Tramadol definition on wiki

 Tramadol hydrochloride (Ultram, Tramal others below) is a centrally acting opioid analgesic, used in treating moderate to severe pain. The drug has a wide range of applications, including treatment for restless leg syndrome and fibromyalgia. It was developed by the pharmaceutical company Grünenthal GmbH in the late 1970s.[1][2]

Tramadol possesses weak agonist actions at the μ-opioid receptor, releases serotonin, and inhibits the reuptake of norepinephrine.[3][4][5][6][7][8][9]

Tramadol is a synthetic analog of the phenanthrene alkaloid codeine and, as such, is an opioid and also a prodrug (codeine is metabolized to morphine, tramadol is converted to O-desmethyltramadol). Opioids are chemical compounds which act upon one or more of the human opiate receptors. The euphoria and respiratory depression are mainly caused by the μ1 and μ2 receptors; the addictive nature of the drug is due to these effects as well as its serotonergic/noradrenergic effects. The opioid agonistic effect of tramadol and its major metabolite(s) are almost exclusively mediated by the substance's action at the μ-opioid receptor. This characteristic distinguishes tramadol from many other substances (including morphine) of the opioid drug class, which generally do not possess tramadol's degree of subtype selectivity.

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Scratching An Itch Affects The Brain

Using imaging technology for the first time to investigate the phenomenon, US researchers have revealed what goes on in the brain when we scratch, giving new clues about why the behaviour brings relief and is hard to stop.

The study is the work of researchers at Wake Forest University Baptist Medical Center in North Carolina, and is published in the 31st January early online issue of the Journal of Investigative Dermatology.

Lead author and dermatologist specializing in itch-related conditions, Dr Gil Yosipovitch said:

"It's important to understand the mechanism of relief so we can develop more effective treatments."

"For some people, itch is a chronic condition that affects overall health," explained Yosipovitch.

He and his colleagues wrote that imaging studies had looked at how the brain reacts to pruritis or itching conditions, but not what happens when the behavioural response, scratching, is going on.

The researchers recruited 13 healthy participants to undergo functional magnetic resonance imaging (fMRI), a type of scan where you can see different areas of the brain light up when the volunteer is doing different things, for instance when using limbs, thinking or talking.

A small brush was used to scratch participants on the lower leg for 30 seconds, then stopped for 30 seconds, then started again, and so on, for five minutes altogether.

The researchers found, to their surprise, that during the 30 seconds of scratching time, parts of the brain normally active when aversive emotions and memories are experienced, became signiificantly less active.

The parts of the brain showing reduced activity during scratching were the anterior cingulate cortex, which is linked with aversion to unpleasant sensory stimuli, and the posterior cingulate cortex, which is associated with memory. Lowest activity in these areas coincided with times when the participants felt the scratching to be most intense.

Yosipovitch said:

"We know scratching is pleasurable, but we haven't known why. It's possible that scratching may suppress the emotional components of itch and bring about its relief."

He said sometime patients find intense scratching, sometimes so hard that the skin bleeds, is the only way to relieve chronic itching.

"This is the first real scientific evidence showing that itch may be inhibited by scratching," said Yosipovitch.

He was keen to point out that scratching is not recommended because it damages the skin, but it is important to find out what is going on when people feel relief from scratching so new treatments can be developed, such as drugs that target the relevant part of the brain to produce the same effect.

As well as finding that some parts of the brain became less active during scratching, Yosipovitch and colleagues found that other parts became more active. This included activtation of both sides of the secondary somatosensory cortex, which is involved in pain, and the prefrontal cortex, which is linked to compulsive behaviour.

Other parts of the brain that also became bilaterally more active during scratching were the insular cortex, the inferior parietal lobe, and the cerebellum.

The activation of the prefrontal cortex, which is associated with compulsive behaviour, might explain the compulsive nature of scratching behaviour - the urge to keep on scratching, said the researchers.

There is one limitation to the study which could be significant, and that is the scratching was not done when itch was present. The scientists are carrying on with the research to see if they get the same results with chronic itch. They suggested that:

"Future studies that investigate the central effects of scratching in chronic itch conditions will be of high clinical relevance."

The researchers said it was important to find new treatments because moderate to severe itch bothers many people, for instance anyone with eczema, which in American alone affects 30 million people.

Another group that will benefit from new treatments are over 40 per cent of kidney dialysis patients, who have a 17 per cent higher risk of dying, probably because of lack of sleep, if they have itch.