Erythropoietin reduces neuronal cell death and hyperalgesia induced by peripheral inflammatory pain in neonatal rats

Painful stimuli during neonatal stage may affect brain development and contribute to abnormal behaviors in adulthood. Very few specific therapies are available for this developmental disorder. A better understanding of the mechanisms and consequences of painful stimuli during the neonatal period is essential for the development of effective therapies. In this study, we examined brain reactions in a neonatal rat model of peripheral inflammatory pain. We focused on the inflammatory insult-induced brain responses and delayed changes in behavior and pain sensation. Postnatal day 3 pups received formalin injections into the paws once a day for 3 days. The insult induced dysregulation of several inflammatory factors in the brain and caused selective neuronal cell death in the cortex, hippocampus and hypothalamus. On postnatal day 21, rats that received the inflammatory nociceptive insult exhibited increased local cerebral blood flow in the somatosensory cortex, hyperalgesia, and decreased exploratory behaviors. Based on these observations, we tested recombinant human erythropoietin (rhEPO) as a potential treatment to prevent the inflammatory pain-induced changes. rhEPO treatment (5,000 U/kg/day, i.p.), coupled to formalin injections, ameliorated neuronal cell death and normalized the inflammatory response. Rats that received formalin plus rhEPO exhibited normal levels of cerebral blood flow, pain sensitivity and exploratory behavior. Treatment with rhEPO also restored normal brain and body weights that were reduced in the formalin group. These data suggest that severe inflammatory pain has adverse effects on brain development and rhEPO may be a possible therapy for the prevention and treatment of this developmental disorder

Pictorial cigarette pack warnings: a meta-analysis of experimental studies

OBJECTIVE: To inform international research and policy, we conducted a meta-analysis of the experimental literature on pictorial cigarette pack warnings. DATA SOURCES: We systematically searched 7 computerised databases in April 2013 using several search terms. We also searched reference lists of relevant articles. STUDY SELECTION: We included studies that used an experimental protocol to test cigarette pack warnings and reported data on both pictorial and text-only conditions. 37 studies with data on 48 independent samples (N=33 613) met criteria. DATA EXTRACTION AND SYNTHESIS: Two independent coders coded all study characteristics. Effect sizes were computed from data extracted from study reports and were combined using random effects meta-analytic procedures. RESULTS: Pictorial warnings were more effective than text-only warnings for 12 of 17 effectiveness outcomes (all p<0.05). Relative to text-only warnings, pictorial warnings (1) attracted and held attention better; (2) garnered stronger cognitive and emotional reactions; (3) elicited more negative pack attitudes and negative smoking attitudes and (4) more effectively increased intentions to not start smoking and to quit smoking. Participants also perceived pictorial warnings as being more effective than text-only warnings across all 8 perceived effectiveness outcomes. CONCLUSIONS: The evidence from this international body of literature supports pictorial cigarette pack warnings as more effective than text-only warnings. Gaps in the literature include a lack of assessment of smoking behaviour and a dearth of theory-based research on how warnings exert their effects