Low formalin concentrations induce fine-tuned responses that are sex and age-dependent: A developmental study

The formalin test is increasingly applied as a model of inflammatory pain using high formalin concentrations (5–15%). However, little is known about the effects of low formalin concentrations on related behavioural responses. To examine this, rat pups were subjected to various concentrations of formalin at four developmental stages: 7, 13, 22, and 82 days of age. At postnatal day (PND) 7, sex differences in flinching but not licking responses were observed with 0.5% formalin evoking higher flinching in males than in females. A dose response was evident in that 0.5% formalin also produced higher licking responses compared to 0.3% or 0.4% formalin. At PND 13, a concentration of 0.8% formalin evoked a biphasic response. At PND 22, a concentration of 1.1% evoked higher flinching and licking responses during the late phase (10–30 min) in both males and females. During the early phase (0–5 min), 1.1% evoked higher licking responses compared to 0.9% or 1% formalin. 1.1% formalin produced a biphasic response that was not evident with 0.9 or 1%. At PND 82, rats displayed a biphasic pattern in response to three formalin concentrations (1.25%, 1.75% and 2.25%) with the presence of an interphase for both 1.75% and 2.25% but not for 1.25%. These data suggest that low formalin concentrations induce fine-tuned responses that are not apparent with the high formalin concentration commonly used in the formalin test. These data also show that the developing nociceptive system is very sensitive to subtle changes in formalin concentrations.Ihssane Zouikr, Melissa A. Tadros, Vicki L. Clifton, Kenneth W. Beagley, Deborah M. Hodgso

Evaluation of the Bonapace Method: a specific educational intervention to reduce pain during childbirth

Julie Bonapace,1 Nils Chaillet,2 Isabelle Gaumond,3,4 &Eacute;milie Paul-Savoie,5 Serge Marchand3,41D&eacute;partement des Sciences de l&#39;&Eacute;ducation, Universit&eacute; du Qu&eacute;bec en Abitibi-T&eacute;miscamingue, Rouyn-Noranda, Qu&eacute;bec, 2Centre de Recherche de l&#39;H&ocirc;pital Sainte-Justine, Universit&eacute; de Montr&eacute;al, Montr&eacute;al, Qu&eacute;bec, 3D&eacute;partement de chirurgie, Facult&eacute; de M&eacute;decine et des Sciences de la Sant&eacute;, Universit&eacute; de Sherbrooke, Sherbrooke, Qu&eacute;bec, 4D&eacute;partement des Sciences de la Sant&eacute;, Universit&eacute; du Qu&eacute;bec en Abitibi-T&eacute;miscamingue, Rouyn-Noranda, Qu&eacute;bec, 5&Eacute;cole des sciences infirmi&egrave;res, Facult&eacute; de m&eacute;decine et des sciences de la sant&eacute;, Universit&eacute; de Sherbrooke, Sherbrooke, Qu&eacute;bec, CanadaObjective: As pain during childbirth is very intense, several educational programs exist to help women prepare for the event. This study evaluates the efficacy of a specific pain management program, the Bonapace Method (BM), to reduce the perception of pain during childbirth. The BM involves the father, or a significant partner, in the use of several pain control techniques based on three neurophysiological pain modulation models: (1) controlling the central nervous system through breathing, relaxation, and cognitive structuring; (2) using non-painful stimuli as described in the Gate Control Theory; and (3) recruiting descending inhibition by hyperstimulation of acupressure trigger points.Methods: A multicenter case control study in Quebec on pain perception during labor and delivery compared traditional childbirth training programs (TCTPs) and the BM. Visual analog scales were used to measure pain perception during labor. In all, 25 women (TCTP: n = 12; BM: n = 13) successfully reported their perceptions of pain intensity and unpleasantness every 15 minutes.Results: A positive correlation between the progression of labor and pain was found (pain intensity: P < 0.01; pain unpleasantness: P < 0.01). When compared to TCTP, the BM showed an overall significant lower pain perception for both intensity (45%; P < 0.01) and unpleasantness (46%; P < 0.01).Conclusion: These significant differences in pain perception between TCTP and the BM suggest that the emphasis on pain modulation models and techniques during labor combined with the active participation of a partner in BM are important variables to be added to the traditional childbirth training programs for childbirth pain management.Keywords: labor pain, yoga, perinatal care, DNIC, gate control theory, cognitive structuring, massage, fathe

Exploring the role of GHRH antagonist MIA-602 in overcoming Doxorubicin-resistance in acute myeloid leukemia

Acute myeloid leukemia (AML) is characterized by the rapid proliferation of mutagenic hematopoietic progenitors in the bone marrow. Conventional therapies include chemotherapy and bone marrow stem cell transplantation; however, they are often associated with poor prognosis. Notably, growth hormone-releasing hormone (GHRH) receptor antagonist MIA-602 has been shown to impede the growth of various human cancer cell lines, including AML. This investigation examined the impact of MIA-602 as monotherapy and in combination with Doxorubicin on three Doxorubicin-resistant AML cell lines, KG-1A, U-937, and K-562. The in vitro results revealed a significant reduction in cell viability for all treated wild-type cells. Doxorubicin-resistant clones were similarly susceptible to MIA-602 as the wild-type counterpart. Our in vivo experiment of xenografted nude mice with Doxorubicin-resistant K-562 revealed a reduction in tumor volume with MIA-602 treatment compared to control. Our study demonstrates that these three AML cell lines, and their Doxorubicin-resistant clones, are susceptible to GHRH antagonist MIA-602

The Application of GHRH Antagonist as a Treatment for Resistant APL

GHRH is a hypothalamic peptide shown to stimulate the proliferation of malignant cells in humans. We have previously shown that the use of GHRH antagonist MIA-602 successfully suppressed the growth of many human cancer cell lines, spanning more than 20 types of cancers. In this study, we demonstrate the presence of GHRH-R in the NB4, NB4-RAA, and K-562 model cell lines. Furthermore, we demonstrate the inhibited proliferation of all three cell lines in vitro after incubation with MIA-602. The treatment of xenografts of human APL cell lines with MIA-602 led to a significant reduction in tumor growth. Additionally, combination therapy with both doxorubicin (DOX) and MIA-602 showed a marked synergistic effect in reducing the proliferation of the K-562 AML cell line. These findings suggest that MIA-602 could be utilized to address resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) therapies, as well as in augmenting anthracycline-based regimens