Steroids Corticosteroids Prednisone Cortisone Dexamethasone —Sensitize Microglia & Prime Glial Over-Responsiveness


.

.

.

.

Glucocorticoids prime later immune &

.

glial over-responsiveness that

.

 induces cellular damage/stress in the brain

.

.

 

.
.

The permissive role of glucocorticoids in neuroinflammatory priming: mechanisms and insights.

Frank MG, Watkins LR, Maier SF.
Curr Opin Endocrinol Diabetes Obes. 2015 Aug;22(4):300-5. doi: 10.1097/MED.0000000000000168. Review.
.
“In light of these findings, we propose a model of glucocorticoid-induced neuroinflammatory priming whereby stress and glucocorticoids induce cellular damage/stress in the brain, the products of which prime the NLRP3 inflammasome. “
PMID: 
26087336 

Free PMC Article

Select item 255593332.
Barrientos RM, Thompson VM, Kitt MM, Amat J, Hale MW, Frank MG, Crysdale NY, Stamper CE, Hennessey PA, Watkins LR, Spencer RL, Lowry CA, Maier SF.
Neurobiol Aging. 2015 Mar;36(3):1483-95. doi: 10.1016/j.neurobiolaging.2014.12.003. Epub 2014 Dec 11.
PMID: 
25559333 

Free PMC Article

Select item 254331703.
Fonken LK, Frank MG, Kitt MM, Barrientos RM, Watkins LR, Maier SF.
Brain Behav Immun. 2015 Mar;45:171-9. doi: 10.1016/j.bbi.2014.11.009. Epub 2014 Nov 26.
PMID: 
25433170 

Free PMC Article

Select item 244854914.
Frank MG, Hershman SA, Weber MD, Watkins LR, Maier SF.
Psychoneuroendocrinology. 2014 Feb;40:191-200. doi: 10.1016/j.psyneuen.2013.11.006. Epub 2013 Nov 27.
PMID: 
24485491 

Free PMC Article

Select item 234590265.
Frank MG, Watkins LR, Maier SF.
Brain Behav Immun. 2013 Oct;33:1-6. doi: 10.1016/j.bbi.2013.02.004. Epub 2013 Mar 1. Review.
PMID: 
23459026
Select item 220412966.
Frank MG, Thompson BM, Watkins LR, Maier SF.
Brain Behav Immun. 2012 Feb;26(2):337-45. doi: 10.1016/j.bbi.2011.10.005. Epub 2011 Oct 24.
PMID: 
22041296
Select item 219074187.
Hains LE, Loram LC, Taylor FR, Strand KA, Wieseler JL, Barrientos RM, Young JJ, Frank MG, Sobesky J, Martin TJ, Eisenach JC, Maier SF, Johnson JD, Fleshner M, Watkins LR.
J Neuroimmunol. 2011 Oct 28;239(1-2):53-60. doi: 10.1016/j.jneuroim.2011.08.011. Epub 2011 Sep 9.
PMID: 
21907418 

Free PMC Article

Select item 215361238.
Loram LC, Taylor FR, Strand KA, Frank MG, Sholar P, Harrison JA, Maier SF, Watkins LR.
Brain Behav Immun. 2011 Oct;25(7):1408-15. doi: 10.1016/j.bbi.2011.04.013. Epub 2011 Apr 23.
PMID: 
21536123 

Free PMC Article

Select item 212569559.
Frank MG, Watkins LR, Maier SF.
Brain Behav Immun. 2011 Jun;25 Suppl 1:S21-8. doi: 10.1016/j.bbi.2011.01.005. Epub 2011 Jan 21. Review.
PMID: 
21256955
Select item 1964707010.
Frank MG, Miguel ZD, Watkins LR, Maier SF.
Brain Behav Immun. 2010 Jan;24(1):19-30. doi: 10.1016/j.bbi.2009.07.008. Epub 2009 Jul 30.
PMID: 
19647070

Select item 1738382611.

Stress-induced glucocorticoids suppress the antisense molecular regulation of FGF-2 expression.

Frank MG, Der-Avakian A, Bland ST, Watkins LR, Maier SF.
Psychoneuroendocrinology. 2007 May;32(4):376-84. Epub 2007 Mar 26.
PMID: 
17383826

Similar articles

.

.
.
.

 

 

 

 

 

 

.

.

.

.

.

.

.

 

.


The material on this site is for informational purposes only, and is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

~

Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

~

~

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

.

.

.

The advertising below is not recommended by me.

.

 

 

CRPS & All Patients – pills no help for this severe pain


.

.

Yes, people with nerve pain, CRPS pain, any pain, and often those without pain have this. It can lurk for decades before pain is obvious. But find the right spot and you’ve got it. Doctors and patients fail to understand one of the worst disabling causes of severe pain. Pills, drugs fail to help, but doctors reflexively respond with pills because they often have no training in this. The slightest movement, a sudden flicker of being jarred and pain explodes up to a 9. Pain may catch you by surprise, you yelp, you can’t help it, and you stop instantly. It’s unbearable, the slightest jolt, the wrong angle, a split second. Some reach for a handful of pills, and cut back activity until they are completely unable to walk or move without fear. For others, no jolt or yelp, it just appears and silently gets worse without your knowing, until it manifests decades later and now you cannot function. You forget the incident that set it off.

.

CASE

.

Healthy 19 year old with pain on standing, walking, wanted a motorized wheelchair on first visit

.

This young student had suddenly dropped out of UC Berkeley before the end of the quarter due to severe pain, difficulty walking. The only patient in 41 years of medicine who asked for a motorized wheelchair, was only 19, had no medical illness, no neurological deficit, no inflammatory markers, no injury, but unbearable pain on standing and walking.

.

After four months of physical therapy, he was pain free and regained full function, out in the park running with his dog and his friends. Nineteen years old and able to live a normal life. It hurts like crazy. Physical therapy had to get out all the “snags” in muscle and fascia that prevented normal function and caused excruciating pain. There is no magic.

.

CASE

.

A grandmother with pain in both feet had not been able to stand for six long years. She loved cooking for family and grand kids, but was unable to stand to do anything. She could not walk. In less than two weeks of physical therapy, she was walking 1 to 2 miles a day and loving her life again. Depression vanished. Building her strength to walk more each day.

 

~

.

Oh, need I explain that when you taper off opioid in a case like these, yes, they will have pain just from withdrawing the opioid – the body wants its opioid back and taper creates pain that may stay high for weeks even months, until the body stops klanging for its opioid and the psyche stops catastrophizing to figure out it can live without vegetating by sedating the brain. Each cell in the body goes wild for its opioid and does not want to give up its drug. The autonomic nervous system goes into overdrive, patients leave your practice to find any of hundreds of thousands of doctors for more opioid that perpetuate the desire to lie back and do nothing to trigger any slight jolt. Just narcotize the brain.

.

CAUSE

.

Stasis. Inactivity. Not moving. Immobilization. Sedentary muscle, just sitting, or in a cast or after knee surgery, bedridden. Stasis. Simply stasis. Muscles and fascia develop “knots” that you are not aware of until suddenly, the wrong jolt, the slightest move, and you freeze, screaming in pain. Prolonged sitting often causes hip flexion contractures. “Knots” can be felt in muscle,  tender points are highly localized. P.T. finds them and causes screaming pain to get them out. My own body has it now in several muscles, both thighs. It’s common. They’re quiet until you find them and mash them. It hurts like crazy to treat it, but that’s the only way to get this silent killer that takes lives. Pills do nothing. Blood curdling yelps and bruises appear during P.T. If you don’t do it, it gets worse. They are not always easy to find, not always a “knot” that can be felt, but zingers they are.

.

HOW

.

What’s in blood besides red cells, white cells, oxygen? Fibrin and collagen. If you cut yourself, fibrin instantly seals the bleed and forms a clot. The body then builds collagen, a major component of connective tissue. What had been soft tissue can turn into a tough fibrous matrix. Nutrients and oxygen cannot get to it. The “knots” must be properly and precisely released by a skilled physical therapist to find them all, to release them all.

.

Just this week, a patient with back pain who quit P.T. early, told me she learned to reduce back pain in bed by placing pillows under the knees, two pillows. Perfect! to develop hip flexion contractures that prevent standing erect, thus throwing out the spine and soon a 3rd or 4th back surgery. Undiagnosed, untreated hip flexion contractures are surely one of the major causes leading to preventable spine surgery.

.

Doctors don’t know how or perhaps don’t care to diagnose it.

.

Pills do NOTHING to relieve it.

.

There is no hope until the knots are undone.

.

Compliance is crucial. We have a choice. But in 2003, W.H.O reported: 50% of people don’t comply w/ chronic disease management. Insurance denies medications, insurance limits physical therapy, you are left with rapidly increasing disability and a miserable hell that does not respond to pills of any kind, not even massive doses of opioids.

.

STASIS – OBESITY

 

.

Obesity leads to increasing stasis. Let’s not dwell on obesity in itself that causes inflammation and increases estrogen production in fat all over the body – that’s one of the reasons obese men develop breasts. Every woman knows estrogen can cause horrific disabling pain. The more fat we pack on is like adding estrogen producing ovaries all over the body. And fat cells remain hungry for 10 years before new ones arise. We take to walkers and wheelchairs instead of the obvious: lose weight, take pounds of fat off joints, muscles and spine, rid the system of excess pain-producing estrogen, and then work out the knots with physical therapy. Thin people get knots in muscle too but obesity and its load of estrogen is a big culprit.

.

Motorized wheelchairs:  How many obese individuals are willing to lose weight, even when it means regaining life and use of body? You don’t have to pay money to eat less. Exercise helps but it is not the only way to lose weight, and people may eat more after exercise.

.

Seize the day. Failure is not a healthy option but I’ve chosen favorite foods too often. Eat well, nothing between meals, limit protein to 4 oz of fish/chicken/meat or 8 oz dairy/legumes, one piece of fruit in AM with protein, add loads of veggies – 5 cups per day, the low glycemic veggies, one tablespoon oil/butter with each meal. Never skip meals. Plan ahead, carry your own food if you work away from home. Most of all, avoid anything that is high glycemic. Stomach will feel very full, but very eager at the time of next meal. You will find your mood is stabilized. Your joints will not bother you as much or not at all.  You will have more energy and less depression.

.

If you are unsure what foods are considered high glycemic, use the old axiom for weight loss “if it’s white, don’t bite” with some exceptions such as cauliflower. Here is a link to a list of glycemic food levels to get you started.

 

 

 

 

 

 

.

.

.

.

.

.

.

 

.

 


The material on this site is for informational purposes only, and is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

~

Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

~

~

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

.

.

.

The advertising below is not recommended by me.

.

 

 

Glia regulate glucose & metabolism – diabetes, obesity, Alzheimers – will change treatment


 

.

.

.

Sugar has a stronger effect on our brains than we even realised, study finds

.

The complete opposite of what scientists thought.

.

.

.

From publication today in Cell

.

Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability

.

 

Quoting from the Sciencealert report:

.

“German scientists have discovered that our brains are actively taking in sugar from the blood stream, overturning the long-held assumption that this was a purely passive process.

.

Even more surprising, they also found that it’s not our neurons that are responsible for absorbing all that sugar – it’s our glial cells, which make up 90 percent of the brain’s total cells, and . . .

.

Not only does the find go against conventional wisdom on how our brains respond to sugar intake, it also shows how cells other than our neurons can actively play a role in controlling our behaviour.

.

Astrocytes – which are a specialised form of glial cell that outnumber neurons more than fivefold – have long been thought of as little more than ‘support cells’, helping to maintain the blood-brain barrier, carry nutrients to the nervous tissue, and play a role in brain and spinal cord repair.

.

But we now have evidence that they also play a role in human feeding behaviours, with researchers finding that their ability to sense and actively take in sugar is regulating the kinds of appetite-related signals that our neurons send out to the rest of the body. 

.

And we’re not talking about a little bit of sugar here: the human brain experiences the highest level of sugar consumption out of every organ in the body. 

.

“Our results showed for the first time that essential metabolic and behavioural processes are not regulated via neuronal cells alone, and that other cell types in the brain, such as astrocytes, play a crucial role,” explains study leader Matthias Tschöp from the Technical University of Munich.

.

“This represents a paradigm shift and could help explain why it has been so difficult to find sufficiently efficient and safe medicines for diabetes and obesity until now.”

.

Tschöp and his team decided to investigate how the brain decides to take in sugar from the blood – and how much – because this is directly related to our feelings of hunger.

.

 

. . .The team used positron emission tomography (PET) scans to observe how insulin receptors act on the surface of the brain’s astrocytes. Insulin is a hormone produced by the pancreas to allow the body to use or store sugar (in the form of glucose) from carbohydrates in the food we eat.

.

They found that if these receptors were missing on certain astrocytes, it would result in less activity in the neurons that are responsible for curbing food uptake, called proopiomelanocortin neurons. 

.

Not only that, but they found that astrocytes missing insulin receptors actually became less efficient over time in transporting glucose into the brain – particularly in a region of the hypothalamus that sends out signals that you’re full, or satiated.

.

So it looks like glial cells, not the neurons, are the true ‘gate-keepers’ for how much sugar our brains absorb, and we now know that sugar has such a powerful influence on them, they’re seeking out sugar, rather than just passively absorbing it.

.

A better understanding of how this works could change everything about how we treat obesity in the future.”

.

.

References to whet the appetite:

.

Kleinridders, A., Ferris, H.A., Cai, W., and Kahn, C.R. Insulin action in brain regulates systemic metabolism and brain function. Diabetes. 2014; 63: 2232–2243

.

De Felice, F.G. and Ferreira, S.T. Inflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer disease. Diabetes. 2014; 63: 2262–2272

 .

Ferreira, S.T., Clarke, J.R., Bomfim, T.R., and De Felice, F.G. Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer’s disease. Alzheimers Dement. 2014; 10: S76–S83

.

.

.

.

.

.

.

.

 

.

 

~

~


The material on this site is for informational purposes only, and is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

~

Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

~

~

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

.

.

.

The advertising below is not recommended by me.

.

.

.

Opioid taper – please comment. Your story matters


.

.

.

.

Opioids

.

Americans use 80% of prescription opioids in the world.

.

If you have voluntarily tapered off opioids, please comment

..

.

In 1991, America was not even among the top 10% prescribing opioids for cancer pain. Now look where opioid induced pain has led the way medicine is practiced. We have created disability like throwing gasoline on fire. It is costing lives.

.

Patients with intractable pain who have failed all  procedures, nerve blocks, injections and opioids, why are they still taking them if pain is still severe, if they are not able to function? They do worse than nothing.

.

Opioids create pain: They trigger the brain to produce pro-inflammatory cytokines that cause pain. It is drowning in a universe of delusion to ignore the data. Clinging to fear.

.

Data: Here’s an old Stanford study from 2005 Journal of Pain:

.

Opioid Tolerance and Hyperalgesia in Chronic Pain Patients After One Month of Oral Morphine Therapy: A Preliminary Prospective Study

 

Abstract

.

There is accumulating evidence that opioid therapy might not only be associated with the development of tolerance but also with an increased sensitivity to pain, a condition referred to as opioid-induced hyperalgesia (OIH). However, there are no prospective studies documenting the development of opioid tolerance or OIH in patients with chronic pain. This preliminary study in 6 patients with chronic low back pain prospectively evaluated the development of tolerance and OIH. Patients were assessed before and 1 month after initiating oral morphine therapy. The cold pressor test and experimental heat pain were used to measure pain sensitivity before and during a target-controlled infusion with the short-acting μ opioid agonist remifentanil. In the cold pressor test, all patients became hyperalgesic as well as tolerant after 1 month of oral morphine therapy. In a model of heat pain, patients exhibited no hyperalgesia, although tolerance could not be evaluated. These results provide the first prospective evidence for the development of analgesic tolerance and OIH by using experimental pain in patients with chronic back pain [my emphasis]. This study also validated methodology for prospectively studying these phenomena in larger populations of pain patients.

.

Perspective

.

Experimental evidence suggests that opioid tolerance and opioid-induced hyperalgesia might limit the clinical utility of opioids in controlling chronic pain. This study validates a pharmacologic approach to study these phenomena prospectively in chronic pain patients and suggests that both conditions do occur within 1 month of initiating opioid therapy.

.

Of course when you stop the opioid, the system rebounds like wild, stronger pain. It’s one thing to publish this important study, but how to offer better relief than the adjuvants that failed?

.

How has opioid’s overwhelming inflammatory imbalance in brain affected the ability to recover? ever. The brain is maxed out. Is it permanent? How long does this last? There are those who think, I won’t taper off, I’ll wait till the very last minute, do rapid detox and expect instant change. Do not allow brain recovery. Opioids are still in system for weeks after stopped.

.

People more likely to remain on disability if opioids are even once started. Doctors then prescribe tramadol, Nucynta, buprenorphine in patches or film for sublingual use. Those are still opioids.

.

And one week ago, two more opioids approved. They make billions, guaranteed lifelong. Why should pharma try something that will actually relieve pain without causing inflammation centrally in brain?

.

The problem is that patients who taper off have been offered nothing adequate to replace the opioid.

.

The question is, if FDA refuses to approve any more opioids, will pharma do anything to relieve pain?

.

.

.

.

.

 

.

 

~

~


The material on this site is for informational purposes only, and is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

.

~

Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

~

~

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

.
.
.
.
.
.
.

Earth’s crammed with heaven – Elizabeth Browning


 

.

.

.

Earth’s crammed with heaven,
And every common bush afire with God,
But only he who sees takes off his shoes;
The rest sit round it and pluck blackberries.

 

.

Elizabeth Browning

.

.

.

.

.

.

.

.

.

I do not endorse any advertising. This is a free blog and I have no control over ads.

.

.

.

.

.

 

Opioids “Two Novel Opioids Win Tepid Backing From FDA Panel” – really? 2 more opioids?


.

.

.

Two Novel Opioids

Win Tepid Backing From FDA Panel

.

Two more opioids . . . . . . . . oh boy! more opioids

.

The only class of pain drugs that rakes in $40,000 per month or more for a single patient. We’d see pharma thinking about something better than opioids if they were blocked from charging more than gabapentin. Opioids cost pennies yet these formulations can cost more than $1,000 a day and they are poorly effective for chronic pain.

.

.

.

.

 

..

“Both committees — the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) and the Drug Safety Risk Management Advisory Committee (DSaRM) — were asked to consider a proposed indication of pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate.”

.
“Many of the committee members said their “yes” votes on approval came with some hesitation — while Teva’s product may be an incremental step in the right direction, there needs to be better outcome measures for reductions in abuse resulting from reformulations, as well as improved outcomes for the treatment of pain, they said.
Meeting a second day, the same panel also voted 9-6 to “recommend” approval of a different abuse-deterrent product, this one combining extended release oxycodone with naltrexone (Troxyca). The slim margin is often seen a null recommendation.”

.

.

.

Don’t get excited about naltrexone in these formulations. When injected into vein, it will block the effect of the opioid.

.

.

.

 

.

.

.

~

~

~


The material on this site is for informational purposes only, and is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

.

~

 

Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

~

~

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

~
~
 

Neuropathic Pain Medications – review & metanalysis of 229 studies


.

.

.

.

.

This review was done by many of the best pain specialists from all over the world. You will not find answers in that large review if neuropathic pain has already failed tricyclic antidepressants (Elavil, amitriptyline, Norpramin desipramine, others), gabapentin (Neurontin), pregabalin (Lyrica), lidocaine, capsaicin, or opioids. That is the current paradigm. A new paradigm – glial modulators  – that I discuss on this site, may or may not give relief.

.

A member of the International Association for Study of Pain, IASP, published a brief critique of that comprehensive review of 229 trials of medications for neuropathic pain published in Lancet Neurology February 2015. The critique is posted below, done by a member of the Neuropathic Pain Special Interest Group, NeuPSIG.

 

.

To understand the metanalysis of these 229 trials, you need to understand the simple concept of number needed to treat, NNT.

.

NNT is an estimate of “the number of patients that need to be treated in order to have an impact on one person.”

.

The smaller the number, the more effective the drug. Example, NNT of 7.2 for gabapentin means you need to treat  7.2 people before a response. If 3, need to treat 3 before a response.

.

Barsook (Harvard, ref. below) reviewed ketamine studies in 2009:  “they did show a level of efficacy (of ketamine) based on NNT that equals or betters most drug trials for this condition.”

.

.

“NeuPSIG has just published an up to date systematic review on the effectiveness of pharmacotherapy in Lancet Neurology. They have negotiated with the journal to make it available beautifully open access. You can download it for free here.”

.
Neil O’Connell, Brunel University London

.

“This is a comprehensive review, containing 229 trials of the full range of pharmacological agents using robust methods, to synthesize, summarise and make value judgements about the quality of the available evidence. So what are the take home messages?”

.

“Using a primary outcome of achieving at least 50% pain relief trial outcomes were described as “generally modest”. The number of patients needed to treat with the drug compared to a placebo for one more person to achieve this outcome ranged from a relatively rosy 3.6 (95% confidence interval 3 to 4.4) for tricyclic antidepressants such as amitryptiline, 4.3 (95%CI 3.4 to 5.80 for strong opioids to a less impressive 7.2 (95%CI 5.9 to 9.21) for gabapentin, and 7.7 (6.5 to 9.4) for pregabalin (often sold under the brand-name Lyrica). It’s interesting, at least to me, how much better the older more traditional agents seem to have fared compared on effectiveness to the more modern (and commonly more expensive) agents although the safety and tolerability of gabapentin seems superior.”

.

“The spectre of publication bias also raises its head. The reviewers carefully took a number of routes to try to unpick this notoriously difficult issue and estimate that there has been overall a 10% overstatement of treatment effects. Published studies reported larger effect sizes than did unpublished studies. This is not a problem restricted to the field of pain trials. It is a burning issue across the world of clinical trials. It is very important because if we fail to base our clinical recommendations on the totality of relevant evidence (because some data are hidden from us) we are in danger of mis-estimating the benefits and the harms and as a result patients are put at risk. If you think that is pretty important then there are ways that you can help. Check out the All-Trials campaign.”

.

“Overall what does this mean? Many drugs are effective but not as effective as we would wish them to be. No pharmacological agent really impresses and for any drug the most probable outcome is failure to produce 50% pain relief. There are various potential reasons for this. The first is that the drugs may only be moderately or marginally effective, another is that neuropathic pain includes quite a mixed bag and our ability to accurately diagnose and to target drugs to specific mechanisms in the clinic is currently fairly poor.”

.

“The NeuPSIG review team formulate a number of recommendations for revision of their clinical guideline for managing NP pain, balancing the benefits, harms, costs and strength of the evidence.”

  • a strong recommendation for use and proposal as a first-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin;

    .

    • a weak recommendation for use and proposal as a second line treatment for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only.

      .

“This email [from IASP’s NeuPSIG] is also published as a blogpost at www.bodyinmind.org”

.

References

.

Finnerup NB, Attal N, Haroutounian S et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14:2:162-73.

.

.

.

.

Glial modulators – another paradigm

.

From my January 2012 brief review of publications on ketamine, only one of a handful of glial modulators, this author says reviews “show a level of efficacy based on NNT that equals or betters most drug trials for this condition.

.

 .

Ketamine and chronic pain – Going the distance, David Barsook, Director, P.A.I.N. Group, Massachusetts General, McLean and Children’s Hospitals, Harvard Medical School, Boston, MA;

~

This paper covers essential points not mentioned by many, thus quoted at length below:

.

Our current therapeutic armamentarium is quite limited in terms of analgesic efficacy in controlled trials. Some would argue that the small efficacy (both at a population level and the magnitude of change in VAS score) this is related to the fact that we need to consider mechanistic approaches to chronic pain subgroups. However, patients and clinicians find themselves in a position of “what to do now”.

.

Ketamine, brain function and therapeutic effect – neuroprotective or neurotoxic

.

With the onset of chronic pain (including CRPS) a number of changes in brain function occur in the human brain including but not limited to: (1) central sensitization ; (2) functional plasticity in chronic pain and in CRPS; (3) gray matter volume loss in CRPS ; (4) chemical alterations ; and (5) altered modulatory controls. Such changes are thought to be in part a result of excitatory amino acid release in chronic pain. Excitatory amino acids are present throughout the brain and are normally involved in neural transmission but may contribute to altered function with excessive release producing increased influx of calcium and potentially neural death. Here lies the conundrum the use of an agent that potentially deleteriously affect neurons that may already be compromised but may also have neuroprotective properties by mechanisms that include reducing phosphorylation of glutamate receptors resulting in decreased glutamatergic synaptic transmission and reduced potential excitotoxicity . Alternatively, ketamine may affect glia regulation of glutamate and inhibit glutamate release within glia. However, by whatever mechanism ketamine acts on CRPS pain, there does seem to be a dose/duration effect in that longer doses at levels tolerated by patients seem to prove more effective in terms of the duration of effects.

.

So what could be happening in the brain and what is required to alter brain systems and reverse the symptomatic state? Ketamine may diminish glutamate transmission and “resets” brain circuits, but it seems that a minimal dose and/or duration of treatment is required. Alternatively, ketamine may produce neurotoxicity and damage or produce a chemical lesion of affected neurons. These two issues are important to be understood in future trials. Reports from patients who have had anesthetic doses have included prolonged pain relief for many months. While the authors did not address issues such as the effect of dosing duration or repetitive dosing at say 6weeks, they did show a level of efficacy based on NNT that equals or betters most drug trials for this condition.”

….

Conclusions

.

As a community we have a major opportunity to define the efficacy and use of a drug that may offer more to CRPS (and perhaps other) patients than is currently available. This is clearly an opportunity that needs urgent attention and a number of questions remain to be answered. For example, is ketamine more effective in early stage disease? How does ketamine provide long-term effects? Further controlled trials evaluating dose, duration, anesthetic vs. non-anesthetic dosing are needed. Few of us really understand what it is like to suffer from a chronic pain condition such as CRPS. Ketamine therapy may be a way forward that can be brought into our clinical practice through further controlled studies that will allow for appropriate standards for use in patients.

.

.

.

~
~
~


The material on this site is for informational purposes only, and is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

.

~

Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

~

~

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

~
~
~
~
~
%d bloggers like this: