neuromodulator

What  does  the term  Neuromodulator  means ? Here you are wiki :

A neuromodulator is a substance other than a neurotransmitter, released by a neuron at a synapse and conveying information to adjacent or distant neurons, either enhancing or dampening their activities.

A neuromodulator is a relatively new concept in the field and it can also be considered as a neurotransmitter that is not reabsorbed by the pre-synaptic neuron or broken down into a metabolite. Such neuromodulators end up spending a significant amount of time in the CSF (cerebrospinal fluid) and influencing (or modulating) the overall activity level of the brain. For this reason, some neurotransmitters are also considered as neuromodulators. Examples of neuromodulators in this category: serotonin and acetylcholine. Substance P and Octopamine are also being shown as a neuromodulators.

Types :

• Opioid peptides – important neuromodulator. These substances block nerve impulse generation in the secondary afferent pain neurons. These peptides are called opioid peptides because they have opium-like activity. The types of opioid peptides are:
  • Endorphins
  • Enkephalins
  • Dynorphins

The membrane potential of an excitable cell in a resting (unexcited) state is called the resting potential. (important concept associated with the nervous system )

Brain to blame for addiction

By Carolyn Susman

Brain scans of smokers studied by researchers at Duke University revealed three regions deep within the brain that appear to control dependency on nicotine and craving for cigarettes.

These regions play important roles in some of the key motivations for smoking: to calm down when stressed, to achieve pleasure and to help concentration.

“If you can’t calm down, can’t derive pleasure and can’t control yourself or concentrate, then it will be extremely difficult for you to break the habit,” said lead study investigator Dr. Jed E. Rose, director of the Duke Center for Nicotine and Smoking Cessation Research. “These brain regions may explain why most people try to quit several times before they are successful.”

Understanding how the brain responds to cigarette cravings can help doctors change nicotine cessation treatments to address all three of these components of withdrawal, Rose said. Drugs or therapies that target these regions may help smokers stave off the cravings that often spoil their attempts to quit.

The research was funded by Phillip Morris USA.

In the study, the researchers manipulated the levels of nicotine dependence and cigarette craving among 15 smokers, then scanned their brains using positron emission tomography, or PET scans, to see which areas of the brain were most active.

Three specific regions of the brain demonstrated changes in activity when the smokers craved cigarettes.

One region that lights up, called the thalamus, is considered to be the key relay point for sensory information flowing into the brain.

Some of the symptoms of withdrawal among people trying to quit stem from the inability to focus thoughts and the feeling of being overwhelmed, and could thus be explained by changes in this region, according to the researchers

Stress and Memory

 

Carmen Sandi¹ and M. Teresa Pinelo-Nava^2,3

1	Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland
2	Departamento de Psicobiología, Universidad Nacional de Educación a Distancia, Juan del Rosal s/n, Madrid 28040, Spain
3	Departamento de Psicología, Universidad Iberoamericana, Prolongación Paseo de la Reforma 880, Santa Fe, México 01219, Mexico

Received 21 December 2006; Accepted 14 February 2007
Recommended by Georges Chapouthier

Stress is a potent modulator of learning and memory processes. Although there have been a few attempts in the literature to explain the diversity of effects (including facilitating, impairing, and lack of effects) described for the impact of stress on memory function according to single classification criterion, they have proved insufficient to explain the whole complexity of effects. Here, we review the literature in the field of stress and memory interactions according to five selected classifying factors (source of stress, stressor duration, stressor intensity, stressor timing with regard to memory phase, and learning type) in an attempt to develop an integrative model to understand how stress affects memory function. Summarizing on those conditions in which there was enough information, we conclude that high stress levels, whether intrinsic (triggered by the cognitive challenge) or extrinsic (induced by conditions completely unrelated to the cognitive task), tend to facilitate Pavlovian conditioning (in a linear-asymptotic manner), while being deleterious for spatial/explicit information processing (which with regard to intrinsic stress levels follows an inverted U-shape effect). Moreover, after reviewing the literature, we conclude that all selected factors are essential to develop an integrative model that defines the outcome of stress effects in memory processes. In parallel, we provide a brief review of the main neurobiological mechanisms proposed to account for the different effects of stress in memory function. Glucocorticoids were found as a common mediating mechanism for both the facilitating and impairing actions of stress in different memory processes and phases. Among the brain regions implicated, the hippocampus, amygdala, and prefrontal cortex were highlighted as critical for the mediation of stress effects.

Movement control function is identified

SAN DIEGO, April 4 (UPI) — U.S. scientists have identified the region of the human brain that’s involved in sudden decisions and reactions to stimuli.

Researchers led by cognitive neuroscientist Adam Aron, an assistant professor of psychology at the University of California-San Diego, discovered white matter tracts — bundles of neurons that form direct, high-speed connections, between distant regions of the brain — appear to play a significant role in rapid behavior control.Aron said the study is the first to identify white matter tracts in humans, confirming similar findings in monkeys, and the first to relate them to the brain’s activity while people voluntarily control their movements.

“The findings could be useful not only for understanding movement control, but also ’self-control’ and how control functions are affected in a range of neuropsychiatric conditions such as addiction, Tourette’s syndrome, stuttering and Attention Deficit Hyperactivity Disorder.”

The research appears in the April 4 issue of the Journal of Neuroscience.

Copyright 2007 by United Press International. All Rights Reserved.

Information Processing In The Central Nervous System

Research by Renee Theiss, Jason Kuo and C J Heckman, which has just been published in The Journal of Physiology, throws light on how information is processed in the Central Nervous System (CNS) to drive movement. The findings are relevant to understanding mechanisms underlying movement and disorders such as spinal cord injury and motor neurone disease (ALS).

Interneurones in the spinal cord integrate command signals from the brain, with information from the senses, and their own internal pattern generating activities to send appropriate instructions to motorneurones controlling movement. Spinal interneurones exhibit a remarkable variety of firing patterns in response to a pulse of injected current, with important implications for information processing. These patterns range from repetitive to delayed, to bursting and to single spiking.

In the ventral spinal cord, interneurones process both motor commands and sensory inputs. Steady firing interneurones integrate these inputs, while bursting neurons may emphasize input variations and single spiking neurons probably serve as coincidence detectors. Although these different processing modes suggest a diversity in ion channels, Robert Lee (now at Emory University) and C J Heckman hypothesized that a small component of the total current mediated by sodium channels plays a critical role in determining firing patterns. This component is persistent instead of transient and is essential for action potential initiation during prolonged input.

The research by Theiss et al. on slices of spinal cord taken from rats indicates that reducing persistent sodium current in ventral interneurones converted both steady firing and bursting patterns into a single spike pattern, and thus its modulation may provide the CNS with the capacity to mediate dramatic changes in neural computations. This result is an important step forward in our understanding of neuronal processing and should lead to more research on how persistent sodium currents interact with other currents to generate the full array of firing patterns of neurons throughout the CNS.

Dr. Theiss noted that “Abnormal regulation of persistent sodium currents in disease states like spinal injury and ALS could seriously impair the integration of motor commands with sensory inputs, which is essential for normal movement patterns”.

Blame The Brain For High Blood Pressure

The controversial idea that one cause of high blood pressure lies within the brain, and not the heart or blood vessels, has been put forward by scientists at the University of Bristol, UK, and is published this week in the journal Hypertension.

Dr. Hidefumi Waki, working in a research group led by Professor Julian Paton, has found a novel role for the protein, JAM-1 (junctional adhesion molecule-1), which is located in the walls of blood vessels in the brain.

JAM-1 traps white blood cells called leukocytes which, once trapped, can cause inflammation and may obstruct blood flow, resulting in poor oxygen supply to the brain. This has led to the idea that high blood pressure — hypertension — is an inflammatory vascular disease of the brain.

One in three people in the UK are likely to develop hypertension, and with 600 million people affected world wide, it is of pandemic proportions. The alarming statistic that nearly 60 per cent of patients remain hypertensive, even though they are taking drugs to alleviate the condition, emphasises the urgency of looking for new mechanisms by which the body controls blood pressure, and finding new therapeutic targets to drive fresh drug development.

Professor Paton said: “We are looking at the possibility of treating those patients that fail to respond to conventional therapy for hypertension with drugs that reduce blood vessel inflammation and increase blood flow within the brain. The future challenge will be to understand the type of inflammation within the vessels in the brain, so that we know what drug to use, and how to target them. JAM-1 could provide us with new clues as to how to deal with this disease. “

Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, commented: “This exciting study is important because it suggests there are unexpected causes of high blood pressure related to blood supply to the brain. It therefore opens up the possibility of new ways to treat this common, but often poorly managed, condition.”

As there is still poor understanding about what changes occur in people when hypertension develops, the finding of JAM-1 is of great interest and opens up multiple new avenues for further research and potential treatment.

Funded primarily by the British Heart Foundation, Professor Julian Paton and colleagues have been working on the problems of hypertension for 12 years. Although the idea that the brain is to blame for high blood pressure is controversial, recent evidence from both animal models and patients supports this.

Article: Junctional Adhesion Molecule-1 Is Upregulated in Spontaneously Hypertensive Rats. Evidence for a Prohypertensive Role Within the Brain Stem. Hidefumi Waki, Beihui Liu, Masao Miyake, Kiyoaki Katahira, David Murphy, Sergey Kasparov, and Julian F.R. Paton, in Hypertension.

Note: This story has been adapted from a news release issued by University of Bristol

Physio-NeuroModulation Concept

Just performing simple search to any search engine for ” Neuromodulation” ,the search will reveal many results ,checking or reading any link you got the imperssion that Neuromodulation can be applied only through Invasive methods of surgery and appliances surgically implianted .

The Physio-Neuromodulation concept is a simple process of motion , thoughts , behavior and mood input to the Nervous System which is a plastic system capable of picking non-threat inputs responding appropriately .

Currently , there is storng evidence and research supports the neuromodulatory process (Neural Plasticity ) using simple , non-invasive inputs .

Cheers
Emad

DermoNeuromodulation

Diane ,Physiotherpist from Canada , was the first one used the Skin to modulate the Nervous System spicifically in pain , on my blog roll there is a link to her blog ,and here you are what she thinks of DNM.

At last, after several years of probing, searching, trying on and then rejecting one name after another for what I physically do with patients' bodies, trying to encompass the whole of the nervous system and the whole of one's interaction with it within a single name, I've settled on dermoneuromodulation.

It has these main important inclusions:
1. The "neuro" portion is the most important. It provides the concept that the nervous system is central to the any treatment interaction, at any and at every level, the whole way from the attempt to include only slowadapting non-nocioceptive stretch receptors (Ruffini endings in the skin), to answering any and every question a patient may have, to providing an overview of how the nervous system works and how pain is generated, as a standard part of every encounter with every new patient.
2. The term "modulation" is what the nervous system is doing in response to an input. It modulates itself in response to any sensory input. It does this continually from its initial formation in utero until the moment it dies, at whatever age one dies.
3. The prefix "dermo" means, sensory input through the skin, kinesthetic sensory input. Other prefixes mean other things. For example "psychoneuromodulation" would lean more toward describing psychological input that could result in modulation delivered to the human organism via the (cultural, social) mind, as opposed to kinesthetic input that could result in modulation delivered to the human organism via the physically sensing brain. Not that both couldn't happen simultaneously, or don't all the time in manual treatment. (If we try to pretend they don't we're kidding ourselves.)

It has these important exclusions:
1. It is a brand new word combination that I've seen nowhere else.
2. It therefore carries no baggage.
3. It will never (as long as I am in control of this new meme I'm introducing) contain anti-scientific or pseudo-scientific ideas.
4. Most importantly, there is not a speck, not one hint of any reference to any mesodermal derivative embedded in this term anywhere. This means;
- no mention of mobilizing of any joints
- no reference to moving bones
- no suggestion of releasing fascia
- no talk of muscle lengthening
If any of these things happen during or after dermoneuromodulation, fine, but any changes in any mesodermally derived tissue will be as a result of the brain/nervous system of the patient in question deciding to modulate itself to allow such a thing to happen, not a direct result of a practitioner's applied force.

I have spent years working my way out of confusing conceptual traps by learning all I can about how the human organism with an intact nervous system actually works, how it can end up in trouble (i.e., pain), how it actually interacts with another system (e.g., mine) to its own benefit. The hits now outweigh the misses by far, because my own nervous system (including my own mind) and motor output has adapted over many years, has become the best possible human primate social grooming nervous system it can be, has learned to be slow and gentle and patient on the one hand, nitpicky and precise and persistent on the other, when treating other nervous systems.

This naming process has been a long time coming, mainly because those exact same personal traits carried over into it. It feels like a long-awaited birth has finally occurred, but (thankfully) not as exhausting as the teaching experience was

Pain hypersensitivity

Pain hypersensitivity

Clifford J Woolf

Pain systems need to be sensitive enough to detect potentially harmful stimuli. But often they become too sensitive, causing us pain that provides no benefit. This hypersensitivity arises because our pain pathways actually increase in sensitivity when they relay pain messages, and the mechanisms of this sensitization are beginning to be revealed.

Normally, pain is produced only by intense stimuli that are potentially or actually damaging to tissue (technically known as noxious stimuli, although commonly referred to as pain stimuli). This pain is mediated by a specific system of high-threshold peripheral and central neurons designed to respond only to such noxious stimuli (the nociceptive system, also see Sensing damage), which is responsible for the ‘ouch’ pain we experience in response to a needle prick or on touching a hot surface.

Nociceptive pain is an essential early warning device that helps protect us from the dangerous environment we find ourselves in. To do this the sensation of pain needs to be so unpleasant that we cannot ignore it.

Clinical pain, by contrast, occurs in response to tissue injury and inflammation (inflammatory pain), damage to the nervous system (neuropathic pain) and alterations in the normal function of the nervous system (functional pain). It features both spontaneous pain that arises without any apparent peripheral stimulus and hypersensitivity to peripheral stimuli.

Pain hypersensitivity takes two forms:

• thresholds are lowered so that stimuli that would normally not produce pain now begin to (allodynia).
• responsiveness is increased, so that noxious stimuli produce an exaggerated and prolonged pain (hyperalgesia).

Pain hypersensitivity after an injury helps healing by ensuring that contact with the injured tissue is minimized until repair is complete – an adaptive response. However, pain hypersensitivity may persist long after an injury has healed or occur in the absence of any injury. In this case, pain provides us with no benefits, and is a manifestation of pathological change in the nervous system.

What produces pain hypersensitivity and how can we normalize it? Two mechanisms are known to be involved: peripheral and central sensitization. ‘Sensitization’ here means an increase in the excitability of neurons, so they are more sensitive to stimuli or sensory inputs.

Peripheral sensitization
Peripheral sensitization is a reduction in threshold and an increase in responsiveness of the peripheral ends of nociceptors, the high-threshold peripheral sensory neurons that transfer input from peripheral targets (skin, muscle, joints and the viscera) though peripheral nerves to the central nervous system (spinal cord and brainstem).

Peripheral sensitization contributes to the pain hypersensitivity found at the site of tissue damage and inflammation. A good example of this is the change in heat sensitivity after sunburn, when a normally warm stimulus such as a shower feels burning hot in the sunburned areas.

Sensitization arises due to the action of inflammatory chemicals or mediators released around the site of tissue damage or inflammation. Some of these, such as ATP, can directly activate the ends of the peripheral nociceptors, signalling the presence of inflamed tissue and producing pain. Other chemical mediators are produced by activated inflammatory cells, such as neutrophils (a type of white blood cell). When activated, these cells begin making an enzyme known as Cox-2, which leads to the production and secretion of prostaglandin PGE2. This mediator act as a sensitizer, altering pain sensitivity by increasing the responsiveness of peripheral nociceptors. Aspirin-like pain-killing drugs act by inhibiting Cox-2 and prostaglandin production.

Central sensitization
Central sensitization is an increase in the excitability of neurons within the central nervous system, so that normal inputs begin to produce abnormal responses.

The increased excitability is typically triggered by a burst of activity in nociceptors (such as that evoked by an injury), which alter the strength of synaptic connections between the nociceptor and the neurons of the spinal cord (so-called activity-dependent synaptic plasticity).

Low-threshold sensory fibres activated by very light touch of the skin, for example, begin to activate neurons in the spinal cord (for inputs from the body) or in the brainstem (for inputs from the head) that normally only respond to noxious stimuli. As a result, an input that would normally evoke an innocuous sensation now produces pain. In effect, the synaptic changes increase the ‘gain’ of the system.

Although the pain feels as if it originates in the periphery, it is actually a manifestation of abnormal sensory processing within the central nervous system.

Central sensitization is responsible for tactile allodynia (pain in response to light brushing of the skin) and for the spread of pain hypersensitivity beyond an area of tissue damage so that adjacent non-damaged tissue is tender. Central sensitization can also occur after surgery, contributing to pain on movement or touch, in migraine attacks where brushing hair is often painful, and in some patients with nerve damage where even blowing on the skin produces excruciating burning pain.

More recently, it has been suggested that diseases such as fibromyalgia (a condition associated with a tender painful muscular pain) or irritable bowel syndrome may be manifestations not of peripheral pathology but of altered function of the nervous system (functional pain).

What are the mechanisms responsible for peripheral and central sensitization? At a cellular level they are quite different, but at a molecular level they share several similarities.

Mechanisms: peripheral sensitization
Peripheral sensitization is the result of changes in key proteins and ion channels (known as transduction proteins) that determine the excitability of the nociceptor terminal. The transduction proteins are the means by which a noxious stimulus, for example excessive heat, is converted into electrical activity. Normally for heat this only occurs at around 42°C, the heat pain threshold. After peripheral inflammation, though, the threshold falls considerably.

Two processes have been implicated in this increase in sensitivity:

• changes to existing nociceptor proteins (post-translational processing)
• changes to the proteins being made by the nociceptor (altered gene expression).

Post-translational changes usually involve the addition of phosphate groups to some of the protein’s amino acids, by enzymes known as kinases. This phosphorylation can dramatically alter the properties of a protein, for example reducing the temperature required to open an ion channel. Sodium ion channels that determine the excitability of the nociceptor terminal can also be phosphorylated. As well as lowering the threshold at which they open, phosphorylation also makes the channel open for longer, so that any stimulus to the terminal will evoke a greater response.

The kinases are activated by a cascade of intracellular signals initiated by inflammatory mediators (such as prostaglandins) acting on receptors present on the peripheral ends of the nociceptor. Most of these signals act locally in the terminal to change the properties of proteins present on the membrane.

Some signals, however, are transported from the terminal along the axon or nerve fibre to the cell body of the sensory neurons in the dorsal root ganglion. Here they either change transcription (increase expression of particular genes) or increase translation (ensure more protein is produced from messenger RNA). The increased protein is then shipped back down to the terminal where it contributes to an increased responsiveness of the terminal to peripheral stimuli. One example is the TRPV1 protein, an ion channel that responds to heat stimuli. Activation of kinases takes minutes, changes in protein levels a day or so.

Central mechanisms
Central sensitization also has two phases:

• an immediate but relatively transient phase; and
• a slower onset but longer-lasting phase.

Again, the first phase depends on changes to existing proteins while the second phase relies on new gene expression.

The early phase reflects changes in synaptic connections within the spinal cord, after a signal has been received from nociceptors. The central terminals of the nociceptor release a host of signal molecules, including the excitatory amino acid synaptic transmitter glutamate, neuropeptides (substance P and CGRP) and synaptic modulators including BDNF.

These transmitters/modulators act on specific receptors on the spinal cord neurons, activating intracellular signaling pathways that lead to the phosphorylation of membrane receptors and channels, particularly the NMDA and AMPA receptors for the glutamate neurotransmitter. These post-translational changes lower the threshold and opening characteristics of these channels, thereby increasing the excitability of the neurons.

A later transcription-dependent phase of central sensitization is mediated by increased levels of protein production. The net effect of these changes is that normally subliminal inputs begin to activate the neurons and pain sensibility is drastically altered.

Among the proteins mediating this effect are dynorphin, an endogenous opioid that increases neuronal excitability, and Cox-2, the enzyme that produces prostaglandin E2. As well as being involved in peripheral sensitization, prostaglandins also affect central neurons, contributing to central sensitization. Indeed, the analgesic action of aspirin-like drugs may derive more from their central than peripheral actions on Cox-2.

Therapeutic leads
The increased responsiveness of peripheral and central neurons plays the major role in the production of abnormal pain. The molecular components of the intracellular signalling cascades responsible for sensitization are key targets for new interventions aimed at reducing such pain. Many promising therapies are being tested, based on small drug molecules that interfere with the action of these newly discovered targets.

Clifford J Woolf is Director of the Neural Plasticity Research Group and Professor of Anesthesia Research, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts USA. Web http://www.mgh.harvard.edu/nprg/

Further reading
Hunt SP, Mantyh PW. The molecular dynamics of pain control. Nature Review Neuroscience 2001 2:83-91.

Ji RR, Kohno T, Moore KA, Woolf CJ. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends in Neurosciences 2003 26:696-705.

Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature. 2001 413:203-10.

McCleskey EW, Gold MS. Ion channels of nociception. Annual Review Physiology 1999 61:835-56.

Scholz J, Woolf CJ. Can we conquer pain? Nature Neuroscience 2002 Supplement 5:1062-7.

Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000 288:1765-9

Blocking Pain memories

Memories of Pain Can Come Back To Hurt

By William J. Cromie
Gazette Staff

Clifford Woolf (left) and Ru-Rong Ji study ways to block the activity of molecules that increase sensitivity to pain. One way is to give painkillers before surgery. This has been tried successfully by giving morphine before prostate surgery instead of afterwards. Photo by Jon Chase.

Newly found connections between pain and memory are leading to novel ways to control pain.

Nerves carry pain signals to the spinal cord and brain where they excite cells involved with making memories of pain, according to Clifford Woolf, Kitz Professor of Anesthesia Research at Harvard Medical School. This excitation is a main contributor to post-injury pain. It produces an increased sensitivity that can last for months. “As we search for the molecular basis of pain, we keep uncovering associations between pain and memory,” Woolf says. “Blocking such associations can provide a new basis for treating pain.” As an example, to decrease excitability, patients were given spinal injections of painkillers before prostate surgery. Compared with those not so treated, they experienced less pain while hospitalized and were more active after surgery. The pain reduction lasted as long as nine and a half weeks. “When you think about it, the link makes sense,” Woolf points out. “During evolution, animals had to learn to recognize what causes pain and to remember to avoid such things. A one-celled amoeba moves away from too much heat just as a human avoids a hot stove.” ERKs Signal Hurts Woolf came to Harvard-affiliated Massachusetts General Hospital in Boston two years ago to research the origins of pain and to apply the results to treating patients. While working in London in 1983, he discovered that pain alters the nervous system in a way that makes parts of it sensitive to pain for hours to months. That memory, he concluded, is responsible for the pain we experience after surgery, a tooth removal, or any wound that makes an area sore to the touch for some time. But how is this memory made? A few years ago, researchers found molecules they call ERKs – extracellular signal-related kinases. These proteins carry signals from the surface of cells to the genes in their nuclei, changing how the cells function by changing the way genes are turned on or off. In others words, an ERK can change the memory of cells in the spinal cord and brain. In the past few months, Woolf and colleague Ru-Rong Ji put the two findings together to show how ERKs provide a link between pain and memory. If you have abdominal surgery, you don’t feel any pain because you are under anesthesia. However, the cutting of skin and muscle produces a barrage of distress signals that travel, via nerves, to ERKs in nerve cells of the spinal cord. The ERKs, in turn, cause short- and long-term changes to nerve cells in the spinal cord and the brain area where the sensation of pain is “felt.” When you awake from anesthesia, these altered cells retain their excitability, or sensitization, prolonging your pain and soreness. “The post-operative pain is a manifestation of switching on the memory of the pain that occurred during the surgery,” Woolf says. Giving Drugs Before Pain That conclusion opens the way for novel ways to treat pain. One obvious way is to give painkillers before patients feel pain, not after, a procedure doctors call “preemptive analgesia.” In the prostate study mentioned above, researchers at the University of Pennsylvania School of Medicine injected painkillers into the spines of 66 patients before surgery to remove the prostate gland. These patients then compared their pain experiences with those of 30 other men who got general anesthesia only. Allan Gottschalk and his research team reported that the “preemptive analgesia significantly decreases postoperative pain during hospitalization and long after discharge, and is associated with increased [physical] activity levels after discharge” from the hospital. The powerful drug morphine is now being used this way. “By administering it before, rather than after treatment, we have shown in patients undergoing hysterectomies that much smaller doses can be given,” Woolf points out. “Such acute use of the drug produces no addiction.” However, morphine has unpleasant side effects, including nausea, sedation, depression, and the potential for abuse. “It’s an effective but not an ideal drug,” Woolf comments. “What we want is a drug with the same efficacy but much fewer side effects. We think one answer lies in finding substances that block the action of specific ERKs in the spinal cord.” Woolf and his colleagues reported in the December issue of Nature Neuroscience that they used this technique to block pain in rats. The animals received injections of capsaicin, the active ingredient of chili peppers that produces an intense burning sensation. Capsaicin is sometimes given this way to humans who volunteer for tests of new painkillers. Drugs used to block ERKs in rats won’t do the job in humans, so Woolf is collaborating with several pharmaceutical companies to develop more selective drugs. ERKs act on practically all cells in the body, and the aim is to find inhibitors that specifically target ERKs in the human spinal cord. At the same time, the researchers pursue such basic questions as precisely how ERKs produce pain. “We believe we have found the receptor on spinal-cord cells that these proteins act upon,” Woolf notes. “Called NMDA, it’s a key to controlling the excitability of nerve cells.” The next step involves learning how ERKs change NMDA to produce the sensation of pain and form a memory of it. Finally, there’s the question of which genes are switched on in nerve cells to produce pain and its memory. “We’re becoming gene hunters,” Woolf comments, “hunting for genes that cause both ‘good’ and ‘bad’ pain.” The researchers don’t want to turn off the kind of pain that warns you to avoid something that’s too hot, sharp, or chemically noxious. People who can’t feel this kind of pain may suffer severe mutilation and reduced life spans. The goal is to avoid the increased excitability that produces the hurt of arthritis, postoperative surgery, broken bones, and other wounds and diseases. “When ether was first introduced in 1846 at Massachusetts General Hospital, it was hailed as an anesthetic that would eliminate pain,” Woolf notes. “After 150 years, this has yet to be achieved; there’s still a tremendous unmet need for relieving pain. But by understanding the mechanisms involved at the level of cells and molecules, eliminating pain is becoming a more realistic prospect.”

Mirroring-Neuromodulation

The mirror neurons are fanastic really , We have not used it yet to  its possible role effectively within physiotherapy . We can use mirror neurons to apply neuromodulation input in cases like pain and paralysis . Just sitting in front of the patient with cervical pain performing  neck free-pain motions will fire his/her mirror neurons to perform the same excuation in pain-free state . This is just My suggesation the apply practically mirror neurons researches.

Emad