Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter.

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1 SEROTONIN AND PAIN LEARNING OBJECTIVES At the end of lecture students should be able to know, Chemistry of serotonin. Understand the role of serotonin in CNS. Understand the relationship of serotonin and pain. Levels of serotonin. Function of serotonin. Serotonin toxicity. INTRODUCTION Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS) of animals including humans. It is thought to be a contributor to feelings of wellbeing and happiness. Approximately 90% of the human body's total serotonin is located in the enterochromaffin cells in the alimentary canal (gut), where it is used to regulate intestinal movements.

2 The remainder is synthesized in serotonergic neurons of the CNS, where it has various functions. These include the regulation of mood, appetite, and sleep. Serotonin also has some cognitive functions, including memory and learning. Serotonin secreted from the enterochromaffin cells eventually finds its way out of tissues into the blood. There, it is actively taken up by blood platelets, which store it. When the platelets bind to a clot, they disgorge serotonin, where it serves as a vasoconstrictor and helps to regulate homeostasis and blood clotting. EFFECT OF SEROTONIN ON PAIN Serotonin is a chemical substance that is located in the brain and a neurotransmitter that has an effect on the amount of pain that a person can withstand. Serotonin normally reduces the intensity of pain signals sent to the brain. Serotonin level, can have an effect on pain threshold too. Because serotonin helps keep pain gates closed, a lack of it can make you feel more pain

3 Serotonin blocks the perception of pain in the brain. It is dispatched to the area of the spinal cord where substance P (neuropeptide) is being released, helping to counteract it. Low serotonin levels can cause elevated substance P levels. These elevated levels, sometimes three times greater in patient suffering with fibromyalgia syndrome (FM). It s a physical suppressing of the pain signal.

4 Serotonin also increases the flexibility of veins, arteries and capillaries. The more flexible they are, the less likely they are to generate pain. Serotonin has also been found to play an important key role in sleep regulation. Both sleep and serotonin have a positive impact on pain. Serotonin is linked in some way to sleep. Regardless of which is accurate, both sleep and serotonin have a positive impact on pain. Serotonin levels are also naturally lower in women as compared to men, possibly making them more susceptible to developing chronic pain symptoms. The beneficial impact of serotonin could possibly help back pain or pain in the neck or other extremities, arthritis pain, fibromyalgia pain, or neuropathic pain (nerve pain).

5 Depression, anger, hostility, sleep disturbances all result in increase pain transmission to the brain. Although a number of neurotransmitters, neuromodulators, and receptors are likely involved in modulating the ascending and descending pain pathways, serotonin and nor epinephrine have been implicated as principal mediators of endogenous analgesic mechanisms in the descending pain pathways.

6 The imbalance of serotonin and nor epinephrine in endogenous pain inhibitory pathways may contribute to persistent pain. Serotonin blocks the perception of pain in the brain. It is dispatched to the area of the spinal cord where substance P is being released, helping to counteract it. This goes beyond mood it's a physical suppressing of the pain signal.

7 LOW SEROTONIN LEVELS During long bouts of stress, your body works diligently to keep your brain's serotonin levels high to protect you from burning out. Serotonin, a chemical that regulates processes like sleep and body temperature, is also susceptible to wearing out over time. This is especially true if your body is burning through your serotonin levels are high. Slightly Low Serotonin Levels - As your body burns through its supply of serotonin and your serotonin levels gradually drop, you may begin to feel a bit scatterbrained. Low serotonin levels, may lead to feel worn out by small tasks like walking out to your mailbox. Moderately Low Serotonin Levels - As serotonin levels continue to decrease, patient may begin to feel so sleepy that he want to go to sleep at dusk and wake up at noon. During this sleep, though, he may wake up a lot and worry about small things.

8 He may not feel quite up to hanging out with his friends after work. Patient hungry all the time or have no appetite at all, and everything family says to him seems to make him feel angry or hurt. In addition to all this, if moderately low serotonin levels, he may have unexplained body sensations like hot flashes, stomach pains and headaches. Overall, he feel sad and insecure, but he can't always put your finger on the reason why. Extremely Low Serotonin Levels - As low serotonin levels begin to decrease out, patient may feel a shift in his thinking patterns. He may begin to think on super speed about thoughts you can't control. These thoughts may be about horrible scenes from past or they may be imagined. In addition to this, he may feel numb to everything around him. Extremely low serotonin levels can cause patient to overreact to small problems. If serotonin levels are this low, it is likely to have scary ("evil") fantasies, feel like need to escape by taking off in car.

9 When there is extremely low serotonin levels body may continue to feel terrible or worsen temperature fluctuates, stomach hurts, and head feels like it's about to explode. Lowest Serotonin Levels - When serotonin levels drop dangerously low, it is most likely be suicidal. It will feel as though the world would be better off without you, and you consider ways to end your life. If those around you begin to wonder if you are depressed, seek help as soon as you can. Depression is extremely common but it is very treatable. SEROTONIN TOXICITY Serotonin syndrome is a potentially lifethreatening drug reaction that may occur following therapeutic drug, overdose or the recreational use of certain drugs. Serotonin syndrome is a predictable consequence of excess serotonergic activity at central nervous system (CNS) and peripheral serotonin receptors. For this reason, some experts strongly prefer the terms serotonin toxicity because these more

10 accurately reflect the fact that it is a form of poisoning. It may also be called serotonin sickness, serotonin poisoning, hyperserotonemia, or serotonergic syndrome. The excess serotonin activity produces a spectrum of specific symptoms including,cognitive,autonomic, and somatic effects. The symptoms may range from barely perceptible to fatal. Numerous drugs and drug combinations have been reported to produce serotonin syndrome. Diagnosis of serotonin syndrome includes observing the symptoms produced and a thorough investigation of the patient's history The syndrome has a characteristic picture but can be mistaken for other illnesses in some people, particularly those with neuroleptic malignant syndrome. No laboratory tests can currently confirm the diagnosis. Treatment consists of discontinuing medications which may contribute and in moderate to severe cases administering a serotonin antagonist. An important treatment includes controlling agitation with benzodiazepine sedation. SIGN AND SYMPTOMS

11 Symptom onset is usually rapid, often occurring within minutes. Serotonin syndrome encompasses a wide range of clinical findings. Mild symptoms may only consist of increased heart rate, shivering, sweating, dilated pupils, intermittent tremor or twitching, as well as over responsive reflexes. Moderate intoxication includes additional abnormalities such as hyperactive bowel sounds, high blood pressure and hyperthermia; a temperature as high as 40 C (104 F) is common in moderate intoxication. The overactive reflexes in moderate cases may be greater in the lower limbs than in the upper limbs. Mental status changes include hyper vigilance and agitation. Severe symptoms include severe increases in heart rate and blood pressure that may lead to shock. Temperature may rise to above 41.1 C (106.0 F) in life-threatening cases. Other abnormalities include metabolic acidosis, seizures, renal failure, and disseminated intravascular coagulation these effects usually arise as a consequence of hyperthermia.

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