The antinociceptive mechanisms of melatonin: role of L-arginine/nitric oxide/cyclic GMP/KATP channel signaling pathway.

Pain is one of the most common medical challenges, reducing life quality. Despite the progression in pain management, it has remained a clinical challenge, which raises the need for investigating novel antinociceptive drugs with correspondence signaling pathways. Besides, the precise antinociceptive mechanisms of melatonin are not revealed. Accordingly, owing to the critical role of L-arginine/nitric oxide (NO)/cyclic GMP (cGMP)/KATP in the antinociceptive responses of various analgesics, the role of this signaling pathway is evaluated in the antinociceptive effects of melatonin. Male NMRI mice were intraperitoneally pretreated with the injection of L-arginine (NO precursor, 100 mg/kg), N(gamma)-nitro-L-arginine methyl ester [L-NAME, NO synthase (NOS) inhibitor, 30 mg/kg], S-nitroso-N-acetylpenicillamine (SNAP, NO donor, 1 mg/kg), sildenafil (phosphodiesterase inhibitor, 0.5 mg/kg), and glibenclamide (KATP channel blocker, 10 mg/kg) alone and before the administration of the most effective dose of melatonin amongst the intraperitoneal doses of 50, 100, and 150 mg/kg. The formalin test (2%, 25 µL, intra-plantarly) was done following the melatonin administration, then the nociceptive responses of mice were evaluated during the early phase for 5 min and the late phase for 15 min. The results showed that 100 mg/kg dose of melatonin carried out the most antinociceptive effects. While the antinociceptive effect of melatonin was increased by L-arginine, SNAP, and sildenafil, it was significantly reduced by L-NAME and glibenclamide in both phases of the formalin test, with no relation to the sedative effects of melatonin evaluated by the inclined plane test. In conclusion, the antinociceptive effect of melatonin is mediated through the L-arginine/NO/cGMP/KATP pathway.

Sharp-object-induced open-globe injuries in Iranian children admitted to a major tertiary center: a prospective review of 125 cases.

UNLABELLED: Ocular trauma in children can result in catastrophic visual and psychological outcomes both for the child and his/her family. According to the WHO, childhood blindness is one of the major causes of avoidable blindness and so target of the Vision 2020 program. To achieve this program's goals, it is necessary to explore the epidemiological patterns of ocular trauma in different countries which in its turn could be a valuable means to guide us in developing preventive measures. Our study is a hospital-based prospective study which was conducted to reveal detailed information about children who were admitted to a large tertiary care hospital with the diagnosis of lacerating globe injury due to a sharp object. PATIENTS AND METHODS: During a 6-month period (December 2006 to June 2007), 125 eyes of 125 children (age ≤16 years) with the diagnosis of open-globe injury were enrolled. Clinical data were documented. Demographic data and details of the event were explored and documented based on the study questionnaire (adopting the Birmingham Eye Trauma Terminology and the United States Eye Injury Registry model as basis) by interviewing the parents and the child. RESULTS: The mean age was 8.5 years (SD = 4.36 years, range: 1-16). The boys:girls ratio was 2.5:1; this ratio was age dependent, showing a significant increase with age. The home was the most frequent place (61.7%) for the trauma to occur in. Most traumas (50%) occurred in the afternoon (12 midday to 6 p.m.). Almost half of the traumas were unintentional self-injuries and occurred when the child was alone. A knife and fireworks were the two most frequent causes of injury. CONCLUSION: As the home is the most common place of ocular trauma in this age group and as lack of proper supervision and accessibility of sharp objects such as knives are the background of the event in most cases, it is strongly recommended to educate parents about providing a safe environment at home for their children. Work-related eye injuries in this age group should also be reduced by regulations for prohibiting children's work or at least providing the necessary education and safety goggles.