Clinical trials have shown that SSP low frequency electrical stimulation facilitates the discharge of endorphins (morphine like substances) as does traditional acupuncture. (6)

In 1999, clinical researchers reported that inserting acupuncture needles into specific body points triggers the production of endorphins. (7)

In another study, a high level of endorphins was noted to form in cerebrospinal fluid after patients underwent acupuncture. (8)

Also in another study, investigators showed a significant rise of plasma endorphin levels after electrocompulsive therapy (ECT) for treating depression. (9) (10)

The term endorphin consists of two parts; Endo (endogenous) and Orphis (Morphines) intended to mean "morphine - like substance" originating from within the body. (11)

Endorphins are endogenous opoiod polypeptide compounds. They are produced by the pituitary gland and the hypothalamus in vertebrates during certain circumstances and act via opioid receptors in the body (Table 2). (12)(13)(14)

Strenuous exercise Excitement Pain Death Orgasm Over exposure to sun Spicy food

Opioid neuropeptides were first discovered in 1975 by two independent groups of investigators.
The first group was led by John Hughes and Hans Kasterbits who succeeded in isolating opioid neurotransmitters from the brain of a pig and call it enkephalins. (15)
The second group was led by Simantov R and Soloman H Synder and they succeed in isolating these opioid neurotransmitters from the brain of calves. (16)
Until now, there are four types of endorphins created in the human body. They are named alpha, beta, gamma and sigma endorphins. These endorphins are differing in number and types of amino acids; they have between 16-31 amino acids in each molecule. (17)
Beta endorphins are the most powerful endorphins in the body. They are usually found in the hypothalamus and pituitary gland.

All endorphins bind to the opioid receptors in the brain. They cleared very rapidly from the blood. Acupuncture is thought to result in the release of more endorphins. (18) Also some suggest that endorphins have a role in the development of obesity, diabetes and psychiatric diseases. (17)

Beta endorphins are released into the blood and into the spinal cord and brain from hypothalamic neurons. The beta endorphins that are released into blood cannot enter the brain in large quantities because of the blood brain barrier. Also, beta endorphin has the highest affinity for the U1-opioid receptor (Table 3). (19) (20)

Table 3: Affinity of Opioid receptors to beta endorphin

Classically U receptors are presynaptic and inhibit neurotransmitter release, through this mechanism they inhibit the release of GABA and disinhibit the dopamine pathways causing more dopamine to be released (19).

Opioid receptors have many other important roles in the brain and periphery (Table 4). (21)

Table 4: Function of Opioid receptors

Smoking and dependency

Cigarette smoking is a cycle of craving, smoking, calming and craving. Within seconds, smoking sends nicotine to the brain. Nicotine starts a series of biochemical reactions causing the release of dopamine and other substances giving the feeling of pleasure and calm. (22)

Evidence indicates that people smoke primarily to experience the psychological properties of nicotine and that the majority of smokers become dependent upon nicotine. (22) In humans, nicotine produces positive reinforcing effects including mild euphoria (23), increased energy, heightened arousal, reduced stress and anxiety and appetite suppression. (24)(25) Although nicotine produces its effects through nicotine acetylcholine receptors, other neurological systems involved in nicotine reinforcement interact with the midbrain dopamine system. These systems include the opioid system.
Stimulation of the dopamine system appears to be of critical importance for acute positive reinforcing properties of nicotine.

Nicotine also affects the release of endogenous opioid peptides. (26) The endorphin system has been hypothesized to be involved in mood regulation, psychomotor stimulation, analgesia reproduction and temperature regulation. (27)

How can endorphins help in smoking cessation?

Endorphins compete with nicotine on the receptors responsible from positive reinforcement feelings. While the smokers begin to withdraw from the smoking habit, the endorphins produced by electrotherapy (SSP) continue to give the same feelings. After time the body restarts to secrete endorphins endogenously without the need of nicotine. In such way the smoker can quit smoothly without passing through the vicious cycle of craving, smoking, calming and craving.

The relation between endorphins and glucose homeostasis

In an animal model study, investigators examined the administration of beta endorphins introduced centrally on glucose homeostasis on a conscious dog. (28) Intracerebroventricular administration of beta endorphin (0.2mg/h) caused a 70% increase in plasma glucose.

The mechanism of hyperglycemia was thought through:
- Early increase of glucose production
- Lack of inhibition of glucose clearance

The changes explains the marked increases in plasma epinephrine (30 fold) and norepinephrin (6 fold) that occurred during infusion. Interestingly intravenous administration of beta-endorphin did not alter glucose homeostasis. The investigators in this study concluded that beta endorphins act centrally to cause hyperglycemia by stimulating sympathetic out flow and pituitary - adrenal axis. (28)

In another study (29), Paolisso G et al evaluated the effect of human beta endorphins on pancreatic hormone levels and on glucose metabolism in normal subjects. The study showed that infusion of 143 nmol/h beta endorphins in 7 subjects caused a significant rise in plasma glucose concentrations (+1.7 +0.3 mmol/L) which was preceded by a significant increase in peripheral plasma glucagons levels (+44 +13ng). From this study the investigators concluded that naturally occurring opioid peptide beta endorphin produced hyperglycemic effects in man which appears to be mediated by Glucagon. The opioid seems to have no direct effect on glucose metabolism.

Back to animal model studies, an interesting study (30) aimed to determine whether supraphysiological levels of beta endorphin inhibit the ACTH and CRH response to insulin induced hypoglycemia in human subjects. The researchers in this study noted that IV infusion of beta endorphin increases glucose and delays the onset of hypoglycemia following insulin. (30)

CONCLUSION

Back to our patient, Mr X's doctor explained to him the previous information and encouraged him to try the SSP device but also advised him to monitor his blood glucose closely during the period of using the device. Also he was advised to contact his doctor if he noticed unexplained rising in his blood glucose.

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