Barbara St.

Marie, MA, ANP, GNP

PhD Candidate
University of Wisconsin – Milwaukee
Nurse Practitioner – Supervisor
Pain and Palliative Care – Fairview Ridges Hospital
Objectives:
 Basic Neurophysiology of Pain Pathways
 Pharmacological and Non-pharmacological
Interventions of Pain Pathways
 Matching neurophysiology with pharmacology
 Pathophysiology of Pain
 When Pain becomes Chronic or Persistent Pain
 Interventions of Chronic or Persistent Pain
 Nursing Contributions to Pain Management
Combination Analgesics
Rationale
 Multimodal analgesia
 Multiple sites of action target multiple pain
pathways
 Complementary pharmacokinetic activity
 Potentially synergistic analgesic effect
 Reduced adverse event profile with comparable
efficacy

Raffa, RB, 2001

Pain Process
 The neural mechanisms by which pain is perceived
involves a process that has four major steps:
 Transduction
 Transmission
 Modulation
 Perception
Facilitating Transduction
 Biochemical mediators: “Chemical Soup”
Prostaglandins
Bradykinins
Serotonin
Histamines
Cytokines
Leukotrienes
Substance P
Norepinephrine
 Peripheral Excitatory Mediators
(Pain)
Substance Receptor Mechanism
Substance P NK1  neuronal excitability, edema
(SP)
Prostaglandin ? Sensitize nociceptors,
(PG) inflammation, edema
Bradykinin B2 (normal) Sensitize nociceptors
B1 (inflammation)  PG production
Histamine H1 C-fiber activation, edema,
vasodilatation
Serotonin 5-HT3 C-fiber activation, release SP

Norepinephrine 1 Sensitize nociceptors

(NE) Activate nociceptors
Peripheral sensitization

 Peripheral opioid receptors

 Management of histamine
Diclofenac
Acetaminophen (Tylenol)
 Analgesic, antipyretic

 Inhibits prostaglandin synthetase in the CNS, weak

peripheral anti-inflammatory activity

 Serotonergic effect at descending pathway

 Used to treat osteoarthritis

Acetaminophen (Tylenol)
 American Pain Society: Maximum dose 4,000
mg/day,

 American Liver Foundation: 3,000 mg/day

 Risk of hepatotoxicity with higher doses

 Antidote – acetylcysteine (Mucomyst, Acetadote)

Transmission of pain
Defined as:
Projection of pain
into the
Central Nervous System
Transmission
A synapse contains three
elements:
the presynaptic terminal
the synaptic cleft
the receptive membrane
Transmission
The presynaptic terminal is the
axon terminal of the
presynaptic neuron
Here that the presynaptic
neuron releases
neurotransmitters which are
found in vesicles
 Peripheral Nerves:
Transmission of Action Potential
myelin Na+

K+
A
spinal
A cord
peripheral
nerve
C
Capsaicin
 Hot peppers
 May deplete & prevent re-
accumulation of substance P
in primary afferent neurons
responsible for transmitting
painful impulses from
peripheral sites to the CNS.
 Absorption, distribution,
metabolism & excretion, half
life – unknown
 May produce transient
burning with application,
usually disappears in 2-4
days, but may persist for
several weeks.
 Transmission
The synaptic cleft is the narrow
intercellular space between
neurons.
Neurotransmitters cross the
synaptic cleft and bind to specific
receptors on the postsynaptic
neurons
This will excite or inhibit the
postsynaptic neurons.
Muscle Pain
 Correlated with Lactic acid levels

 Lactic acid levels in the blood vessels of the muscle

influence neuronal noxious stimuli

 What might that tell us about intervening with muscle

pain?
Neuropathic Pain Features
 Burning, prickling, tingling
 Shock-like
 May or may not be lancinating
 Paresthesia
 May be associated with
 Allodynia
 Hyperalgesia
 Hyperethesia
 Referred Pain
 More intense at noc
Local Anesthetic Agents
 On-Q delivery

 Synera patch (topical)

 Emla: Lidocaine and Prilocaine 1:1 (topical)

 LMX 4% lidocaine (topical)

 Local Anesthetics

Blocks conduction of nerve impulses by

decreasing or preventing an increase in
the permeability of excitable
membranes to Na+.
Inhibits depolarization of nerve
Blocks neuronal firing

Challapalli, V., et. al., 2005

Lidoderm 5% Patch
Mentholatum
Menthol generates
analgesic
activity through:
 Ca2+ channel blocking
activity
 Binding to kappa opioid
receptors

Stanos, S.P., 2007

Methyl Salicylate Toxicity
 Salicylic acid derivative (a.k.a. wintergreen oil,
sweet birch oil)
 Lipid solubility increases toxicity
 More toxic than aspirin
 1 teaspoon (5ml) wintergreen oil contains 4,000 mg
salicylate
 30ml wintergreen oil is a fatal dose in adults
 Risk of toxicity reduced with use for acute pain,
limited to a small area of dermal application

Chyka, P.A., et al., 2007

 Anticonvulsants
1) Inhibit sustained high-frequency neuronal firing by
blocking Na+ channels after an action potential,
reducing excitability in sensitized C-nociceptors.
2) Blockade of Na+ channels and increase in synthesis
and activity of GABA, in inhibitory neurotransmitter,
in the brain.
3) Modulates Ca+ channel current and increases
synthesis of GABA.
Deglin, J.H. & Vallerand, A.H., 2001
 Antiepileptic Agents
 Broad clinical actions in  Three proposed
the CNS: mechanisms of action:
 Reduce seizures  Blockade of voltage gated
 Neuropathic pain sodium channels
 Bipolar disorder
( glutamate release)
 Blockade of voltage gated
 Anxiety
calcium channels – alpha 2
 Schizophrenia
delta subunits (reduces
 Agitation excessive neurotransmitter
 Impulse dyscontrol release)
 Dementia
 Enhancement of GABA
 Delirium
actions
Lyrica Pregabalin
Schedule V
Modulation
Sympathetic Chain ganglion
Substantia gelatinosa
Post synaptic jct
Contralateral spinothalamic
Ascending Pain Pathways

Ascending
fibers
Perception
 Review:

 Impulses go through the postsynaptic junction

 Cross the dorsal horn

 To the spinothalamic tract

Meperidine (Demerol)
 Duration 2-3 hrs
 PO doses 1/4 analgesic effect
 Toxic metabolite - normeperidine
 dysphoria, irritability, seizures
 t1/2 =12-15 hrs; not reversible with Narcan
 Do not use Demerol for more than 48 hrs or at
doses >600 mg/24hr
 Only indications: rigors, short term use, i.e.
endoscopy.
Methadone
FDA Indications: Severe pain, narcotic detoxification,
and temporary maintenance of narcotic addiction

Reference: Am Family Physician, 71(7), 2005

Methadone
 Inexpensive
 Accumulates with repeated dosing
 85% protein bound
 Slowly released up to 10 days after dose increase
 Available in 10 mg tablet or oral solution, use of 40 mg
diskette no longer available for pain mgt use
 Patient may be subjected to scrutiny, stigma &
misconceptions
Federal Regulation
 Prevention of withdrawal in opioid addiction
 Special annual registration with DEA
 Use only in an established addiction treatment
program
 Maintenance patients may continue tx when
admitted to acute care facility
 Treatment for pain
 Any clinician licensed to prescribe Schedule II drugs
may prescribe methadone for pain
 Methadone

 Incomplete Cross-Tolerance
 Inverse relationship with dosing
 Monitor ekg for QT prolongation
 Clinical Indications for Electrocardiogram in
Patients Receiving Methadone
 History of long-QT syndrome or torsades de pointes
 Family history of long-QT syndrome or early sudden cardiac death
 Cardiac arrhythmia and heart block (2nd or 3rd degree AV block)
 Anorexia nervosa
 Frequent electrolyte depletion (K, Ca, Mg)
 HIV patients on multiple-antiretroviral therapy
 Methadone dosages greater than 150mg/day
 Initiation of a P-450 inhibitor
 Initiation of medications associated with QTc prolongation
 Presyncopal or syncope symptoms
 Unexplained tonic-clonic seizures with abnormal
electroencephalogram

Schmittner, J., 2006

Routhier, D., et al., 2007
Methadone Black Box Warning
 Deaths during initiation and conversion from
other opioids
 Respiratory depression – chief hazard
 Use of concomitant sedatives including alcohol
 Self-titration – iatrogenic overdose
 QTc prolongation
Key Teaching Points
 Careful of mix up between long acting and short
acting with same mg amount (ex. MS Contin and
MSIR)
 Remove old patch before new one put on
Safe disposal issues
 Drinking, driving issues
 Tell all of your healthcare providers everything that
you take, always
 Careful about buying on the Intranet
 Sleepers, sedatives
 Teach S & S of withdrawal
Key Teaching Points
 Never take more or less than prescribed without
calling us
 Only you take your pain medication, do not share!
 Never alter the medication, i.e. splitting sustained
release medications
 Keep in a safe place always!
 Medication parties
 Middle & High School students; #1 medicine cabinet
thefts
Inciardi, J.A., et al., 2007
Some of our biggest safety issues

 Careful of look alike names and sustained release

versus immediate release
 Only witness waste when you see it first, protect your
hard earned license
 Careful of which line is which
 PCA pumps; double check, double check and double
check-settings and syringe concentration, medication
and document
 Instruct patient only to press button
ISMP, February 2007
Descending Pathway
 Anatomic path
 From cerebral cortex
 Brain stem
 To dorsal horn
 Pain inhibition
 Enkephalin excites inhibitory interneurons in the dorsal
horn
Descending Pathway
 Mediates voluntary and involuntary motor control

 Regulates somatic sensory processing

 Regulates the autonomic nervous system

Coexisting CD and Pain
 Unique experiences
 Anatomic paths of the nervous system have
commonalities
 Addictive responses are altered by the physiological
presence of pain
 Pain responses are altered by the physiological
presence of addiction.
Endocannabinoids
 Research on the adaptations of cells continue with the
recent discover of the cannabinoid receptor and the
subsequent searching and findings of the endogenous
cannabinoids.
 Two endocannabinoids, anandamine and 2-
arachidonyl glycerol or 2-AG.
Endocannibinoids
 Found in most brain function
 Equal balance between endocannibinoids and their
receptors occur (Fride, 2005)
 Role in brain plasticity leading to
 long term effects on movement and coordination
 habit formation
 reward and addiction
Figure 5. Concept map of endocannabinoids.
Opioid-Induced Pain Hypersensitivity
 Opioids may produce abnormally heightened pain
sensations
 May share mechanisms with antinociceptive tolerance
 Possibly dose related?
 Observed both with acute and chronic use
 Current research indicates potential for targets for new
therapies
Questions
Nursing Research in Pain
Management
 Peggy Compton, PhD, RN
 Pain and Addiction
 Christine Miaskowski, PhD, RN
 Gender and Pain
 Christine Kovach, PhD, RN
 Elders and Pain
 Margo McCaffrey, MSN, RN
 “Pain is what the patient says it is”
 Betty Morgan, PhD, RN
 Pain and Addiction
Nursing Research in Pain
Management
 Rosemary Polomano, PhD, RN
 Pain, Rat lab
 Keela Herr, PhD, RN
 Geriatric Pain
 Jo Eland, PhD, RN
 Pediatric Pain
 Donna Wong, PhD, RN
 Smiley Faces, Faces Scale for Pain assessment
What is Flare of Pain?
 Same Pain as Chronic (Persistent) Pain
 Same Location as Chronic (Persistent) Pain
 Different Pain Intensity from Chronic (Persistent) Pain
 Temporary increase in pain intensity from a more
stable baseline pain with otherwise similar
characteristics.
Pain Flare Study
 2001-2002 Pain Flare Study
 Descriptive study
 N= 67
 Location: University of Minnesota – Fairview Pain
Management Center
 Survey mailed to 75 patients, 67 responses
 IRB approval
Pain Flare Study
 Purpose of study

 Describe the characteristics of and factors contributing

to pain flares in patients with chronic pain who receive
care from the nurse practitioner in Fairview Pain
Management Center
Conclusions
 Pain Flare definition: Same Pain, same location,
different intensity

 This definition implies that

 Pain flare should not represent new pathology
 Patient has an ongoing pain problem that has been
relatively stable
 No presumption of what baseline pain intensity was
Conclusions
 Studying flare gives meaning to the patients
experiences of flare of their pain
 Gave patients a “voice”
 Assurance that it is not permanent condition
 Universality of flares in chronic pain
 Pain intensity rating less important in chronic non-
malignant pain than changes in pain intensity
 Once contributing factors to pain flares have been
resolved, chronic pain returns to baseline
Envision the Future
 Better pain control with fewer side effects
 Genome pain management
 Helping the brain erase persistent pain
 Social Policy that enhances comprehensive approach
to pain management rather than reinforce procedures
to get rid of pain
 Abuse deterrent opioid formulations that significantly
reduce diversion and are available for those who need
it.