sb-334867-a and Inflammation

Stress activates multiple neural pathways and neurotransmitters that often suppress pain perception, the phenomenon called stress-induced analgesia (SIA). Orexin neurons from the lateral hypothalamus project to entire brain structures such as the hippocampus. The present study examined this hypothesis that orexinergic receptors in the CA1 region of the hippocampus may play a modulatory role in the development of SIA in formalin test as an animal model of persistent inflammatory pain. One hundred-two adult male Wistar rats were administered with intra-CA1 orexin-1 receptor (OX1r) antagonist, SB334867, at the doses of 3, 10, 30, and 100 nmol or TCS OX2 29 as orexin-2 receptor (OX2r) antagonist at the doses of 1, 3, 10, and 30 nmol. Five min later, rats were exposed to forced swim stress (FSS) for a 6-min period. Then, pain-related behaviors induced by formalin injection were measured at the 5-min blocks during a 60-min period of formalin test. The current study indicated that solely stress exposure elicits antinociception in the early and late phases of the formalin test. The FSS-induced analgesia was prevented by intra-CA1 administration of SB334867 or TCS OX2 29 during either phase of the formalin test. Moreover, the contribution of the OX2r in the mediation of analgesic effect of stress was more prominent than that of the OX1r during both phases of the formalin test. It is suggested that OX1r and OX2r in the CA1 region of the hippocampus are involved in stress-induced analgesia in the animal model of persistent inflammatory pain.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzoxazoles; CA1 Region, Hippocampal; Cyclophosphamide; Disease Models, Animal; Doxorubicin; Etoposide; Inflammation; Isoquinolines; Male; Microinjections; Naphthyridines; Orexin Receptor Antagonists; Orexin Receptors; Pain; Pain Measurement; Prednisone; Pyridines; Rats, Wistar; Stress, Psychological; Urea; Vincristine

The Hippocampus has a role not only in nociception but also in modulation of pain perception. In addition, orexinergic neurons present in the lateral hypothalamus (LH) have a recognized role in pain modulation. The presence of orexinergic projections from the lateral hypothalamus (LH) to the dorsal hippocampal Cornu Ammonis 1 (CA1) region raises the question of whether pain modulatory role of LH is mediated through the CA1. To elucidate the interactions between the LH and neural substrates involved in modulation of formalin-induced nociception, the study aimed to test the pain modulatory role of CA1 orexin receptors in the formalin test. Seventy-one male Wistar rats were unilaterally implanted with two cannulae above the LH and CA1. In the treatment groups, intra-CA1 administration of SB-334867, as an orexin-1 receptor antagonist, was performed 5min before intra-LH microinjection of carbachol, as a cholinergic receptor agonist. In dimethyl sulfoxide (DMSO)-control group, DMSO and saline as well as in carbachol-control group, DMSO and carbachol were microinjected into the CA1 and LH, respectively. In all rats, the procedure was followed by subcutaneous injection of formalin after 5-min time interval. Carbachol reduced both phases of formalin-induced nociception. Intra-CA1 administration of SB-334867 antagonized the LH-induced analgesia during both phases in a dose-dependent manner. It seems that the blockade of orexin-1 receptors has more effects on reduction of antinociception during the late phase compared to the early phase. Pain modulatory role of orexinergic system in the formalin test through a neural pathway from the LH to CA1 provides the evidence that orexins can be useful therapeutic agents for chronic pain treatment.

Topics: Analgesics; Animals; Benzoxazoles; CA1 Region, Hippocampal; Carbachol; Catheters, Indwelling; Cholinergic Agonists; Dose-Response Relationship, Drug; Formaldehyde; Hypothalamic Area, Lateral; Inflammation; Male; Naphthyridines; Nociceptive Pain; Orexin Receptor Antagonists; Orexin Receptors; Pain Perception; Rats, Wistar; Stimulation, Chemical; Urea

The aim of this study was to investigate the effect of fasting-induced orexin-A (OXA) on inflammation and macrophage phagocytic activity. Fifty six male wistar rats were fasted for 36 h to stimulate OXA synthesis. In 24 rats, air pouches were induced subcutaneously in the intrascapular area. After (6 h) carrageenan injection into the pouches, the contents of the air pouches were removed. The exudate volume, protein content and cell count were measured. After the determination of fasting on inflammation, the peritoneal macrophages were collected from 32 rats to investigate the effect of fasting-induced OXA on macrophage phagocytic activity. Plasma OXA levels were markedly higher in fasted rats compared with control rats. The phagocytic capability of peritoneal macrophages was obtained as a percentage of phagocytosing macrophages and number of phagocytosed particles per cell. In spite of increased blood OXA level SB-334867, selective orexin type 1 receptor antagonist (10 mg/kg) did not change phagocytic activity of peritoneal macrophages. These findings indicate that 36 h fasting-induced OXA has no significant effect to phagocytosis of peritoneal macrophages.

Topics: Animals; Benzoxazoles; Chondrus; Exudates and Transudates; Fasting; Inflammation; Intracellular Signaling Peptides and Proteins; Macrophages, Peritoneal; Male; Naphthyridines; Neuropeptides; Orexin Receptors; Orexins; Phagocytosis; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Time Factors; Urea