What Do We Know About Chronic Pain

Today's post is the third in a series from 4therapy.com (see link below), which looks at the psychological aspects of having neuropathy and other forms of chronic pain. This one looks at pain itself, what it does and why it happens. It also considers various options for tackling pain in the future - a very useful guide to understanding your pain.

A Pain Primer: What Do We Know About Pain?
Source: National Institute of Neurological Disorders and Stroke

We may experience pain as a prick, tingle, sting, burn, or ache. Receptors on the skin trigger a series of events, beginning with an electrical impulse that travels from the skin to the spinal cord. The spinal cord acts as a sort of relay center where the pain signal can be blocked, enhanced, or otherwise modified before it is relayed to the brain. One area of the spinal cord in particular, called the dorsal horn, is important in the reception of pain signals.

The most common destination in the brain for pain signals is the thalamus and from there to the cortex, the headquarters for complex thoughts. The thalamus also serves as the brain's storage area for images of the body and plays a key role in relaying messages between the brain and various parts of the body. In people who undergo an amputation, the representation of the amputated limb is stored in the thalamus.

Pain is a complicated process that involves an intricate interplay between a number of important chemicals found naturally in the brain and spinal cord. In general, these chemicals, called neurotransmitters, transmit nerve impulses from one cell to another.

There are many different neurotransmitters in the human body; some play a role in human disease and, in the case of pain, act in various combinations to produce painful sensations in the body. Some chemicals govern mild pain sensations; others control intense or severe pain.

The body's chemicals act in the transmission of pain messages by stimulating neurotransmitter receptors found on the surface of cells; each receptor has a corresponding neurotransmitter. Receptors function much like gates or ports and enable pain messages to pass through and on to neighboring cells. One brain chemical of special interest to neuroscientists is glutamate. During experiments, mice with blocked glutamate receptors show a reduction in their responses to pain. Other important receptors in pain transmission are opiate-like receptors. Morphine and other opioid drugs work by locking on to these opioid receptors, switching on pain-inhibiting pathways or circuits, and thereby blocking pain.

Another type of receptor that responds to painful stimuli is called a nociceptor. Nociceptors are thin nerve fibers in the skin, muscle, and other body tissues, that, when stimulated, carry pain signals to the spinal cord and brain. Normally, nociceptors only respond to strong stimuli such as a pinch. However, when tissues become injured or inflamed, as with a sunburn or infection, they release chemicals that make nociceptors much more sensitive and cause them to transmit pain signals in response to even gentle stimuli such as breeze or a caress. This condition is called allodynia -a state in which pain is produced by innocuous stimuli.

The body's natural painkillers may yet prove to be the most promising pain relievers, pointing to one of the most important new avenues in drug development. The brain may signal the release of painkillers found in the spinal cord, including serotonin, norepinephrine, and opioid-like chemicals. Many pharmaceutical companies are working to synthesize these substances in laboratories as future medications.

Endorphins and enkephalins are other natural painkillers. Endorphins may be responsible for the "feel good" effects experienced by many people after rigorous exercise; they are also implicated in the pleasurable effects of smoking.

Similarly, peptides, compounds that make up proteins in the body, play a role in pain responses. Mice bred experimentally to lack a gene for two peptides called tachykinins-neurokinin A and substance P-have a reduced response to severe pain. When exposed to mild pain, these mice react in the same way as mice that carry the missing gene. But when exposed to more severe pain, the mice exhibit a reduced pain response. This suggests that the two peptides are involved in the production of pain sensations, especially moderate-to-severe pain. Continued research on tachykinins, conducted with support from the NINDS, may pave the way for drugs tailored to treat different severities of pain.

Scientists are working to develop potent pain-killing drugs that act on receptors for the chemical acetylcholine. For example, a type of frog native to Ecuador has been found to have a chemical in its skin called epibatidine, derived from the frog's scientific name, Epipedobates tricolor. Although highly toxic, epibatidine is a potent analgesic and, surprisingly, resembles the chemical nicotine found in cigarettes. Also under development are other less toxic compounds that act on acetylcholine receptors and may prove to be more potent than morphine but without its addictive properties.

The idea of using receptors as gateways for pain drugs is a novel idea, supported by experiments involving substance P. Investigators have been able to isolate a tiny population of neurons, located in the spinal cord, that together form a major portion of the pathway responsible for carrying persistent pain signals to the brain. When animals were given injections of a lethal cocktail containing substance P linked to the chemical saporin, this group of cells, whose sole function is to communicate pain, were killed. Receptors for substance P served as a portal or point of entry for the compound. Within days of the injections, the targeted neurons, located in the outer layer of the spinal cord along its entire length, absorbed the compound and were neutralized. The animals' behavior was completely normal; they no longer exhibited signs of pain following injury or had an exaggerated pain response. Importantly, the animals still responded to acute, that is, normal, pain. This is a critical finding as it is important to retain the body's ability to detect potentially injurious stimuli. The protective, early warning signal that pain provides is essential for normal functioning. If this work can be translated clinically, humans might be able to benefit from similar compounds introduced, for example, through lumbar (spinal) puncture.

Another promising area of research using the body's natural pain-killing abilities is the transplantation of chromaffin cells into the spinal cords of animals bred experimentally to develop arthritis. Chromaffin cells produce several of the body's pain-killing substances and are part of the adrenal medulla, which sits on top of the kidney. Within a week or so, rats receiving these transplants cease to exhibit telltale signs of pain. Scientists, working with support from the NINDS, believe the transplants help the animals recover from pain-related cellular damage. Extensive animal studies will be required to learn if this technique might be of value to humans with severe pain.

One way to control pain outside of the brain, that is, peripherally, is by inhibiting hormones called prostaglandins. Prostaglandins stimulate nerves at the site of injury and cause inflammation and fever. Certain drugs, including NSAIDs, act against such hormones by blocking the enzyme that is required for their synthesis.

Blood vessel walls stretch or dilate during a migraine attack and it is thought that serotonin plays a complicated role in this process. For example, before a migraine headache, serotonin levels fall. Drugs for migraine include the triptans: sumatriptan (Imitrix®), naratriptan (Amerge®), and zolmitriptan (Zomig®). They are called serotonin agonists because they mimic the action of endogenous (natural) serotonin and bind to specific subtypes of serotonin receptors.

Ongoing pain research, much of it supported by the NINDS, continues to reveal at an unprecedented pace fascinating insights into how genetics, the immune system, and the skin contribute to pain responses.

The explosion of knowledge about human genetics is helping scientists who work in the field of drug development. We know, for example, that the pain-killing properties of codeine rely heavily on a liver enzyme, CYP2D6, which helps convert codeine into morphine. A small number of people genetically lack the enzyme CYP2D6; when given codeine, these individuals do not get pain relief. CYP2D6 also helps break down certain other drugs. People who genetically lack CYP2D6 may not be able to cleanse their systems of these drugs and may be vulnerable to drug toxicity. CYP2D6 is currently under investigation for its role in pain.

In his research, the late John C. Liebeskind, a renowned pain expert and a professor of psychology at UCLA, found that pain can kill by delaying healing and causing cancer to spread. In his pioneering research on the immune system and pain, Dr. Liebeskind studied the effects of stress-such as surgery-on the immune system and in particular on cells called natural killer or NK cells. These cells are thought to help protect the body against tumors. In one study conducted with rats, Dr. Liebeskind found that, following experimental surgery, NK cell activity was suppressed, causing the cancer to spread more rapidly. When the animals were treated with morphine, however, they were able to avoid this reaction to stress.

The link between the nervous and immune systems is an important one. Cytokines, a type of protein found in the nervous system, are also part of the body's immune system, the body's shield for fighting off disease. Cytokines can trigger pain by promoting inflammation, even in the absence of injury or damage. Certain types of cytokines have been linked to nervous system injury. After trauma, cytokine levels rise in the brain and spinal cord and at the site in the peripheral nervous system where the injury occurred. Improvements in our understanding of the precise role of cytokines in producing pain, especially pain resulting from injury, may lead to new classes of drugs that can block the action of these substances.

http://www.4therapy.com/life-topics/chronic-pain/pain-primer-what-do-we-know-about-pain-2860

Quell Neurodevice For Nerve Pain Will It Be Any Good

Today's post from diabetesselfmanagement.com (see link below) anounces another electro-stimulant device designed to reduce neuropathic pain. Not quite on the market (later this year), it reflects the growing interest in electro-neurostimulation but it has to be said that so far, results from these sorts of devices have been patchy to say the least. Maybe this one will provide more people with a positive result. It's lightweight and wearable and can be tracked with a smart phone, so these things at least stand in its favour. Time will tell.

CES Dispatches: Pain-Relieving Device for Diabetic Neuropathy
January 6, 2015 by Diane Fennell


(Quell[TM] Wearable Pain Relief Device [Photo: Business Wire])

Quell, a device that can relieve chronic pain in people with conditions such as diabetes, sciatica, and fibromyalgia, was unveiled this week at the 2015 International Consumer Electronics Show (CES), taking place in Las Vegas from January 6–9.

Roughly 60% to 70% of people with diabetes have some form of the often painful condition neuropathy (nerve damage), according to the National Diabetes Information Clearinghouse, and surveys of people with diabetes reflect rates of chronic pain ranging from 20% to 60%.

Created by NeuroMetrix, Quell is lightweight, wearable device that uses noninvasive neurostimulation technology to reduce chronic pain. The device, which has been approved by the U.S. Food and Drug Administration (FDA) for use without a prescription, can be worn both during the day and at night, and users will have the option of using their smartphone to track and personalize their pain treatment.

“Recent studies have shown that chronic nerve pain dramatically reduces the quality of life in people with diabetes,” notes Shai N. Gozani, MD, PhD, President and Chief Executive Officer of NeuroMetrix. “We believe that Quell may help many of these people reclaim their life from chronic pain.”

Quell is expected to be available for purchase by consumers later this year.

For more information, see the press release from NeuroMetrix.

http://www.diabetesselfmanagement.com/blog/ces-dispatches-pain-relieving-device-diabetic-neuropathy/

New Explanation For Diabetes Related Neuropathic Pain

Today's post from Sciencedaily.com (see link below) brings a dilemma with it. A study has shown that changes in 'dendritic spines' in the brain may play an important part in explaining neuropathic pain in diabetes-related cases! Yet nowhere does it say that this is exclusively a diabetes-related occurence. The article states that the reason why diabetes can cause neuropathy is still a mystery, so there is really no reason to assume that these changes in the nerve endings in the brain only occur in diabetes patients. We need the study to include HIV-related neuropathy and many other forms too, If the dendritic spines are not altered in other forms of neuropathy, then they have some important information but at the moment, to a layman like me, it's just not clear.
 Many people with HIV looking for information on neuropathy, may skip over articles about diabetic neuropathy because they think it doesn't apply. This is generally just not true. Most of the information about diabetic neuropathy applies to all neuropathies; it's just that diabetic neuropathy is by far the most common form amongst the general population. If you ask 99 out of a 100 diabetic neuropathy patients what their symptoms are, you'll find that they are exactly the same as your own. What the researchers mean to say is that they don't really understand the processes behind why neuropathy occurs in most of its forms and tying it to one disease depends on who their target readership is. If there are any experts out there who can explain (in relatively simple terms)  the real differences in disease-based neuropathies, please let us know - very many people are interested.

Unexpected Source for Diabetic Neuropathy Pain

ScienceDaily (May 15, 2012)

Normal dendritic spines — microscopic projections on the receiving branches of nerve cells — are shown at top compared to those of diabetic rat. At bottom, spines after receiving treatment. Yale study suggests that neuropathic pain associated with diabetes may be caused by reshaping of these spines in nerve cells, and might be treated by drugs. (Credit: Image courtesy of Yale University)

Nearly half of all diabetics suffer from neuropathic pain, an intractable, agonizing and still mysterious companion of the disease. Now Yale researchers have identified an unexpected source of the pain and a potential target to alleviate it.

A team of researchers from Yale and the West Haven Veterans Affairs Medical Center describes in the May 15 issue of the Journal of Neuroscience how changes in the structure of dendritic spines -- microscopic projections on the receiving branches of nerve cells -- are associated with pain in laboratory rats with diabetes.

"How diabetes leads to neuropathic pain is still a mystery," said Andrew Tan, an associate research scientist in neurology at the Yale School of Medicine and lead author of the study. "An interesting line of study is based on the idea that neuropathic pain is due to faulty 'rewiring' of pain circuitry."
With a growing number of diabetics, the condition represents a huge unmet medical need. Once neuropathic pain is established, it is a lifelong condition.

"Here we reveal that these dendritic spines, first studied in memory circuit processing, also contribute to the sensation of pain in diabetes," Tan said. A single neuron may contain hundreds to thousands of dendritic spines.

The Yale team led by Tan and senior author Dr. Stephen G. Waxman, the Bridget Marie Flaherty Professor of Neurology, professor of neurobiology and pharmacology,found abnormal dendritic spines were associated with the onset and maintenance of pain. They also found that a drug that interferes with formation of these spines reduced pain in lab animals, suggesting that targeting abnormal spines could be a therapeutic strategy.

Tan said that these dendritic spines in nerve cells seem to store memory of pain, just as they are crucial in memory and learning in the human brain.

"We have identified a single, key molecule that controls structural changes in these spines and hopefully we can develop therapeutic approaches that target that molecule and reduce diabetic pain," Waxman said.

Other authors on the paper are Omar A. Samad, Tanya Z. Fischer, Peng Zhao and Anna-Karin Persson,
The research was funded by the Department of Veterans Affairs.

http://www.sciencedaily.com/releases/2012/05/120515203056.htm

Shellfish Toxins For Nerve Pain

Today's interesting post is a press release from labspaces.net (see link below) and talks about something for the future of neuropathy treatment. It describes using liposomes, which are lipid spheres smaller than a red blood cell, to deliver powerful anaesthetics (sourced from shellfish) to the source of neuropathic pain. It still looks to be very much work in progress but is yet another sign that serious efforts are being made to research new nerve damage treatments and that can only be a good thing.

Putting a block on neuropathic pain before it starts

Tuesday, October 9, 2012 Thanks to Boston Children's Hospital for this article.

Using tiny spheres filled with an anesthetic derived from a shellfish toxin, researchers at Boston Children's Hospital and the Massachusetts Institute of Technology have developed a way to delay the rise of neuropathic pain, a chronic form of pain that arises from flawed signals transmitted by damaged nerves.

 The method could potentially allow doctors to stop the cascade of events by which tissue or nerve injuries evolve into neuropathic pain, which affects 3.75 million children and adults in the United States alone.

The researchers, led by Daniel Kohane, MD, PhD, of Boston Children's Department of Anesthesia and Robert Langer, ScD, of MIT, reported the results of animal studies online the week of October 8 in the Proceedings of the National Academy of Sciences.

Neuropathic pain can be long lasting and debilitating. Caused by shingles, nerve trauma, cancer and other conditions, it arises because damaged nerves send unusual signals to the spinal cord and the brain. The constant signaling effectively reprograms the central nervous system to react to any stimulus to the affected area, or even no stimulus at all, by triggering unpleasant sensations ranging from tingling and numbness to shooting, burning pain.

"Currently neuropathic pain is treated with systemic medications, but there has been significant interest in using powerful local anesthetics to block aberrant nerve discharges from the site of injury to prevent the onset of neuropathic pain," said Kohane. "Others have tried with varying degrees of success to do this in animal models using a variety of methods, but if applied clinically, those methods would require surgical intervention or could be toxic to tissues. We want to avoid both of those concerns."

The team's method combines saxitoxin, a powerful local anesthetic, and dexamethasone, which prolongs saxitoxin's effects. The two are packaged in liposomes—lipid spheres about 5.5 micrometers wide, or a bit smaller than a red blood cell—for nontoxic delivery to the site of nerve or tissue damage.

To assess whether the anesthetic-loaded liposomes (called SDLs for saxitoxin dexamethasone liposomes) might work as a potential treatment for neuropathic pain, Kohane and Langer—along with Sahadev Shankarappa, MBBS, MPH, PhD (a fellow in the Kohane lab) and others—attempted to use them to block the development of signs of neuropathy in an animal model of sciatic nerve injury. They found that a single injection of SDLs had a very mild effect, delaying the onset of neuropathic pain by about two days compared to no treatment. Three injections of SDLs at the site of injury over the course of 12 days, however, delayed the onset of pain by about a month.

The signal blockade mounted by the SDLs also appeared to prevent reprogramming of the central nervous system. The team noted that astrocytes in the spine, which help maintain the pain signaling in neuropathic patients, showed no signs of pain-related activation five and 60 days after injury in animals treated with SDLs.

"Ultimately we'd like to develop a way to reversibly block nerve signaling for a month with a single injection without causing additional nerve damage," Kohane explained. "For the moment, we're trying to refine our methods so that we can get individual injections to last longer and figure out how to generalize the method to other models of neuropathic pain.

"We also need to see whether it is safe to block nerve activity in this way for this long," he continued. "We don't want to inadvertently trade one problem for another. But we think that this approach could be fruitful for preventing and treating what is really a horrible condition."

http://www.labspaces.net/124304/_Putting_a_block_on_neuropathic_pain_before_it_starts_

Puffer Fish Poison For Nerve Pain

Today's post from smithsonianmag.com (see link below) talks about yet another poison (tetrodotoxin) from the animal world which may turn out to be useful in the struggle to control nerve pain. This time it's the Simpson's favourite - the Puffer fish, which kills a handful of trainee chefs every year. It's not such a stretch as you might think. Most animal poisons work by attacking the nervous system of their victims, so it's logical to assume that with modification, these poisons can be used to develop drugs which will act positively on the nervous system itself. Along with spiders, snakes, scorpions and others, this is the latest toxin which may be the answer to relentless nerve pain and that of course, affects all people living with neuropathy. Watch this space.

Pufferfish’s Deadly Toxin Could Help Chemo Patients
By Mary Beth Griggs smithsonian.com June 27, 2013

Researchers in New Jersey are working on an experimental drug that they hope will provide pain relief to cancer patients going through chemotherapy. The drug uses tetrodotoxin, the neurotoxin found in pufferfish.

Cancer is awful. And treatments for cancer, including chemotherapy, can be incredibly painful. Even the treatments for the pain, usually opioids like morphine, can be debilitating, with side effects like dizziness, vomiting, constipation and addiction.

Because of this, medical researchers are very interested in developing alternatives to opioid medications. Researchers at the John Theurer Cancer Center at Hackensack University Medical Center, in New Jersey, are working on an experimental drug that they hope will provide pain relief to cancer patients going through chemotherapy. The drug uses tetrodotoxin, the neurotoxin found in pufferfish.

In a statement, lead investigator Dr. Samuel Goldlust said, “Tetrodotoxin has been found to be 3,000 times more potent than morphine without the negative side effects of opioids.”

Tetrodotoxin is better known for providing a dangerous allure to foodies who enjoy living on the edge. Even though pufferfish contain enough of the toxin to kill 30 people, they are considered a delicacy—delicious if prepared correctly, deadly if not.

From io9:

chefs have to be trained for two years, during which they will eat many of the fish that they themselves prepare. And make no mistake, people do die from fugu poisoning. About five people a year make puffer fish their last meal, and many more get violently sick from it. It’s not a pleasant way to go.

The poison, tetrodotoxin, is actually produced by the bacteria that the fish allows to colonize its various parts. Tetrodotoxin is a neurotoxin, meaning it takes out the nervous system as it moves through the body. This may sound like a relatively painless death, with the brain going offline quickly. That’s not the case. The toxin starts with the extremities. The first place people notice it is in the lips. Then the fingers. There’s a tingling numbness, and a loss of control. This is a sign that it’s time to get to the hospital. The toxin moves inwards from there, taking out the muscles, often causing weakness, while paradoxically bringing on vomiting and diarrhea. Then tetrodotoxin hits the diaphragm. This is the large, muscular membrane in the chest that lets the lungs breathe in and out. The respiratory system is paralyzed while the person is still fully conscious. Eventually the toxin does get to the brain, but only after the person involved has felt their body being paralyzed completely, entombing them inside. Even then, some people aren’t lucky enough to completely lose consciousness. There are people who report being conscious, either occasionally or continually, throughout their coma.

The same qualities that make tetrodotoxin so deadly—taking out parts of the nervous system—are being harnessed by these researchers to block pain signals from parts of the damaged nervous system from getting to the brain. Forty percent of patients undergoing chemotherapy report having this kind of pain, and it is one of the more common reasons that patients will cite as a reason they choose to stop chemotherapy.

Dining on pufferfish, though, isn’t even remotely a good idea for chemo patients: The treatment developed by Goldlust and WEX Pharmaceuticals uses 300 times less toxin than is found in a single puffer fish and has a very long way to go before it is available to patients. It’s currently in a phase II trial (one of about 100-300 people, according to the FDA, which looks at how effective—and, extra key in this case, how safe—the drug is) and is being tested specifically on its ability to treat patients with “chemotherapy-induced neuropathic pain”—pain caused when chemotherapy treatment damages parts of the nervous system.

There’s two more phases after this, one before and one after the drug goes to market. Only about a third of experimental drugs make it through phases I and II of testing, and phase III is the most expensive and lengthiest part of the FDA approval process. But when dealing with painkillers, particularly painkillers that are based on deadly neurotoxins, it certainly makes sense to take the time to make sure the treatment is safe.

 http://www.smithsonianmag.com/smart-news/pufferfishs-deadly-toxin-could-help-chemo-patients-3446252/#hvJxYvYMcFAsV2B2.99

The Pitfalls Of Caring For Someone In Chronic Pain

Today's post from paincommunity.org (see link below) is a very useful article describing how difficult it can be to be a care giver for someone living with chronic pain. As many of you will know, neuropathy pain can reduce the quality of someone's life dramatically but not only the patient suffers. Their family and friends and the person who has had the responsibility of primary care thrust upon him or her, has to learn to adapt to a whole new relationship scenario and that can be very difficult indeed. Via the writer's own personal experiences, this article sums up the main problems and gives some hints as to how to learn to cope. Certainly worth a read if you're in that position, either as patient or carer.

“Angry, Sad and Frustrated”– The Unspoken Feelings of a Caregiver
Posted by Jim Stemple | March 19, 2014

As a caregiver to a very special lady for the last 20+ years I have learned it is ok to be angry and frustrated. This understanding did not come overnight.
Here is what I learned.
 
1: Chronic pain comes along and turns the lives of everyone involved upside down. Everything you knew is no more. Your life isn’t your life anymore, it is now a life filled with uncertain days and nights. You see the pain doesn’t only affect the person living with pain, it affects all those around them. It affects the whole household and those close to them outside the home. I may not live with chronic pain myself but I do live with someone who does and I am affected on so many different levels.

All the plans you had made for the future are put on hold or forgotten about. You find that each day life can and does throw something new at you and your loved one. It can be breakthrough pain, it can be a new health issue, insurance problems, finding a provider or just plain old frustration that threatens to blow the top of your head off.

The stress of not being able to know from day to day what the pain is going to decide to do to your loved one is over-whelming some days. As a caregiver you constantly worry what each day will bring.
 
2: Sometimes the one who is living with pain doesn’t realize how much it affects those around them. You see they are so consumed with trying to deal with the pain each day that sometimes they forget about the ones around them. The one living with pain will feel as if their partner/ caregiver doesn’t care enough, is angry at them or doesn’t believe that they “really have pain”.

But you know, it isn’t that at all. We, as caregivers, are pulled in so many directions that sometimes we think our heads may spin off of our necks. We do not know if we are coming or going—I know that I have felt that way.

3: For many partners/caregivers the financial stability of the family is always on your mind. For some families you lose the 2nd income that you were dependent on when your loved one is no longer able to work due to the pain. This can and does cause much discomfort and friction within the family. You don’t lay the blame on your loved one because they are unable to work but you cannot help but to feel frustrated at what the pain has done to your family and your dreams.

So what is the secret to success?

Over the years I have found that the most important thing is to communicate. It is ok for the caregiver to lose it once in a while. It is ok to be angry, sad, frustrated and overwhelmed. Share what you are feeling with your family or loved one. Let them know that you aren’t feeling all these things because of them, you are feeling all of this because of the situation—the pain and what it has done to the family and the one for whom you care so deeply.
Communicate with each other.

It is a two-way street. Share those feelings rather than holding on to the frustration, fear and anger. You are borrowing trouble that you nor your loved ones need, if you do not remain open. Holding in those nasty feelings may come back and haunt you– one day you are going to blow and it is not going to be pretty. Don’t wait until the fuse is lit because then things are said that hurt your loved one. Things that cannot be taken back no matter how much you wish you could.

I have been guilty of opening my mouth in frustration and saying some very hurtful things to her. Things that I didn’t mean and things that I wish I could take back more than anything. I am thankful because she knows that it is the anger and frustration talking and she can and does let my slips of hurtful words roll on by her and doesn’t dwell on them.

Trust me, we were not always like that but over the years we have learned to understand that the pain can make each of we say things that we truly don’t mean. We have learned that the pain is a vixen waiting for the right moment to spring forward and turn our lives in to a “he said, she said” fight of the century.

As a caregiver, I have found times where I feel torn between providing for the family and being there when I am needed. This push and pull really sucks! My job consists of taking me out of state each week. There are Mondays that I want nothing more than to stay at home and comfort her. Yet, I know that this will not happen, as I must be the provider which means leaving her and heading out to work. It doesn’t matter how much pain she is in. I have to leave her and go to work.

Yes, there are times she gets angry at me as she wants me there with her. It isn’t that I can really do anything to make the pain better. It is just knowing that she isn’t alone. I understand that but I am helpless to do anything about it. Even though she gets upset, I know she understands that if I could, I would never leave her alone.

As a caregiver, don’t you feel pulled and pushed in a hundred different directions at the same time? Do you find yourself angry, sad and frustrated because you want nothing more than to help your loved one? Would you take the pain from them in a heartbeat? I know I would. After all, I feel it was my job to protect her and help make her life a fairy tale come true.

The pain changes all that but remember even though you are angry, sad and frustrated you can make the world of difference for your loved one by just being there for them. You can make a difference by just listening, by holding their hand or giving a gentle hug when they need it the most.

Help find the humor in this world of pain and share it with them. You will be surprised how much laughter can help both of you. My special gal tells people all the time that if she had a penny for every time I have made her laugh we would be millionaires. That makes me smile.
Here is the pearl:

Remember the pain affects the whole family unit and it is up to everyone in that unit to make the best of the situation. Sure, you can choose to be miserable, depressed and find yourselves fighting all the time. A better option is to choose to communicate with each other and find the love, laughter and the ability to still see all that is good in your lives. Live the life that you want to live and refuse to let the pain destroy what means the world to you.

http://paincommunity.org/angry-sad-frustrated-unspoken-feelings-caregiver/

Educating The Nervous System To Ignore Pain

Today's post from pbs.org (see link below) is an excellent explanation of the complexity of chronic pain as a condition and how modern drugs are frequently ineffective in dealing with it. The need is for new drug compounds to address new neural receptors but although progress is being made, it will still take a very long time before the processes and drugs can be explored and refined. It is thought that by interrupting the signal between the pain and the brain (to put it very simply) there is a brief period when old pain memories can be erased. It's working in this area that may bring the most progress for nerve damage patients in the future. A fascinating article - definitely worth a read.

Teaching the Nervous System to Forget Chronic PainBy Eleanor Nelsen on Wed, 13 Aug 2014

“It was an emergency situation,” she says. The horse Sally was riding was barreling straight towards another, younger horse, and the only way to stop him was to pull back on one rein, hard. She felt a pop in her wrist. Heat shot up her arm, excruciating pain fast on its heels.

That was four years ago. No one knows quite what happened to her wrist that day, but whatever it was has left her with constant pain that stretches from her fingertips to her neck, and sometimes creeps into her ribs. On the really bad days, even a hug is unbearably painful.

Sally is my youngest sister, and she is one of an unlucky fraction of people for whom an injury catapults their nervous system into a state of chronic pain. The injury itself heals, but like an insidious memory, the pain lingers. We don’t know why. “The whole issue of the transition from acute pain to chronic pain—why some individuals develop that chronic pain and many don’t—is a major, major question,” says Allan Basbaum, a professor at the University of California, San Francisco. Genetics may play a role. So can the severity of the original injury. 
Today's painkillers are based on well-known compounds like morphine and are often highly addictive.

But what we do know is that once that pain has gotten a foothold, doctors and patients don’t have very many choices. “The irony is that morphine, the 2,000-year-old drug, still remains the number-one weapon against pain,” says Yves De Koninck, a professor of neuroscience at Université Laval in Canada.

And it’s not a weapon that anyone enjoys using. Opioids like morphine and oxycodone are famously addictive, and the numbers of people who abuse them are climbing. Painkiller overdoses now kill more people than cocaine and heroin combined. And while opioids are invaluable for acute pain, they’re less effective for persistent, chronic pain. In fact—in a particularly cruel irony—long-term opioid treatment can actually make pain worse. Non-opioid pain medications exist, but they don’t work for the majority of patients, and even then they are only partly effective. Chronic pain is like “a maladaptive memory.”

Opioids work so well for acute pain because they bind to the receptors the body has designed for its own painkillers—molecules like endorphins and dynorphins that blunt the pain response. Finding good alternatives to opioids for treating chronic pain will mean finding different neurological mechanisms to target—mechanisms that explain not just why people hurt, but why some people hurt for so long.

De Koninck has found such a mechanism. One of the keys to understanding chronic pain, he believes, is to pay attention to the similarities between long-lasting pain and another, very familiar, neurological process that makes some connections stick around longer than others: memory.

Chronic pain is like “a maladaptive memory,” Basbaum explains. Both constitute patterns etched in your brain and nervous system that quicken the connections between “snake” and “poison” or between “bump” and “ouch.” Evidence has been piling up that chronic pain and memory share some of the same cellular mechanisms—and now, De Koninck’s work has shown that a neurochemical trick used to erase memory may be able to turn off chronic pain, too. An Unmet Need

The number of people struggling with chronic pain has been hotly debated, and the fact that chronic pain is broadly defined and difficult to quantify doesn’t help. But even conservative estimates suggest that about 20% of the population have had at least one episode of serious, chronic pain. In the United States alone, that’s more than 60 million people. “It’s a major unmet need,” De Koninck says.

Pain is physically and psychologically debilitating in way that few other conditions are. “In fact, it’s often the most debilitating component of many diseases,” De Koninck notes. And it sharply circumscribes the lives of people who suffer from it. People can find a way to live with the other challenges of painful conditions like arthritis, cancer, even paralysis, he says, but “if you actually ask the patient, their number-one concern, and the one thing that they want us to cure, is the pain.” When pain pathways are functioning properly, they play a protective role.

When chronic pain gets severe, many patients withdraw, sometimes even from their families. Sally says that she’s constantly nervous, afraid to accept invitations or do things that she loves—like riding horses—in case it makes her arm even worse. The ride that day, Sally says, “changed my life.” For some patients, chronic pain can lead to serious mental health problems—it’s strongly correlated with depression and suicide risk.

When pain pathways are functioning properly, they play a protective role. They are a relay of chemical and electrical signals that move from nerve endings to our brains. Pain teaches us to avoid things that are sharp, prickly, or hot. It’s the way our nervous system has adapted to living in a hazardous world. People who can’t feel any pain typically don’t live very long.

Our skin is packed with millions of specialized nerve endings, programmed to detect dangerous conditions like heat or pressure. When one of these pathways is activated, the neuron sends an electrical current shooting up its long, thin axon towards the spinal cord. When it reaches the end of the neuron, that electrical signal prompts the release of chemicals called neurotransmitters into the synapse, or the gap between the first neuron and the next. The neurotransmitters dock in receptors on the next neuron, triggering pores to open in the cell’s membrane. Charged particles rush in through these open pores, creating a new electrical current that carries the signal farther up the nervous system.
Nerve cells, like these seen here from a mouse's spinal cord, send impulses along their axons and connect over synapses.

The first handoff occurs in a region of the spinal cord known as the dorsal horn, a column of grey matter that looks, in cross-section, like a butterfly. From this first relay point, the signal travels to the thalamus, one of the brain’s switchboards, and eventually to the cerebral cortex, where the signal is processed and decoded.

After an injury, it’s normal for the damage sensors near the trauma site to be touchy for a little while. During that time, your nervous system is encouraging you to protect the damaged tissue while it’s healing. But sometimes that extra sensitivity, called “hyperalgesia,” sticks around long after it’s useful. Hyperalgesia is often a major component of chronic pain, and it means that people with chronic pain have to be unceasingly alert. For example, Sally says, before she hurt her arm, hot coffee sloshing onto her hand might have hurt for a few seconds. Now, a careless moment like that means days of burning pain.

Symptoms like this suggest that changes in the nervous system have migrated to the spinal cord. De Koninck believes that a major factor is the number of receptors on the signal-receiving neurons in the dorsal horn. If those neurons synthesize too many receptors, they’ll pick up too many neurotransmitter molecules. Then the neurons’ pores will flutter open to let charged particles in more often than they should, sending electrical signals shooting up to the brain at too high a frequency. The result is a pain signal that’s much stronger than it should be. De Koninck’s work gives us a new window into how it happens, and how to stop it. Recall, Then Erase

The key lies in a study about memory that was published nearly 15 years ago. Long-term memories seem to depend on the synthesis of extra receptors, too, and scientists knew that blocking the synthesis of those receptors during a memorable event could keep memories from forming.

But what a group of researchers at New York University discovered was that there is a brief period when interrupting receptor synthesis can actually erase old memories. Memories are reinforced when they’re retrieved, but, paradoxically, during that process, even well-established memories have a brief window of vulnerability—like jewelry in a safe deposit box, memories are useless when they’re stored but accessible to thieves when they’re being used. A chemical called anisomycin blocks the production of receptors that neurons need to form memories. When the researchers injected anisomycin into rats’ brains right after triggering a particular memory, that memory didn’t just fail to get reinforced—it was erased altogether. The right chemical injected at just the right place at just the right time could erase the physiological “memory” of pain.

Accumulating evidence that pain and memory use similar mechanisms led De Koninck to wonder if this same neurochemical trick could erase chronic hyperalgesia. De Koninck and his colleagues made mice hypersensitive to pain by injecting their paws with capsaicin, the chemical responsible for chili peppers’ fiery bite. Capsaicin activates the same pain sensors that respond to extreme heat and can turn on hyperalgesia without the tissue damage that an actual burn would cause. After their capsaicin injection, the mice’s paws were more sensitive to pressure for hours afterward.

Before that sensitivity had had a chance to wear off, the team gave the mice a second capsaicin injection—and this time, they added an injection of anisomycin. What happened after this second injection is “like magic,” De Koninck says. When the second injection initiated the same flurry of neurotransmitters and electrical signals that encoded the hyperalgesia the first time—the pain analogue of recalling a memory—anisomycin shut down the pain-amplifying mechanism by keeping the spinal cord neurons from making extra receptors. “It’s in the process of reorganizing itself,” De Koninck explains, “and there there’s that window of opportunity to actually shut it back down.” The mice lost seventy percent of their hypersensitivity to pain.

The theory that overdeveloped connections other than memories could be attenuated by retriggering them “is not a new idea,” Basbaum says, “but the fact is, there really has been very little evidence that it’s doable.” De Koninck’s results suggest that the right chemical injected at just the right place at just the right time, can erase the physiological “memory” of pain. Ted Price, a professor at the University of Texas-Dallas, says that this “ paves the road to disease modification instead of just palliatively treating people with these terrible drugs like opioids, which everybody, everybody in the field wants to get away from.” New Options

For now, there are a few other types of treatment doctors can turn to besides opioids. Antidepressants help some people, as do certain antiseizure medications. A controversial technique called “transcutaneous electrical nerve stimulation” may work by making sure that there are plenty of receptors in the dorsal horn for the body’s natural opioid chemicals; a wearable device using this technology was just approved for over-the-counter sale by the FDA.

Treatments based on De Konick’s capsaicin-anisomycin model would constitute an entirely new category of drugs. “When you find a new mechanism,” De Koninck says, “boy, it opens a whole new array of things.” But finding the right combination of chemicals won’t be easy. Capsaicin patches are already sold over the counter at drugstores, but anisomycin is far too indiscriminate for clinical use. Brian Wainger, a physician and researcher at Massachusetts General Hospital, says, “It’s obviously going to be a long time for a discovery like this to work towards a clinical approach, but I think it sort of sets a framework for some options.”

“Options” is a word that seems to come up a lot among pain specialists. One of the reasons chronic pain is so difficult to treat is because “there’s a lot of different forms of chronic pain,” De Koninck says. “But the arsenal that we have so far to treat it is still quite meager.” And the weapons we do have are woefully inadequate.

Still, discovering that this retrigger-and-erase phenomenon works for hyperalgesia, as well as for memory, suggests that it may be useful in other parts of the nervous system. If that’s true, these kinds of treatments could help with pain syndromes more complicated than hyperalgesia—conditions that are so severe that even light touches become painful, or in cases where patients experience pain with no stimulus at all.

One big advantage of De Koninck’s strategy is that it isn’t just an incremental improvement, a way to make a slightly more effective or slightly less addictive analgesic. It’s a totally different angle on the problem. It targets the “chronic” part of chronic pain. “What the field I think really needs is options,” Price says. “And more importantly, patients need options.” For millions of people, and their doctors, a totally different angle is exactly what they’ve been looking for.

Tell us what you think on Twitter #novanext, Facebook, or email.

Eleanor Nelsen
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Eleanor Nelsen is NOVA's 2014 AAAS Mass Media Fellow. She has also written for QUEST Science and Wisconsin Public Television.

Other posts from this contributor

http://www.pbs.org/wgbh/nova/next/body/chronic-pain

8 Gly Carb To Help Reduce Neuropathic Pain

Today's post from fiercebiotechresearch.com (see link below) talks about microglia, which are cells in the spinal cord that are responsible for releasing nitrous oxide when there's nerve damage. This nitrous oxide is partly responsible for the extent of your neuropathic pain at a later stage. Scientists have found a compound which (simply put) can inhibit nitrous oxide release and thus theoretically, reduce pain and other symptoms. The compound is called 6-chloro-8-(glycinyl)-amino-β-carbolin, or 8-Gly carb which hardly rolls off the tongue for patients but the name isn't important, its potential is.As usual, the end product is still somewhere in the future but every little snippet of news increases our general understanding of our condition and puts pressure on the relevant authorities to work as fast as they can to improve our lives with neuropathy.

UC Davis team finds a prime drug candidate for neuropathic pain  

February 10, 2015 | By John Carroll

Neuropathic pain has been linked closely to microglia, immune cells in the spinal cord which are known to release cytokines and other chemicals including nitrous oxide in the wake of peripheral nerve damage. A team of UC Davisresearchers says that inhibiting nitrous oxide at the time that nerve damage is done could prevent neuropathic pain from occurring later. And they've found a compound that they say is very effective at doing just that.

The compound is 6-chloro-8-(glycinyl)-amino-β-carbolin, or 8-Gly carb, which belongs to a class of compounds known to blunt nitrous oxide. The team says that this compound is significantly better at that task than any other known compound. And it appears to do its work without blocking cytokine expression.

Neuropathic pain often doesn't begin until well after physical trauma. And once it does begin it can linger for years as the brain is believed to be misinterpreting nerve signals from the site of the damage.

"A compound like 8-Gly carb that selectively targets nitrous oxide production and does not block cytokine expression makes a promising candidate for drug development aimed at preventing a neuropathic pain syndrome without interfering with recovery," said Fredric Gorin, professor and chair of the UC Davis Department of Neurology and co-principal investigator for the study.

Now new preclinical work is being planned that could set the stage for clinical studies.

- here's the release

http://www.fiercebiotechresearch.com/story/uc-davis-team-finds-prime-drug-candidate-neuropathic-pain/2015-02-10

Lower Back Pain Pregnancy

Vertebral Body Spinal Column Anatomy

Easing labor pain may help reduce postpartum depression in some women, early research suggests 3D tumors grown in the lab provide new perspective for cancer drug .The best possible care starts with finding an experienced doctor who can treat you at a top-rated hospital. But it's also important to be an informed patient, so .If you have lower back pain, you are not alone. About 80 percent of adults experience low back pain at some point in their lifetimes. It is the most common .

Someone With Lower Back Pain

Lower Back Pain Exercises Stretches

If you have lower back pain, you are not alone. About 80 percent of adults experience low back pain at some point in their lifetimes. It is the most .The best possible care starts with finding an experienced doctor who can treat you at a top-rated hospital. But it's also important to be an informed patient, so .Easing labor pain may help reduce postpartum depression in some women, early research suggests 3D tumors grown in the lab provide new perspective for cancer .

Dont Worry If Your Pain Is Also Emotionally Based Its A Chicken And Egg Situation

Today's post from thelightmedia.com (see link below) doesn't seem to be directly related to neuropathy as such but if any group of pain patients understands the correlation between emotional states and their physical pain, it's nerve damage patients. They are also frequent victims of pain stigma; where outsiders accuse them of having a psychosomatic problem and in effect...faking it. You don't need telling that this makes the problem so much worse. However, if psychosomatic pain is pain that is 'created' and not 'real', then nerve pain is exactly that because nerve pain stems from faulty nerve cell signals moving to and from the brain cells. People living with neuropathy can also have other forms of pain that are nociceptive (stemming from injury and physical damage) and not neuropathic and this can cause all sorts of confusion, both for the patient and the concerned onlooker. This article takes a look at forms of pain that are influenced by and influence, emotions. If nothing else, it may help you sort out what you're feeling en help you better deal with it.

10 Types Of Pain That Are Directly Linked To Your Emotions
2017

“Psychosomatic means mind (psyche) and body (soma). A psychosomatic disorder is a disease which involves both mind and body. Some physical diseases are thought to be particularly prone to be made worse by mental factors such as stress and anxiety.”

(A quick note before we begin: it is extremely important that any severe physical symptoms must be attended to by a licensed medical professional, such as a physician.)

If there is a mental aspect to virtually every type of disease, isn’t it then rational to assume there is a mental aspect to virtually every type of physical pain? The simple truth is that mental states affect physical states and vice-versa.

Traditional medicine has labeled this the psychosomatic effect. Interestingly, the specialty of psychosomatic medicine is the latest sub-specialty in psychiatry to become board-certified. Board-certified physicians comprise the “best of the best” in 24 different medical specializations (e.g. neurology, dermatology, psychiatry, etc.) As important, these medical specialties are universally recognized by the medical and scientific communities as vital to public health.

Indeed, pain can be caused by emotional and mental states. In science, it has been demonstrated that both mental/emotional and physical pain activates the same areas of the brain: the anterior insula and the anterior cingulate cortex. So – a physiological connection between brain and body exists as well.

Here we are going to discuss 10 different types of pain that are directly linked to feelings, emotions and thoughts. Equipped with this knowledge, one can begin to make whatever adjustments necessary to feel better (we’ll also provide some recommendations).

Here are 10 types of pain caused by feelings/emotions/thoughts:

1. Back pain

Areas of the back and shoulders are arguably where we feel muscle tension the most. Chiropractors, osteopaths and other medical professionals have been explaining the stress/anxiety connection between back pain and mental/emotional health for years.

Making matters worse, this type of pain is cyclical. We begin to stress and worry about back pain, which tenses back the muscles; the muscles tense, and then we begin to feel things like frustration and anger.

2. Headaches and migraines

Dr. Christina Peterson, a board-certified physician, writes: “Stress comes in many varieties, including time stress, emotional stress, and the stress of physical fatigue…and (these) emotions pack a wallop for the migraine sufferer.” Furthermore, emotions like anger, anxiety, crying/sadness and depression trigger headache pains.

The good doctors recommend practicing relaxation techniques, meditation, and to seek the help of a counselor in the event that this pain doesn’t subside.

3. Neck pain

The buildup of emotions; more specifically, negative emotions, can affect virtually every area of the body. Neck pain, according to Calm Clinic, is one of the most common complaints of people suffering from anxiety-related disorders.

It’s nearly impossible to explain every one of the multitude of ways that anxiety can manifest. Financial problems/worries, relationship problems, sadness, fatigue, etc.

4. Shoulder pain

Many kinesiologists believe that our shoulders are the area of the body most prone to feeling the adverse effects from pressure. Ever wonder where the axiom “Carrying the weight of the world on your shoulders” comes from?

Us too. But it turns out there is a whole lot of truth to it.

5. Stomach aches and/or cramps

Our poor stomach is where we house most of our worries, fears, and anxieties. Experiencing these emotions repeatedly, without surprise, can cause stomach aches and pains. In fact, as it turns out, chronic stress can develop into stomach ulcers.

6. Elbow pain and/or stiffness

Dr. Alan Fogel, in a piece published by Psychology Today, writes, “All emotions have a motor component.” The elbow is no different. While medical conditions such as arthritis and others may be the reason for pain or stiffness; mental states such as anxiety and depression can also manifest in strange areas…including the elbows.

7. Pain in hands

Similar to the elbows, pain in the hands can arise from legitimate medical conditions. Some even say that hand pain may result from feelings of isolation or confinement. As Dr. Fogel said, every one of our emotions manifests into a physical symptom…so, anything is possible, right?

8. Hip pain

Aside from a documental medical condition, some type of emotional trigger is almost assuredly the cause of hip pain. The human body has more nerve connections in the hip than we would think; so distress can manifest into physical pain in this area as well.

9. Knee pain

The rationale given for knee pain experienced from emotions is pretty much the same as that given for hip pain. Of course, there are many nerve endings in the knee; hence, more of a brain/body connection. As such, it is perhaps more likely that emotional triggers such as anxiety, fear, depression, etc. will manifest into knee pain than other, less sensitive areas, such as the hip.

10. Foot pain

Here’s what one podiatrist says about the relationship between mental/emotional states and foot pain: “Stressed people present with a wide range of biomechanical issues. I am not trying to be a guru…but I am convinced there is an anecdotal connection between lower limb and foot presentation and their emotional status.”

Experts at Columbia University admit that “there’s some evidence that there are psychological conditions that may be associated with physical symptoms,” and that treating the real cause of the pain may be the answer.

Related article: This Simple Mind-Body Exercise Reduces Negative Thoughts and Improves Health

After investigating the physical pain or stress, it’s worthwhile to do the same with any emotional state(s). What are you feeling?

Relaxation techniques (e.g. progressive muscle relaxation), controlled breathing, meditation, guided imagery, and many other techniques and practices exist to help people who are experiencing both physical and/or emotional pain.

http://thelightmedia.com/posts/55199-10-types-of-pain-that-are-directly-linked-to-your-emotions