Pharmacology & Pathophysiology of Pain Hawai’i ANA, March 217

John P. McDonough, CRNA, EdD, Dr.(habil.)NScA, ARNP, FRSM

Professor & Director, Graduate Nursing Programs Director, Nurse Anesthetist Program

COLLEGE of HEALTH SCHOOL of NURSING

NURSE ANESTHETIST PROGRAM

CRNAs und deren Tätigheit im amerikanischen Gesundheitwesen

(u. Insbesondere: Schmerztherapy) Duetsche Kongress für Schmerathereupeutischen

München, Februar2017 Univ-Prof. Dr. Dr. (habil) John P. McDonough

Professor u. Vorstand Programme Für Anästhesiepflegepersonal Direktor, Fortbildungsprogramme

Facultät für Gesundheit Institut für Pfelegewißenshaft

Was ist Ihre Spezialität? Sie können es durch den Fleck herausfinden.

Benedictus de Spinoza (1632-1677)

• “Pain is a localized form of sorrow”

Specificity theory Hard-Wired CNS

Pattern theory – Software

Psychosocial Factors

• Intrapersonal • Interpersonal • Social

Q: Where does pain happen?

A: “Pain isn’t pain until it gets to your brain”

Patrick Wall Ronald Melzack

Melzack & Wall’s Gate

I Inhibitory Interneuron P Projection Neuron - inhibition (blocking); + excitation (activation)

“Primary Source” Documentation

No PAIN

Inhibition

PAIN

Disinhibition

Open the Gate – Pain

Close the Gate – No Pain

DH Neurotransmitters

• Excitatory amino acids (glutamate & aspartate) – found in large cells of DRG

• Small cells contain – fluoride-resistant acid phosphatase (FRAP), sP,

vasoactive intestinal polypeptide (VIP), somatistatin, cholecystokinin (CCK), gastrin-releasing peptide (GRP), calcitonin-gene-related peptide (CGRP) leuenkephalin (ENK), dynorphin (DYN)

Ascending Pain Pathways

• Primary pathways to the brain – spinothalamic tract (STT) – spinoreticular tract (SRT) – spinomesencephalic tract (SMT)

Supraspinal Mechanisms

• Acute pain is a multidimensional experience

• somatic events termed in: – space, time, intensity – motivational-emotional mechanisms – aversive behavior

• psychological components – sensory-discriminative, motivational-affective,

cognitive-evaluative

Visceral Structures

• C afferent fibers, A-delta fibers – disease, inflammation, isometric contraction,

ischemia, rapid distention

• activated by noxious stimuli & alogenic substances

• act as transducers • conducted to dorsal horn or medulla

– influenced by intensity, duration and microenvironment

Augmentation of Nociception

• Augmentation – sensitization by repeated noxious stimuli – lowering threshold by alogenic substances – segmental reflex response provoked by injury

• Inhibition – counterirritation

• rubbing, vibration, more sophisticated methods

What opens the gate after nerve injury?

Decreased Inhibition Increases Excitation

The question d’jour: • Does peripheral nerve injury pain-related

behavior result from a loss of inhibitory transmission in the spinal cord?

decay t = 3.9 ms

Spared Nerve Injury

Control

decay t = 26.7 ms

5 ms

25 pA

Moore et al 2002

Inhibitory postsynaptic currents

Is the reduction in inhibitory postsynaptic currents the consequence of 1) Decreased GABA release, or 2) Decreased GABA responsiveness?

“Cut to the chase”

• The answer is that the reduction in inhibitory postsynaptic currents is caused by decreased GABA responsiveness

What causes the decreased GABA release and consequent reduced inhibition?

PAIN Apoptosis

Cell Death After Peripheral Nerve Injury

TUNEL

TdT-mediated X-dUTP nick end labeling = Apoptosis (Cell suicide)

Scholz et al 2005

DNA fragmentation

Ipsilateral

Contralateral

NeuN

Scholz et al 2005

~25% loss of neurons In superficial dorsal horn

Scholz et al 2005

Scholz et al 2005

zVAD prevents Reduction in GABAergic neurons

GAD67 mRNA

Anti-apoptotic treatment reduces: Mechanical Allodynia

-5 0 5 10 15 20 250.1

1

10

100 Mechanical allodynia

Days after surgery

With

draw

al th

resh

old

(g)

Scholz et al 2005

+ pinprick hyperalgesia and cold allodynia

Contralateral zVAD vehicle

TNFα

Neuro-immune Interaction

Microglia

neuron

Neuronal death

Neuropathic Pain is a Neurodegenerative Disease

Neuroprotective Treatment Can Abort Neuropathic pain

? Disease-Modifying Therapy to come

Major Goals of an Organized Program

• Educate patients

• Reduce incidence & severity of pain

• Enhance patient comfort and satisfaction

• Reduce post-op complications

Effects of Unrelieved Pain

• Delayed healing • Altered immunity • Increased stress • Anxiety and/or depression • General physical and psychological decline • Economic adversity

And yet…….

• Pain continues to be inadequately understood and treated

Contributing Factors

• Inadequate education of healthcare providers about pain pathophysiology and the phenomenon of pain conditions and diseases

• Poor understanding of the differences among pain syndromes

• Lack of sensitive and specific diagnostic tools

Contributing Factors

• Patient, societal and healthcare provider attitudes and beliefs regarding pain

• Organizational and reimbursement barriers • Inadequate treatment guidelines for

specific pain conditions and problems

Contributing Factors

• Poor understanding of the drugs used to treat pain

• Reluctance to use some pharmacologic agents

• Lack of knowledge of complementary therapies

• Drug side effects

Principles

• Assessment requires rapport

• unrelieved pain has negative effects

• All pain will not be eliminated

• Prevention is better than treatment

• Communication problems require special attention

Controllable Factors Hemodynamics

•Heart rate

•preload

• afterload

The Approach Must Be:

• Collaborative & interdisciplinary

• Individual & proactive

• Assessment intensive

• Formal & structured

Pain Assessment

• Patient self report: very reliable, but not universal

• Numerical or visual analog scales

• Tools must be appropriate for cognitive status

Psychological Response

• Fear • Anxiety • General sense of unpleasantness/unease • Communication issues:

– 70% hospitalized pain patients did not discuss – negative social connotations – insignificant compared to others – ↑ 66% do not mention pain until severe

Use 1 or More of the Following:

• Cognitive-behavioral techniques

• Systematic administration of opioids or NSAIDS

• Patient controlled analgesia

• Epidural analgesia

• Intermittent neural blockade

• Physical agents

• TENS

People have been known to “self medicate”

Epidural

Contraindications

• Patient refusal

• Coagulopathy

• Infection at injection site • Uncorrected hypovolemia

Epidural (cont.)

Complications

• Hypotension

• Total spinal

• Local anesthetic toxicity

• Headache

• Local site pain

• Zebras

Continuous Epidural Analgesia (a, not THE recipe)

• 10 ml 0.25% bupivicaine

• 100 mics fentanyl

• 8 ml PF normal saline

• after this as loading, maintain at 3-5 ml/hour

ITA Advantages

•Excellent Analgesia

•No sympathetic block

•Ambulatory patient

Intrathecal Analgesia (with or without anesthetic)

•25 mics fentanyl

•100-150 mics (0.2-0.3 ml) Astromorph

Combined Technique (“Best of Both Worlds”)

•Perform ITA

•Place epidural catheter for later use if needed.

Chronic Pain

• Prolonged pain ( more than 6 months) • Persistent Vs intermittent

– eg. low back pain Vs migraines

• May have ↓ endorphins • May have predominance of C neuron

stimulation • Due to adaptation, physical signs may be

normal

Music and the experience of

pain

Therapeutic Use of Music

• Reduces pain

• Reduces anxiety

• Reduces medication usage

• Improves “pleasantness” of recall

History of Music

Primitive Man: Incantations & songs to ward off evil spirits.

Egyptians: Influence the fertility of women.

Homer: To avoid negative emotions such as anger, sorrow and fear.

Romans: To rouse armies for battle and calm down

Music Appropriate for Anxiety Reduction

Classical: Bach’s “Air for G-String”

- Jesu joy of man’s desiring

Vivaldi “Four Seasons”

Movie Sound Track: “Born Free”

“Chariots of Fire”

Religious: “The Lord is my Shepard”

Acupuncture

• Dates from 1500 B.C.

• Balance of :

– “Yin” - female, cold, death

– “Yang” - male, warm, life

• > 360 points along “meridians”

• Probably works via “Gate Control”

Hypnosis and the experience of

pain

History of Hypnosis

• Egyptian “sleep temples”

• Franz Mesmer (1795-1855)

• James Braid (1795-1860)

• Sigmund Freud (1856-1939)

• British Medical Society (1955)

• American Medical Association (1958)

Misconceptions

• Loss of consciousness

• Weakening of the will

• Giving away secrets

• Loosing control to the therapist

• Inability to dehypnotize

Phases of Hypnosis

I Induction

II Deepening & Maintenance

III Utilization

IV Termination

Induction Techniques

•Closed eye deep breathing

•Progressive relaxation

•Eye fixation

Parting thoughts…

• One size does not fit all • Bottom line = use what works!