Neighbourhood relationships moderate the positive association between family caregiver burden and psychological distress in Japanese adults: a cross-sectional study.

OBJECTIVES: Family caregiver burden is associated with higher psychological distress. However, little is known about the impact of neighbourhood relationships on caregivers' psychological distress. We examined whether neighbourhood relationships of caregivers moderate the association between family caregiver burden and psychological distress. STUDY DESIGN: This was a cross-sectional study. METHODS: We recruited 5321 Japanese adults who participated in the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2013 and 2017. Participants completed self-reported questionnaires to measure psychological distress (Kessler 6: K6), subjective caregiver burden, and neighbourhood relationships. We performed a multivariable linear regression analysis in which caregiver burden was designated as an independent variable and the K6 score as a dependent variable, adjusting for demographics. The interaction term between caregiver burden and neighbourhood relationships was also included in the analysis. RESULTS: Data from a total of 5069 participants were included (mean age [standard deviation]: 63.1 years [10.3 years]; 2226 [43.9%] female). Caregiver burden was significantly and positively associated with psychological distress (compared with no burden, mild burden: ß = 0.24, P = 0.197; severe burden: ß = 0.60, P < 0.01; P for trend < 0.01). There was a significant negative interaction effect of caregiver burden × neighbourhood relationship on psychological distress (severe burden × good neighbourhood relationship: ß = -3.29, P < 0.01). CONCLUSIONS: A higher caregiver burden was associated with higher psychological distress, and neighbourhood relationships moderated this association. Our findings suggest that good neighbourhood relationships can buffer caregiving-associated psychological distress.

A combination of ultrasound-guided rectus sheath and transversus abdominis plane blocks is superior to either block alone for pain control after gynecological transumbilical single incision laparoscopic surgery.

PURPOSE: To investigate the efficacy of the combination of ultrasound-guided rectus sheath (RS) and transversus abdominis plane (TAP) blocks compared with TAP or RS block alone in gynecological single-incision laparoscopic surgery (SILS). MATERIALS AND METHODS: Bilateral TAP blocks (Group A, n = 12), TAP and RS blocks (Group B, n = 12), and RS blocks (Group C, n = 12) with 40 ml ropivacaine/patient were performed for ovarian tumor SILS. The analgesic effects were evaluated using a numerical rating scale (NRS) at zero, six, 12, 24, and 48 hours post-surgery. RESULTS: Umbilical pain on completion of general anesthesia was significantly less frequent in Group B (1/12) than Group A (7/12) (p = 0.03). The postoperative NRS scores were significantly lower in Group B than Group A at zero (p = 0.02) and six (p = 0.03) hours and Group C at zero (p = 0.001), six (p = 0.02), and 12 (p = 0.004) hours. CONCLUSION: The combination of RS and TAP blocks reduced early postoperative pain compared with RS or TAP block alone for gynecological SILS.

Effectiveness of ultrasound-guided transversus abdominis plane block and rectus sheath block in pain control and recovery after gynecological transumbilical single-incision laparoscopic surgery.

PURPOSE: To evaluate the effectiveness of ultrasound-guided transversus abdominis plane (TAP) and rectus sheath (RS) blocks in pain management and recovery after gynecological single-incision laparoscopic surgery (SILS). MATERIALS AND METHODS: Abilateral TAP block (Group A, n = 9), bilateral TAP and RS blocks (Group B, n = 10), and a bilateral RS block (Group C, n = 9) with 40 ml ropivacaine per patient were conducted in 28 patients undergoing SILS for ovarian tumors. A pain score and walking distance in a 6-minute walk test (6MWT) were examined. RESULTS: Pain scores were significantly lower on postoperative day (POD) 3 than on POD 1 in Groups B (p = 0.03) and C (p = 0.02). The walking distance on POD 3 was comparable with that before surgery in Group C (p = 0.75), but shorter in Groups A (p = 0.004) and B (p = 0.02). CONCLUSIONS: The RS block alone was the most effective in relieving pain and accelerating general recovery after gynecological SILS.

A missense mutation in type VII collagen in two affected siblings with recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa is a severe mutilating genodermatosis. Previous ultrastructural demonstrations of altered anchoring fibrils, and recent genetic linkage analyses have suggested that type VII collagen, the major component of anchoring fibrils, is a candidate gene. We have identified a homozygous methionine-to-lysine mutation in two affected siblings, while their unaffected mother and half-brother are heterozygous carriers. The mutation resides in a highly conserved region of the C-terminus of type VII collagen, strongly suggesting that it is the cause of the disease in this family.

An analysis of the survival rate after radiotherapy in lung cancer patients with bone metastasis: is there an optimal subgroup to be treated with high-dose radiation therapy?

We investigated the prognostic factors after radiotherapy for bone metastasis from lung cancer while taking the recent findings in the treatment of such cases into consideration. A total of 132 patients with bone metastases from pathologically confirmed lung cancer were evaluated regarding the following potential prognostic factors: treatment for primary site (surgery vs. other), treatment site (spine vs. other), number of bone metastases (solitary vs. multiple), number of metastatic organs (0 vs. 1 vs. ≥2), neurological symptoms (no symptoms vs. numbness vs. paresis), degree of pain (no pain vs. mild pain vs. severe pain), performance status [PS] (0-1 vs. ≥2), biological effective dose [BED] (≥40 Gy vs. <40Gy), time to distant metastasis (≥1 year vs. <1 year), histology (adenocarcinoma vs. others), and use of epidermal growth factor receptor [EGFR]-targeted agents (Yes vs. No). The univariate analysis demonstrated that all factors except for the treatment site were significant. Surgery as treatment for primary site, solitary bone metastasis, no visceral organ metastasis, no symptoms or numbness, no pain, PS<2, BED≥40 Gy, time to distant metastasis ≥ 1year, adenocarcinoma histology, and use of EGFR-targeted agents were correlated with a favorable prognosis. In a multivariate analysis, solitary bone metastasis, PS<2, BED≥40 Gy, adenocarcinoma histology, and the use of EGFR-targeted agents were significantly correlated with a better survival (p = 0.038, 0.006, 0.003, 0.014, and <0.001, respectively). A contingency table to assess the relationship between each variable and the median survival time of the patients according to the administered BED showed that in patients with the time to distant metastasis ≥ 1year and the use of EGFR-targeted agents, the subgroups treated with BED≥40 Gy had a favorable prognosis. Our study suggests that high-dose radiotherapy is associated with a better prognosis in combination with other favorable prognostic factors.

Molecular composition of the submicrosomal membrane lipid of rat brain.

Rough-surfaced and light and heavy smooth-surfaced microsomes were isolated from rat brain by means of discontinuous sucrose gradient centrifugation. Electron microscopically, the rough-surfaced microsomes were characterized by vesicles with ribosomes and the light and heavy smooth-surfaced microsomes by fairly homogeneous membrane features without ribosomes. The rough-surfaced microsomal membranes were distinguished by the absence of glycolipids, such as ganglioside, cerebroside, and sulfatide. Cerebroside was exclusively recovered in the light smooth-surfaced microsomal membranes. Ganglioside and Na,K-ATPase were contained in larger amounts in the heavy smooth-surfaced microsomal membranes than in the light smooth-surfaced microsomal membranes in terms of protein content. Among the three submicrosomal membranes, cholesterol and phospholipid were found in the largest amounts in the light smooth-surfaced microsomal membranes, where the molar ratio of cerebroside-cholesterol-phospholipid was about 1:10:10. The membranes of rough- and smooth-surfaced microsomes were very similar in regards to the composition of phospholipid classes, although the fatty acid composition of the former contained a greater proportion of unsaturated fatty acids than that of the latter. When the membrane proteins were analyzed by sodium dodecyl sulfate gel electrophoresis, some differences were observed between the light and heavy smooth-surfaced microsomal membranes.

Cytokeratins 8 and 19 in the mouse placental development.

To investigate the expression and biological roles of cytokeratin 19 (K19) in development and in adult tissues, we inactivated the mouse K19 gene (Krt1-19) by inserting a bacterial beta-galactosidase gene (lacZ) by homologous recombination in embryonic stem cells, and established germ line mutant mice. Both heterozygous and homozygous mutant mice were viable, fertile, and appeared normal. By 7.5-8.0 days post coitum (dpc), heterozygous mutant embryos expressed lacZ in the notochordal plate and hindgut diverticulum, reflecting the fact that the notochord and the gut endoderm are derived from the axial mesoderm-originated cells. In the adult mutant, lacZ was expressed mainly in epithelial tissues. To investigate the possible functional cooperation and synergy between K19 and K8, we then constructed compound homozygous mutants, whose embryos died approximately 10 dpc. The lethality resulted from defects in the placenta where both K19 and K8 are normally expressed. As early as 9. 5 dpc, the compound mutant placenta had an excessive number of giant trophoblasts, but lacked proper labyrinthine trophoblast or spongiotrophoblast development, which apparently caused flooding of the maternal blood into the embryonic placenta. These results indicate that K19 and K8 cooperate in ensuring the normal development of placental tissues.

An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3.

Cell polarity is fundamental to differentiation and function of most cells. Studies in mammalian epithelial cells have revealed that the establishment and maintenance of cell polarity depends upon cell adhesion, signaling networks, the cytoskeleton, and protein transport. Atypical protein kinase C (PKC) isotypes PKCzeta and PKClambda have been implicated in signaling through lipid metabolites including phosphatidylinositol 3-phosphates, but their physiological role remains elusive. In the present study we report the identification of a protein, ASIP (atypical PKC isotype-specific interacting protein), that binds to aPKCs, and show that it colocalizes with PKClambda to the cell junctional complex in cultured epithelial MDCKII cells and rat intestinal epithelia. In addition, immunoelectron microscopy revealed that ASIP localizes to tight junctions in intestinal epithelial cells. Furthermore, ASIP shows significant sequence similarity to Caenorhabditis elegans PAR-3. PAR-3 protein is localized to the anterior periphery of the one-cell embryo, and is required for the establishment of cell polarity in early embryos. ASIP and PAR-3 share three PDZ domains, and can both bind to aPKCs. Taken together, our results suggest a role for a protein complex containing ASIP and aPKC in the establishment and/or maintenance of epithelial cell polarity. The evolutionary conservation of the protein complex and its asymmetric distribution in polarized cells from worm embryo to mammalian-differentiated cells may mean that the complex functions generally in the organization of cellular asymmetry.

Axonal projections of single auditory neurons in the thalamic reticular nucleus: implications for tonotopy-related gating function and cross-modal modulation.

Tonotopically comparable subfields of the primary auditory area (AI) and nonprimary auditory areas (non-AI), i.e. posterodorsal area (PD) and ventral auditory area (VA), in the rat cortex have similar topographies in the projection to the ventral division of the medial geniculate nucleus (MGV), but reverse topographies in the projection to the thalamic reticular nucleus (TRN). In this study, we examined axonal projections of single auditory TRN cells, using juxtacellular recording and labeling techniques, to determine features of TRN projections and estimate how the TRN mediates corticofugal inhibition along with the reverse topographies of cortical projections to the TRN. Auditory TRN cells sent topographic projections to limited parts of the MGV in a manner that relays cortical inputs from tonotopically comparable subfields of the AI and non-AI (PD and VA) to different parts of the MGV. The results suggest that corticofugal excitations from the AI and non-AI modulate thalamic cell activity in the same part of the MGV, whereas corticofugal inhibitions via the TRN modulate cell activity in different parts of the MGV with regard to tonotopic organization. The AI and non-AI could serve distinctive gating functions for auditory attention through the differential topography of inhibitory modulation. In addition, we obtained an intriguing finding that a subset of auditory TRN cells projected to the somatosensory but not to the auditory thalamic nuclei. There was also a cell projecting to the MGV and somatosensory nuclei. These findings extend the previously suggested possibility that TRN has a cross-modal as well as an intramodal gating function in the thalamus.

The human 230-kD bullous pemphigoid antigen gene (BPAG1). Exon-intron organization and identification of regulatory tissue specific elements in the promoter region.

The 230-kD bullous pemphigoid antigen (BPAG1), a hemidesmosomal protein, is encoded by a gene at the human chromosomal locus 6p11-12. We have elucidated the exon-intron organization of the entire human BPAG1 gene, including approximately 2.6 kb of 5'-flanking DNA. Seven overlapping genomic clones, spanning approximately 20 kb, contained the entire approximately 9 kb coding sequence of BPAG1 and consisted of 22 separate exons, which varied from 78 to 2,810 bp in size. The 5' flanking region of DNA, upstream from the ATG initiation codon for translation, was found to contain several putative transcriptional response elements. Most interestingly, two motifs potentially conferring keratinocyte specific expression to the gene were detected. The presence of such elements was suggested by approximately 20-fold higher expression of a promoter/chloramphenicol acetyl transferase (CAT) construct in normal human epidermal keratinocytes that express the endogenous gene, as compared to several non-expressing cell types. Transient transfections with 5'-deletion clones of the promoter/reporter gene (CAT) constructs identified a region containing a putative tissue specific element, KRE2, which also conferred tissue specificity to the expression of the truncated promoter downstream from this element, however, a mutated derivative of KRE2 was not functional. Detailed knowledge of the structure and regulation of the BPAG1 gene will aid in further elucidation of diseases affecting the cutaneous basement membrane zone.

Activation of central 5HT2A receptors reduces the craniofacial nociception of rats.

We assessed the contribution of central 5HT2A receptors to the craniofacial tissue nociception in naïve male rats. First, we tested whether activation of central 5HT2A receptors affected nociceptive neural activities recorded from superficial laminae of the trigeminal subnucleus caudalis (Vc)/upper cervical spinal cord junction (Vc/C2) region. Two types of units, such as deep-nociceptive or skin-wide dynamic range (WDR) units were identified from extracellular recordings. Topical administration of 5HT2A receptor agonist, (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) onto the Vc/C2 region significantly reduced deep-nociceptive unit discharges evoked by formalin injection into the masseter muscle. Noxious pinch stimulation to the facial skin-evoked skin-WDR unit discharges was significantly reduced by topical administration of 0.1 mg/rat DOI onto the Vc/C2 region. Second, we tested whether i.c.v. administration of DOI affected Fos-like immunoreactivity (-LI) evoked by formalin injection into the masseter muscle. Fos-LI was significantly induced mainly at the ventrolateral (vl) area of trigeminal subnucleus interpolaris (Vi)/Vc junction (vl-Vi/Vc) region and Vc/C2 region in vehicle-treated rats. Formalin-evoked Fos-LI was significantly reduced in laminae I-II of the Vc/C2, but not vl-Vi/Vc region after i.c.v. administration of DOI. Finally, orofacial nocifensive behavioral activities evoked by formalin injection into the masseter muscle were significantly reduced by intracisternal administration of DOI. These results suggest that 5HT2A receptors in the Vc/C2 region mediate antinociceptive effects in the craniofacial nociception.

Transcriptional and post-transcriptional control of PHO8 expression by PHO regulatory genes in Saccharomyces cerevisiae.

A DNA fragment bearing the PHO8 gene, which encodes repressible alkaline phosphatase of Saccharomyces cerevisiae, was cloned. Northern hybridizations with the PHO8 DNA as probe indicated that the PHO8 transcript is 1.8 kilobases in length and is more abundant in cells grown in low-phosphate medium than in high-phosphate medium. The pho9 mutant, whose phenotype is defective in the activity of repressible alkaline phosphatase, produced as much of the PHO8 transcript as did the PHO9+ cells. Hence, the PHO9 product should act at the post-transcriptional level. The pho4 mutant could not derepress the PHO8 transcript, whereas the pho80 mutant could, irrespective of the amount of Pi in the medium, as has been suggested by genetic study.

"Ventral" area in the rat auditory cortex: a major auditory field connected with the dorsal division of the medial geniculate body.

The rat auditory cortex is made up of multiple auditory fields. A precise correlation between anatomical and physiological areal extents of auditory fields, however, is not yet fully established, mainly because non-primary auditory fields remain undetermined. In the present study, based on thalamocortical connection, electrical stimulation and auditory response, we delineated a non-primary auditory field in the cortical region ventral to the primary auditory area and anterior auditory field. We designated it as "ventral" area after its relative location. At first, based on anterograde labeling of thalamocortical projection with biocytin, ventral auditory area was delineated as a main cortical terminal field of thalamic afferents that arise from the dorsal division of the medial geniculate body. Cortical terminal field (ventral auditory area) extended into the ventral margin of temporal cortex area 1 (Te1) and the dorsal part of temporal cortex area 3, ventral (Te3V), from 3.2-4.6 mm posterior to bregma. Electrical stimulation of the dorsal division of the medial geniculate body; evoked epicortical field potentials confined to the comparable cortical region. On the basis of epicortical field potentials evoked by pure tones, best frequencies were further estimated at and around the cortical region where electrical stimulation of the dorsal division of the medial geniculate body evoked field potentials. Ventral auditory area was found to represent frequencies primarily below 15 kHz, which contrasts with our previous finding that the posterodorsal area, the other major recipient of the dorsal division of the medial geniculate body; projection, represents primarily high frequencies (>15 kHz). The posterodorsal area is thought to play a pivotal role in auditory spatial processing [Kimura A, Donishi T, Okamoto K, Tamai Y (2004) Efferent connections of "posterodorsal" auditory area in the rat cortex: implications for auditory spatial processing. Neuroscience 128:399-419]. The ventral auditory area, as the other main cortical region that would relay auditory input from the dorsal division of the medial geniculate body to higher cortical information processing, could serve an important extralemniscal function in tandem with the posterodorsal area. The results provide insight into structural and functional organization of the rat auditory cortex.

Contribution of peripheral 5-HT2A or 5-HT3 receptors to Fos expression in the trigeminal spinal nucleus produced by acute injury to the masseter muscle during persistent temporomandibular joint inflammation in rats.

We investigated the contribution of peripheral 5-HT2A or 5-HT3 receptors to Fos expression in the trigeminal spinal nucleus (VSP) following acute masseter muscle injury in male rats with or without temporomandibular joint (TMJ) inflammation persisting for 7 days. TMJ inflammation was evoked by an injection of complete Freund's adjuvant (CFA). Two hours after formalin injection into the masseter muscle produced Fos-like immunoreactivity (Fos-LI) in several regions of the VSP and upper cervical spinal cord (C2), such as ventrolateral (vl) area of the trigeminal subnucleus caudalis (Vc)/subnucleus interpolaris (Vi) transition (vl-Vi/Vc), paratrigeminal nucleus (dPa5), middle portion of the Vc (mid-Vc) and Vc/C2 transition (Vc/C2) regions in both groups. Significant increases in the number of Fos-LI were observed in these areas in CFA group compared with non-CFA group. TMJ inflammation alone did not induce a significant level of Fos-LI in the VSP. In order to assess the effect of antagonizing 5-HT2A or 5-HT3 receptors on formalin-induced Fos-LI, rats were pre-treated with local (masseter muscle) administration of ketanserin or tropisetron (0.01, 0.1 mg/rat) 20 min prior to formalin injection. In CFA group, these antagonists given locally reduced the Fos-LI response in the laminae I-II at the mid-Vc and Vc/C2 regions. These antagonists reduced the Fos-LI response in the dPa5, but not in the vl-Vi/Vc region. The Fos-LI response was not affected by i.v. administration of ketanserin (0.01, 0.1 mg/rat) or tropisetron (0.01 mg/rat). In non-CFA group, these antagonists given locally did not reduce the Fos-LI response. These results suggest that peripheral 5-HT2A and 5-HT3 receptors contribute to nociceptive processing in the masseter muscle in TMJ inflammatory conditions.

Colonic hamartoma development by anomalous duplication in Cdx2 knockout mice.

To determine the biological role of caudal-like homeobox gene CDX2, we constructed knockout mice in which its mouse homologue Cdx2 was inactivated by homologous recombination, placing a bacterial lacZ gene under the control of the Cdx2 promoter. Although the homozygous mutants died in utero around implantation, the heterozygotes were viable and fertile and expressed lacZ in the caudal region in early embryos and in the gut tissues in adults. The heterozygotes developed cecal and colonic villi by anteriorization and formed hamartomatous polyps in the proximal colon. The hamartoma started to develop at 11.5 days of gestation as an outpocket of the gut epithelium, which ceased to express the remaining Cdx2 allele. The outpocket then expanded as a partially duplicated gut but was contained as a hamartoma after birth. In adult mice, these hamartomas grew very slowly and took a benign course. None of them progressed into invasive adenocarcinomas, even at 1.5 years of age. Whereas the cecal and colonic villi expressed lacZ, the hamartoma epithelium did not, nor did it express Cdx2 mRNA from the wild-type allele. However, genomic DNA analysis of the polyp epithelium did not show a loss of heterozygosity of the Cdx2 gene, suggesting a mechanism of biallelic Cdx2 inactivation other than loss of heterozygosity. These results indicate that the Cdx2 haploin-sufficiency caused cecal and colonic villi, whereas the biallelic inactivation of Cdx2 triggered anomalous duplications of the embryonic gut epithelium, which were contained as hamartomas after birth.

Study of amphibian lipids. I. Characterization of monoglycosylceramides from the skin of Rana nigromaculata (Japanese pond frog).

1. Monoglycosylceramide was isolated from the skin of Rana nigromaculata (Japanese pond frog), and further fractionated into three subgroups (Fraction I, Fraction II and Fraction III) by borate-impregnated Florisil column chromatography. 2. Fraction I and Fraction II contained mainly glucose as their hexose components, while Fraction III contained galactose. 3. Major long chain bases of Fraction I and Fraction III were D-erythro-1, 3-dihydroxy-2-amino-4-trans-octadecene (4-sphingenine) and D-erythro-1, 3-dihydroxy-2-aminooctadecane (sphinganine), whereas those of Fraction II were D-ribo-1, 3, 4-trihydroxy-2-aminooctadecane (4D-hydroxysphinganine) and 1, 3, 4-trihydroxy-2-aminoeicosane (C20 homologues of 4D-hydroxysphinganine). This is the first evidence of the presence of trihydroxy base-containing glycolipids in the skin of vertebrates. 4. All three subgroups of monoglycosylceramide contained both hydroxy and nonhydroxy fatty acids ranging from C14 and C26. Saturated fatty acids represented more than 90% of the total. Some differences of the fatty acid composition in the three subgroups were also observed.

Effect of immunoglobulin G on membrane-bound enzyme activity of sarcoma 180 cells.

Changes in the activity of membrane bound ATPase of Sarcoma 180 cells caused by immunoglobulin G (IgG) of anti-Sarcoma 180 was investigated in relation to the incorporation of amino acid by the cells. Enzymatic activity of ATPase was increased up to 160% of the original activity upon incubation of the cell with IgG. Kinetic studies showed that IgG did not change the affinity of this enzyme for the substrate, but exerted influence upon catalytic efficiency of the enzyme. The rate of incorporation of leucine into Sarcoma 180 cells was also affected by IgG, as observed in the effect of IgG on the enzymatic reaction of the cells.

Biochemical characterization of the submicrosomal membrane of the rat brain. Selective solubilization of the components of the light smooth-surfaced membrane by lysophosphatidylcholine.

The light smooth-surfaced membrane, one of the three membrane fractions derived from the rat brain microsomal fraction, was fractionated into its soluble and insoluble parts by the use of lysophosphatidylcholine and the chemical composition of these was investigated. Under the condition whereby the maximal amount of the membrane protein was solubilized by lysophosphatidylcholine (0.5% lysophosphatidylcholine at 37 degrees C for 10 min), the insoluble residue, which accounted for approximately 30% of the membrane protein, was ultracentrifugally homogeneous and showed a granular structure under the electron microscope. The lipid composition of the soluble and insoluble fractions, as well as their protein composition, revealed a preferential and limited solubilization of the constituents of the membrane by lysophosphatidylcholine.

Topography of projections from the primary and non-primary auditory cortical areas to the medial geniculate body and thalamic reticular nucleus in the rat.

The functional significance of parallel and redundant information processing by multiple cortical auditory fields remains elusive. A possible function is that they may exert distinct corticofugal modulations on thalamic information processing through their parallel connections with the medial geniculate body and thalamic reticular nucleus. To reveal the anatomical framework for this function, we examined corticothalamic projections of tonotopically comparable subfields in the primary and non-primary areas in the rat auditory cortex. Biocytin was injected in and around cortical area Te1 after determining best frequency at the injection site on the basis of epicortical field potentials evoked by pure tones. The rostral part of area Te1 (primary auditory area) and area temporal cortex, area 2, dorsal (Te2D) (posterodorsal auditory area) dorsal to the caudal end of area Te1, which both exhibited high best frequencies, projected to the ventral zone of the ventral division of the medial geniculate body. The caudal end of area Te1 (auditory area) and the rostroventral part of area Te1 (a part of anterior auditory field), which both exhibited low best frequencies, projected to the dorsal zone of the ventral division of the medial geniculate body. In contrast to the similar topography in the projections to the ventral division of the medial geniculate body, collateral projections to the thalamic reticular nucleus terminated in the opposite dorsal and ventral zones of the lateral and middle tiers of the nucleus in each pair of the tonotopically comparable cortical subfields. In addition, the projections of the non-primary cortical subfields further arborized in the medial tier of the thalamic reticular nucleus. The results suggest that tonotopically comparable primary and non-primary subfields in the auditory cortex provide corticofugal excitatory effects to the same part of the ventral division of the medial geniculate body. On the other hand, corticofugal inhibition via the thalamic reticular nucleus may operate in different parts of the ventral division of the medial geniculate body or different thalamic nuclei. The primary and non-primary cortical auditory areas are presumed to subserve distinct gating functions for auditory attention.

The role of peripheral 5HT2A and 5HT1A receptors on the orofacial formalin test in rats with persistent temporomandibular joint inflammation.

The role of peripheral serotonin (5HT) 2A and 5HT1A receptors on the orofacial nocifensive behavioral activities evoked by the injection of formalin into the masseter muscle was evaluated in the rats with persistent temporomandibular joint (TMJ) inflammation evoked by Complete Freund's Adjuvant (CFA). The orofacial nocifensive behavioral activities evoked by the injection of formalin into masseter muscle were significantly enhanced at 1 day (CFA day 1 group) or 7 days (CFA day 7 group) during TMJ inflammation. Pretreatment with local administration of 5HT2A receptor antagonist, ketanserin (0.01, 0.1 mg/rat) into the masseter muscle or systemic administration of ketanserin via i.p. injection (1 mg/kg) reduced the orofacial nocifensive behavioral activities of the late phase evoked by formalin injection into masseter muscle on the side of TMJ inflammation (CFA day 7 group). However, local (0.001-0.1 mg/rat) or systemic (1 mg/kg) administration of 5HT1A receptor antagonist, propranolol, into masseter muscle did not produce the antinociceptive effect in CFA day 7 group. Moreover, local administration of ketanserin (0.1 mg) or propranolol (0.1 mg) into masseter muscle did not inhibit nocifensive orofacial behavior in rats without TMJ inflammation. These data suggest that persistent TMJ inflammation causes the elevation of the orofacial nocifensive behavior, and peripheral 5HT2A receptors play an important role in mediating the deep craniofacial tissue nociception in rats with TMJ inflammation.