Review: 5-HT1, 5-HT2, 5-HT3 and 5-HT7 Receptors and their Role in the Modulation of Pain Response in the Central Nervous System.

BACKGROUND: The aim of this review was to identify the mechanisms by which serotonin receptors involved at the central level are able to modulate the nociceptive response. Pain is a defense mechanism of the body that entails physiological, anatomical, neurochemical, and psychological changes, and is defined as an unpleasant sensory and emotional experience with potential risk of tissue damage, comprising the leading cause of appointments with Physicians worldwide. Treatment for this symptom has generated several neuropharmacological lines of research, due to the different types of pain and the various drugs employed to treat this condition. Serotonin [5- HydroxyTryptamine (5-HT)] is a neurotransmitter with seven families (5-HT1-5-HT7) and approximately 15 receptor subtypes. Serotonin modulates neuronal activity; however, this neurotransmitter is related with a number of physiological processes, such as cardiovascular function, gastric motility, renal function, etc. On the other hand, several researches reported that serotonin modulates nociceptive response through 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the Central Nervous System (CNS). METHOD: In this review, a search was conducted on PubMed, ProQuest, EBSCO, and the Science Citation Index for studies evaluating the effects of 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS on the modulation of different types of pain. CONCLUSION: We concluded that 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS modulate the pain, but this depends on the distribution of the receptors, dose of agonists or antagonists, administration route, pain type and duration in order to inhibit, excite, or even maintain the nociceptive response.

Prenatal stress alters the developmental pattern of behavioral indices of sexual maturation and copulation in male rats.

Gestation and pre-puberty are critical periods during which several environmental factors can drastically affect the adequate development of subjects. Considering that stress is one of the most common factors to which subjects may be exposed during gestation, the present study evaluated the effects of prenatal stress on the behavioral indices of sexual maturation in male rats, including genital grooming (GG), preputial separation (PS), and spontaneous penile erections (SPE) during puberty, and on copulatory parameters during adulthood. Stress was exerted by immobilizing the female rats once per day for 2h from days 14-21 of pregnancy. The young rats born to the dams in the stressed group (SG) later presented a delayed occurrence of PS with a delayed onset and lower frequency and duration of GG compared to a control group (CG). Less than half of the subjects in SG presented SPE, and those that did showed delayed onset and lower frequency and duration. In adulthood, fewer subjects in SG showed sexual behavior responses (intromission and ejaculation), and their mount and intromission latencies on the first day they ejaculated were longer than those of the CG rats. Findings from this study provide additional evidence that stress caused by immobilization during the third period of pregnancy exerts a negative effect in the short-term (i.e., around puberty) by altering the typical development of GG and SPE and the occurrence of PS, while also demonstrating that this effect persists in the long-term, when it affects the performance of copulatory behavior in mature male rats.

Chronic unpredictable mild stress generates oxidative stress and systemic inflammation in rats.

Stress is considered to be a causal agent of chronic degenerative diseases, such as cardiovascular disease, diabetes mellitus, arthritis and Alzheimer's. Chronic glucocorticoid and catecholamine release into the circulation during the stress response has been suggested to activate damage mechanisms, which in the long term produce metabolic alterations associated with oxidative stress and inflammation. However, the consequences of stress in animal models for periods longer than 40days have not been explored. The goal of this work was to determine whether chronic unpredictable mild stress (CUMS) produced alterations in the redox state and the inflammatory profile of rats after 20, 40, and 60days. CUMS consisted of random exposure of the animals to different stressors. The following activities were measured in the liver and pancreas: reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and protein oxidation. Similarly, serum cytokine levels (IL-6, TNF-α, IL-1ß, and IL-10) were determined. CUMS activated the stress response from day 20 until day 60. In the liver and pancreas, GHS levels were decreased from day 40, whereas protein lipid peroxidation and protein oxidation were increased. This is the first work to report that the pancreas redox state is subject to chronic stress conditions. The TAC was constant in the liver and reduced in the pancreas. An increase in the TNF-α, IL-1ß, and IL-6 inflammatory markers and a decrease in the IL-10 level due to CUMS was shown, thereby resulting in the generation of a systemic inflammation state after 60days of treatment. Together, the CUMS consequences on day 60 suggest that both processes can contribute to the development of chronic degenerative diseases, such as cardiovascular disease and diabetes mellitus. CUMS is an animal model that in addition to avoiding habituation activates damage mechanisms such as oxidative stress and low-grade chronic inflammation, which allows the study of physio-pathological stress aspects over prolonged time periods of at least 60days.