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THE INS AND OUTS OF
PAIN
Kyle P. Edmonds, MD
Fellow, Scripps Health & The Institute for Palliative Medicine at San Diego
H...
OBJECTIVES
• Review the definitions, pathophysiology &
classifications of pain.
• Perform a standardized assessment of pai...
PAIN

International Association
for the Study of Pain ( IASP ):
“An unpleasant sensory
and emotional experience
associated...
PAIN

Margo McCaffery:
“Pain is whatever
the person says it is…”
TOTAL PAIN

CICELY SAUNDERS 1964
Physical

Social

Patient
with
Pain
Existential

Emotional
MECHANISM OF PAIN- DESCARTES
NOCICEPTOR
• Nerve cell
• Activation
• Thermal
• Chemical
• Mechanical

• Transmits signal
NOCICEPTION

• Activation of receptors

• Transmitting
• Processing
• Leads to pain perception
BASIC STEPS: PAIN PROCESSING

• Transduction
• Transmission
• Perception
• Modulation
PAIN TRANSDUCTION
Mechanical

Thermal
Chemical

Aδ or C fibers

Judith A. Paice, AAHPM, 2008
TRANSMISSION

• Stimulus to cord
• Cord to brain stem

• Brain stem to higher
cortex
TRANSMISSION

Somatosensory
Cortex
Associative
Cortex

Thalamus
Judith A. Paice, AAHPM, 2008
PERCEPTION

• Experience
• Conscious
• Multidimensional

• Interaction of
transmission/transduction
MODULATION

• Changing
• Inhibiting
• Spinal cord level
PAIN PROCESSING

• Transduction
• Transmission

• Modulation
• Perception
CLASSIFICATION OF PAIN
• Physiologic
• Nociceptive
• Neuropathic
• Mixed

• Temporal
• Acute
• Chronic
NOCICEPTIVE PAIN
• Somatic
• Visceral
• “Sharp”
“Aching”
“Throbbing”
NEUROPATHIC PAIN
• Damaged or
dysfunctional nerves
• Central
• Peripheral

• “Burning” “Tingling”
“Numbness” “Electric”
MIXED PAIN

• Experiencing
• nociceptive and
• neuropathic
CLASSIFICATION OF PAIN
• Physiologic
• Nociceptive
• Neuropathic
• Mixed

• Temporal
• Acute
• Chronic
TEMPORAL CLASSIFICATION:
ACUTE

• Sudden or recent onset
• Identifiable cause

• Short duration
• Sympathetic response
TEMPORAL CLASSIFICATION:
CHRONIC
• Persistent
• May have no obvious
cause
• Prolonged functional
impairment
• No sympathet...
INTERVAL SUMMARY

Understanding the pathophysiology
leads to improved assessment and targeted
management that will improve...
PAIN ASSESSMENT

1. Location
2. Description (type)
3. Change over time
4. Severity (0 – 10)
5. Effect of treatments
• Bene...
1. LOCATION

• Where is it ?
• Does it move ?
2. DESCRIPTION

• What does the pain feel
like ?
• Does it ever feel burning or
shooting ?
• How does the pain impact
your...
3. CHANGE OVER TIME
• Constant

• Breakthrough

• Intermittent
acute
4. PAIN SEVERITY = 5TH VITAL SIGN

29
5. EFFECT OF TREATMENTS

• Therapies tried
• What worked ?
• What didn‟t work ?
• Any affects you didn‟t
like ?
EXAMINATION

• General exam
• Changes in behavior
• Focused exam
• Psychological exam
INTERDISCIPLINARY TEAM
• Physician
•Assess
•Diagnose
•Prescribe
•Monitor
•Communicate

• Nurse
•Assess
•Deliver
•Monitor
•...
INTERVAL SUMMARY

Assessment of pain requires a thoughtful
history and physical. Standardizing the process
helps prevent m...
PAIN MANAGEMENT:
DEFINITIONS
• Opioid: anything that binds the
opioid receptor
• Opiate: derived from the opium
poppy (Pap...
PAIN MANAGEMENT PRINCIPLES

• Don‟t delay control
• Unmanaged pain
nervous system changes
• Treat underlying cause
WHO LADDER

3, Pain 7 – 10
Morphine

2, Pain 4 – 6

Hydromorphone
Fentanyl

Codeine

Oxycodone

Tramadol

Methadone

A / C...
First Order Kinetics
Plasma Concentration

When biological effect
follows plasma concentration

Absorption

0

Excretion

...
Maximum Concentration ( Cmax )

10

Plasma Concentration

20

= maximum concentration
during the dosage interval
Cmax

0

...
Time to Maximum
Concentration ( t Cmax )

10

Plasma Concentration

20

= time it takes to get to
maximum concentration
Cm...
IV

Time to Maximum
Concentration ( t Cmax )

Plasma Concentration

SC / IM

Cmax

0

PO / PR

Half-life (t1/2)

Time
Half-Life ( t ½ )

10

Plasma Concentration

20

= time it takes for the body
to excrete half the dose

Morphine
all route...
CLEARANCE CONCERNS
MORPHINE
Liver

Analgesia

•Morphine  M3G . . .

+

 M6G . . . +++

CNS
+++
+

Urine
90 – 95 %

Colli...
PRINCIPLE
FOR CONTINUOUS PAIN

For constant pain
• To achieve steady-state,
dose routinely every halflife ( t ½ )
CONTINUOUS PAIN PRINCIPLE
Dosing every half-life ( t ½ )
Plasma Concentration

Oral morphine = 4 hours

100%

97%
93.75%

87.5%
75%
50%

0

4

8

12...
Steady state after 5 half-lives
Plasma Concentration

Morphine ≈ 20 hours
Concentration
where side-effects
start to occur
...
PRINCIPLE
FOR BREAKTHROUGH PAIN
• Dose once every
Time to Cmax

• PO

1h

• Dose =10% of total
24 hr routine dose
Breakthrough Pain

Plasma Concentration

PO / PR
≈ 1 hr
Cmax

0

Time
OPIOID ADVERSE EFFECTS
Common
• Constipation

Uncommon
• Bad dreams / hallucinations

• Dry mouth

• Delirium

• Nausea

•...
EQUIANALGESIC DOSES

Oral/Rectal

Analgesic

IV/SC/IM

150

Codeine

--

15

Hydrocodone

--

15

Morphine

5

10

Oxycodo...
MORPHINE PO  OXYCODONE PO
Morphine 15 mg PO = Oxycodone 10 mg PO
• Patient is on Morphine ER 90mg BID PO

• Oral Morphine...
MORPHINE PO 
HYDROMORPHONE IV
Morphine 15 mg PO = Morphine 5 mg IV =
Hydromorphone 1 mg IV
• Patient is on Morphine IR 20...
MORPHINE PO 
HYDROMORPHONE IV
Morphine 15 mg PO = Morphine 5 mg IV =
Hydromorphone 1 mg IV
• Patient is on Morphine ER 90...
MORPHINE PO 
HYDROMORPHONE IV
Morphine 15 mg PO = Morphine 5 mg IV =
Hydromorphone 1 mg IV
• Patient is getting 8mg IV Mo...
INTERVAL SUMMARY
Understanding the way these medications enter
and leave the body can help you safely and
effective treat ...
SARAH, 43 YO
• Metastatic colorectal CA
• Sacral plexus destruction
• Multiple opioid trials
• Pain 6 / 10
• Drowsiness
• ...
“TOTAL PAIN”
Disease
Mgmt
EOL
Worry

Physical

Pain
Practical

Spiritual

Psych

Social

58
ADJUVANT THERAPIES
• Pharmacological

• Interventional Anesthesia
• Non-pharmacological
• Acupuncture

• Biofeedback
• TEN...
ADJUVANT EVIDENCE
• Therapies
extrapolated from
non-cancer pain

• Few RCTs
• Very few
comparative trials
GUIDING THERAPY
• Diagnosis

• Assessment
• Efficacy
• Safety / tolerability
• Ease of use
• Cost
OPIOIDS
• Nociceptive pain >
neuropathic pain
• First-line for mod to
severe
neuropathic pain
• Titrate to effect or
side-...
METHADONE
• Long half-life
• NOT first order kinetics
• Experienced palliative
care / pain experts
• Coanalgesic: 2.5 – 5+...
GABAPENTINOIDS

• Sodium channel antagonist
• Positive RCT‟s
• NNT less favorable than
TCAs
• First-line 2º safety
GABAPENTINOIDS…
• Trial gabapentin
•Start 100-300 mg qhs

•Daily, increase 100 mg q8h
•Effective 900 - 1800 mg / 24 hr
•Ma...
ANTIDEPRESSANTS

• 3º amine TCAs (amitriptyline)
• 2º amine TCAs (desipramine,
nortriptyline)
• Mixed SNRIs (duloxetine,
v...
OTHER ANTICONVULSANTS

•  excitation
• Limited data, trial-anderror
• Newer drugs have
better safety profiles
CORTICOSTEROIDS
• Limited data, widely used in
• Bone pain
• Neuropathic pain
• Lymphedema
• Other conditions

• Dexametha...
OTHER OPTIONS
• Lidocaine (IV or SC)

• Sodium channel blockade
• Good evidence
• Ketamine (PO, IV, SC)
• NMDA blocker
• D...
SARAH, 43 YO, CA COLON

• Touch
• Simplify meds ( ! )

• Address total suffering
• Feb 14…Pain 6 / 10
INTERVAL SUMMARY
Sometimes the best long-acting medicine for a
patient may not be an opioid. Poor opiateresponsiveness is ...
CLARIFYING
ADDICTION
TOLERANCE
• Reduced effectiveness over
time
• Not clinically significant with
chronic dosing
• Suspect disease progression
PHYSICAL DEPENDENCE
• Process of neuro-adaptation
• Abrupt cessation
withdrawal

• Titrate down if stopping

• Avoid anta...
DRUG DIVERSION

• Regulation
• Record keeping
• Accountability
PSEUDO-ADDICTION
• Most common cause
of apparent
drug „ failure ‟ is
under-dosing
• Behavior LOOKS like
drug seeking
ADDICTION: CHARACTERISTICS
• Psychological dependence
• Compulsive use
• Loss of control over drugs
• Loss of interest in
...
ADDICTION: HALLMARK

• Continued use of drugs
in spite of harm
• Rare outcome of pain
management
SUBSTANCE USERS

• Can have pain too
• Treat with compassion

• Consultation with pain or
addiction specialists
INTERVAL SUMMARY

True addiction is rare in the management of
pain and pain can occur in those with a history
of substance...
SUMMARY
• Pain may be nociceptive, neuropathic or both and the
history tells you which.
• A standardized approach to the a...
THE INS AND OUTS OF
PAIN
Kyle P. Edmonds, MD
Faculty, UCSD Division of Palliative Medicine
928.853.1483
Kyle.p.edmonds@gma...
The Ins and Outs of Pain
The Ins and Outs of Pain
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The Ins and Outs of Pain

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Geared towards advanced pain nurses for the hospital-based and evidence-based management of pain. Overview of physiology, pathophysiology, assessment and management.

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The Ins and Outs of Pain

  1. 1. THE INS AND OUTS OF PAIN Kyle P. Edmonds, MD Fellow, Scripps Health & The Institute for Palliative Medicine at San Diego Hospice Adapted from the Palliative Care International Curriculum Series Editor, Frank R. Ferris, MD
  2. 2. OBJECTIVES • Review the definitions, pathophysiology & classifications of pain. • Perform a standardized assessment of pain and state why it is important for team communication. • State how Cmax and half-life relate to opioid dosing. • Describe the hallmark of addiction and the low likelihood of occurrence in pain management.
  3. 3. PAIN International Association for the Study of Pain ( IASP ): “An unpleasant sensory and emotional experience associated with actual or potential tissue damage.”
  4. 4. PAIN Margo McCaffery: “Pain is whatever the person says it is…”
  5. 5. TOTAL PAIN CICELY SAUNDERS 1964 Physical Social Patient with Pain Existential Emotional
  6. 6. MECHANISM OF PAIN- DESCARTES
  7. 7. NOCICEPTOR • Nerve cell • Activation • Thermal • Chemical • Mechanical • Transmits signal
  8. 8. NOCICEPTION • Activation of receptors • Transmitting • Processing • Leads to pain perception
  9. 9. BASIC STEPS: PAIN PROCESSING • Transduction • Transmission • Perception • Modulation
  10. 10. PAIN TRANSDUCTION Mechanical Thermal Chemical Aδ or C fibers Judith A. Paice, AAHPM, 2008
  11. 11. TRANSMISSION • Stimulus to cord • Cord to brain stem • Brain stem to higher cortex
  12. 12. TRANSMISSION Somatosensory Cortex Associative Cortex Thalamus Judith A. Paice, AAHPM, 2008
  13. 13. PERCEPTION • Experience • Conscious • Multidimensional • Interaction of transmission/transduction
  14. 14. MODULATION • Changing • Inhibiting • Spinal cord level
  15. 15. PAIN PROCESSING • Transduction • Transmission • Modulation • Perception
  16. 16. CLASSIFICATION OF PAIN • Physiologic • Nociceptive • Neuropathic • Mixed • Temporal • Acute • Chronic
  17. 17. NOCICEPTIVE PAIN • Somatic • Visceral • “Sharp” “Aching” “Throbbing”
  18. 18. NEUROPATHIC PAIN • Damaged or dysfunctional nerves • Central • Peripheral • “Burning” “Tingling” “Numbness” “Electric”
  19. 19. MIXED PAIN • Experiencing • nociceptive and • neuropathic
  20. 20. CLASSIFICATION OF PAIN • Physiologic • Nociceptive • Neuropathic • Mixed • Temporal • Acute • Chronic
  21. 21. TEMPORAL CLASSIFICATION: ACUTE • Sudden or recent onset • Identifiable cause • Short duration • Sympathetic response
  22. 22. TEMPORAL CLASSIFICATION: CHRONIC • Persistent • May have no obvious cause • Prolonged functional impairment • No sympathetic response
  23. 23. INTERVAL SUMMARY Understanding the pathophysiology leads to improved assessment and targeted management that will improve outcomes
  24. 24. PAIN ASSESSMENT 1. Location 2. Description (type) 3. Change over time 4. Severity (0 – 10) 5. Effect of treatments • Benefit (+) • Unwanted effects (-)
  25. 25. 1. LOCATION • Where is it ? • Does it move ?
  26. 26. 2. DESCRIPTION • What does the pain feel like ? • Does it ever feel burning or shooting ? • How does the pain impact your life ?
  27. 27. 3. CHANGE OVER TIME • Constant • Breakthrough • Intermittent acute
  28. 28. 4. PAIN SEVERITY = 5TH VITAL SIGN 29
  29. 29. 5. EFFECT OF TREATMENTS • Therapies tried • What worked ? • What didn‟t work ? • Any affects you didn‟t like ?
  30. 30. EXAMINATION • General exam • Changes in behavior • Focused exam • Psychological exam
  31. 31. INTERDISCIPLINARY TEAM • Physician •Assess •Diagnose •Prescribe •Monitor •Communicate • Nurse •Assess •Deliver •Monitor •Teach •Communicate • Pharmacist •Assess •Provide •Monitor •Teach •Communicate
  32. 32. INTERVAL SUMMARY Assessment of pain requires a thoughtful history and physical. Standardizing the process helps prevent miscommunication.
  33. 33. PAIN MANAGEMENT: DEFINITIONS • Opioid: anything that binds the opioid receptor • Opiate: derived from the opium poppy (Papaver somniferum) • Narcotic: archaic term, associated with illicit use 35
  34. 34. PAIN MANAGEMENT PRINCIPLES • Don‟t delay control • Unmanaged pain nervous system changes • Treat underlying cause
  35. 35. WHO LADDER 3, Pain 7 – 10 Morphine 2, Pain 4 – 6 Hydromorphone Fentanyl Codeine Oxycodone Tramadol Methadone A / Codeine ASA Levorphanol A / Hydrocodone Paracetamol / Acetaminophen ± Adjuvants A / Oxycodone 1, Pain 1 – 3 NSAID’s ± Adjuvants A / Dihydrocodeine ± Adjuvants WHO. Geneva, 1996.
  36. 36. First Order Kinetics Plasma Concentration When biological effect follows plasma concentration Absorption 0 Excretion Time
  37. 37. Maximum Concentration ( Cmax ) 10 Plasma Concentration 20 = maximum concentration during the dosage interval Cmax 0 4 Time ( hours )
  38. 38. Time to Maximum Concentration ( t Cmax ) 10 Plasma Concentration 20 = time it takes to get to maximum concentration Cmax 0 1 Morphine PO / PR Cmax = 1 hour 4 Time ( hours )
  39. 39. IV Time to Maximum Concentration ( t Cmax ) Plasma Concentration SC / IM Cmax 0 PO / PR Half-life (t1/2) Time
  40. 40. Half-Life ( t ½ ) 10 Plasma Concentration 20 = time it takes for the body to excrete half the dose Morphine all routes t ½ = 4 hours 0 4 Time ( hours )
  41. 41. CLEARANCE CONCERNS MORPHINE Liver Analgesia •Morphine  M3G . . . +  M6G . . . +++ CNS +++ + Urine 90 – 95 % Collins SL, et al. J Pain Symptom Manage. 1998. Mercadante S, Arcuri E. J Pain. 2004.
  42. 42. PRINCIPLE FOR CONTINUOUS PAIN For constant pain • To achieve steady-state, dose routinely every halflife ( t ½ )
  43. 43. CONTINUOUS PAIN PRINCIPLE
  44. 44. Dosing every half-life ( t ½ ) Plasma Concentration Oral morphine = 4 hours 100% 97% 93.75% 87.5% 75% 50% 0 4 8 12 16 20 24 Time ( hours )
  45. 45. Steady state after 5 half-lives Plasma Concentration Morphine ≈ 20 hours Concentration where side-effects start to occur Peak Trough 0 Concentration needed to control pain Time
  46. 46. PRINCIPLE FOR BREAKTHROUGH PAIN • Dose once every Time to Cmax • PO 1h • Dose =10% of total 24 hr routine dose
  47. 47. Breakthrough Pain Plasma Concentration PO / PR ≈ 1 hr Cmax 0 Time
  48. 48. OPIOID ADVERSE EFFECTS Common • Constipation Uncommon • Bad dreams / hallucinations • Dry mouth • Delirium • Nausea • Myoclonus / seizure • Sedation • Pruritis / urticarial • Sweats • Respiratory depression • Urinary retention
  49. 49. EQUIANALGESIC DOSES Oral/Rectal Analgesic IV/SC/IM 150 Codeine -- 15 Hydrocodone -- 15 Morphine 5 10 Oxycodone -- 3 Hydromorphone 1 51
  50. 50. MORPHINE PO  OXYCODONE PO Morphine 15 mg PO = Oxycodone 10 mg PO • Patient is on Morphine ER 90mg BID PO • Oral Morphine Equivalent? • (90 mg x 2 = )180mg • This equals how much Oxycodone? • ( 180 mg x 15 / 10 =) 120mg • How much Oxycodone ER? • 60mg PO BID
  51. 51. MORPHINE PO  HYDROMORPHONE IV Morphine 15 mg PO = Morphine 5 mg IV = Hydromorphone 1 mg IV • Patient is on Morphine IR 20mg q2hrs PO PRN • Now can‟t take PO, how much HM? • ( 20mg / 3 then 6.67 mg / 5 =) 1.3mg IV
  52. 52. MORPHINE PO  HYDROMORPHONE IV Morphine 15 mg PO = Morphine 5 mg IV = Hydromorphone 1 mg IV • Patient is on Morphine ER 90mg BID (OME 180mg) • How much IV Hydromorphone in a day? • ( 180mg / 3 then 60 mg / 5 =) 12mg IV / 24hrs
  53. 53. MORPHINE PO  HYDROMORPHONE IV Morphine 15 mg PO = Morphine 5 mg IV = Hydromorphone 1 mg IV • Patient is getting 8mg IV Morphine hourly PRN without relief • What is this equal to in Hydromorphone IV? • ( 8 mg / 5 =) 1.6 mg
  54. 54. INTERVAL SUMMARY Understanding the way these medications enter and leave the body can help you safely and effective treat pain. Always have someone independently check your work when changing medications.
  55. 55. SARAH, 43 YO • Metastatic colorectal CA • Sacral plexus destruction • Multiple opioid trials • Pain 6 / 10 • Drowsiness • Confusion
  56. 56. “TOTAL PAIN” Disease Mgmt EOL Worry Physical Pain Practical Spiritual Psych Social 58
  57. 57. ADJUVANT THERAPIES • Pharmacological • Interventional Anesthesia • Non-pharmacological • Acupuncture • Biofeedback • TENS • Counseling • Integrative therapies
  58. 58. ADJUVANT EVIDENCE • Therapies extrapolated from non-cancer pain • Few RCTs • Very few comparative trials
  59. 59. GUIDING THERAPY • Diagnosis • Assessment • Efficacy • Safety / tolerability • Ease of use • Cost
  60. 60. OPIOIDS • Nociceptive pain > neuropathic pain • First-line for mod to severe neuropathic pain • Titrate to effect or side-effect
  61. 61. METHADONE • Long half-life • NOT first order kinetics • Experienced palliative care / pain experts • Coanalgesic: 2.5 – 5+ mg • Cost PO << parenteral
  62. 62. GABAPENTINOIDS • Sodium channel antagonist • Positive RCT‟s • NNT less favorable than TCAs • First-line 2º safety
  63. 63. GABAPENTINOIDS… • Trial gabapentin •Start 100-300 mg qhs •Daily, increase 100 mg q8h •Effective 900 - 1800 mg / 24 hr •Max 3600 - 5400 mg / 24 hr • If ineffective, pregabalin •Start 25-75 mg q12h •Increase 25 mg q12h •Effective 100-150 mg / 24 hr •Max 300 - 600 mg / 24 hr
  64. 64. ANTIDEPRESSANTS • 3º amine TCAs (amitriptyline) • 2º amine TCAs (desipramine, nortriptyline) • Mixed SNRIs (duloxetine, venlafaxine) • SSRIs (citalopram, paroxetine)
  65. 65. OTHER ANTICONVULSANTS •  excitation • Limited data, trial-anderror • Newer drugs have better safety profiles
  66. 66. CORTICOSTEROIDS • Limited data, widely used in • Bone pain • Neuropathic pain • Lymphedema • Other conditions • Dexamethasone • Start high dose 8+ mg daily • Taper to lowest effective dose
  67. 67. OTHER OPTIONS • Lidocaine (IV or SC) • Sodium channel blockade • Good evidence • Ketamine (PO, IV, SC) • NMDA blocker • Dose-limiting psychological effects
  68. 68. SARAH, 43 YO, CA COLON • Touch • Simplify meds ( ! ) • Address total suffering • Feb 14…Pain 6 / 10
  69. 69. INTERVAL SUMMARY Sometimes the best long-acting medicine for a patient may not be an opioid. Poor opiateresponsiveness is a sign that multimodal therapies may be necessary to achieve pain relief.
  70. 70. CLARIFYING ADDICTION
  71. 71. TOLERANCE • Reduced effectiveness over time • Not clinically significant with chronic dosing • Suspect disease progression
  72. 72. PHYSICAL DEPENDENCE • Process of neuro-adaptation • Abrupt cessation withdrawal • Titrate down if stopping • Avoid antagonists
  73. 73. DRUG DIVERSION • Regulation • Record keeping • Accountability
  74. 74. PSEUDO-ADDICTION • Most common cause of apparent drug „ failure ‟ is under-dosing • Behavior LOOKS like drug seeking
  75. 75. ADDICTION: CHARACTERISTICS • Psychological dependence • Compulsive use • Loss of control over drugs • Loss of interest in pleasurable activities
  76. 76. ADDICTION: HALLMARK • Continued use of drugs in spite of harm • Rare outcome of pain management
  77. 77. SUBSTANCE USERS • Can have pain too • Treat with compassion • Consultation with pain or addiction specialists
  78. 78. INTERVAL SUMMARY True addiction is rare in the management of pain and pain can occur in those with a history of substance use.
  79. 79. SUMMARY • Pain may be nociceptive, neuropathic or both and the history tells you which. • A standardized approach to the assessment of pain helps prevent miscommunication. • For constant pain, dose on the half-life (q4hrs). For breakthrough pain, dose on the Cmax (routedependent). • True addiction is uncommon in pain management. 81
  80. 80. THE INS AND OUTS OF PAIN Kyle P. Edmonds, MD Faculty, UCSD Division of Palliative Medicine 928.853.1483 Kyle.p.edmonds@gmail.com Kylepedmonds.com

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