Pain, Brain, Placebo & Nocebo - Manuellterapi.no · ABSTRACT quoted by Benson, 1997) Background Many patients report symptomatic relief after undergoing arthroscopy of the knee for

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Pain, Brain, Placebo & Nocebo

Dr. Hannu Luomajoki, PhD, PT OMT, MPhty, NOI Instructor

H. Luomajoki 2011 Lillehammer

Nevrologi, immunologi og manuellterapi – utredning og evidensbasert behandling Radisson Blu Lillehammer Hotel 11.-13. mars 2011



MEG-Center Tübingen

Functional magnetic resonance imaging (fMRI)

© Gustin & Schwarz


Courtesy Dr. Lorimer Moseley

H. Luomajoki 2011 Lillehammer H. Luomajoki 2011 Lillehammer

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Pain is an unpleasant sensory and emotional experience which follows actual or potential tissue damage or is described in terms of such damage

IASP H. Luomajoki 2011 Lillehammer


© Gustin & Schwarz

before treatment: areas active during clenching the affected hand

Primary Sensory Motor Cortex

before treatment: areas active during clenching the unaffected hand



Primary Sensory Motor Cortex

© Gustin & Schwarz

after treatment:

areas active during clenching the unaffected hand

after treatment:

areas active during clenching the affected hand



before treatment: areas active during clenching the affected hand

before treatment: areas active during clenching the unaffected hand

© Gustin & Schwarz

Cingulate Gyrus


Representation of Pain in the Brain – 5 key points

1. Common areas are frequently “ignited”, 2. Via connections, recursive and backfiring

neurones, pain is perceived – the pain “neurotag”

3. Representational “ignition” is not dependant on a specific tissue

4. Ignited areas can be easily modified 5. Smudging of some key “nodes” can occur

Eg. Flor H, Bushnell MC, Casey KL, Petrovic P, Ingvar M


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Areas of brain ignited in a pain experience have functions other than pain

Absolutely vital clinical point


Image courtesy Dr. Lorimer Moseley

A thought is a nerve inpulse



Do I need to worry?

The role of therapists and doctors

Estimated cause on chronification: 30 - 40 %! • “Beliefs” • Reinforcing rest • “Over information” • Not enough time NOCEBO


Psycho social issues – by all musculoskeletal Patients !

Pain behaviour

Cognition / Thoughts about pain

Beliefs & Attitudes Yellow flags


Linton 2005


Pain behaviour: Fear Avoidance Cognition • Catastrophizing

• Mystification • Hopelessness • Magnification

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Cognitive factors: Attention, Focusing, Hypervigilance • Locus of control; self-efficacy • Conditioning • Expectation • Patient’s own thoughts about the pain cause • „Iatrogenic“ causes; Doctors / physios

attitude – or own fears? Overestimation of diagnosis


Beliefs & Attitudes = Hurt is Harm • Emotions • Worry = Threat • Attribution; someone else is fault Yellow flags • Social situation, support, Overprotecting • Spouse • Work satisfaction • Communication • Etc.

Pain, Depression, Fear

Pain and depression are interrelated,

Depression and fear are interrelated

Fear and pain are interrelated


Attention, Focusing, Hypervigilance


Evidence…

Current guidelines and evidence conclude that the factors predicting a poor outcome and chronicity by LBP are more related to cognitive and psychosocial issues than to anatomical structures (Airaksinen et al., 2006, van Tulder et al., 2006, Linton, 2000, Linton 2005

Components for predicting persistent disabling low back pain were maladaptive pain coping behaviours, nonorganic signs, functional impairment, general health status, and presence of psychiatric comorbidities. A systematic review (Chou and Shekelle 2010)

Strongest predictors for bad outcome after whiplash are high score in catastrophizing and causal beliefs that something is wrong in the neck (Buitenhuis 2008) H. Luomajoki 2011 Lillehammer

Neurophysiologically Catastrophizing is associated with higher level IL-6 by inducing acute

pain on healthy subjects (Edwards 2008). It disturbs the opioid lead endogene anagesic system (Camplee 2008), and has been stated to be the most constant co variabel of altered pain perception (Sullivan 2001)

It has been shown on neuroimaging that pain is rated as more

unpleasant after sad mood induction, when compared with a neutral mood induction (Berna et al 2010).

Multiple cortical and subcortical structures are involved in chronic pain (Apkarian, 2008). It has been suggested that long-term pain alters the functional connectivity of cortical regions known to be active at rest, the so called “default mode network” (Baliki et al., 2008), which have been shown to display a reduced deactivation in chronic back pain. These findings demonstrate that chronic pain has widespread impact on overall brain function and this may underlie the cognitive and behavioural impairments accompanying chronic pain. But brain areas can be changed not only functionally but even structurally; Apkarian et al (2004) showed that prefrontal and thalamic grey matter is decreased by chronic back pain. Perception of pain is always accompanied with negative emotions (Apkarian, 2008), and chronic pain patients suffer from more than just pain, they can also suffer from depression and anxiety, sleep disturbances and decision-making abnormalities (Baliki et al., 2008). H. Luomajoki 2011 Lillehammer

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Important pain areals by pain processing


Cognition

Personality, Emotions

Autonomic, primitive reactions Memory, Fear, Conditioning

Main areals of the brain for feeling good or

feeling bad

… Producing Placebo … Or Nocebo


Serotonin system: good feelings

Noradrenalin system: Alert


Brain stem Limbic system = Feelings, attitude, primitive reactions (also fear & joy): Hypothalamus, Amygdala, Hippocampus Good connections to: Nucleus accumbens (rewarding centrum) Hypophyse, Pituitry (cortisol system) Locus coereleus (noradrenalin) Nucleus raphe (Serotonin)

Neuroendocrine system Stresshormon nr. 1.

Cortisol: Pain, Fear, Catastrophizing

cause a stress reaction: Hypotalamus – CRH Pituitry – ACTH Cortex of kidneys – Cortisol Cortisol – Hippocampus Nocebo


Sapolsky 1998

Neuroimmunologic system: Hypotalamus- Pituitry- Cortisol - axis

Immunologic changes like:

Leucocytes, Cytocines in blood

Typical by stress

Sapolsky 1998


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Amygdala - Hippocampus

Fear conditioning Pain memory Cortisol Oxytocin Serotonin


Placebo

The most powerful part in physiotherapy?


Definitions A Placebo is any treatment that is

used for its ameliorative effect on a symptom or disease but that actually is ineffective or is not specifically effective for the condition being treated

A Placebo therapy may be used with or without knowledge that it is a placebo (Shapiro & Shapiro, 1997)


“The history of medicine is a history of the placebo”

(Shapiro & Shapiro, 1997)

“Who wants to gain fame has only to accept what I have been able to establish” (Galen)

“Faith produces miracles” (Paracelsus)

“The art of medicine is to amuse the

patient while nature cures the illness” (Voltaire) H. Luomajoki 2011 Lillehammer


Previous

Volume

347:81-88

July 11, 2002

Number 2

Next

A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee J. Bruce Moseley, M.D., Kimberly O'Malley, Ph.D., Nancy J. Petersen, Ph.D., Terri J. Menke, Ph.D., Baruch

A. Brody, Ph.D., David H. Kuykendall, Ph.D., John C. Hollingsworth, Dr.P.H., Carol M. Ashton, M.D., M.P.H., and Nelda P. Wray, M.D., M.P.H.

ABSTRACT Background Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis, but it is unclear how the procedure achieves this result. We conducted a randomized, placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee. Methods A total of 180 patients with osteoarthritis of the knee were randomly assigned to receive arthroscopic débridement,

arthroscopic lavage, or placebo surgery. Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope. Patients and assessors of outcome were blinded to the treatment-group assignment. Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores — three on scales for pain and two on scales for function — and one objective test of walking and stair climbing. A total of 165 patients completed the trial. Results At no point did either of the intervention groups report less pain or better function than the placebo group. For example, mean (±SD) scores on the Knee-Specific Pain Scale (range, 0 to 100, with higher scores indicating more severe pain) were similar in the placebo, lavage, and débridement groups: 48.9±21.9, 54.8±19.8, and 51.7±22.4, respectively, at one year (P=0.14 for the comparison between placebo and lavage; P=0.51 for the comparison between placebo and débridement) and 51.6±23.7, 53.7±23.7, and 51.4±23.2, respectively, at two years (P=0.64 and P=0.96, respectively). Furthermore, the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinically meaningful difference. Conclusions In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic débridement were no better than

those after a placebo procedure

The magnitude of nocebo

Voodoo death (Basedow, 1925; Cannon 1942, as quoted by Benson, 1997)

80% of patients vomiting from sugar water told being emetic (Kissel & Barrucand 1964, as quoted by Hahn, 1997a)

Asthmatic patients reaction to nebulized saline 47.5% negative by expectation (Luparello et al., 1966)

Hypochondriasis up to 79 % by medicine students (Hahn, 1997a)


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Placebo as a societal phenomenon

Marketing (think on Marlboro man) Weintasting – Etikette, Price Business barometers – beliefs of

customers Religion Attidudes – manager courses

Effect mechanisms of placebo

Endogenous analgesia

(Fields & Price, 1997; ter Riet et al., 1998)

Conditioning

(Voudoris et al., 1989, 1990; Ader & Cohen, 1993)

Expectancy (Voudoris et al., 1989, 1990; Montgomery & Kirsch, 1997)

Neuroendocrine / psychoneuro-immunology effects

(Ader & Cohen, 1993; Jamieson, 1996; Sapolsky, 1988)


Placebo effect through release of opioids from Periaqueductal grey matter (PAG) and from rostroventral medulla (RVM)

Endogenous Analgesia (Fields & Price, 1997, ter Riet et al., 1998)

Placebo effect; Opioid-rich regions = PAG & RVM

«GOOD GUYS» Feeling good; nucleus accumbens: Serotonin from raphe nucleus Dopamin from substantia nigra

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Neuroendocrine / psychoneuro-immunology effects

(Ader & Cohen, 1993; Jamison, 1996; Sapolsky, 1998)

Effect mechanism of Nocebo


Benedetti 2005. Mind and Body.

Nocebo effect: Locus coeruleus= Noradrenalin system = Alert, worry Anxiety? = CCK release

Responsible for Nocebo Response: Cholecystokinin CCK

Cholecystokinin release increases pain - Proglumide reverses this (Cck antagonist)


Anxiety produces CCK

CCK causes: a. Pain and

hyperalgesia

b. Alert: cortisol response through

Pituitry gland

CCK antagonist Proglumide reverses the pain but not cortisol response Diazepam reverses Cortisol response, but not the pain Benedetti 2005

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Nocebo response: High expectancy of high temperature compared To low expectancy of high temperature Benedetti 2005

Brain decides through cues within seconds whether a stimulus (voice, touch, light, atmosphere…) is pleasant or worrying… This reaction is carried out through neurotransmitters (Tracey 2010)

„Peptid power“

Excitatory neurotransmitters:

Glutamate Aspartate Substance P Adrenalin Kortisol Cholecystokinin (cck)

Inhibitory neurotransmitters:

Serotonin Dopamin Opioids Enkephalins Oxytocin GABA = „Happy hormons“


Placebo - Nocebo

« To please» A non specific effect

causes an amelioration of a problem (mostly pain)

Placebos in man. Therapy?: voice, look, infrastructure, secureness of the therapist… etc.

«To harm» A non specific effect

causes a deteriation of a disposition (mostly more pain)

Nocebo in man.therapy?: negative information, overestimation of diagnosis, prohibitions….


Clinical reasoning and Placebo

“Gray Zones” Our reasoning might be false, when we think the

patient got better through waht we did… … Maybe it was more what we said… The therapeutic interaction per se is not a placebo,

but it might turn to placebo when we are not concious of the importance of it…

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Placebo in manual therapy ?

“Hands on” therapies are , in many cases, very powerful, on short hand ….long term Outcomes evidence… not very good

Significance of Manipulation ? Expectation? Conditioning?


Good questions to ask when estimating

Placebo Nocebo effects :

Did you already have therapy? – How was it?

What do you think is the problem?

What do you think, should happen that you get fit again?

What did your doctor say? What do you think about that?

Are you anxious? Do you fear, it is

something serious? What dp you think,

what is this problem? Do you think it might

get worse? Do you still have hope?

What interests all patients?

What is this problem? How long will it last? (Prognosis) What can I do myself? Can it be something serious? What did they see on those exams? (X-

Rays, Lab.; Mri etc)

Try to answer these questions by all patients (even if they not ask…)


Further questions…

Has anyone ever explained….?

Did your doctor tell you, what this problem is?

Do you have the feeling that no one understands your problem?

Do you have the feeling, people think you are hypochonder?

Etc. H. Luomajoki 2011 Lillehammer

Thank you!

www.noigroup.com

Pain, Brain, Placebo & Nocebo - Manuellterapi.no · ABSTRACT quoted by Benson, 1997) Background Many patients report symptomatic relief after undergoing arthroscopy of the knee for

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