We investigated the role of the central MAPK pathways in extra-territorial (referred) pain resulting from inflammation of the temporomandibular joint (TMJ). Experiments were carried out on male Sprague-Dawley rats weighing 220-280 g. Under anesthesia, these animals were injected with 50 microL of complete Freund's adjuvant (CFA) into the TMJ using a Hamilton syringe. In the control group, saline was injected into the TMJ. To identify the extent of inflammation of the TMJ, Evans blue dye (0.1%, 5 mg/kg) was injected intravenously at 1, 3, 6, 9, 12 and 15 days after CFA injection. The concentration of Evans blue dye in the extracted TMJ tissue was found to be significantly higher in the CFA-treated animals than in the saline-treated group. Air-puff thresholds in the vibrissa pad area were evaluated 3 days before and at 3, 6, 9, 12, 15 and 18 days after CFA injection into the TMJ. Referred mechanical allodynia was established at 3 days, remained until 12 days, and recovered to preoperative levels at 18 days after CFA injection. This referred mechanical allodynia was observed in contralateral side area. To investigate the role of central MAPK pathways, MAPK inhibitors (10 microg) were administrated intracisternally 9 days after CFA injection. SB203580, a p38 MAPK inhibitor, significantly attenuated referred mechanical allodynia, as compared with the vehicle group. PD98059, a MEK inhibitor, also reduced CFA-induced referred mechanical allodynia. These results suggest that TMJ inflammation produces extra-territorial mechanical allodynia, and that this is mediated by central MAPK pathways.
Anesthesia ; Animals ; Evans Blue ; Flavonoids ; Freund's Adjuvant ; Humans ; Hyperalgesia ; Imidazoles ; Inflammation ; Male ; p38 Mitogen-Activated Protein Kinases ; Pain, Referred ; Pyridines ; Rats ; Rats, Sprague-Dawley ; Syringes ; Temporomandibular Joint

The present study investigated the role of ERK in the onset of mechanical and cold allodynia in a rat model of compression of the trigeminal ganglion by examining changes in the air-puff thresholds and number of scratches following the intracisternal injection of PD98059, a MEK inhibitor. Male Sprague Dawley rats weighing between 250 and 260 g were used. Under anesthesia, the rats were mounted onto a stereotaxic frame and received 4% agar (10 microl) solution to compress the trigeminal ganglion. In the control group, the animals were given a sham operation without the application of agar. Changes in behavior were examined at 3 days before and at 3, 7, 10, 14, 17, 21, 24, 30, and 40 days after surgery. Compression of the trigeminal ganglion significantly decreased the air-puff thresholds. Mechanical allodynia was established within 3 days and persisted over postoperative day 24. To evaluate cold allodynia, nociceptive scratching behavior was monitored after acetone application on the vibrissa pad of the rats. Compression of the trigeminal ganglion was found to produce significant cold allodynia, which persisted for more than 40 days after surgery. On postoperative day 14, the intracisternal administration of 1 microg or 10 microg of PD98059 in the rat model significantly decreased the air-puff thresholds on both the ipsilateral and contralateral side. The intracisternal administration of 10 microg of PD98059 also significantly alleviated the cold allodynia, compared with the vehicle-treated group. These results suggest that central ERK plays an important role in the development of mechanical and cold allodynia in rats with compression of the trigeminal ganglion and that a targeted blockade of this pathway is a potential future treatment strategy for trigeminal neuralgia-like nociception.
Acetone ; Agar ; Anesthesia ; Animals ; Cold Temperature ; Flavonoids ; Humans ; Hyperalgesia ; Male ; Nociception ; Rats ; Rats, Sprague-Dawley ; Salicylamides ; Trigeminal Ganglion ; Trigeminal Neuralgia

Voltage dependent calcium channel (VDCC), one of the most important regulator of Ca2+ concentration in neuron, play an essential role in the central processing of nociceptive information. The present study investigated the antinociceptive effects of L, T or N type VDCC blockers on the formalin-induced orofacial inflammatory pain. Experiments were carried out on adult male Sprague-Dawley rats weighing 220-280 g. Anesthetized rats were individually fixed on a stereotaxic frame and a polyethylene (PE) tube was implanted for intracisternal injection. After 72 hours, 5% formalin (50 microL) was applied subcutaneously to the vibrissa pad and nociceptive scratching behavior was recorded for nine successive 5 min intervals. VDCC blockers were administered intracisternally 20 minutes prior to subcutaneous injection of formalin into the orofacial area. The intracisternal administration of 350 or 700 microg of verapamil, a blocker of L type VDCC, significantly decreased the number of scratches and duration in the behavioral responses produced by formalin injection. Intracisternal administration of 75 or 150 microg of mibefradil, a T type VDCC blocker, or 11 or 22 microg of cilnidipine, a N type VDCC blocker, also produced significant suppression of the number of scratches and duration of scratching in the first and second phase. Neither intracisternal administration of all VDCC blockers nor vehicle did not affect in motor dysfunction. The present results suggest that central VDCCs play an important role in orofacial nociceptive transmission and a targeted inhibition of the VDCCs is a potentially important treatment approach for inflammatory pain originating in the orofacial area.
Adult ; Animals ; Calcium ; Calcium Channel Blockers ; Calcium Channels ; Calcium Channels, L-Type ; Calcium Channels, N-Type ; Calcium Channels, T-Type ; Dihydropyridines ; Facial Pain ; Formaldehyde ; Humans ; Injections, Subcutaneous ; Male ; Mibefradil ; Neurons ; Pain Measurement ; Polyethylene ; Rats ; Rats, Sprague-Dawley ; Verapamil

OBJECTIVES: This study aimed to investigate the efficacy and safety of Metadate CD (MCD) when given to Korean children and adolescents with attention-deficit hyperactivity disorder (ADHD). We also explored the effects of the drug on diverse neurocognitive functions. METHODS: Ninety-one subjects with ADHD (mean age 8.6+/-2.2 years) were recruited at 6 outpatient clinics in Seoul, Korea. We used the ADHD Rating Scale (ARS), Clinical Global Impression (CGI), and comprehensive attention test (CAT) to measure the drug's effects. RESULTS: After 0.92+/-0.32mg/kg/day of MCD were administered for 57.4+/-7.6 days, there was a 48.5% reduction in the mean total ARS scores (p<.001). Fifty-seven subjects (64.8%) showed either much improved or very much improved outcomes on the CGI-Improvement scale. The CGI-Severity scale also decreased from an average of 4.7 to an average of 2.9 (p<.001). Errors and response time standard deviations of the CAT, sustained attention test-to-response tasks, the flanker test, and divided attention test scores decreased after treatment (p<.05). The forward memory span of the spatial working memory test scores increased (p<.05). Thirty-five patients (39.8%) experienced side effects, of which the most common were headache (14.8%), nausea (12.5%), and anorexia (9.1%). CONCLUSION: This open-label study suggests that MCD is effective and safe in improving the symptoms and neurocognitive functions of Korean children and adolescents with ADHD.
Adolescent ; Ambulatory Care Facilities ; Animals ; Anorexia ; Cats ; Child ; Corneal Dystrophies, Hereditary ; Headache ; Humans ; Korea ; Memory ; Memory, Short-Term ; Methylphenidate ; Nausea ; Reaction Time

OBJECTIVES: This study aimed to investigate the efficacy and safety of Metadate CD (MCD) when given to Korean children and adolescents with attention-deficit hyperactivity disorder (ADHD). We also explored the effects of the drug on diverse neurocognitive functions. METHODS: Ninety-one subjects with ADHD (mean age 8.6+/-2.2 years) were recruited at 6 outpatient clinics in Seoul, Korea. We used the ADHD Rating Scale (ARS), Clinical Global Impression (CGI), and comprehensive attention test (CAT) to measure the drug's effects. RESULTS: After 0.92+/-0.32mg/kg/day of MCD were administered for 57.4+/-7.6 days, there was a 48.5% reduction in the mean total ARS scores (p<.001). Fifty-seven subjects (64.8%) showed either much improved or very much improved outcomes on the CGI-Improvement scale. The CGI-Severity scale also decreased from an average of 4.7 to an average of 2.9 (p<.001). Errors and response time standard deviations of the CAT, sustained attention test-to-response tasks, the flanker test, and divided attention test scores decreased after treatment (p<.05). The forward memory span of the spatial working memory test scores increased (p<.05). Thirty-five patients (39.8%) experienced side effects, of which the most common were headache (14.8%), nausea (12.5%), and anorexia (9.1%). CONCLUSION: This open-label study suggests that MCD is effective and safe in improving the symptoms and neurocognitive functions of Korean children and adolescents with ADHD.
Adolescent ; Ambulatory Care Facilities ; Animals ; Anorexia ; Cats ; Child ; Corneal Dystrophies, Hereditary ; Headache ; Humans ; Korea ; Memory ; Memory, Short-Term ; Methylphenidate ; Nausea ; Reaction Time

Previous clinical studies have demonstrated that gabapentin, a drug that binds to the voltage-gated calcium channel alpha2delta1 subunit proteins, is effective in the management of neuropathic pain, but there is limited evidence that addresses the participation of glial cells in the anti-allodynic effects of this drug. The present study investigated the participation of glial cells in the anti-nociceptive effects of gabapentin in rats with trigeminal neuropathic pain produced by mal-positioned dental implants. Under anesthesia, the left mandibular second molar was extracted and replaced by a miniature dental implant to induce injury to the inferior alveolar nerve. Mal-positioned dental implants significantly decreased the air-puff thresholds both ipsilateral and contralateral to the injury site. Gabapentin was administered intracisternally beginning on postoperative day (POD) 1 or on POD 7 for three days. Early or late treatment with 0.3, 3, or 30 microg of gabapentin produced significant anti-allodynic effect in the rats with mal-positioned dental implants. On POD 9, in the mal-positioned dental implants group, OX-42, a microglia marker, and GFAP, an astrocyte marker, were found to be up-regulated in the medullary dorsal horn, compared with the naive group. However, the intracisternal administration of gabapentin (30 microg) failed to reduce the number of activated microglia or astrocytes in the medullary dorsal horn. These findings suggest that gabapentin produces significant anti-nociceptive effects, which are not mediated by the inhibition of glial cell function in the medullary dorsal horn, in a rat model of trigeminal neuropathic pain.
Amines ; Anesthesia ; Animals ; Astrocytes ; Calcium Channels ; Cyclohexanecarboxylic Acids ; Dental Implants ; gamma-Aminobutyric Acid ; Horns ; Mandibular Nerve ; Microglia ; Molar ; Neuralgia ; Neuroglia ; Proteins ; Rats

Practice parameters for non-pharmacological treatment of children and adolescents with pervasive developmental disorders are based on the scientific literature for evidence-based practices. Appropriate educational and behavioral interventions are important in improving the long-term outcome in pervasive developmental disorders. Early and sustained intervention appears to be particularly important. The goal for interventions is to gain pragmatic skills for verbal communication, playing with peers, daily living routines, self-management, and social adaptation. Appropriate involvement and collaboration with parents and family are essential for well-functioning intervention programs. The life-long nature of autism implies that the clinician should maintain an active role in long-term treatment planning and family support. Vocational training and training for more independent living are important for adolescents with autism. Professionals should be knowledgeable about local and national resources and opportunities for family support as well as support of the individual.
Adolescent ; Autistic Disorder ; Child ; Cooperative Behavior ; Humans ; Independent Living ; Parents ; Self Care

The objective of this review is to establish practice parameters for pharmacological treatment of children and adolescents with pervasive developmental disorders. We performed a detailed review of the literature, including a wide range of controlled clinical trials, open trials, case reports, and side-effect profiles of related drugs. Few medications have a treatment indication for pervasive developmental disorders, and few studies with well-controlled methodology are available for evaluating treatment results. Pharmacological treatments focus on associated target symptoms because symptom reduction may improve educational and social ability and enhance quality of life. Well-controlled trials have been conducted for some SSRI(selective serotonin reuptake inhibitor) antidepressants, risperidone, and methylphenidate, and showed reduction of some target symptoms. Since the medications are not specific to autism and do not treat core symptoms of the disorder, their potential side effects should be carefully considered. Family education is necessary to give proper information on target symptoms, limitation of drug treatments, and risks.
Adolescent ; Antidepressive Agents ; Autistic Disorder ; Child ; Education ; Humans ; Methylphenidate ; Quality of Life ; Risperidone ; Serotonin

The new research data and rapid development of psychotropic drugs over the past few years have warranted the development of clinical practice guidelines for managing pervasive developmental disorder(PDD). These guidelines are urgently needed due to the recent changes in social circumstances and clinical situations in Korea. Despite the many limitations and problems surrounding the development of these guidelines, the Korean Academy of Child and Adolescent Psychiatry(KACAP) has decided to develop the Korean Practice Parameters for the Treatment of PDD. The goal, basic principles, organization, and implications of this development project are introduced in this special paper. We expect these practice parameters to be a useful reference not only for child psychiatrists and other healthcare professionals in clinical practice, but also for the autistic patients themselves and their caregivers. The practice parameters shall be revised and improved in the near future.
Adolescent ; Caregivers ; Child ; Delivery of Health Care ; Humans ; Korea ; Psychiatry ; Psychotropic Drugs

OBJECTIVES: To investigate the role of TGF (Transforming growth factor-beta) involved in the paracrinic communication during decidualization between UEC (uterine epithelial cells) and USC (uterine stromal cells), we have employed a co-culture system composed of human endometrial epithelial and stromal cells in defined hormonal conditions. DESiGN: in the co-culture, endometrial epithelial cells cultured in the matrigel-coated cell culture insert are seeded on top of the endometrial stromal cells cultured within a collagen gel. The co-culture was maintained for 48 hours under the following hormonal conditions: progesterone dominant condition (100 nM P4 and 1 nM E2) or estrogen-dominant condition (100 nM E2 and 1 nM P4). 10 ng/ ml HGF and/or 10 ng/ml TGF-beta1 are added. METHODS: RT-PCR is utilized to detect mRNAs quantitatively. Enzyme-linked immunosorbent assay (ELiSA) and immunohistochemical staining are utilized to detect proteins in the tissue. RESULTS: Prolactin mRNA is expressed in the co-cultured stromal cells under the progesterone dominant condition. TGF-beta1 and its receptors are expressed in both the co-cultured epithelial and stromal cells irrespective of the steroid present, which is in contrast with no or negligible expression of TGF-beta1 or its receptor in cells separately cultured. Both estrogen and progesterone significantly elevate the concentration of hepatocyte growth factor (HGF) in the conditioned medium of the co-culture with the value of 4,325 pg/ml in E2-dominant and 2,000 pg/ml in P4-dominant condition compare to 150 pg/ ml in no hormone. in separately cultured stromal cells, administration of HGF induces the expression of TGF receptor 1 in both hormonal conditions, but induction of TGF receptor 2 is only manifest in the P4-dominant condition. Administration of TGF-beta and HGF directly induce the decidualization marker prolactin mRNA in separately cultured stromal cells. CONCLUSION: it is likely that steroid hormones induces prolactin mRNA indirectly by promoting the cell to cell communication between the stromal and the epithelial cells. TGF-beta and HGF are two possible paracrine mediators in the human endometrial decidualization.
Cell Communication ; Cell Culture Techniques ; Coculture Techniques ; Collagen ; Culture Media, Conditioned ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; Estrogens ; Hepatocyte Growth Factor ; Humans* ; Progesterone ; Prolactin ; RNA, Messenger ; Stromal Cells ; Transforming Growth Factor beta ; Transforming Growth Factor beta1