Naloxone could limit morphine hypersensitivity: Considering the molecular mechanisms.

BACKGROUND: Naloxone has been used as an opioid antagonist to prevent multiple adverse side effects of opioid-like tolerance and hyperalgesia. This study has investigated naloxone combined with morphine to limit pain hypersensitivity. In addition, the expression of brain-derived neurotrophic factor (BDNF) and K+ Cl- cotransporter2 (KCC2) were also studied. METHODS: Forty-eight adult male Wistar rats (180-220 g) were divided into eight groups, with six rats in each group. Rats were divided into two tolerance and hyperalgesia groups; the sham group, the morphine group, the treatment group (naloxone along with morphine), and the sham group (naloxone along with saline) for eight consecutive days. Tail-flick test was performed on days 1, 5, and 8, and the plantar test on days 1 and 10. On days 8 and 10, the lumbar segments of the spinal cord were collected, and BDNF and KCC2 expression were analyzed using western blotting and immunohistochemistry, respectively. RESULTS: Results showed that tolerance and hyperalgesia developed following eight days of repeated morphine injection. BDNF expression significantly increased, but KCC2 was downregulated. Co-administration of naloxone and morphine decreased tolerance and hyperalgesia by decreasing BDNF and increasing KCC2 expression, respectively. CONCLUSION: This study suggests that BDNF and KCC2 may be candidate molecules for decreased morphine tolerance and hyperalgesia.

Induction of spinal long-term synaptic potentiation is sensitive to inhibition of neuronal NOS in L5 spinal nerve-transected rats.

The role of neuronal nitric oxide synthase (nNOS) in the central mechanism of neuropathic pain and long-term potentiation (LTP) of peripheral afferents remains obscure. The current study investigated the effect of intrathecal application of 7-nitroindazole (7-NI), a selective nNOS inhibitor (8.15 µg/5µl), on mechanical allodynia on day 14 after L5 spinal nerve transection. Furthermore, using in vivo single unit extracellular recording, we examined the effect of 7-NI on the induction of LTP of Aδ- and C-fiber-evoked responses. We have demonstrated that 7-NI attenuates nerve-injury-evoked mechanical allodynia. Additionally, our electrophysiological study has shown that the spinal administration of 7-NI significantly inhibits the induction of the LTP of Aδ- and C-fiber-evoked responses on day 14 after neuropathy. These data suggest that activation of nNOS may be crucial for the induction of the spinal LTP of Aδ- and C-fiber-evoked responses following peripheral nerve damage.

Parents' adulthood stress induces behavioral and hormonal alterations in male rat offspring.

Exposure to stress can influence hypothalamo-pituitary-adrenal (HPA) axis in mammals and impair their behavioral/hormonal development. Stress during fetal or early life may have wide range effects on the offspring phenotype in rodents. Since the role of parents' adulthood stress before mating is not fully understood yet, we investigated the effects of parents' adulthood stress on behavioral and hormonal parameters in 10- and 30-day-old male offspring. To induce stress in the adult male and female rats, a repeated forced swimming paradigm was employed daily over the course of 21 days. Then, they were categorized into four parental breeding groups: stressed parents (SP), stressed mother (SM), stressed father (SF) and non-stressed parents (NSP). Anxiety-like behavior was tested in adult rats and 30-day-old male pups, using the elevated plus maze (EPM). The level of serum corticosterone was measured by ELISA in all groups. Stressed adult rats showed enhanced serum corticosterone concentration and anxiety-like behavior. Serum corticosterone level of the 10- and 30-day-old pups of the SP, SM and SF groups was significantly higher than pups from the non-stressed group. Furthermore, 30-day-old pups of the SP, SM and SF groups had lower time spent in the open arms compared to the control group, but stress had no significant effects on the percent of entries into the open arms. In addition, serum corticosterone level in 30-day-old pups were raised by a stressed mother was markedly more than 10-day-old pups. These findings revealed that parents' adulthood stress have negative impacts on behavioral and hormonal responses of their male offspring.