BREAKTHROUGH PAIN (BTP) PLENIERE/11...(Colleau, S.M. (1999). o Another definition: It is usually related to background pain and is typically of rapid onset, severe in intensity, and

Dr Abdalla Fekry ElsayedConsultant Anesthesia & Pain Management ( GOTHI)

ESMP TreasurerESA Treasurer

ESAM Secretary GeneralIASP Member

BREAKTHROUGH PAIN (BTP)

6th National Congress of Pain,19 and 20 March 2010 El Aurassi hotel - Algiers

Overview

o Introductiono Definitions of Breakthrough Pain (BTP) o Prevalenceo Clinical subtypeso Managemento Investigational rescue drugso Conclusiono References

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o Knowledge is exchange of experience.”

o “Medicine is not only a science; it is also an art. It does not consist of compounding pills and plasters; it deals with the very processes oflife, which must be understood before they may be guided”

o “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.”

o “The dose makes the poison“.

Introduction

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Paracelsus (1493-1541)

“…whatever the experiencing person says it is, existing whenever she/he says it does”

A subjective experience so we should have self reporting as a reliable indicator

Mc Caffery M. 1968

Pain

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An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

Pain is a complex experience that includes multiple dimensions (sensory, affective, cognitive)

International association for the study of pain® 1979

Pain

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o Pain is inevitable.

o Suffering is optional.

o “However long the night, the dawn will breakthrough.”

Andrew Parchman

Introduction

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IntroductionBackground pain:

Background pain refers to ‘constant or continuous pain of long duration’ ≥ 12 hours.It also called: persistent pain, ongoing pain, basal pain; baseline pain, steady pain, stable pain….

PAIN TEMPORAL PROFILE

Acute

Constant

Breakthrough

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o First definition: 'A transitory increase in pain to greater than moderate intensity, which occured on a baseline pain of moderate intensity or less . (Portenoy, R.K., Hagen, N. A (1990)

o Another definition: Transitory exacerbation of pain experienced by the patient who has relatively stable and adequately controlled baseline pain. (Hanks, 1998)

o Another definition: Transient exacerbation of pain that occurs in patients with otherwise stable baseline persistent pain. (Coluzzi, 1998)

o Another definition: A transitory exacerbation of pain that occurs on a background of otherwise stable pain in a patient receiving chronic opioid therapy. (Portenoy, R.K., Payne, D., Jacobsen, P. (1999)

Definitions for BTP

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o Another definition: 'A tranistory exacerbation of pain experienced by the patient who has relatively stable and adequately controlled baseline pain’ (Colleau, S.M. (1999).

o Another definition: It is usually related to background pain and is typically of rapid onset, severe in intensity, and generally self- limiting with an average duration of 30 minutes (Zeppetella 2003).

o Another definition: A transitory exacerbation of pain experienced by the patient who has relatively stable and adequate controlled baseline pain (Portenoy et al, 2004).

o Another definition: Moderate to excruciating acute pains that occur intermittently, often on a background of well-controlled chronic pain (Abrahm, 2005).

Definitions for BTP

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o Another definition: “an abrupt, short lived and intense pain that ‘breaks through’ the around the clock analgesia that controls persistent pain.” (Bennett, 2005)

o Broad Definition: Any acute transient pain that flares over baseline. Or Transient worsening of pain in patients with an ongoing steady pain

o Recent definition: Intense increases in pain that occur with rapid onset even when pain-control medication is being used. Breakthrough pain can occur spontaneously or in relation to a specific activity. ( NCI National Cancer Institute, 2009).

o Recent definition: It is a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain. (Zappettella , 2009, Davies et al., 2009).

Definitions for BTP

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Around-the-ClockMedication (ATC)

Breakthrough Pain(Transient Pain)

Background Pain and Breakthrough Pain

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Recent definition BTP in cancer patients:It is a surge of intense pain that breaks through otherwise stable opioid analgesia, it peaks within minutes typically lasts for 30 minutes and can

occur many times a day. ( www.europeanjournalpain.com 2009 ).

BTP in cancer patients

o Prevalence: The prevalence of breakthrough pain (BTP) has been evaluated in a number of studies of cancer patients and ranges from 19 to 95%.

o Frequency: In cancer patients the median number of breakthrough pain episodes per patient / day was 4.

o Characteristics of breakthrough pain episodes: In a study by Goméz-Batiste et al.(2002) 60% of the breakthrough pain episodes was reported to have a rapid onset (as described by the patient).

o The mean duration of the breakthrough pain episodes was 33.8 minutes.

o 64% of breakthrough pain episodes had a duration of less than 30 minutes and 87% of breakthrough pain episodes had a duration of 60 minutes or less.

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Gómez-Batiste et al. Breakthrough Cancer Pain: Prevalence and Characteristics in Patients in Catalonia, Spain. J. Pain and Symptom Management, 2002, vol 24; 45-52.

BTP in non-cancer patients

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o Prevalence: The prevalence of breakthrough pain in non-cancer patients with pain appears to be similar to that of cancer patients with pain. One study reported a prevalence of 74% amongst a mixed group of chronic pain patients.

o Frequency: In non-cancer patients the median number of break-through pain episodes per patient / day was 1.5.

o Characteristics of breakthrough pain episodes: In a study by Portenoy et al.(2006) it was reported that median time to maximum severity for breakthrough pain episodes was found to be 10 minutes in non-cancer patients.

o The median duration of breakthrough pain episodes was 60 minutes.o 33% of breakthrough pain episodes had a duration of less than 30 minutes

and 58% of breakthrough pain episodes had a duration of 60 minutes or less.

Portenoy et al. Prevalence and Characteristics of Breakthrough Pain in Opioid-Treated Patients With Chronic Non-cancer Pain. 2006. The Journal of Pain, vol 7(8); 583-591.

Gómez-Batiste et al. Breakthrough Cancer Pain: Prevalence and Characteristics in Patients in Catalonia, Spain. J. Pain and Symptom Management, 2002, vol 24; 45-52.

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Portenoy et al. Prevalence and Characteristics of Breakthrough Pain in Opioid-Treated Patients With Chronic Non-cancer Pain. 2006. The Journal of Pain, vol 7(8); 583-591.

BTP Cancerous pts Non cancer pts

Episode mean time 3 min 10 min

Mean duration 33.8 min 60 min

Patients % 1-60min 87% 58%

In Non Cancer Patients

14%

19%

25%

17%

7%4%

6%

In Cancer Patients

6%2%

23%

33%31%

5%

Characteristics of BTP in Cancer

Characteristics Average Range

Time to peak 3-5 minutes 10 sec to 180 min

Severity Severe or excruciating

Mild to excruciating

Duration 15-30 minutes 1 sec to 24 hours

No of episodes 1-5 Less than 1 to 3600

Precipitated by event

55- 60% 52-77%

Predictable 50-60% 41-81%

Bennett et al. Pharmacol &Ther. 2005;30(5):296-30115

Pathophysiology

Type of pain:o Nociceptive pain

o Visceralo Somatic

o Neuropathic paino Mixed pain

Davies, A. (2006). General principles of management. In Davies, A, ed. Cancer-related breakthrough pain. Oxford University Press, Oxford, 31–42.

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Direct effect

Of Cancer

Indirecteffect

Of Cancer

Effect Of

Cancer TTT

Associated diseases

AetiologyOf BTP

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Portenoy, R.K., Hagen, N.A. (1990). Breakthrough pain: definition, prevalence and characteristics. Pain, 41: 273–281.

Portenoy, R.K., Payne, D., Jacobsen, P. (1999). Breakthrough pain: characteristics and impact in patients with cancer pain. Pain, 81: 129–134.

Zeppetella, G., Ribeiro, M.D. (2003). Pharmacotherapy of cancer-related episodic pain. Expert Opinion on Pharmacotherapy, 4: 493–502.

Zeppetella, G., O’Doherty, C., Collins, S., (2000). Prevalence and characteristics of breakthrough pain in cancer patients admitted to a hospice. Journal of Pain and Symptom Management, 20: 87–92.

BTP may be experienced by patients at all stages of cancer (at diagnosis, during active treatment, during remission,

during relapse/progression, following cure).

Aetiology of BTP

Study Cause of BTP PainCancer Cancer

treatmentAssociateddiseases

Portenoy & Hagen,

1990

76% 20% 4%

Portenoy et al, 1999

65% 35% 0%

Zeppetella et al, 2000

71% 11% 18%

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Type of BTP PainNociceptive

pain Neuropathic

painMixed pain

53% 27% 20%

38% 10% 52%

75% 9% 16%

Mean 70.6 22 7.3 55.3 15.3 29.3

Payne, R. (2007)Recognition and diagnosis of breakthrough pain. Pain Med 8: S 2-7

Portenoy, R.K. (1997). Treatment of temporal variations in chronic cancer pain. Seminars in Oncology, 5: (Suppl 16): S16–7–12.

Portenoy, R.K., Payne, D., Jacobsen, P. (1999). Breakthrough pain: characteristics and impact in patients with cancer pain. Pain, 81: 129–134.

Clinical features

o BTP is not a single entity, but a spectrum of different entities.

o The clinical features vary from individual to individual and may vary within an individual over time.

o The clinical features of the BTP are often related to the clinical features of the background pain.

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ProceduralWound dressing

Non VolitionalDistensionIschemia

Bladder spasmCough

VolitionalWallingBathing

End of Dose Failure

Related to analgesic dose regimen

IncidentStimulus dependent

Episodic or IdiopathicStimulus non dependent

Clinical BTP subtypes

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Davies, A. (2005). Current thinking in cancer breakthrough pain management. European Journal of Palliative Care, 12 (Suppl): 4–6.Payne, R. (2007)Recognition and diagnosis of breakthrough pain. Pain Med 8: S 2-7McCarberg BH. (2007) The treatment of breakthrough pain. Pain Med. 8 Suppl 1:S8-13.

Around-the-ClockMedication (ATC)

Background Pain

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Expert Working Group of the European Association for Palliative Care (EAPC) has suggested that the term ‘breakthrough pain’ should be replaced by the terms ‘episodic pain’ or ‘transient pain’. However, the term ‘breakthrough pain’ is still widely used in the medical literature, and still used by members of the Expert Working Group of the EAPC.

Around-the-ClockMedication (ATC)

Background Pain

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End of Dose failure

Around-the-ClockMedication (ATC)

Breakthrough Pain(Transient Pain)

Background Pain and Breakthrough Pain

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Incident or Spontaneous Pain

‘Typical' BTP episodeTypical BTP episode Characteristics:

o Rapid onset o High frequency o High severity o Short duration

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Portenoy, R.K., Hagen, N.A. (1990). Breakthrough pain: definition, prevalence and characteristics. Pain, 41: 273–281.Portenoy, R.K., Payne, D., Jacobsen, P. (1999). Breakthrough pain: characteristics and impact in patients with cancer pain. Pain, 81: 129–134.Zeppetella, G., O’Doherty, C.A., Collins, S., (2000). Prevalence and characteristics of breakthrough pain in cancer patients admitted to a hospice. Journal of Pain and Symptom Management, 20: 87–92.Hwang, S.S., Chang, V.T., Kasimis, B. (2003). Cancer breakthrough pain characteristics and responses to treatment at a VA medical center.Gómez-Batiste, X., Madrid, F., Moreno, F., et al. (2002). Breakthrough cancer pain: prevalence and characteristics in patients in Catalonia, Spain. Journal of Pain and Symptom Management, 24: 45–52.Pain, 101: 55–64.

Diagnostic criteria

These criteria are:

1. The presence of stable analgesia in the last 48 hr.

2. The presence of controlled background pain in the previous 24 hr (i.e. average pain intensity of none, mild or moderate for over half of the previous 24 hr).

3. The presence of ‘ temporary flares of severe or excruciating pain ’ in the previous 24 hr.

Caraceni, A., Martini, C., Zecca, E., et al. (2004). Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey. Palliative Medicine, 18: 177–183.

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Algorithm for diagnosing (BTP) patients with breakthrough pain

Caraceni, A., Martini, C., Zecca, E., et al. (2004). Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey. Palliative Medicine, 18: 177–183.

Does the patient has background pain?

Does background pain adequately controlled?

Does the patient has transient exacerbation of pain?

Patient has Breakthrough Pain

Patient DOES NOT have Breakthrough Pain

YesNo

Yes

Yes

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o Understanding the meaning of total pain.

o Understanding of different causes of pain.

o Adequate Assessment of pain.

o Appropriate Management of pain.

o Adequate monitoring and Reassessment.

The keys to good pain assessment and management are:

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What can I do?

Davies, A. (2005). Current thinking in cancer breakthrough pain management. European Journal of Palliative Care, 12 (Suppl): 4–6.

Payne, R. (2007)Recognition and diagnosis of breakthrough pain. Pain Med 8: S 2-7

Assessment

o History (pain, general).

o Examination (area of pain, general).

o Investigations ( lab , radiological).

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Assessment (pain history)

o Frequency of episodes.o Site pain, radiation & duration pain.o Character / quality pain.o Severity / intensity pain.o Precipitating & Relieving factors.o Response to analgesics & other treatments.o Associated physical symptoms.o Interference with activities of daily living.

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Consequences of Untreated PainWhat happens if pain isn’t properly treated?

o Physical burdenoImmobility oInsomniaoOther problems

o Psychological burdenoAnxietyoDepression

o Decreased quality of lifeoInability to work oInability to undertake activities of daily living oSocial isolation

o Social burdenoIncreased use of healthcare resources oIncreased use of social care resources

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What I must know

Before BTP Management

You have to be sure that:

o Breakthrough pain is heterogeneous in nature.

o Management needs to be individualised.

o Management is often multi-dimensional.

o Management is often multi-professional.

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PharmacotherapyOpioid Analgesics

Non opioid analgesiaAdjuvants

Interventional ApproachesInjections, Neurostimulation

Neuraxial infusions, Neuroablation

Multimodal Therapeutic strategies for pain and associated disability

Complementary & Alternative Medicine Life Style Changes

Psychological Support

Physical Medicine &

Rehabilitation

Management

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Management

Management strategy: it is not a pure science but also it is an ART

1. Adequate Assessment.

2. Rapid Reassessment.

3. Titrated proper Treatment.

Inadequate assessment ------- ineffective & inappropriate treatment --------inadequate reassessment ------------ vicious circle.

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1. Treatment of cause of pain:– Treatment of cancer;

(e.g. surgery, radiotherapy, chemotherapy).– Treatment of effects of cancer;

(e.g. orthopaedic surgery, bisphosphonates).– Treatment of precipitating factors of

pain.2. Symptomatic treatment of pain:

– Pharmacological methods.– Non-pharmacological methods.– Interventional techniques:

Injections, Neurostimulation, Neuraxial infusions, Neuroablation

– Combination of treatments.34

Treatment Plan

Treatmento Pharmacological methods: BTP

medications work directly to control severe flare-ups.

o Modification of the background analgesia (“around the clock” ATC analgesia)

o Titration of opioid drug.o Opioid switching (drug, route).o Addition of additional analgesic.o Addition of “adjuvant” analgesic.

o Use of rescue analgesia (“as required” analgesia)

o Opioid drugs.o Non opioid drugs.

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Use of opioid “rescue” medication

o The cornerstone of the management of breakthrough pain episodes is the use of so-called “rescue” medication.

o Rescue medication is taken as required, not on a regular basis:Oral opioid analgesics are commonly used, but they have a delayed onset of action (and a prolonged duration of effect).

o Alternative routes of administration would appear to be more appropriate; there already is an oral transmucosal fentanyl (buccal, sublingual), intranasal, intrapulmonary and subcutaneous products.

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o A rapid onset of analgesia, within minutes.

o Provide a durable response to resolve pain; Sustain pain relief for up to 30 minutes.

o Combines well with ATC around the clock medicines.

o Easy to administer ( self administer).

o Easy to dose adjust.

Matching Opioid Therapy to characteristics of BTP

Bennett et al. Pharmacol &Ther. 2005;30(5):354-361

Ideal Rescue medication:Potent; good efficacy Rapid onset of action Short duration of effect Good tolerability Easy to use Acceptable to the patient Available Affordable

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Opioid rescue medicationo Opioid rescue drugs will only be useful for

management of breakthrough pain episodes if:o Pain is opioid-sensitive o Formulation is appropriate (i.e. normal vs. modified

release)o Pharmacokinetic profile is appropriateo Pharmacodynamic profile is appropriate

o Opioid rescue drugs useful for management of BTP pain episodes if:o Patient can use the opioido Patient can tolerate the opioido Dosage is appropriate

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Opioids in Breakthrough pain

LAOLong Acting Opioid

1-2hours- 8-12 hours

SAOShort Acting Opioid

30-45 minutes- 4:6 hours

ROORapid Onset Opioid5-15min -1:2 hours

Fentanyl Trans-dermal system

Morphine, Oxycodone,

Hydrmorphone

Codeine

Hydrocodone

Hydromorphone

Morphine

Oxycodone

Tramadol

OTFC *

FBT **

* Oral Transmucosal Fentanyl Citrate (Actiq)

** Fentanyl Buccal Tablet (Fentora)

*** Fentanyl buccal soluble film (Onsolis)

**** Nasal Fentanyl (nasalfent)

***** Instanyl (nasal fentanyl citrate)

****** Sublingual Fentanyl (Abstral)

FBSF ***

Nasalfent ****

Abstral ******

Instanyl*****

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Transmucosal Rescue Medication

1. ACTIQ®: First transmucosal fentanyl preparation

• ‘Lozenge on a stick’• Fentanyl in hard sweet matrix• Lozenge placed inside cheek

and moved constantly up and down, and changed at intervals to other cheek

• Aim to consume lozenge in 15 mins

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Transmucosal routesBuccal

2. Fentora®, Effentora®:Place tablet in upper portion of

buccal cavity above upper rear molar between cheek and gum

Less permeable75% is actually swallowed,

reducing bioavailabilityProlonged contact with mucosa

and lozenge – problematic if inflamed mucosa

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3. Onsolis® : BEMA® fentanyl (buccal administration) Fentanyl citrate; soluble film (BEMA® technology)

• Moisten mouth• Pick up with dry finger and hold film between thumb a & finger• Place pink side against inside of cheek• Hold film against inside of cheek for 5 seconds• Immediately adheres upon contact and starts to dissolve in seconds up to 10-15

minutes.

Oral rescue medication

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Transmucosal routeso Sublingual

4. Abstral®:– Place tablet under tongue– Rapid absorption– Highly vascularised under the tongue– Highly permeable– High bioavailability

DIRECTIONS FOR USEWait 4 hours between dosesNo food/drink while tablet in mouthTablet disintegration takes 15-30 mins

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Transmucosal fentanyl citrateTics & Tricks

Buccal and Sublingual Medications; Pain relief in 5-10 minDo not suck/chew/ swallow as this decreases plasma concentration 25% of dose is absorbed rapidly into systemic circulationRemainder is swallowed or absorbed more slowly, this is subject to hepatic first pass metabolism; only 1/3 of this amount is available systemically, 25% of the total doseXerostomia – drink water prior to tablet placement

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Other rescue medication

Intranasal rescue medicationThe intranasal route of administration is also

well established in the management of breakthrough pain episodes:

1. Instanyl® : Fentanyl citrate; aqueous spray; nasal administration

2. Nasalfent® : Fentanyl citrate; aqueous spray (PecSys® technology); nasal administration

Intrapulmonary rescue medication:Aerolized liposome-encapsulated fentanyl

Liposomes are microscopic phospholipids vesicles that can entrap drug molecules. Liposomal delivery of fentanyl has the potential to control the uptake of fentanyl by the lungs and thus provide sustained drug release.

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Treatment should be tailored to the type of BTP

Incident pain:o The current European Association for Palliative Care

(EAPC) recommendation is to use the same as the four-hourly dose of normal-release morphine (approximately 16% of the daily dose) when necessary (Hanks 2001).

o A Cochrane review of opioids for breakthrough pain concluded that it is appropriate to titrate the dose of rescue medication (Zeppetella, 2006)

o Pre-emptive use of a short acting opioid 30 minutes before activity (McCarberg, 2007).

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Idiopathic/ spontaneous:o Peak intensity can occur in 3-5 minutes and episodes usually last

for 30 minutes or less, so analgesics with a delayed onset are not helpful for this type of pain.

o A Cochrane review found that oral transmucosal fentanyl citrate (OTFC) was shown to be “an effective treatment for breakthrough pain. When compared to placebo and morphine, participants gave lower pain intensity scores and higher pain relief scores for OTFC at all time points. Global assessment scores also favoured OTFC”. (Zepetella, 2006)

End of dose failure: o Alter the around the clock medication to increase the dose or

shorten the dosing interval ( McCarberg, 2007)

Pharmacological treatment should be tailored to the type of BTP

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Ideal Breakthrough Medication

Slow Release

Medication

Ideal: Slow Release + Immediate ReleaseShort Acting Opioid(SAO)+Rapid Onset Opioid(ROO)

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Non-pharmacological methods:o Physical treatments

o Rubbing / massageo Heat applicationo Cold applicationo TENS

o Psychological treatments o Distraction techniqueso Relaxation techniques

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Treatment Plan

Conclusiono BTP Occurs in chronic pain in cancer or non cancer patients.

Prevalence 55: 85% of chronic pain patients.o The cause of pain due to tumor or tumor related treatment or associated

disease.o Subtypes of BTP :

o Spontaneous paino Incident paino End of dose failure

o The choice of therapy should be based on:o Subtype of BP.o Drug characteristics.o Patient risk.o Monitoring structure.

o Management: BTP because it is heterogynous; management must be individualised, multiprofessional and multimodal.

o Proper management (not science only but it is an ART) it means:o Adequate Assessment.o Rapid Reassessment.o Titrated Treatment.

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