becon own educational program modules. module 1 an introduction to cancer pain date of preparation:...

BeCOn OWN Educational Program

Modules

Module 1An introduction to cancer pain

Date of preparation: June 2015 HQ/EFF/15/0024

Contents

Pathophysiology of pain

Types of cancer pain

Incidence, assessment and burden of cancer pain

Challenges in management of cancer pain

Pathophysiology of pain

A protective mechanism that provides survival benefitor contributes to the healing process

Pain can be described in two major categories

Merskey H, Bogduk N. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 2nd ed. Seattle: IASP; 2012. National Pharmaceutical Council. http://www.npcnow.org/publication/pain-current-understanding-assessment-management-and-treatments. Accessed 8 Jun 2015.

Chronic pain has been defined as a pain that lasts beyond the duration of insult to the body or beyond the duration of the healing process

Acutepain

Chronicpain Chronic pain that involves pathology of neural structures

Arises from abnormal neural function as a

result of direct damage or indirect insult to a

neural tissue involved in pain processing

Pain that is a combination of nociceptive and

neuropathic pain

Noxious stimulusto a tissue (somatic)or to a visceral organ

(visceral)

Classification of pain

http://www.iasp-pain.org/PublicationsNews/Content.aspx?ItemNumber=1673. Accessed 15 Jun 2015.

In cancer, pain can be the presenting symptom of cancer in an otherwise healthy patient or emerge as disease progresses

Nociceptivepain

Neuropathicpain

Mixedpain

http://www.iasp-pain.org/PublicationsNews/Content.aspx?ItemNumber=1673

http://www.iasp-pain.org/PublicationsNews/Content.aspx?ItemNumber=1673

Classification of pain

Nociceptive pain results from an acute or persistent injury to visceralor somatic tissues

– Somatic nociceptive pain: site specific, described by patients as “aching”, “stabbing” or “throbbing” , “tender”, “squeezing” and involves injury to bones, joints, skin, mucosa or muscles

– Visceral nociceptive pain results from injury to organs or viscera, is poorly localised and/or referred and may be characterised as “cramping” or “gnawing” if it involves a hollow viscus(e.g. bowel obstruction), or as “aching”, “stabbing” or “sharp” (similar to somatic nociceptive pain) if it involves other visceral structures such as the myocardium

Neuropathic pain suggests injury to the peripheral or central nervous system. Neuropathic pain may be associated with referred pain along nerve distribution(pain is perceived in a location that is not the source of the pain), and all other descriptors of pain. It is described as “shooting”, “sharp”, “stabbing”, “tingling”, “ringing”, “numbness”. It is caused by radiculopathy, peripheral neuropathy, phantom limb, spinal cord compression

Ripamonti CI, Bossi P. Cancer pain. Rehabilitation issues during cancer treatment and follow-up. ESMO Handbook, 2014.

Pain terms

Allodynia: Pain due to a stimulus that does not normally provoke pain

Causalgia: a syndrome of sustained burning pain, allodynia, and hyperpathia after a traumatic nerve lesion, often combined with vasomotor and sudomotor dysfunction and later trophic changes

Central neuropathic pain: Pain caused by a lesion or disease of the central somatosensory nervous system

Dysesthesia: an unpleasant abnormal sensation, whether spontaneous or evoked

Hyperalgesia: increased pain from a stimulus that normally provokes pain

Hyperpathia: painful syndrome characterised by an abnormally painful reaction to a stimulus, especially a repetitive stimulus, as well as an increased threshold.

Paraesthesia: an abnormal sensation, whether spontaneous or evoked

http://www.iasp-pain.org/Taxonomy. Accessed 15 Jun 2015.

http://www.iasp-pain.org/Taxonomy

http://www.iasp-pain.org/Taxonomy

Nociceptive vs. neuropathic pain


Initiated or caused by primary lesion or dysfunction in the

nervous system

Caused by a combination of both primary injury and secondary effects

Postoperativepain

Cancer pain may be due to a variety of causes

Mechanicallow back pain

Sport/exerciseinjuries

Sickle cellcrisis

Arthritis

Caused by activity in neural pathways in

response to potentially tissue-damaging stimuli

Postherpeticneuralgia

Neuropathiclow back pain

Distalpolyneuropathy

(eg, diabetic, HIV)

Trigeminalneuralgia

Complex regional pain syndrome

Nociceptivepain

Neuropathicpain

MixedType

Central post-stroke pain

Physiology of pain perception

Transduction

Transmission

Modulation

Perception

Interpretation

Behaviour


Brain

Ascendingpathways

Spinal cord

Dorsalhorn

Dorsal rootganglion

Descendingpathway

Injury

Peripheralnerve

C-fiber

A-beta fiber

A-delta fiber

Cortex

Thalamus

Brainstem

Spinal cord

Central perception

Relay and Descending Modulation

Transmission

Conduction Peripheral stimulus

Signal transduction

Nociceptive pain: transmission

Fornasari D. Clin Drug Investig. 2012;32 Suppl 1:45-52.

Normal pain signalling in the body is transmitted to the spinal cord dorsalhorn through nociceptors.

Neuropathic pain: peripheral sensitisation

Fornasari D. Clin Drug Investig. 2012;32 Suppl 1:45-52.

Peripheral sensitisation takes place in inflammatory pain, in some formsof neuropathic pain and in ongoing nociceptive stimulation

MechanicalChemicalThermal

Sensitisingagents

↑Actionpotential

TyrNa+

↑Reachvoltage-gated

sodium channel threshold

↑Generatorpotential

(membranedepolarisation)

↑Na+/Ca2+

influx

TrkA

PKC activation

PKA activationP

P

Neuropathic pain: central sensitisation

Woolf CJ, et al. Lancet. 1999;353:1959-64.

Central sensitisation occurs in inflammatory,functional and neuropathic pain

AB fibremechanoreceptor

Increased nociceptor drive leads to central sensitization of dorsal horn neurons

Normal sensory function

Innocuousstimulus

Weaksynapse

Nonpainfulsensation

Na+channel

Na+channel

Innocuousstimulus

Increasedsynapsisstrength

Painfulsensation

Na+channel

Na+channel

Neuropathic pain, central sensitisationand inflammation

http://www.uq.edu.au/pain-venom/about-pain. Accessed 7 May 2015.

Inflammatory souphistamine, bradykinin, 5-HT,

H+, prostaglandins, TNFa,NGF, ATP etc

PKC/A

EPB1/2P2X3TRPV1

Nav 1.8

Nav 1.9

+

Inflammatory pain(skin, joint and viscera)DRGDRG

Central sensitisation(neuropathic/inflammatory)

Neuropathic pain(peripheral nerve damage)

PGE2+-

+

-

NK1 mGluREPGABA

Gly

NMDA

dorsal horn neuron

a2-AR

Cava2d1

skin

5HT3

EPASICTRPV1

TRPM8

¯Nav 1.8

a2-AR

Nav 1.3¯Kv 1.4

Cava2d1

¯Nav 1.9

Nav b3

cold, hot,acid, mechanical

Brain (“pain”)

Types of cancer pain

Somatic pain

Tumour-related bone pain: directly dueto metastasis itself or oncogenic hypophosphataemic osteomalacia

Tumour-related soft-tissue pain like pleural pain/ear pain/eye pain

Paraneoplastic syndromes:hypertrophic osteoarthropathy, muscle cramps, Raynaud’s phenomenon

Visceral pain

Peritoneal carcinomatosis

Chronic intestinal obstruction

Malignant perineal pain

Ureteric obstruction

Chronic cancer pain: tumour-related pain

Esin E, Yalcin S. Onco Targets Ther. 2014;7:599-618.

Chronic cancer pain: neuropathic pain

Neuropathic pain syndromes

Leptomeningeal metastases

Trigeminal neuralgia

Glossopharyngeal neuralgia

Lumbosacral radiculopathy (damage to nerve root)

Lumbosacral plexopathy (affecting a network of nerves)

Cervical radiculopathy

Brachial plexopathy

Painful peripheral mononeuropathies

Paraneoplastic sensory/motor/autonomic neuropathic pain

Esin E, Yalcin S. Onco Targets Ther. 2014;7:599-618.

Chronic cancer pain: treatment-related pain

Esin E, Yalcin S. Onco Targets Ther. 2014;7:599-618.Ripamonti C, et al. Ann Oncol. 2014; 25: 1097-106.

Papulopustular rashErythemaHand-foot skin syndromeParonychiaFingertip fissuresRadiation dermatitisEyelashes growth distortionOral and anal mucositisAbdominal discomfort with diarrhoea

Targeted therapy-related pain

Painful peripheral neuropathyRaynaud’s phenomenonChronic glucocorticoid-treatment complicationsCompression fractures dueto osteoporosis

Chemotherapy

Postmastectomy painPost-thoracotomy painPhantom limb/breast painPain due to neck dissectionLymphoedema pain

Surgery

Late-onset brachial plexopathyChronic radiation myelopathyRadiation enteritisLymphoedema painOsteoradionecrosis

Radiotherapy

Temporal classification of pain in cancer

ACUTE PAIN follows injury to the body and generally disappears when the body injury heals. It is usually due to a definable nociceptive cause. It has a definite onset and its duration is limited and predictable (i.e. pain related to surgery, biopsy, pleurodesis, pathologic fracture, chemotherapy, radiotherapy, diagnostic and interventional procedures). It is often associated with objective physical signs of autonomic nervous system activity. Acute pain may also indicate a progression of disease and is often accompanied by anxiety.

CHRONIC PAIN is due to the presence and/or progression of the disease and/or to treatments (i.e. chemotherapy-induced neuropathy and/ or osteoporosis, post- surgery, post- radiotherapy). Chronic pain may be accompanied by changes in personality, lifestyle, and functional abilities and by symptoms and signs of depression. Chronic pain with overlapping episodes of acute pain (i.e. breakthrough pain) is probably the most common pattern observed in patients with ongoing cancer pain. This indicates the necessity for monitoring the intensity of pain and associated symptoms and the analgesic treatments. Furthermore, the appearance of acute pain, or progression of a previously stable chronic pain, is suggestive of a change in the underlying organic lesion and requires clinical re-evaluation.

Ripamonti CI, Bossi P. Cancer pain. Rehabilitation issues during cancer treatment and follow-up. ESMO Handbook, 2014.

Cancer patients may have multiple types of pain

Pain associated with cancer can be understood as multiple types of pain

However, patients with cancer can experience non-cancer pain simultaneouslywith cancer pain, such as pain from cancer treatment or unrelated conditions

Pergolizzi JV, et al. Pain Pract. 2014 Dec 3. doi: 10.1111/papr.12253. [Epub ahead of print].

Patients ≥ 4 types of painPatients with cancer

have ≥ 2 types of pain

33%≈80%

Incidence, assessment and burdenof cancer pain

Overall incidence of cancer pain

of patients with cancer report pain

at the time of diagnosis

of advanced patients with cancer experience pain over the course of their disease, which is caused

by tumour infiltration, treatment, or both


25 to 30% 70 to 80%

Incidence of severe pain is high in ambulatorypatients with newly diagnosed stage IV cancerHighest pain intensity score within one year of follow-up among newly diagnosed stage IV cancer patients, according to cancer type (n=505)

Isaac T, et al. Pain Res Manag. 2012; 17(5): 347–52.

Perc

enta

ge

0

20

60

40

50

30

10

Breast Thoracic Gastrointestinal Urogenital Head and Neck Other

None Low Moderate Severe

The incidence of severe pain pain is highestin gastrointestinal and head and neck cancers

40-year meta-analysis of patients with cancer pain

Of patients with pain, more than one-third graded their pain as moderate or severe

Pooled prevalence of pain was >50% in all cancer types with the highest prevalence in head/neck cancer patients (70%; 95% CI: 51% to 88%)

van den Beuken-van Everdingen MH, et al. Ann Oncol. 2007;18(9):1437-49.

Pooled prevalence rates of pain

Patie

nts

(%)

0

20

100

60

80

40

10

Patients aftercurative treatment

(95% CI: 21% to 46%)

Patients underanticancer treatment(95% CI: 44% to 73%)

Patients characterisedas advanced/metastatic/

terminal disease (95% CI: 58% to 69%)

Patients at alldisease stages

(95% CI: 43% to 63%)

CI= Confidence Interval

90

70

50

30

33%

59%64%

53%

Incidence of pain by cancer type

Breivik H, et al. Ann Oncol. 2009;20(8):1420-33.

Cancers involving the pancreas, bone, brain, lymphoma, lung, head and neckare associated with a pain prevalence >85%

Perc

enta

ge p

atien

ts (%

)

Tota

l (n

= 49

47)

Panc

reati

c (n

= 14

2)Bo

ne/m

uscle

(n =

173

)Br

ain

(n =

135

)NH

L (n

= 61

)Lu

ng (n

= 4

17)

SCCH

N (n

= 2

13)

Bow

el/C

RC (n

= 5

04)

Testi

cula

r (n

= 15

0)Bl

ood

born

e (n

= 9

0)

Gyna

ecol

ogica

l (n

= 41

1)Ly

mph

oma

(n =

102

)

Leuk

aem

ia (n

= 1

25)

Brea

st (n

= 1

427)

Pros

tate

(n =

624

)

0

20

60

100

40

80 73

90

70

50

30

10

93 92 90 87 86 86 82 8277 77 75

6662

53

Cancer type

Bandieri E, et al. Leuk Res. 2010;34(12):e334-5.

Is pain in patients with haematologicalmalignancies under-recognised?

Patients with moderateto severe pain

The results from Italian ECAD-O survey

Percentage

0 20 40 60 80 100

Solid tumours 59.4%

Haematological cancers 67.3%

No pain Low Moderate Severe

Pain in haematological malignancies deserves greater

consideration

Pts with ST

Pts with HT

32.6

30.6

26.8

36.7

24.2

16.3

16.4

16.3

Prevalence of pain during the last 3 monthsof patients’ lives

1,271 oncology patients with 3 months of life expectancy. Pain was seen in:82.3% of patients

Haematological patients presented with pain as frequently as those with solid tumours

Costantini M, et al. Ann Oncol. 2009; 20: 729-35.

Prevalenceof pain

Prevalence of verydistressing pain

% 95% CI % 95% CI

Primary tumour

Head and neck 85.4 64.6-95.0 68.1 48.5-82.8

Oesophagus and stomach 88.4 81.0-93.2 62.9 52.3-72.4

Colon and rectum 84.8 77.7-89.9 64.9 57.3-71.9

Liver and bile ducts 73.7 63.6-81.8 56.1 46.4-65.3

Pancreas 80.3 68.6-88.4 67.0 54.5-77.6

Larynx, lung, and pleura 83.4 76.5-88.6 60.3 54.2-66.1

Breast 75.8 66.4-83.2 52.8 43.8-61.6

Female genital organs 89.9 76.9-96.0 69.2 52.7-82.0

Prostate 90.9 78.5-96.5 58.6 43.5-72.2

Bladder and kidney 89.3 76.1-95.6 70.4 56.6-81.2

Central nervous system 51.9 27.4-75.5 21.1 9.2-42.4

Lymphoma and leukaemia 83.0 73.6-89.5 63.4 53.0-72.7

Multiple myeloma 86.1 66.4-95.1 66.3 41.4-84.6

Other and unspecified 77.6 69.8-83.8 62.9 55.2-70.0

p = 0.098 p = 0.035

Breakthrough cancer pain: a pan-European survey


European survey of 5,084 patients with cancer across 11 countries and Israel

Patie

nts

(%)

0

20

60

100

40

80

90

70

50

30

10

Experienced moderate to severe pain at least once a

month

Described pain as severe

Reported pain-related difficulties

with everyday activities

Believed that their quality of life was not considered a priority in their overall care by their health care

professional

56%

44%

69%

50%

The reported prevalence of breakthroughcancer pain varies widely

The prevalence of breakthrough pain has been reported to be 19–95% amongst various groups of patients, reflecting differences in the definition and methods utilised, and in the populations studied

Davies A. Cancer-related breakthrough pain. Oxford University Press 2012.

Prevalence of breakthrough pain in studies applying standard criteriafor breakthrough pain

Study Type of population Prevalence of breakthrough pain

Portenoy & Hagen, 1990 Hospital inpatients (pain team referrals) – USAn = 90 63%

Fine & Busch, 1998 Hospice homecare patients – USAn = 22 86%

Portenoy et al, 1999 Hospital inpatients – USAn = 178 51%

Zeppetella et al, 1999 Hospice inpatients – UKn = 414 89%

Fortner et al, 2002 Cancer patients (home setting) – USAn = 1000 63%

2 3 4 5 61

Worstpossible

pain

Veryseverepain

Moderatepain

Mildpain

Nopain

Severepain

Universal pain assessment toolsVerbal Pain Intensity Scale

Faces Pain Scale – Revised (FPS-R)

National Pharmaceutical Council. http://www.npcnow.org/publication/pain-current-understanding-assessment-management-and-treatments. Accessed 8 Jun 2015.Ripamonti CI. Ann Oncol. 2012;23 Suppl 10:x294-301.

Validated assessment tools for the assessment of pain

Ripamonti CI, et al. Ann Oncol. 2012 Oct;23 Suppl 7:vii139-54.

Visual analogue scale VAS

Worstpain

Nopain

10 cm

Nopain1 Very

severeSevereModerateMildVerymild2 3 4 5 6

Verbal rating scale VRS

Numerical rating scale NRS

Worstpain

Nopain 0 101 2 3 4 5 6 7 8 9

Cancer pain can add additional burden to patients


Cancer pain can be exacerbated by thenormal worries that accompany cancer diagnosis

ANXIETY

CONCERNS ABOUTFINANCES

WORRIES OVERFAMILIAL SUPPORT

DEPRESSION

HOPELESSNESS

CATASTROPHISING

Cancer pain affects many aspects of daily life


Patie

nts

(%)

0

20

60

100

40

80

90

70

50

30

10

Pain impacts work

performance

Described pain as distressing

Pain creates difficulty in performing

normal activities in daily life

Being in too much pain

to be able to care sufficiently for themselves

52%

67% 69%

30%

Pain stopsthem from

concentratingor thinking

51%

BTcP affects all areas of daily life

Davies A, et al. J Pain Symptom Manage. 2013;46(5):619-28.

Interference with various aspects of daily living

Numerical rating (0-10)

Enjoyment of life

Relations with other people

Walking ability

Mood

0 2 3 4 5 6 7 8 9 10

Sleep

Normal work

General activity

1

2nd quartile 3rd quartile

BTcP has a significant negative effect on quality of life that is related to a direct effect (suffering) and an indirect effect (interference with activities of daily living)

Study of 1000 cancer patients from 13 European countries.

National Breakthrough Pain Study

Narayana A, et al. Pain. 2015;156(2):252-9.

Interview of 2198 patients with opioid-treated chronic pain

80% of patients reported BTP

Patients had a median of 2.0 episodes of BTP per day (range, 1-50) and a median duration of BTP of 45 minutes (range, 1-720)

Compared with patients without BTP, patients with BTP had more pain-related interference in function, worse physical health and mental health, more disability and worse mood

BTP is highly prevalent and associated with negative outcomes

There are many barriers to better controlof cancer pain


Patient-related barriers

Clinician-related barriers

Healthcare-system-related

barriers

Barriers topain

control

Multidisciplinaryteams led by

oncologists whofocus on cancertreatment and

regard painas a secondary

matter

Inadequatepain

assessment

Fear to talkabout pain,

thinking it meanstheir conditions

is worsening

Absence ofnational policies

on opioid use andno prioritisationof pain control in

public health

Costs

Lack ofavailability of

opioid analgesicsin some

countries/regions

Unwillingnessto report pain for

any number of reasons,including not wantingto distract the doctor

from fightingthe cancer

Failure todiagnose

breakthroughpain

Tendencyto trivialise

pain in light ofseriousness

of cancer

Little progress has been made in adequatetreatment of cancer pain


Rate

of u

nder

trea

ted

canc

er p

ain

(%)

0

20

60

80

40

70

50

30

10

1994 2012

40%

33%

Year

The many consequences of undertreatmentof cancer pain


Psychologicalconsequences

Withdrawalfrom social and

familialinteractions

Feelingsof isolation

Otherpsychological

distressexistential and

spiritual

SufferingReduced

coping skills

AnorexiaInsomnia

andother sleep

disturbances

Profoundfatigue

Variousforms of

incapacity

Reducedcognition

Physicalconsequences

Challenges in management of cancer pain

Pain management primarily involvesmedical oncologists


Medical oncologist, 42

Don’t know, 1

None, 3

Other, 5

Physiotherapist, <1

Radiation oncologist, <1

Anaesthetist, <1

Nurse/Specialist nurse, 1

Neurologist, 1

Obstetrician/gynaecologist, 1

Palliative care specialist, 2

Pain specialist, 3

Haematologist, 4

General surgeon, 4

Medical doctor, 8

GP/Primary care provident, 19

Patients believe that healthcare providers give inadequate attention to pain management


Patie

nts

(%)

0

20

60

40

50

30

10

HCP does not consider

patient QoL to a great extent

HCP does not recognise pain as a problem

HCP treats cancer rather

than pain

HCP does not always ask about pain

50%

12%

38%

27%

HCP does not have time to discuss pain

33%

HCP does not know how to control pain

26%

A multidisciplinary approach is preferredin management of cancer pain

Ideally, there should be communication among the various specialists, with oncologists often coordinating the patient’s care.


ONCOLOGIST

PAIN SPECIALIST

PALLIATIVIST

RADIOTHERAPIST

GENERALPRACTITIONER

NEUROLOGIST

Patient adherence to pain guidelines remains insufficient

In a study of 193 inpatients, 109 met the inclusion criteria of which 70 were guideline adherent and 39 non-adherent

63% of patients initiated on NCCN adherent guidelines obtained analgesia at 24 hours vs. 41% in the non-adherent group

Average pain scores across the 24-hour period were lower in the adherent compared with the non-adherent group (3.5 vs. 4.4)

Chronic home opioid exposure was significantly associated with non-adherent therapy (OR=3.04; P=0.01) and achievement of analgesia at 24 hours

Mearis M, et al. J Pain Symptom Manage. 2014;48(3):451-8.

Medical oncologists do not always follow practice guidelines on pain management

In a survey of 268 medical oncologists (24% completers):

– Adherence to the different recommendations of the guideline ranged from 18 to 100%

te Boveldt N, et al. Support Care Cancer. 2015;23(5):1409-20.

Adhered to prescribing paracetamolas first-line pain treatment

Percentage

Prescribed a laxative in combination with opioids to prevent constipation

Adhered to the guideline when first-line treatment had insufficient effect

Adhered to recommendationsfor insomnia treatment

Adhered to the recommendation to performa multidimensional pain assessment

when disease worsens and pain increases

0 10 20 30 40 50 60 70 80 90 100

94%

100%

24%

35%

18%

Combined pain consultation and pain education programmes can improve outcomes

In oncology outpatients randomly assigned to SC (n=37) or PC-PEP (n=35):

The overall reduction in pain intensity and daily interference was significantlygreater after randomisation to PC-PEP than to SC (average pain 31% vs. 20%, P=0.03; current pain 30% vs. 16%, P=0.016; interference 20% vs. 2.5%, P=0.01)

Patients were more adherent to analgesics after randomisation to PC-PEP thanto SC (P=0.03)

SC, stanard care; PC-PEP, pain consultation and pain education programme

Oldenmenger WH, et al. Pain. 2011;152(11):2632-9.

PC-PEP improves pain, daily interference and patient adherence

Summary

Cancer pain may be nociceptive, neuropathic, or mixed

Cancer pain is often under-recognised and undertreated

Cancer pain adds additional suffering to patients, affecting many areas of daily life

More adequate management of cancer pain is needed through a multidisciplinary approach

becon own educational program modules. module 1 an introduction to cancer pain date of preparation:...

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