Fig. 3. Decision tree for hybrid sequencing strategy. For organisms with a small genome size (Ͻ3 Mb) and͞or a small number of gaps and͞or high levels of repetitive structure inducing physical ends, we found 8ϫ Sanger sequencing to be the most cost-effective approach. For organisms with a large genome size, many sequencing gaps, and͞or hard stops, we found initial sequencing of 5.3ϫ Sanger data followed by the addition of two 454 runs to be the most cost-effective approach.
It is well admitted that stress induces analgesia (SIA) via endogenous opioid release. However, there is evidence that stressful events play a role in the pathogenesis of pain, but little is known about mechanisms underlying such pain vulnerability. Previous studies reported that a single opioid exposure activates NMDA-dependent pronociceptive systems leading to long-term pain vulnerability after analgesia. Here, we studied whether prior inflammatory pain or/and opioid experiences may favour the development of pain vulnerability after nonnociceptive environmental stress (NNES). Nociceptive threshold (NT) changes were evaluated by paw pressure vocalization test. By contrast to discrete SIA observed in naive rats, 1 h stress induced hyperalgesia (SIH) for several hours (15-65% NT decrease) in pain and opioid experienced rats. Repetition of NNES induced an 18-to 22-fold SIH enhancement (3-4 days), whereas SIA decreased. SIH was still observed 4 months after pain and opioid experiences. This phenomenon is referred to as latent pain sensitization. Furthermore, a fentanyl ultra-low dose (ULD, 50 ng/kg) administration, mimicking SIA in naive rats, induced hyperalgesia (65% NT decrease, 4 h), not analgesia, in pain and opioid-experienced rats. This indicates that low levels of opioids induce opposite effects, that is analgesia vs hyperalgesia dependent on prior life events. In pain and opioid-experienced rats, NMDA receptor antagonists, ketamine or BN2572, completely prevented hyperalgesia when injected just before NNES or fentanyl ULD. This latent pain sensitization model may be important for studying the transition from acute to chronic pain and individual differences in pain vulnerability associated with prior life events.
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