Introduction: In the present study we attempted to investigate the alterations of cytological parameters of NRM (Longaxis and intranuclear rods) in the absence of its excitatory VL PAG afferent with or without the formalin pain model.Materials and Methods: We used male rats in 4 groups: 1- control group (n=4), 2- formalin group (n=4), 3- chemical lesion of VL PAG by Ibotenic Acid (0.2 َl, 0.5 َL) without formalin test (n-6), 4- chemical lesion of VL PAG by Ibotenic Acid (0.2َL) with formalin test. One week after formalin test or chemical lesion of VL PAG, animals were perfused and 3-5 mm blocks of their brainstem were stained by Thionin. Serial sections (5-8 micrometer) were examined by light microscope.Results: Our results revealed that three types of neurons were observed within NRM: fusiform, triangle and multipolar. In addition, following chemical lesioning of VL PAG or formalin induced pain, a marked alteration in some cytological characteristics of these neurons has been observed.Conclusion: We conclude that the VL PAG-NRM pathway is involved in the tonic pain nociceptive control system. Moreover, NRM neurons could react to noxious stimuli with cytological changes.

It has been reported that neurons in the VL PAG projecting to nucleus raphe magnus (NRM) utilize excitatory amino acids as neurotransmitter. This projection plays an important role in the descending pain modulatory system. In order to determine the role of this pathway in pain perception, male rats received unilateral injection of ibotenic acid stereotaxically. For lesioning VL PAG, unilateral injection of ibotenic acid (0.2 and 0.5µl) (a specific neurotoxin for EAA-containing neurons) was made. After an I-week recovery period, the nociception was evaluated using formalin test for a period of 60 min. At the end of experiments, animals were perfused by formaldehyde 10%.Serial sections (80 µm) were prepared using vibrato me. The sections were then Nissl stained and examined to determine the lesion location. The results revealed a significant increase in the first phase of formalin test. However, in the second phase, only 0.5 µl of the neurotoxin caused a significant decrease in pain perception.It is concluded that NMDA receptors within the PAG are involved in the perception of pain as measured in the formalin test.

Background: The nucleus raphe magnus (NRM) is involved in thermoregulatory processing. There is a correlation between changes in the firing rates of the cells in the NRM and the application of the peripheral thermal stimulus. Introduction: we examined the effect of reversible inactivation and excitation of NRM on mechanisms involved in tail blood flow (TBF) regulation in hypothermia. Methods: Hypothermia was induced in Male Wistar rats and cannula was implanted above the NRM. To evaluate the effect of nucleus inactivation on TBF, the amount of TBF was measured by Laser Doppler in hypothermic rats, before and after lidocaine microinjection into NRM. TBF was also measured after glutamate microinjection to assess the effect of nucleus excitation in hypothermic rats. Results: Results indicated that after dropping TBF by hypothermia, microinjection of lidocaine into NRM significantly decreased TBF from 54.43 ± 5.7 to 46.81 ± 3.4, whereas glutamate microinjection caused a significant increase from 44.194 ± 0.6 to 98 ± 10.0 Conclusion: These data suggest that NRM have thermoregulatory effect in response to hypothermia.

In order to evaluate effects of gamma irradiation on ruminal dry matter (DM) and crude protein (CP) degradability, in vitro CP digestibility, anti-nutritional factors and chemical composition of native rapeseed meal (NRM) and canola meal (CM), present study was carried out. Bags were filled with untreated or irradiated NRM and CM at doses of 15, 30 and 45 kGy, then incubated in the rumen of three ruminally fistulated Taleshi bulls for periods of 0, 2, 4, 8, 16, 24 and 48 h and resulting data were fitted to non-linear degradation model to calculate degradation kinetics of DM and CP. Digestibility of rumen undegraded CP was estimated using the three-step in vitro procedure. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was used to monitor protein subfractions and the fate of true proteins of untreated and gamma irradiated NRM and CM in the rumen. The phytic acid of NRM and CM decreased (P<0.05) as irradiation doses increased, but irradiation up to 30 kGy decreased (P<0.05) the total glucosinolate content of NRM and CM. g-irradiation had no effect on chemical composition of NRM and CM. The washout fractions and effective degradability of DM and CP decreased (P<0.05) and potentially degradable fractions of DM and CP of NRM and CM increased (P<0.05) as irradiation doses increased. Gamma irradiation increased (P<0.05) in vitro CP digestibility of NRM and CM. Electrophoresis results of NRM and CM revealed that gamma irradiation at doses of 30 and 45 kGy reduced degradability of cruciferin and especially napin subunits in the rumen. In conclusion, gamma irradiation reduced ruminal degradability of protein and anti-nutritional factors of NRM and CM and increased in vitro CP digestibility of them at doses higher than 15 kGy.

Introduction: The antinociceptive effect of morphine is, in part, mediated through the activation of a descending pathway. One of the major components of this pathway is the nucleus raphe magnus (NRM). Our previous study demonstrated the involvement of NRM in the analgesic effect of morphine microinjected into the nucleus cuneiformis (NCF) in a descending manner. The aim of the current study was to investigate another aspect of the interaction between these two nuclei in both acute and chronic inflammatory pain models.Methods: In order to calculate 50% effective dose (ED50) of morphine, animals received bilateral morphine injections (1, 2.5, 5 and 10 mg/0.5 ml saline) into the NRM. The obtained ED50 of morphine was applied into the NRM with/without bilateral electrolytic lesion (500 mA, 30 sec) of the NCF. Tail-flick and formalin tests were applied as behavioral analgesic tests in this study.Results: Results interestingly showed that the intra-NRM morphine injection (ED50; 1 mg/0.5 ml saline) resulted in an increase in tail flick latencies (morphine-induced antinociception) at 30-min intervals, while bilateral electrolytic lesions in the NCF could notably decreased the morphine-induced antinociception during 30-90 min after the injection of morphine. Data also showed that bilateral morphine microinjected into the NRM, dose-dependently increases the antinociceptive responses during both early and late phases of formalin test. The antinociceptive effect of morphine microinjected into the NRM was significantly attenuated at the late phase but not early phase following the bilateral destruction of NCF in formalin test.Conclusion: It could be concluded that there is a reciprocal interaction between NRM and NCF during morphine-induced antinociception in both acute and chronic inflammatory pain models in rat.

Objective(s): Nucleus Raphe Magnus (NRM) that is involved in the regulation of body temperature contains nitric oxide (NO) synthase. Considering the effect of NO on skin blood flow control, in this study, we assessed its thermoregulatory role within the raphe magnus.Materials and Methods: To this end, tail blood flow of male Wistar rats was measured by laser doppler following the induction of hypothermia.Results: Intra-NRM injection of SNP (exogenous NO donor, 0.1- 0.2 ml, 0.2 nM) increased the blood flow. Similarly, unilateral microinjection of glutamate (0.1- 0.2 ml, 2.3 nM) into the nucleus increased the blood flow. This effect of L-glutamate was reduced by prior intra NRM administration of NO synthase inhibitor NG-methyl L-arginine or NG‐nitro-L-arginine methyl ester (L-NAME, 0.1 ml, 100 nM).Conclusion: It is concluded that NO modulates the thermoregulatory response of NRM to hypothermia and may interact with excitatory amino acids in central skin blood flow regulation.

for acute leukemia, though outcomes in older patients remain suboptimal due to higher non-relapse mortality (NRM) and relapse rates. Innovations in conditioning regimens and supportive care have made HSCT accessible to patients over 50, but age-related disparities in outcomes persist. Materials and Methods: This 10-year retrospective cohort study reviewed all patients who underwent first-time allogeneic HSCT for acute leukemia. Patients were stratified by age at HSCT (≥ 50 years and < 50 years), and outcomes were assessed for overall survival (OS), disease-free survival (DFS), NRM, and relapse incidence (RI). Results: Of the 1199 patients, 152 were 50 years or older. Five-year OS rates were markedly lower in patients ≥ 50 years compared to younger patients (48. 70% vs. 59. 35%, P= 0. 024 for AML and 23. 60% vs. 41. 96%, P= 0. 025 for ALL). Moreover, older patients demonstrated significantly higher NRM rates (35. 95% vs. 23. 53%, P= 0. 045 for AML and 78. 14% vs. 26. 76%, P= 0. 005 for ALL) and a notably increased incidence of grade III-IV acute graft-versus-host disease (aGVHD). Interestingly, no significant differences were observed between the two age groups regarding DFS rates and RI. Conclusion: Older acute leukemia patients undergoing allogeneic HSCT face significant challenges, including elevated NRM and GVHD rates. While relapse rates were comparable, survival outcomes favored the younger cohort. These findings emphasize the need for age-adapted transplantation strategies, using reduced-intensity conditioning (RIC) regimens and further research to refine risk stratification and improve management approaches for older patients.