5-ALA Is a Potent Lactate Dehydrogenase Inhibitor but Not a Substrate: Implications for Cell Glycolysis and New Avenues in 5-ALA-Mediated Anticancer Action.

In a course of metabolic experiments, we determined that the addition of δ-aminolevulinic acid (5-ALA) to a panel of glioblastoma multiforme (GBM) cells caused a steep reduction in their glycolytic activity. This reduction was accompanied by a decrease in adenosine triphosphate (ATP) production from glycolysis. These results suggested that 5-ALA is an inhibitor of glycolysis; due to the structural similarity of 5-ALA to the established lactate dehydrogenase (LDH) inhibitors oxamate (OXM) and tartronate (TART), we initially investigated LDH inhibition by 5-ALA in silico.

Diminished Cold Avoidance Behaviours after Chronic Cold Exposure - Potential Involvement of TRPM8.

Ambient temperature changes trigger plastic biological responses. Cold temperature is detected by the somatosensory system and evokes perception of cold together with adaptive physiological responses. We addressed whether chronic cold exposure induces adaptive adjustments of (1) thermosensory behaviours, and (2) the principle molecular cold sensor in the transduction machinery, transient receptor potential melastatin subtype 8 (TRPM8).

Role of D1- and D2-like dopaminergic receptors in the nucleus accumbens in modulation of formalin-induced orofacial pain: Involvement of lateral hypothalamus.

The role of dopaminergic system in modulation of formalin-induced orofacial nociception has been established. The present study aims to investigate the role of dopaminergic receptors in the nucleus accumbens (NAc) in modulation of nociceptive responses induced by formalin injection in the orofacial region. One hundred and six male Wistar rats were unilaterally implanted with two cannulae into the lateral hypothalamus (LH) and NAc.

NMDA receptor dependent changes in c-fos and p-CREB signaling following extinction and reinstatement of morphine place preference.

Neural circuitry comprising the ventral tegmental area, nucleus accumbens (NAc), prefrontal cortex (PFC) and hippocampus (HIP) has a main role in reward phenomena. Previous behavioral studies indicated that intracerebroventricular administration of AP5 (NMDA glutamate receptor antagonist) and CNQX (AMPA/kainate glutamate receptor antagonist) during the extinction and before reinstatement of morphine-induced conditioned place preference (CPP) reduced the extinction period and reinstatement of morphine-CPP. Therefore, in the present study, we tried to evaluate the effect of antagonism of NMDA glutamate receptors on the p-CREB/CREB ratio and c-fos expression in the NAc, PFC and HIP during these two phases of morphine-CPP in male adult albino Wistar rats.

Blockade of the orexin receptors in the CA1 region of hippocampus decreased the lateral hypothalamic-induced antinociceptive responses in the model of orofacial formalin test in the rats.

The role of hippocampus and lateral hypothalamus (LH) in modulation of formalin-induced nociception has been established. The present study aims to examine the role of orexin receptors in the Cornu Ammonis 1 (CA1) region of hippocampus in modulation of the LH-induced antinociception in the orofacial formalin test. Male Wistar rats were unilaterally implanted with two cannulae into the LH and CA1.

Role of intra-accumbal orexin receptors in the acquisition of morphine-induced conditioned place preference in the rats.

Orexin receptor shave essential role in the induction of reward-related behaviors to several drugs of abuse. In the present study, we investigated the effects of bilateral administration of SB334867, as an orexin-1 receptor antagonist, and TCS OX2 29, as an orexin-2 receptor antagonist, into the nucleus accumbens (NAc) on the acquisition of morphine-induced conditioned place preference (CPP) in the rats. Adult male Wistar rats (n=80; 220-250g) were entered in a CPP paradigm.

Role of orexin-2 and CB1 receptors within the periaqueductal gray matter in lateral hypothalamic-induced antinociception in rats.

Orexin plays an important role in pain modulation. Orexin-1 and orexin-2 receptors (Ox1r and Ox2r) are found at high density in the ventrolateral periaqueductal gray matter (vlPAG). Our previous study showed that chemical stimulation of the lateral hypothalamus with carbachol induces antinociception in the tail-flick test, a model of acute pain, and Ox1r-mediated antinociception in the vlPAG is modulated by the activity of vlPAG CB1 receptors.

Long-Term Treatment by Vitamin B and Reduction of Serum Proinflammatory Cytokines, Hyperalgesia, and Paw Edema in Adjuvant-Induced Arthritis.

Introduction: Immune system is involved in the etiology and pathophysiology of inflammation and vitamins are important sources of substances inducing nonspecific immunomodulatory effects. Given the proinflammatory role of cytokines in the inflammation and pain induction, this study aimed to assess the effects of long-term administration of vitamin B on the proinflammatory cytokines, edema, and hyperalgesia during the acute and chronic phases of adjuvant-induced arthritis.

Methods: On the first day of study, inflammation was induced by intraplantar injection of complete Freund's adjuvant (CFA) in the hindpaws of rats.

Effects of dorsal hippocampal orexin-2 receptor antagonism on the acquisition, expression, and extinction of morphine-induced place preference in rats.

Rationale: Orexinergic system is involved in reward processing and drug addiction.

Objectives: Here, we investigated the effect of intrahippocampal CA1 administration of orexin-2 receptor (OX2r) antagonist on the acquisition, expression, and extinction of morphine-induced place preference in rats.

Methods: Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) during a 3-day conditioning phase.

Role of orexin-2 receptors in the nucleus accumbens in antinociception induced by carbachol stimulation of the lateral hypothalamus in formalin test.

Orexins, which are mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), play an important role in pain modulation. Previously, it has been established that the nucleus accumbens (NAc) is involved in the modulation of formalin-induced nociceptive responses, a model of tonic pain. In this study, the role of intra-accumbal orexin-2 receptors (OX2rs) in the mediation of formalin-induced pain was investigated.

Chemical stimulation of the lateral hypothalamus by carbachol attenuated the formalin-induced pain behaviors in rats.

Electrical and chemical stimulation of the lateral hypothalamus (LH) produces analgesia. Previous studies emphasized the importance of LH in the modulation of nociceptive behaviors in the acute pain models. In the current study, for the first time, we examined the effect of direct chemical stimulation of the LH with cholinergic receptor agonist, carbachol, on pain-related behaviors in the formalin test as a model of persistent inflammatory pain.