A New Class of Pain Medicine from Cancer Cells – PD-L1 inhibits acute & chronic pain


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For the nonscientist, this report may explain better:

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Cancer actually yields a painkiller

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Scientists have discovered a potent painkiller in an unlikely place — cancer cells.

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This painkiller strongly inhibits acute and chronic pain in mouse models of melanoma, according to a study published Monday in Nature Neuroscience.

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Called PD-L1, the molecule is known to inhibit immune function, which helps cancers evade immune surveillance. It’s also produced in neurons. If it can be used to make an analgesic drug, it would represent a new class of painkillers, something badly needed.

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The molecule acts by targeting a cellular receptor called PD-1 and has been a longstanding target of cancer therapies called checkpoint inhibitors seeking to activate the immune system. But its painkilling effect is news.

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Ru Rong Ji of Duke University was senior author. Gang Chen and Yoang Ho Kim, also of Duke University, were first authors. The study can be found online at j.mp/cancerspain.

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…..Dr. Patel, oncologist from UCSD says: “This could result in a therapy that helps patients in a year or two years, just because so much has been done in the field.”

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The relationship between cancer and pain is complex, Patel said. PD-L1 suppresses inflammation, which activates the immune system, and also causes pain, Patel said. But there are other ways of activating the immune system, such as with the new cancer immunotherapy treatments, which don’t increase pain, he said.

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….The increased pain response is also caused by the cancer drug nivolumab. The drug, sold under the name Opdivo, targets PD-1 and shows success in treating melanomalymphoma and lung cancer. It produced strong allodynia for five hours in the mice, according to the study.

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Nivolumab is one of the new checkpoint inhibitor cancer drugs that targets PD-L1 receptors with immunomodulatory antibodies that are used to enhance the immune system. They can produce a wide spectrum of side effects termed immune-related adverse events (irAEs) with inflammation due to immune enhancement involving several organ systems.

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This is not my field and perhaps I am wrong. But if treating those cancers with immunotherapy causes the worst known neuropathic pain by blocking checkpoint inhibitors, is it possible that a new pain drug having the opposite mechanism could relieve pain but cause cancer?

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This Nature publication references the growing body of work from the lab of Linda Watkins, PhD, et al, published in 2014:

.Pathological pain and the neuroimmune interface

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Reciprocal signalling between immunocompetent cells in the central nervous system (CNS) has emerged as a key phenomenon underpinning pathological and chronic pain mechanisms. Neuronal excitability can be powerfully enhanced both by classical neurotransmitters derived from neurons, and by immune mediators released from CNS-resident microglia and astrocytes, and from infiltrating cells such as T cells.

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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METFORMIN for Nerve Pain


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Is metformin the new wonder pill or snake oil? Based on one man’s response to metformin and recent exciting research on the drug, I am looking forward to finding out how it works clinically for my patients with intractable pain (and possibly treatment resistant depression). Hopefully most will confirm it is well tolerated. I am just beginning to trial it after learning this one man’s amazing story:

 

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50% relief of nerve pain &

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musculoskeletal pain

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after 2nd week on metformin

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One Man’s Story

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A few days ago I spoke with a man, not my patient, who had 50% relief of pain after the second week on metformin. He’s taken it for 3 months now, but the big change came dramatically after the second week when he had been on the 2,000 mg dose a full week. In 2013, he was on the side of the freeway median lane, and had crawled into the engine of his disabled Ford F350 reaching in with his left hand when his vehicle was hit by a Lexus SUV going 70 mph and he was thrown. He doesn’t talk about his pain. Ever. He needs total knee replacement in the next few weeks, and has had four surgeries on his left wrist, mangled in that engine, now with a long steel plate in the wrist. He broke the titanium plate and it wasn’t healing. Since metformin, the skin and surgical scar is healing. He’s one of these quiet guys who don’t ever talk about pain. His wife simply said these days he’s sleeping since on metformin.

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But no one had asked him about pain since on metformin or for years either. It took 30 minutes to get one little bit of information from him on pain, like pulling teeth: Since metformin, he’s had 50% relief including the nerve pain at his wrist.

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She said he used to sit up all night in pain for years and was very irritable. Irritability is what happens with no sleep; pain is worse with no sleep. I could not get him to rate his pain. Stoic. Bright man, stoic. Devilish sense of humor. Severe pain for so many years he would never talk about. His surgeon had him stop the Vicodin 5/325 weeks before his last surgery “to help it heal.”

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Some of his relief may have also been influenced by blood sugar dropping from 170 to 90, no more excessive thirst and urination keeping him awake, but the neuropathic pain at his wrist had been nasty a few years. Pain had kept him up for months. He had no side effects.

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Metformin

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Metformin is a medication approved in Canada in 1972 and in the United States by the FDA in 1994 for type 2 diabetes. It is well tolerated when prescribed for people who do not have diabetes but who have other conditions such as PCOS (polycystic ovary syndrome), infertility; and it is the focus of intense activity being studied for its

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(1) anti-aging (PDF from Wake Forest University or the Albert Einstein Medical School Longevity study clinicaltrials.gov), 

(2) anti-cancer (ithas become the focus of intense research as a potential anticancer agent” per Cancer Treat. Res. publication 2014) and now recently being studied for

(3) anti-inflammatory analgesic effects.

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“Metformin increases the number of oxygen molecules released into a cell, which appears to boost robustness and longevity. It works by suppressing glucose production in the liver and increasing insulin sensitivity, therefore benefiting patients with type 2 diabetes.”

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I am very interested by all the new research being done on an old drug, metformin, that has suddenly turned heads in just the last few months as we learn its mechanisms involving the pain matrix. Is this metformin some miracle drug, another hot trendy bandwagon people jump on in medicine? It’s an old drug already FDA approved, now repurposed, with excellent safety, and four months ago a publication shows it to be a glial modulator and anti-inflammatory, centrally active. Best of all, it was dramatically potent in the setting of this man’s intractable nerve and musculoskeletal pain.

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But how do we get from 1994 to 2017, through the Decade of Pain, seeing patients who have astonishing pain relief without asking a single patient, millions of patients if it helped pain? A recent past president of the American Endocrine Society said: “No good data on metformin to treat pain. Everything else, but not pain.” He also said, “Safe. We do it all the time for people with PCOS, infertility, cancer, etc. The anti-aging people use it all the time. No risk of hypoglycemia. Just be sure their GFR is above 40.” So ask your doctor who may not know it’s hot research right now.

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When was it first mentioned for pain?

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Less than one year ago, a report on metformin’s use for pain was a 2016 poster presentation at the annual meeting of the American Pain Society from Ted Price’s lab at University Texas Dallas. “The AMPK activator metformin has been shown by our lab to reverse the effects of chronic neuropathic pain in various short term studies….The treatment successfully decreased the hypersensitivity and cold allodynia associated with neuropathic pain, and showed persistent relief for several weeks post-injection. Metformin also decreased the activation of microglia in the spinal cord.”

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I have cautiously held back prescribing it for pain until I heard this man’s story a few days ago, and days later I am still astonished at the relief he had. I immediately suspected metformin must be a strong glial modulator and that mechanism was confirmed in a publication four months ago, in animal (discussed at end).

 

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 SIDE EFFECTS

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If some develop side effects, stop the medication until all side effects are zero. Then at your own body’s rate, as slowly as needed, increase if needed to 1000 mg twice daily.

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If you again have side effects, again stop til all are zero. Maybe your top dose with no side effects is less than 2,000 mg/day.

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More information on potential side effects  are on the next metformin post – almost none in 18,000 patient years, and not a single case of lactic acidosis.

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STUDIES NEEDED

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It would be extremely helpful to see a study on metformin’s use for pain in a major cancer center, including the range of all underlying diagnoses of those patients who may not be in best of health.  What are % of side effects?

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INFLAMMATION

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Metformin helps inflammation. Inflammation is the cause of 90% mortality. Almost all disease in the body begins with inflammation including atherosclerosis that leads to plaque, heart attacks, stroke. And the same risk factors for heart disease are same for Alzheimers. Inflammation manifests differently in each of us, but to relieve pain, major depression, bipolar disease, PTSD, it can be very dynamic to see response in a few hours once you have the right dose and combination of glial modulators. If this one can relieve 50% of severe chronic pain in two weeks, with few or no side effects, then millions can benefit now. It is an old generic drug repurposed for pain, that is anti-inflammatory. Best of all anti-inflammatory up there in the brain where the inflammatory cytokines produced by glia make you feel like you have the flu:  difficulty thinking, fatigue, drowsy, achey, irritable, needing sleep. That is inflammation. The innate immune system going into gear to attack a virus or…..damage.

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Studies reported about 2001, NIMH showed brain atrophy and memory loss in chronic depression, and about 2009 others showed the same in chronic low back pain.

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My focus for years has been on inflammation in the CNS (brain, spinal cord) because NSAIDs like ibuprofen, Aleve, do not reach the CNS and do not interact on the cells of interest: glia, the cells of the innate immune system that produce a balance of anti-inflammatory and pro-inflammatory chemicals called cytokines. BALANCE.

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Tolerance is a big issue in treating pain or major depression. I strongly recommend reading yesterday’s post on tolerance, i.e. when the body stops responding to ketamine or morphine or an antidepressant after several days or weeks or years. Inflammation may be one cause.

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A publication four months ago shows metformin has both immune and glial suppressive effects that can relieve tolerance to morphine.  It’s a centrally acting analgesic because that’s where chronic pain or major depression is, in the CNS.

 

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MECHANISM of PAIN RELIEF

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It has both immune and glial suppressive effects: J Neuroinflammation. 2016 Nov 17;13(1):294.

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Metformin reduces morphine tolerance by inhibiting microglial-mediated neuroinflammation.

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ABSTRACT

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BACKGROUND:

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Tolerance [see post on this subject yesterday] seriously impedes the application of morphine in clinical medicine. Thus, it is necessary to investigate the exact mechanisms and efficient treatment. Microglial activation and neuroinflammation in the spinal cord are thought to play pivotal roles on the genesis and maintaining of morphine tolerance. Activation of adenosine monophosphate-activated kinase (AMPK) has been associated with the inhibition of inflammatory nociception. Metformin, a biguanide class of antidiabetic drugs and activator of AMPK, has a potential anti-inflammatory effect. The present study evaluated the effects and potential mechanisms of metformin in inhibiting microglial activation and alleviating the antinociceptive tolerance of morphine.

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RESULTS:

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We found that morphine-activated BV-2 cells, including the upregulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-inflammatory cytokines, and Toll-like receptor-4 (TLR-4) mRNA expression, which was inhibited by metformin.Metformin suppressed morphine-induced BV-2 cells activation through increasing AMPK phosphorylation, which was reversed by the AMPK inhibitor compound C. Additionally, in BV-2 cells, morphine did not affect the cell viability and the mRNA expression of anti-inflammatory cytokines. In bEnd3 cells, morphine did not affect the mRNA expression of interleukin-1β (IL-1β), but increased IL-6 and tumor necrosis factor-α (TNF-α) mRNA expression; the effect was inhibited by metformin. Morphine also did not affect the mRNA expression of TLR-4 and chemokine ligand 2 (CCL2). Furthermore, systemic administration of metformin significantly blocked morphine-induced microglial activation in the spinal cord and then attenuated the development of chronic morphine tolerance in mice.

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CONCLUSIONS:

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Metformin significantly attenuated morphine antinociceptive tolerance by suppressing morphine-induced microglial activation through increasing AMPK phosphorylation.

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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Pain is Worse Than Dying – Insurer Sues to Recover Payment for Opioids


 

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Pain Is Worse Than Dying

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Humana Is Obscene

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Humana Seeks

Repayment of Hundreds of Thousands of Dollars

 From Pharmacy

For Pain Medication of Years Ago.

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Reversal and Recovery

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In 2013, I was privileged to meet an angel, a wonderful soul, a 28 year old woman who was furious that she had permitted her doctor to replace a catheter in the vein (PICC line) that kept her alive for six years with feedings. She was frail, skeletal, vomiting frequently, starving, with no body fat, and had to carry a vomit bag because of involuntary vomiting day and night. She had a mitochondrial disorder that caused many abnormalities and many kinds of pain – acute pancreatitis, Guillain Barre-like nerve pain, hepatic pain, enlarged cervical and lumbar nerve roots, demyelinating polyneuropathy, ICU stays for episodic sepsis. Her stomach was elongated, reaching deep down into the lower abdomen and pelvis. She had extreme pain, was suicidal, deeply spiritual and would never take her own life, but she knew if the catheter had to be removed, she would never give permission for it to be replaced and she would soon die without fluids. 

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“I just want to die. I’m done trying to get well. I did that for 10 years”

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Her entire digestive system was not working.

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She had been hospitalized months at a time, at many hospitals in the country in search of a diagnosis that was finally made by the foremost specialist in mitochondrial disorders. She had been part of an NIH study in Texas for two years, was hospitalized for months at Mayo Clinic, at Columbia University, and wanted to be on hospice the year before she saw me.

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All night long, she would make the most beautiful hand crafted cards— pain and vomiting made it impossible to sleep. I prescribed Subsys, a rapid onset fentanyl to spray under tongue with onset in 10 minutes. The only opioid suited for her pain. She could not take medicine by mouth and had no body fat needed for pain patches.

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Subsys was never enough. She required IV opioids for intractable pain, soon transferred to hospice, refused replacement of the feeding IV PICC line and died surrounded by her loving family.

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Thank goodness mom is an RN, she was able to be at home all those years. Humana saved years of hospital care, saved for a few months with Subsys.

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Humana now wants to recover hundreds of thousands of dollars in payments to the pharmacy for medications for her and others.

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A few years before mom and patient met me, Humana cut her off from her pain meds – cold turkey, forcing mom to take her to the ER. She ended up in the acute care hospital for 6 MONTHS while mom fought with Humana.

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Each time she got turned down, mom appealed.  The case made its way to the Department of Health and Human Services, Office of Medicare Hearings and Appeals after three levels of appeals and a hearing before the Administrative Law Judge. 

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[The case did not reach the Supreme Court as I originally posted – see corrections below photo.]

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Mom won – by herself – no attorney – just organized with good documentation. Mom did have the director of pain management pharmacy from a local hospital on her side as a witness, though. Mom is an RN “Erin Brockovich” and will do whatever she can to fight this egregious action by Humana, the suicidal curse of pain, and all the patients who legitimately suffer with pain.

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Subsys is unique. There is no comparison. Among all the rapid onset fentanyl pain relievers, it is the fastest, with good levels in 10 minutes. When pain spikes rapidly, from low to severe in minutes, it is ideal to use a rapid onset opioid that may begin in 10 minutes rather than a pill that takes 1 or 2 hours to peak effect. Like many rapid onset fentanyl products, Subsys costs perhaps $100 each depending on dosage or $3,000 for 30. If you need 6 per day, that may be $18,000 per month. The raw powder costs pennies. The delivery device is a small spray of 0.1 mL (2 tiny drops) in a fine mist.

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Not all patients are able to use all forms of opioids for pain, yet the FDA approval for rapid onset fentanyl that excluded her. It is approved only for cancer pain – now CDC wishes to allow rapid fentanyl only for actively treated cancer. Your pain does not matter.

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There is no such thing as cancer pain.

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All people including cancer patients may have pain of nerves (neuropathic), organs (visceral) or other tissues (nociceptive). There is no such thing as cancer pain.

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The agony a physician feels when faced with a patient who is suicidal from severe pain and insurers that refuse to pay for needed medication is beyond words. Refusals like this have been happening for years, now far more often with egregious denials and futile “prior authorizations” – just yesterday refusing 20 mg morphine in a patient with many forms of severe pain. Medical ethics is not a business model. Insurers answer to stock holders, not those who buy their policy.

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Americans do not view pain as worthy of attention. Billions of dollars more for cancer. Almost nothing for pain research.

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Unlike most pain specialists, I have spent the last 15 years on alternatives for severe intractable pain, better than opioids, documented on these pages. I am the least opioid apologist, but I do prescribe opioids and taught cancer pain at one of the finest cancer hospitals in the world making me more “fluent” with opioids than most anesthesiologists who, after all, do mostly procedures. I could study for a year or two to take a special test, to be “certified” as a pain specialist – studying things I will never use in my practice, instead I refer to proceduralists when indicated.

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Oral analgesics are more cost effective and usually better than short lasting expensive procedures for chronic pain. Don’t get me started on the lack of research for spinal cord stimulators – use the tiny search box top left above my photo. Their $100,000 cost was effectively lobbied to insurers. Is it effective for more than two years? And the harms?

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Most people with chronic pain have no access to anything as effective as opioid medication. Well, that will be gone soon. You too will someday need help.

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Today FDA announces a sweeping review of agency opioid policy

to CUT access.

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Prepare for an avalanche of denials for your pain medicine. There’s been a storm of denials for years, denials for nonopioid treatment of pain, even more denials in the last few weeks since CDC’s offensive experiment I posted 11 times since late October. The avalanche is coming to bury us.

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It’s really a thankless job treating pain. Pain is devalued by Americans. Patients seem to accuse me of not doing my job when their medication is denied. They are treated like addicts. Doctors, families and pharmacists are suspicious of patients and of us.

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But this is happening for all medications, not just for pain, even generic asthma medicine, low dose estrogen that costs $12. Insurers know congress doesn’t care. Pharma knows congress doesn’t care. It’s a war on patients who are caught in the middle.

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CDC and FDA now want to take opioids away,

before we have an effective alternative.

Anti-opioidists have no science to back their stand.

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There is absolutely no reason any analgesic

should be limited to people with “actively treated” cancer –

CDC only allowed for that one partial change among a long list of changes sought by the American Pain Society.

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Politics has no place in the treatment of pain.

Pain policy in this country is sickening those with chronic pain.

Catering to the deaths of addicts –

politically expedient to deny you pain relief.

Treatment of pain doesn’t fit the American paradigm –  too weak.

War on drugs and addiction is more macho.

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Give us a better alternative.

Better for pain relief.

Better for addiction treatment.

For Pete’s sake look at addiction treatment

in countries who proved prohibition fails to work.

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Better treatment for addiction is not cured by denying pain relief to

116 million Americans with severe chronic pain.

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Or else start studying suicide in pain patients, not addicts.

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War on drugs is war on people with pain.

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My dearest friend who started home hospice in America

changed federal policy and the paradigm to treat cancer pain.

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Doctors threw food at him when he

spoke about treating pain in dying people.

Senior professors, the experts, rushed onstage, frantically

waving their arms in front of him saying:

“Don’t listen to this man, he’s crazy.”

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How much has changed?

Do the ghouls take your medication away?

Do insurance profits own government policy?

Do they destroy neighborhood pharmacies by

retracting hundreds of thousands of dollars years later?

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Bill

William M. Lamers, Jr., MD

December 24, 1931 – February 2, 2012

They are still inadequately treating cancer pain.

We miss you Bill

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Correction February 5, 2016:

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Mom writes to advise the case did not reach the Supreme Court. It went all the way up to the Department of Health and Human Services, Office of Medicare Hearings and Appeals after three levels of appeals and a hearing before the Administrative Law Judge. After 9 months of this process, the judge ruled in favor of having Humana cover Fentora buccal tablets for M – even though she didn’t have cancer. Fentora is another rapid acting fentanyl but not as fast as Subsys that was not yet on market in 2011. Humana APPROVED Fentora on 1/6/11 and then Humana DENIED it on 8/24/11, causing the patient to be hospitalized for several months.

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Hospitalized for months vs use of fentanyl at home for years.

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She had a very rare disease. These are the numbers from 2012.  They may be higher by now (or lower with deaths): It is estimated that 2,500 people throughout the world have Mito.  MNGIE is a rare form of Mito. There are only 70 people in the world known to be diagnosed with it. Twelve of them are in the U.S.  She was one of them.

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment

provided by a qualified health care provider.

Relevant comments are welcome.

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If any questions, please schedule an appointment with my office.

This site is not for email.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please be aware any advertising on this free educational website is

NOT advocated by me and NOT approved by me.

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Opioids Kill White Americans – Is it opioids or suicide or addiction or untreated pain?


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Drug Overdoses Propel Rise in

Mortality Rates of Young Whites

New York Times

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Yes, white Americans, headlined yesterday by Gina Kolata and Sarah Cohen, New York Times science writers.  This article points to the highest mortality in young whites. See post early November on the Princeton researchers who reported deaths in white Americans. True, infants and children have severe pain, but this new article is on young white adults.


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Those who are anti-opioid and those who lost a loved one from opioids and heroin (an opioid that helps pain), will send in comments to the paper so that everyone can see how bad opioids are. Most patients who take opioids are too disabled from pain to write.

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Pain is stigmatized, opioids stigmatized, people in pain are stigmatized, doctors who treat pain are stigmatized. Any wonder 97% of medical schools do not teach pain management?

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Is it opioids or suicide or addiction or untreated pain that is killing our youth?

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How many suicides have opioids prevented? Americans make up less than 5% of the global population but consume 80% of the world’s supply of opioid prescription pills. What if your cancer pain now becomes severe intractable chronic pain? Cancer has been changing. The survival rate has increased, and many of these cancer patients treated with opioid therapy, survived the cancer but have residual chronic pain from cancer or its treatment. Surely they are among the 18,000 white people who died.

 

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Please read the earlier post this week on the ethics of opioid treatment, on

CDC’s imminent radical cut in opioid doses for 100 million patients nationwide.

Use search function above photo – type in CDC or DEA.

Your pain. Your lives. Their profit.

A thorny problem.

Tell us what happened to you. Doctors, tell us what you are seeing.

Have you been denied disability due to pain? Denied non-opioid treatment?

Chronic severe pain affects forty million Americans.

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KONICA MINOLTA DIGITAL CAMERA

Some insurers have denied or limited non-opioid treatments yet continued expensive opioids for decades. Has your insurance refused your treatment? Pain specialists have been barraged by denials for years.  Please comment below.

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As noted last week, I have spent 15 years developing alternatives to failed opioid treatment for chronic intractable pain and writing about that on these pages since April 2009. But opioids must be available as last resort.

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FACT:

  • Opioids killed almost 18,000 Americans in 2014 – prescription opioids, not street drugs.

  • 40 million American millions with severe pain, millions not thousands

  • 100 million with chronic pain.

  • CDC will imminently, radically cut everyone’s opioid dose

  • Health insurers will oblige, and incidentally show increased profit to shareholders

  • Suicide increases with untreated pain

  • Death rates for “whites ages 25 to 34 was five times its level in 1999”

  • This age group has more injuries from work and play that can lead to disability, job loss

  • Insurance is unaffordable or not purchased by many young adults

  • My own colleagues cannot afford high deductibles – prescriptions are now counted in deductibles, now unaffordable

  • Can you afford $20,000 per month for your opioid or is cheap heroin more affordable? Can you afford your usual drugs on Medicare once you are in the “donut hole.” Can you afford $28 per day, $840 per month for gout, when colchicine was 12 cents a day a couple years ago?

    • Do insurance denials increase liklihood of cheaper alternatives such as heroin or illegal marijuana resulting in death by drug dealer?

    • Do exhorbitant costs of opioids lead insurers to deny your medication?

  • Insurers have refused to pay for abuse-deterrent and tamper-resistant formulations of opioids

  •  Insurers have refused to pay for proven, widely accepted, nonopioid analgesics:

    • Lyrica

    • Horizant

    • Gralise

    • Cymbalta

    • Does it help the DEA and NIH and universities to teach those as nonopioid alternatives when they are not covered and not affordable the rest of your life?

    • Insurers deny every known compounded analgesic though low cost and effective, even for Tricare’s disabled veterans, even 5% lidocaine ointment for nerve pain, dextromethorphan, oxytocin, low dose naltrexone – Stanford published research on naltrexone years ago and now doing research on it again for CRPS, many many others

    • Insurers deny proven analgesics that are used by armed forces, university hospitals, select doctors, for life threatening pain: ketamine

    • Insurers deny off-label analgesics that may work better than opioids, e.g. memantine, an Alzheimers drug – can relieve intractable nerve pain (French publication on CRPS/RSD pain)

    • Insurers deny medications that reduce side effects of opioids, e.g. nonaddicting modafinil popular with students, to increase alertness when opioids cause drowsiness that may cause injury, death – gosh 10 years ago!

    • Is drowsiness the cause of some of those 18,000 opioid deaths?

  • Health insurers have refused coverage for treatments such as P.T., psychotherapy for coping skills, blocks.

  • Insurers deny medications that relieve the withering side effects of opioid withdrawal, making it impossible for many to taper off, e.g. Adderall, Wellbutrin (dopamine)

  • Cannabis, a nonopioid, classified by US Congress as Schedule I, illegal federally for human use, illegal to take on a plane or cross state/national borders, found on meteorites, made by sponges and some of the earliest living species on the planet, used for thousands of years for pain, while cocaine and methamphetamine are classified as Schedule II for prescription purposes.

  • Opioids, even vicodin, require monthly doctor visits, costs, monthly for sixty years

  • Why whites dying of opioids? People of color are denied prescription opioids. Stark data published for decades.

  • Heroin is an opioid, cheap and available; its “unAmerican” – used in England for pain, used thousands of years for pain

  • Untreated pain is one reason people turn to heroin, affordable is another

  • Violence and drinking and taking drugs can begin with chronic pain and job loss, not always the other way around, chicken egg

  • Opioids cost pennies to make, patient’s cost is $20,000 per month for Rx. Insurers paid what the market would bear… in the old days. Who is trapped in the middle of this fight for shareholder profit?

    • How many of us would take 2 or 4 extra pain pills when pain spikes to extreme for days?

    • If you are disabled, can you afford insurance or expensive prescription drugs?

  • “Poverty and stress, for example, are risk factors for misuse of prescription narcotics,” Dr. Hayward said.

  • When you are not getting enough sleep and rest, working too many hours overtime or 3 jobs, inflammation and pain spikes

  • Misuse of opioids in > 33% (perhaps 48%?) of cancer patients at Memorial Sloan Kettering Cancer Center in high resource settings when insurance was better, published 1990’s.

  • Cancer pain – usually time limited. Intractable chronic pain – forever.
    .How many jobs will be lost and how many suicides when CDC imminently imposes strict cuts in opioids?

  •  DEA recently requires every pain patient taking opioids, including those with cancer, to be diagnosed “Opioid Dependent” — not only addicts – the same diagnosis for pain patients includes addicts. The term “addiction” has been equated to dependence by most psychiatrist over the past 30 years. It may be interesting to see what criteria are used to define “addiction” if any, in DSM V. Some important members acknowledge that the addition of dependence into addiction in DSM-III was a mistake….the DSM-V criteria will get rid of “abuse”, and will include craving. it will also apparently eliminate the legal/criminal criteria. DSM comments are extracted from here, with many good arguments on this epidemic, such as: “The US is leading the way in eradicating pain, but in doing so has created an unwanted byproduct: painkiller addiction.”
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    What would you want if you had intense chronic pain?

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    “For too many, and especially for too many women,” she said, “they are not in stable relationships, they don’t have jobs, they have children they can’t feed and clothe, and they have no support network.”

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    “It’s not medical care, it’s life,” she said. “There are people whose lives are so hard they break.”

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Opioids kill – or is it untreated pain?

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Pain kills, a maleficent force.

No one can help you. Only you have the tools to do it

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Alarms went off for me on radical opioid cuts in October and I posted when

DEA suddenly held conferences across the nation on sharply cutting opioid doses.

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How many of us especially seniors and male persons refuse to learn or use coping skills that

reduce pain without medication?

How many of us refuse to diet and lose weight to reduce pain and/or disability?

Politicians are sued if they tax sales of sugar loaded soft drinks.

One single can of soda per day exceeds acceptable sugar limits for entire day.

Snacks need to say much much time it takes to burn off fat –

quarter of large pizza 449 calories, walk off 1 hr 23 min;

large coke 140 calories, walk off 30 minutes.

Foods can be anti-inflammatory or pro-inflammatory.

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Obesity is pro-inflammatory.

So is lack of sleep.

People who sleep with animals in their bed and their bedroom, I’m talking to you.

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Yes, pain is in your mind.

Chronic back pain is no longer in the back, it’s in the brain, the pain matrix.

It’s behavior, not just pills. Pain is an emotional and psychosocial  and spiritual experience.

Work on it! Constantly.

Lord forbid we should teach stress reduction and meditation in grade school

and improve school lunches before kids start looking for heroin for pain.

Yes, kids have chronic pain, are sleep deprived, often obese.

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Isn’t this all un-American?

Injuries, pain, habits, pace activities, learn to avoid and treat pain – start young.

Taxpayers end up paying for ignorance and disability.

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I will soon be posting published research that documents health insurers have refused to pay for nonopioid treatment and how health care policy aimed at all people with chronic pain leads to suicide when drastic cuts are made to opioid doses – Washington State we are looking at you. Florida you’ve made headlines and 60 Minutes TV specials years ago.

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Do please comment below if your health insurer has refused medication, physical therapy, psycho-therapy, cognitive behavioral therapy, stress reduction, for chronic pain.

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How many of you have been denied social security disability by doctors who don’t know how to diagnose RSD, Complex Regional Pain Syndrome? Let me know. I will pass on that data to researchers collecting information on untreated pain.

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I have written many times on these pages, and more often than ever these past years as insurers cut back more and more. This will rapidly get worse. We need your data.

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Please send in your stories. You are not alone.

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So many issues. Steven Passik, PhD, was interview by Lynn Webster, MD – emphasis in bold is mine. Dr. Passik pioneered in management of chronic pain and pain in addicts. He has read some of Dr. Webster’s book. “You’re calling, the need for love and connection and all those things in the book, I’ve been – what’s largely lacking is outright, at times animosity towards people with pain and I think there’s a lot of projections sometimes because the therapy – the stigmatized disease – treated in stigmatized people with stigmatized drugs and interventions and so, it’s like a hat trick of stigma.  I’ve been to my share of pain conferences lately that people are really talking about, “Okay, well there’s come a realization that opioid-only, drug-only therapy, is really not going to work to the best majority of this population.  It doesn’t [mean] that opioids should be ignored and we’ll get into that later, but that they’re going to work in isolation and should never been expected to.  And then they start advocating things that are a lot like supportive and cognitive behavioral therapy and to be practiced basically by the primary care physician or the pain doctor.  And the idea that, to me that’s in a way comical because as a psychologist myself, we’re dealing with the system wherein cognitive behavioral therapists can’t even get paid to do cognitive behavioral therapy.  And so, I think something’s got to give, and I think one of the main obstacle is that – and this really gets into the next question as well but I’ll come back to that more specifically – but when people have a set of whatever chronic condition that involves psychiatric motivational, lifestyle, spiritual as well as nociceptive elements, and we put a premium only on what you do to people, prescribed to people, put in people, take out of people, and then that’s only going to relegate the other kinds of treatment or the other kinds of ways in which a caring physician and treatment team would spend time with the patient to the very poorly reimbursed category.  You’ll always going to have a problem with people being treated with the kind of respect that should go along with treating that kind of an illness and it’s not unique even to chronic pain.  I’ve seen treatment scenarios with people who are taking care of people with pancreatic cancer, have an afternoon clinic that has 45 people in it.  I mean how you – something’s got to give in our healthcare systems and I do think that patients are going to have to stand up and say, “I don’t want to be on a conveyor belt.  I want to spend some time and make a connection with the people that are taking care of me and it’s not just about the piece paper in my hands, for a prescription or that I walk out the door with.”

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Clematis Blue.

 The New York Times article further says:

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…This is the smallest proportional and absolute gap in mortality between blacks and whites at these ages for more than a century,” Dr. Skinner said. If the past decade’s trends continue, even without any further progress in AIDS mortality, rates for blacks and whites will be equal in nine years, he said….

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…Not many young people die of any cause. In 2014, there were about 29,000 deaths out of a population of about 25 million whites in the 25-to-34 age group. That number had steadily increased since 2004, rising by about 5,500 — about 24 percent — while the population of the group as a whole rose only 5 percent. In 2004, there were 2,888 deaths from overdoses in that group; in 2014, the number totaled 7,558….

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…For young non-Hispanic whites, the death rate from accidental poisoning — which is mostly drug overdoses — rose to 30 per 100,000 from six over the years 1999 to 2014, and the suicide rate rose to 19.5 per 100,000 from 15, the Times analysis found….

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…For non-Hispanic whites ages 35 to 44, the accidental poisoning rate rose to 29.9 from 9.6 in that period. And for non-Hispanic whites ages 45 to 54 — the group studied by Dr. Case and Dr. Deaton — the poisoning rate rose to 29.9 per 100,000 from 6.7 and the suicide rate rose to 26 per 100,000 from 16, the Times analysis found….

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…Eileen Crimmins, a professor of gerontology at the University of Southern California, said the causes of death in these younger people were largely social — “violence and drinking and taking drugs.” Her research shows that social problems are concentrated in the lower education group.

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The material on this site is for informational purposes only.

It is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

Relevant comments are welcome.

If any questions, please call the office to schedule an appointment.

This site is not email for personal questions.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please be aware any advertising on this free website is

NOT advocated by me and NOT approved by me.

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Neuroimmunology’s Future – Bioelectronics Treats TNF Diseases – Will replace drug industry


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This is an earth changing, once in a century paradigm shift in medicine.

TNF Alpha Diseases

Bioelectronics reduces TNF alpha

Inflammatory Diseases treated without drugs.

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A novel therapy, never done before, is now in clinical trials with Rheumatoid Arthritis patients and it is working well  – with no medication. Electrical stimulation is reducing TNF-alpha, the inflammatory cytokines that underlie many diseases including pain, cancer, autoimmune diseases and major depression. This is a completely new field of medicine reported by The New York Times Magazine. I strongly recommend reading the entire article as I have only a small clip below.

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Several of the foremost neuroscientists are involved with this, starting with the research of Kevin Tracy in 1998 who proved that stimulating the vagus nerve with electricity would alleviate harmful inflammation. He is a neurosurgeon and President of the Feinstein Institute for Medical Research in Manhasset, N.Y.

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Today researchers are creating implants that can communicate directly with the nervous system in order to try to fight everything from cancer to the common cold. “Our idea would be manipulating neural input to delay the progression of cancer,” says Paul Frenette, a stem-cell researcher at the Albert Einstein College of Medicine in the Bronx who discovered a link between the nervous system and prostate tumors….

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The list of T.N.F. diseases is long,” Tracey said. “So when we created SetPoint” — the start-up he founded in 2007 with a physician and researcher at Massachusetts General Hospital in Boston — “we had to figure out what we were going to treat.” They wanted to start with an illness that could be mitigated by blocking tumor necrosis factor and for which new therapies were desperately needed. Rheumatoid arthritis satisfied both criteria. It afflicts about 1 percent of the global population, causing chronic inflammation that erodes joints and eventually makes movement excruciating. And there is no cure for it.

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In September 2011, SetPoint Medical began the world’s first clinical trial to treat rheumatoid-arthritis patients with an implantable nerve stimulator based on Tracey’s discoveries. According to Ralph Zitnik, SetPoint’s chief medical officer, of the 18 patients currently enrolled in the ongoing trial, two-thirds have improved. And some of them were feeling little or no pain just weeks after receiving the implant; the swelling in their joints has disappeared. “We took Kevin’s concept that he worked on for 10 years and made it a reality for people in a real clinical trial,” he says….

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…The biggest challenge is interpreting the conversation between the body’s organs and its nervous system, according to Kris Famm, who runs the newly formed Bioelectronics R. & D. Unit at GlaxoSmithKline, the world’s seventh-largest pharmaceutical company. “No one has really tried to speak the electrical language of the body,” he says. Another obstacle is building small implants, some of them as tiny as a cubic millimeter, robust enough to run powerful microprocessors. Should scientists succeed and bioelectronics become widely adopted, millions of people could one day be walking around with networked computers hooked up to their nervous systems. And that prospect highlights yet another concern the nascent industry will have to confront: the possibility of malignant hacking. As Anand Raghunathan, a professor of electrical and computer engineering at Purdue, puts it, bioelectronics “gives me a remote control to someone’s body.”

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Glaxo has also established a $50 million fund to support the science of bioelectronics and is offering a prize of $1 million to the first team that can develop an implantable device that can, by recording and responding to an organ’s electrical signals, exert influence over its function. Instead of drugs, “the treatment is a pattern of electrical impulses,” Famm says. “The information is the treatment.” In addition to rheumatoid arthritis, Famm believes, bioelectronic medicine might someday treat hypertension, asthma, diabetes, epilepsy, infertility, obesity and cancer. “This is not a one-trick pony.”

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…The subjects in the trial each underwent a 45-minute operation. A neurosurgeon fixed an inchlong device shaped like a corkscrew to the vagus nerve on the left side of the neck, and then embedded just below the collarbone a silver-dollar-size “pulse generator” that contained a battery and microprocessor programmed to discharge mild shocks from two electrodes. A thin wire made of a platinum alloy connected the two components beneath the skin. Once the implant was turned on, its preprogrammed charge — about one milliamp; a small LED consumes 10 times more electricity — zapped the vagus nerve in 60-second bursts, up to four times a day. Typically, a patient’s throat felt constricted and tingly for a moment. After a week or two, arthritic pain began to subside. Swollen joints shrank, and blood tests that checked for inflammatory markers usually showed striking declines.

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Koopman told me about a 38-year-old trial patient named Mirela Mustacevic whose rheumatoid arthritis was diagnosed when she was 22, and who had since tried nine different medications, including two she had to self-inject. Some of them helped but had nasty side effects, like nausea and skin rashes. Before getting the SetPoint implant in April 2013, she could barely grasp a pencil; now she’s riding her bicycle to the Dutch coast, a near-20-mile round trip from her home. Mustacevic told me: “After the implant, I started to do things I hadn’t done in years — like taking long walks or just putting clothes on in the morning without help. I was ecstatic. When they told me about the surgery, I was a bit worried, because what if something went wrong? I had to think about whether it was worth it. But it was worth it. I got my life back.”

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Prostate Cancer – Exercise Cuts Inflammatory Cytokines IL-6 & IL-8, reduces psychological distress


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American Society of Clinical Oncologists (ASCO) in Chicago yesterday report on exercise reducing psychological distress. Whether cancer outcome will be impacted is not yet known and will require study but inflammation may impact cancer progression.

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The usual treatments change metabolism, cause weight gain, “loss of lean muscle mass, change[s] lipids, increase[s] rates of diabetes, and it thins bones.”

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Exercise is even more critical in those undergoing hormone therapies.

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This was a small randomized study for seven weeks.

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Patients receiving usual care experienced a 0.08 log10 increase in pro-inflammatory interleukin-6 production, while patients treated with an exercise program experienced a 0.03 log10 decrease in IL-6 (P<0.05), said Charles Kamen, PhD, research assistant professor at the University of Rochester Medical Center in New York.

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In his oral presentation … Kamen and colleagues observed a similar relationship with another pro-inflammatory cytokine, interleukin-8. In the control patients, the researchers noted a 0.03 log10 increase compared with a 0.04 log10 decrease among the exercise group, Kamen said.

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Using the Profile of Mood States (POMS), the research team determined that psychological distress decreased 5.17 points among the exercise group but increased 2.43 points in the patients who were in the usual control group (P=0.02).

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“This study supports the use of exercise for cancer patients for reducing psychological distress and suggests a potential biological mechanism by which this improvement occurs, namely by reducing systemic inflammation,” Kamen said in his presentation….

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The POMS scores were overall significantly in favor of the exercise group, and the subscales all trended in favor of exercise, except for the anger subscale in which there was virtually no change, Kamen said.

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Cognitive Behavioral Therapy – Being Positive


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I don’t know how the Great Recession may be affecting your mood, but for those with chronic pain, it is often difficult to nurture and maintain a positive attitude.  At times when we need the most help, we may be most reluctant to appreciate the benefits of Cognitive Behavioral Therapy, but that’s how we get help to reorder our thoughts in positive ways that are healing.

A Randomized Trial of a Cognitive-Bahavior Intervention

Compared to information giving and educational approaches, the risk for developing a long-term disability was lowered nine-fold for the cognitive-behavior intervention group. The cognitive-behavior group also demonstrated a significant decrease in physician and physical therapy use as compared with two groups receiving information, in which such use increased. These findings underscore the significance of early interventions that specifically aim to prevent chronic problems.

More recent research is reported by London’s syndication, The Independent, that tells us how much our attitude is harming ourselves.  Don’t forget, it harms everyone you love and constricts their lives too.  But the right frame of mind can lower your pain and other health risks.

PAIN

People showing dispositional optimism may be better able to cope with pain and need less medication. A study at Michigan State University on cancer patients shows that those who were more optimistic tended to report less severe pain. A study at the University of Alabama showed that patients who were optimistic used less medication for pain relief. “More optimistic adolescents are better able to match their medication use to their pain severity. Future research should examine how other psycho-social factors might influence pain medication use in adolescents and adults, and clinicians should take into account psychosocial factors when working with pain populations.”

CANCER

Women who are happy and optimistic may have a lower risk of developing breast cancer. The research also show that adverse life events, such as loss of a loved one or divorce , can increase the risk. Results from the study at Ben Gurion University in Israel show that exposure to more than one adverse life event was associated with a 60 per cent increased risk of disease, while happy and optimistic women were 25 per cent less likely to have the disease. “A general feeling of happiness and optimism seems to play a protective role,” say the researchers. “The relationship between happiness and health should be examined in future studies and possible relevant preventive initiatives should be developed,” say the researchers.

MORTALITY

A review of research into the association between positive wellbeing and mortality shows a signifciant link. The University College London analysis of 35 studies showed that positive psychological wellbeing was associated with an 18 per cent reduced mortality in healthy people and a 24 per cent lower risk in sick people. “Positive feelings – emotional well-being, positive mood, joy, happiness, vigour, energy – and life satisfaction, hopefulness, optimism, sense of humour, were associated with reduced mortality. Results suggest that positive psychological wellbeing has a favourable effect on survival in both healthy and diseased populations.

HEART DISEASE

The positive-minded have a 55 per cent lower risk of dying from heart disease, according to the results of a study which followed 500 men aged 54 to 84 for 15 years. “Our results demonstrate a strong and consistent association between dispositional optimism and lower risk of cardiovascular mortality,” says the researchers from The Netherlands Institute of Mental Health, Delft. Just how low optimism may lead to cardiovascular death, is, say the authors, an intriguing, but unanswered question. One possible mechanism, they say, is that optimism is related to better coping behaviour. Another study at the University of Pittsburgh, and based on 200 women diagnosed with thickening of the arteries, showed that over a 15-year period, the disease progressed more slowly in those women classed as optimists. Other research has shown that optimists have a lower risk of rehospitalisation after coronary artery bypass graft surgery.

The article also covers the field of research as it applies to blood pressure, longevity, infections, even the common cold……..

Practice makes perfect.  Take time out to give yourself some love.  Doctors too.

And read Diana’s blog to see how the addition of 3 kittens have added so much to her family’s mood.  Even if you can’t have a pet, you can still enjoy a friend’s.

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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