Background NIBP/TRAPPC9 is expressed in brain neurons, and human NIBP mutations are associated with neurodevelopmental disorders. The cellular distribution and function of NIBP in the enteric nervous system (ENS) remain unknown. Methods Western blot and RT-PCR analysis were used respectively to identify the protein and mRNA expression of NIBP and other neuronal markers. Multilabeled immunofluorescent microscopy and confocal image analysis were used to examine the cellular distribution of NIBP-like immunoreactivity (IR) in whole mount intestine. Enteric neuronal cell line (ENC) was infected with lentivirus carrying NIBP or its shRNA expression vectors and treated with vehicle or TNFα. Key Results NIBP is expressed at both mRNA and protein levels in different regions and layers of the mouse intestine. NIBP-like-IR was co-localized with various neuronal markers, but not with glial, smooth muscular, or ICC markers. A small population of NIBP-expressing cells and fibers in extra-ganglionic and intra-ganglionic area were negative for pan-neuronal markers HuD or Peripherin. Relatively high NIBP-like-IR was found in 35-44% of myenteric neurons and 9-10% of submucosal neurons. Approximately 98%, 87% and 43% of these relatively high NIBP-expressing neurons were positive for ChAT, nNOS and Calretinin, respectively. NIBP shRNA knockdown in ENC inhibited TNFα-induced NFkB activation and neuronal differentiation, whereas NIBP overexpression promoted it. Conclusions & Inferences NIBP is extensively expressed in the ENS with relatively high level in a subpopulation of enteric neurons. Various NIBP expression levels in different neurons may represent dynamic trafficking or posttranslational modification of NIBP in some functionally-active neurons and ultimately regulate ENS plasticity.

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Unsuccessful anesthesia of the inferior alveolar nerve (IAN) may be due to supplementary innervations of mandibular molars from other branches, namely the cervical plexus (CP). The purpose of this prospective, randomized, double-blind, controlled trial was to determine the effectiveness of an intraoral cervical plexus anesthetic technique (ICPAT) in mandibular molars with symptomatic irreversible pulpitis (SIR) when the IAN and lingual nerve (LN) blocks failed, and to provide a description of the technique. Forty patients diagnosed with SIR received IAN and LN block anesthesia prior to treatment. After clinical signs of anesthesia, patients were subjected to an electrical pulp test (EPT) at 2-min cycles for 10 min post-injection. The anesthesia was considered unsuccessful if there was a positive EPT response ten minutes following profound lip numbness. The experimental group (n = 20) were administered 2% Lidocaine with 1:100,000 epinephrine using the ICPAT. The control group (n = 20) were administered 0.9% sterile saline using the ICPAT. Success was defined as no response on two consecutive readings from an EPT. In the experimental group, 60% of subjects showed successful anesthesia, whereas none of the subjects in the control group had successful anesthesia. A multiple logistic regression analysis showed that the anesthesia success rate using the ICPAT method was significantly higher (P < 0.05) than in the control group, irrespective of molar tooth type. The ICPAT method may be useful as a supplementary anesthetic technique for mandibular molars with SIR in subjects whom the IAN and LN blocks do not provide adequate anesthesia.

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