) in addition to 5-FU. The numbers of hOMK significantly reduced with 5-FU stimulation, whereas it increased with ß-cry treatment. mRNA expression of interleukin (IL)-6, IL-8, metalloproteinase (MMP)-2, and MMP-9 and protein production of IL-6 and IL-8 in hOMK were augmented on 5-FU stimulation. Simultaneously, ß-cry treatment significantly suppressed IL-8 and MMP-9 mRNA expression, and IL-8 production was induced on 5-FU stimulation. Co-stimulation with P. gingivalis LPS and 5-FU enhanced IL-6 and IL-8 production in hOMK. ß-cry could enhance cell proliferation and suppress 5-FU-induced expression of inflammatory cytokines and MMP in hOMK. Thus, ß-cry can alleviate the symptoms of chemotherapy-induced oral mucositis, and its combination with oral care is effective in managing oral mucositis.

A Case of Wide QRS Tachycardia After the Local Administration of Epinephrine to Reduce Bleeding During General Anesthesia.

We report a case of wide QRS tachycardia or ventricular tachycardia with a pulse after the administration of epinephrine under general anesthesia. After induction and achieving a sufficiently deep plane of general anesthesia, gauze soaked in a 1:100,000 epinephrine solution was applied to the patient's nasal mucosa and 1% lidocaine with 1:100,000 epinephrine was administered via intraoral infiltration. Several minutes after the start of surgery, the patient's blood pressure and heart rate suddenly increased and a wide QRS tachycardia was observed on the electrocardiogram, which then reverted to a normal sinus rhythm. According to the past reports, similar arrhythmias have occurred after administration of epinephrine in the head and neck. These findings suggest that anesthesia providers must be aware of the risks associated with epinephrine and local anesthetic use, particularly in the head and neck region.

Enhanced Ocular Surface and Intraoral Nociception via a Transient Receptor Potential Vanilloid 1 Mechanism in a Rat Model of Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA), characterized by low arterial oxygen saturation during sleep, is associated with an increased risk of orofacial pain. In this study, we simulated chronic intermittent hypoxia (CIH) during the sleep/rest phase (light phase) to determine the role of transient receptor potential vanilloid 1 (TRPV1) in mediating enhanced orofacial nocifensive behavior and trigeminal spinal subnucleus caudalis (Vc) neuronal responses to capsaicin (a TRPV1 agonist) stimulation in a rat model of OSA. Rats were subjected to CIH (nadir O2, 5%) during the light phase for 8 or 16 consecutive days. CIH yielded enhanced behavioral responses to capsaicin after application to the ocular surface and intraoral mucosa, which was reversed under normoxic conditions. The percentage of TRPV1-immunoreactive trigeminal ganglion neurons was greater in CIH rats than in normoxic rats and recovered under normoxic conditions after CIH. The ratio of large-sized TRPV1-immunoreactive trigeminal ganglion neurons increased in CIH rats. The density of TRPV1 positive primary afferent terminals in the superficial laminae of Vc was higher in CIH rats. Phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive cells intermingled with the central terminal of TRPV1-positive afferents in the Vc. The number of pERK-immunoreactive cells following low-dose capsaicin (0.33 µM) application to the tongue was significantly greater in the middle portion of the Vc of CIH rats than of normoxic rats and recovered under normoxic conditions after CIH. These data suggest that CIH during the sleep (light) phase is sufficient to transiently enhance pain on the ocular surface and intraoral mucosa via TRPV1-dependent mechanisms.

Crystal structure of N-{N-[N-(tert-but-oxy-carbon-yl)-l-α-aspart-yl]-l-α-aspart-yl}-l-α-aspartic acid 14,24,34-trimethyl ester 31-2-oxo-2-phenyl-ethyl ester {Boc-[Asp(OMe)]3-OPac}.

In the title homotripeptide {Boc-[Asp(OMe)]3-OPac}, C28H37N3O13, all peptide bonds adopt an s-trans conformation with respect to the N-H and C=O groups. In the crystal, N-H⋯O hydrogen bonds result in an infinite parallel ß-sheet structure running along the b-axis direction. The Boc protecting group at the N-terminus of the peptide is disordered over two sites with occupancy factors of 0.504 (5) and 0.496 (5).