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Anti–nerve growth factor therapy attenuates cutaneous hypersensitivity and musculoskeletal discomfort in mice with osteoporosis

Introduction:
The prevalence of osteoporosis is increasing with the aging population and is associated with increased risk of fracture and chronic
pain. Osteoporosis is currently treated with bisphosphonate therapy to attenuate bone loss. We previously reported that improvement in bone mineral density is not sufficient to reduce osteoporosis-related pain in an ovariectomy (OVX)-induced mouse model of osteoporosis, highlighting the need for new treatments. Targeting of nerve growth factor (NGF) with sequestering antibodies is a promising new direction for the treatment of musculoskeletal pain including back pain and arthritis. Its efficacy is currently unknown for osteoporotic pain.
Objective:
To investigate the efficacy of anti-NGF antibody therapy on osteoporotic pain in an OVX-induced mouse model.
Methods:
Ovariectomy- and sham-operated mice were injected with an anti-NGF antibody (10 mg/kg, intraperitoneally, administered 2×, 14 days apart), and the effect on behavioural indices of osteoporosis-related pain and on sensory neuron plasticity was evaluated.
Results:
Treatment with anti-NGF antibodies attenuated OVX-induced hypersensitivity to mechanical, cold, and heat stimuli on the plantar surface of the hind paw. The OVX-induced impairment in grip force strength, used here as a measure of axial discomfort, was partially reversed by anti-NGF therapy. No changes were observed in the rotarod or open-field tests for overall motor function and activity. Finally, anti-NGF treatment attenuated the increase in calcitonin gene-related peptide–immunoreactive dorsal root ganglia neurons observed in OVX mice.
Conclusion:
Taken together, these data suggest that anti-NGF antibodies may be useful in the treatment of prefracture hypersensitivity that is reported in 10% of patients with osteoporosis.
This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author. Address: Center for Preventive Medical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 2608670, Japan. Tel.: +81-43-226-2017; fax: +81-43-226-2016. E-mail address: miyakosuzuki170@chiba-u.jp (M. Suzuki).
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Received October 05, 2017
Received in revised form February 24, 2018
Accepted March 13, 2018
© 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.

Anti–nerve growth factor therapy attenuates cutaneous hypersensitivity and musculoskeletal discomfort in mice with osteoporosis


Orginally Published At: PAIN Reports

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Ethical considerations in the design, execution, and analysis of clinical trials of chronic pain treatments

Introduction:
In the field of
pain research, clinical trials may randomize over 500 subjects and include more than 150 sites spanning over a dozen countries.
Methods:
This review examines the ethical considerations affecting clinical trial design, execution, and analysis of trials for chronic pain. The Belmont Report has been the touchstone for human studies protection efforts since 1979. Commissioned by the U.S. government in response to ethical failures in medical research, such as the Tuskegee Syphilis Study, the report emphasizes 3 basic principles: respect for persons, beneficence, and justice. Trial design and sample size have important ethical implications.
Conclusions:
Measures to enhance trial transparency and combat publication and many other types of bias should be implemented.
This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author. Address: California Pacific Medical Center Research Institute, 475 Brannan St, Suite 130 San Francisco, CA 94107. Tel.: 415-600-1750; fax: 415-600-1725. E-mail address: mcrowbotham@gmail.com (M.C. Rowbotham).
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Received August 10, 2017
Received in revised form February 18, 2018
Accepted February 24, 2018
© 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.

Ethical considerations in the design, execution, and analysis of clinical trials of chronic pain treatments


Orginally Published At: PAIN Reports

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Health Care Utilization and Costs Associated with Pediatric Chronic Pain

• In a 2016 survey of the United States population, 6% of children had chronic pain• Chronic pain was associated with greater odds of using emergency care in past year• Chronic pain was also associated with higher out-of-pocket medical expenses• Chronic pain was not associated with increased odds of using mental health services

Health Care Utilization and Costs Associated with Pediatric Chronic Pain

Orginally Published At: Pain Journal

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A Controlled Pilot Trial of PainTracker Self-Manager, a Web-Based Platform Combined with Patient Coaching, to Support Patients' Self-Management of Chronic Pain

• PainTracker Self-Manager improved patients’ confidence in chronic pain self-management• This intervention also improved patients’ satisfaction with pain treatment• In study completers, the intervention also improved activity engagement and pain• The intervention included web-based assessment and education plus clinician coaching

A Controlled Pilot Trial of PainTracker Self-Manager, a Web-Based Platform Combined with Patient Coaching, to Support Patients’ Self-Management of Chronic Pain

Orginally Published At: Pain Journal

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Pain demands an explanation (even if it’s kooky)

People are prone to having strong explanatory theories for their medical issues…so strong that they leak out onto other people.

This is one more follow-up to going public with my own pain story (probably the last for quite a while). In addition to lots of sympathy and even some hate mail, I also got many diagnostic suggestions, theories about why I am in pain. Naturally, many were kooky, or at least bizarrely overconfident. Some highlights…

  1. “Sounds like it’s all coming from your jaw.” Oh, is that what it sounds like? This is classic (if rather extreme) example of structuralism — attributing too much clinical significance to a single, subtle biomechanical factor.
  2. Several people thought it was obvious that I have chronic lyme disease. But who doesn’t, really?
  3. The tinfoil hat prize must be shared by two readers who were convinced that my problems are caused by electromagnetic sensitivity. One even “cited” Saul Goodman’s brother on the TV show Better Call Saul as a “case study” of someone with this condition. It was unclear if she understood that the character is actually fictional. It is clear that she didn’t understand that the character clearly has a psychogenic illness, not an energy allergy — that’s the point of the finale of the third season.

We all know the type. These amateur diagnosticians probably all believe that they are afflicted with these problems, or were once, and now they are eager to diagnose everyone else with it — to be validated by that, to makes themselves part of an epidemic, and a member in a club of suffering.

One of the principle qualities of pain is that it demands an explanation.

Plainwater, by Anne Carson

When we’re in pain we badly want a “story” about what’s going on, and we’re willing to make it up if we have to, because having any story is a higher priority than intellectual restraint. Most people just aren’t comfortable with not knowing, and are quick to embrace an explanation whether it’s justified or not.

But many go much further than simply believing, and become “condition evangelists.” They believe they’ve found an explanation not only for their own suffering, but many others, and they dedicate themselves to raising “awareness”… of something that doesn’t exist, or isn’t actually what they have, or what anyone has.

[Go to this post on PainScience.com]

Pain demands an explanation (even if it’s kooky)


Orginally Published At: Pain Science

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Why people seek out alternative medicine

One of many excellent points in this article about former naturopath Britt Marie Hermes: The naturopath whistleblower: ‘It is surprisingly easy to sell snake oil’.

I know many wonderful doctors, but they are mostly the ones I’ve chosen to get to know professionally and personally, so of course I like them. The physicians I’ve encountered more or less at random as a patient are a different matter: too many have been stereotypically arrogant and incompetent. (And I think it’s particularly bad for chronic pain patients, who are more likely to run afoul of obnoxious ignorance. Many doctors who otherwise good at their jobs fail patients with chronic pain.)

I think there’s no question that there is a complicated medical “attitude problem,” with many causes, and that it’s a major factor in driving people to alternative medicine, which a lot of people see as a lesser of evils. Many seek it out while holding their noses, with a sheepish reluctance, painfully aware that “it’s probably bullshit.” But they do it anyway, because one too many doctors refused to listen, scoffed at their worries and theories, or otherwise failed at bedside manner or even basic good manners. Of course there are other factors, but this is the one that skeptics chronically underestimate.

[Go to this post on PainScience.com]

Why people seek out alternative medicine


Orginally Published At: Pain Science

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Pain Adaptability in Individuals With Chronic Musculoskeletal Pain Is Not Associated With Conditioned Pain Modulation

The ability of the body to modulate pain without the help of medical interventions is known as endogenous pain inhibition. Conditioned pain modulation (CPM) is one of the well studied endogenous pain inhibitions. It involves the reduction of pain from a painful stimulus when a second painful stimulus is applied distantly or heterotopically.63 Potency of CPM is defined by percentage change in pain threshold or pain rating at baseline to that during or after cold pressor. However, the relationship between potency of CPM and chronic pain is inconclusive; some studies showed that patients with high intensity of chronic pain displayed poorer CPM4,17 whereas other studies showed no association between pain intensity and potency of CPM.

Pain Adaptability in Individuals With Chronic Musculoskeletal Pain Is Not Associated With Conditioned Pain Modulation

Orginally Published At: Pain Journal

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Traumatic Brain Injury and Receipt of Prescription Opioid Therapy for Chronic Pain in Iraq and Afghanistan Veterans: Do Clinical Practice Guidelines Matter?

• Veterans with more severe TBI symptoms were most likely to receive opioid therapy.• Veterans with moderate to severe TBI were more likely to be prescribed opioids.• Veterans with TBI and mental health comorbidity were at highest risk for opioids.

Traumatic Brain Injury and Receipt of Prescription Opioid Therapy for Chronic Pain in Iraq and Afghanistan Veterans: Do Clinical Practice Guidelines Matter?

Orginally Published At: Pain Journal

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Never trust anyone who thinks they can fix you

After announcing early this year that I have suffered from serious and mysterious chronic pain for the last three years, I got hundreds of compassionate, curious, and respectful responses. I was a bit queasy about the intense public vulnerability, but all those nice notes tamed my unease. Thank you, nice people!

But there were also some nasty reactions, because my job involves having more “enemies” than I ever would have believed was possible when I started out. I wasn’t sure if I’d actually hear from anyone like that, but I did, several of them.

One stands out.

Introducing Blamey McBlamerton

This person overtly blames me for my pain. Seriously. He thinks my ongoing pain proves that I cannot possibly be knowledgeable about pain. He thinks that I would not be in pain if I was “competent” and that “lots of good therapists could easily solve this for you.”

Most hilariously obnoxious of all: he also tried to package his opinion in pity! “I can’t decide whether to tell you off or help you.” As if I’d let you “help” me, pal!

And this is coming from a so-called health care professional, a physical therapist with a modest social media following, someone some of my readers will be familiar with, a man who is probably often mistaken for an expert. His attitude involves a lack of compassion bordering on psychopathy, obviously: some people just didn’t get raised right, and/or have legit mental illness (personality disorders). But it’s not just that.

The more interesting problem here

…is that belief that chronic pain is easily treated! The arrogance of ignorance, the Dunning-Kruger effect.

You don’t need to know much about how chronic pain works to know that it’s about as preventable and curable as the common cold. It has countless possible causes and is unpredictable and confounding by nature. Overconfidence in treating chronic pain is not just unjustified, it’s delusional and dangerous. The only way to sustain it is to be oblivious to the complexity of the problem, like the ignoramus who knows exactly how to fix the economy, or the crank inventor who truly believes in his perpetual motion machine.

I hear from a lot of people who are therapy “patriots,” dogmatically convinced of the potency of their methods. They are like dogs barking at the mailman, convinced they can make him go away, bolstered by his daily disappearances. Like psychics, they dine out on their hits and ignore their misses.

For many years people like this have been berating me for debunking their claims and tipping over their sacred cows. It’s a short leap from that kind of outrage to the absurdity of blaming me for hurting. People who believe they can cure are prone to blaming anyone who denies their power. A superiority complex needs other people to be inferior. Bear that in mind the next time you talk to a “professional” who thinks they’ve got answers for chronic pain the rest of us don’t have. Like a petty little god, they are fickle, and their compassion requires your faith and devotion — cross them by doubting, and they’ll turn on you.

[Go to this post on PainScience.com]

Never trust anyone who thinks they can fix you


Orginally Published At: Pain Science

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Pain Sensitivity and Thermal Detection Thresholds in Young Adults Born Preterm with Very Low Birth Weight or Small for Gestational Age at Term Compared to Controls.

• This is the first QST study on adult preterm or term low birth weight individuals• Thermal detection and pain sensitivity are similar in VLBW and control young adults• Adults born SGA at term do not display altered sensory function• Group-wise prevalences of self-reported chronic pain are not reliably different

Pain Sensitivity and Thermal Detection Thresholds in Young Adults Born Preterm with Very Low Birth Weight or Small for Gestational Age at Term Compared to Controls.

Orginally Published At: Pain Journal