Cancer Pain Management

-Beyond WHO Ladder

Prevalence of cancer pain:

Pain is one of the most feared and major complain by cancer patients, particularly by those who are suffering from advanced cancer. Recent studies on the prevalence of pain in cancer patients show figures that vary from 24% to 60% in patients on active anticancer treatment or early cancer (1-4)and 62%–86% in patients with advanced cancer (5-10). Many of the cancer patients are really afraid of pain (11) than impending death.

Types of cancer pain:

In general pain may be of two types. It may be a warning signal from damaged tissue, or it may be due to dysfunction of nerves. In phantom limb pain a person is feeling pain from the limb, which is already amputed. Here the person is feeling pain because the nerves which was taking signals from that limb is till there in brain and spine and are producing abnormal pain signals that is felt as pain coming from that limb which is no longer there. Here pain is not due to tissue damage as there is no question of any tissue in the amputed limb. This type of pain is called neuropathic pain and is due to dysfunction of nerve (anatomical or physiological or both) and there are many such examples. In cancer nearly 30% patients suffer from such kind of neuropathic pain. The other type of pain is due to tissue damage called nociceptive pain.

Treatment of cancer pain with WHO Ladder:

World Health Organisation (WHO) introduced a pain ladder (12) in 1986 that has been accepted worldwide. Combined with appropriate dosage guidelines, it should be able to provide tools for adequate pain relief in 70%–90% of the patients (13–18).

Cancer Pain Management-Beyond WHO Ladder

Prevalence of cancer pain:

Pain is one of the most feared and major complain by cancer patients, particularly by those who are suffering from advanced cancer. Recent studies on the prevalence of pain in cancer patients show figures that vary from 24% to 60% in patients on active anticancer treatment or early cancer (1-4) and 62%–86% in patients with advanced cancer (5-10). Many of the cancer patients are really afraid of pain (11) than impending death.

Types of cancer pain:

In general pain may be of two types. It may be a warning signal from damaged tissue, or it may be due to dysfunction of nerves. In phantom limb pain a person is feeling pain from the limb, which is already amputed. Here the person is feeling pain because the nerves which was taking signals from that limb is till there in brain and spine and are producing abnormal pain signals that is felt as pain coming from that limb which is no longer there. Here pain is not due to tissue damage as there is no question of any tissue in the amputed limb. This type of pain is called neuropathic pain and is due to dysfunction of nerve (anatomical or physiological or both) and there are many such examples. In cancer nearly 30% patients suffer from such kind of neuropathic pain. The other type of pain is due to tissue damage called nociceptive pain.

Treatment of cancer pain with WHO Ladder:

World Health Organisation (WHO) introduced a pain ladder (12) in 1986 that has been accepted worldwide. Combined with appropriate dosage guidelines, it should be able to provide tools for adequate pain relief in 70%–90% of the patients (13–18).

Under-treatment of cancer pain:

There are several pain management indices (PMI) to assess the adequacy of pain control in cancer patients. (19) With these indices under-treatment is well documented and it can involve up to 40% of patients (20) even in centers with availability of opioids (21).

With the above data it is clear that under-treatment of cancer pain is very common and it may involve upto 40% of patients. It is also noted that even with following WHO ladder only 70% patients are getting adequate pain relief. (22)

Barriers in cancer pain management:

Several factors are attributed for inadequate pain relief like:

  1. Inadequate use of opioids.

Several barriers are identified like system barrier, physician barrier, and patient barrier etc. (23)

  1. System barriers are represented by low priority given to cancer pain treatment and by legal and regulatory obstacles to the use of opioids for cancer pain.
  2. Physician barriers to correct cancer pain management consist of the following:
  1. Use of a ‘disease-based’ rather than a ‘symptom-based’ model of care;
  2. Lack of physician education and failure to follow existing guidelines;
  3. Lack of priority given to symptom management;
  4. Analgesia level on the basis of prognosis rather than severity of pain; fear of patient addiction and analgesic tolerance;
  5. Poor assessment of pain and lack of proactive questioning about the symptom;
  6. Insufficient experience of pain management (poor knowledge of opioid pharmacology, conversion, equianalgesia, rotation, doses, and ratio for breakthrough pain medicines);
  7. Failure to use adjuvants; concern about and failure to treat opioid side-effects;
  8. Failure to document information on medicines used, dosages given, timing, breakthrough pain, and laxatives administered; and
  9. Failure to follow-up.
  1. Patient barriers have been identified as follows:
  1. Reluctance to report pain because of the conviction that health professionals must not be distracted from dealing with the main problem, i.e. the tumor, that pain is innately related to the cancer and as such cannot be eliminated, and that the acknowledgement of a higher level of pain indicates awareness of disease progression;
  2. Fear of not being considered a ‘good patient’;
  3. Reluctance in taking pain medications due to the well-known ‘myths about opioids’, represented by fear of addiction and/or of being thought of as an addict, fear of analgesic tolerance, and fear of side-effects. All these factors culminate in a ‘willingness to put up with pain’ and in a determination to take as few medications as possible, prolonging the ‘use as needed’ strategy and refusing an ‘around the clock’ type of administration
  4. Inadequate assessment of pain.
    1. In a 1997 randomized clinical trial, Trowbridge et al. (24) found that standardized painassessment alone improved cancer pain management and reduced patient-reportedpain severity.
  5. Lack of institutional protocol for cancer pain management.
    1. Du Pen and colleagues (25) found that the institutional use of a simple protocol for cancer pain management reduced pain severity.
  6. Criticism of WHO ladder.
    1. Treatment is based on severity and not on physio-pathological mechanisms of the pain itself. (23)
    2. Interventional pain management procedures also were not included in WHO ladder. To overcome this drawback and failure to obtain acceptable pain or symptom relief prompted the inclusion of a fourth step to the WHO analgesic ladder, which includes interventional approaches. (26, 27) So, in addition to the original three-step WHO ladder, inclusion of interventional pain management procedures as fourth step has been well accepted in many centers.

Modalities of Cancer Pain Management:

                Cancer pain has been described as ‘total pain’ presenting physical, psychological, social, and spiritual components, and can thus be defined as a ‘bio-psychosocial experience’. It is very difficult to identify the specific ‘percentage’ of each of these components for a given value in a numerical scale of pain assessment although it has been reported that emotional and cognitive components seem to be proportionally more important in cancer pain than in non-cancer pain. Ascancer pain is a multi-factorial experience and is present together with numerous other symptoms,pain management within the context of palliative care plays an important role in the systematiccontrol of symptoms (23).

                Keeping all these in mind modalities of cancer pain management may be classified as follows:

  1. Pharmacological therapy
    1. Opioids
      1. Weak opioids e.g. Codeine, Tramadol etc.
      2. Strong Opioids e.g. Morphine, Methadone etc.
    2. Non-opioids
      1. Paracetamol
      2. NSAIDs e.g. Ibuprofen, Diclofenac etc.
    3. Adjutants and others
      1. Anticonvulsants e.g. Pregabalin, Carbamazepine etc.
      2. Antidepressants e.g. TCA etc.
      3. Bisphosphonates e.g. PamidronateIbandronateetc.
      4. Steroids e.g. Betamethasone etc.
      5. Sympatholytics e.g. Clonidine etc.
  2. Psychological interventions
    1. Cognitive Behavioral Therapy
    2. Coping techniques etc.
  3. Interventional Pain Management procedures
  4. Alternative therapy and others
    1. Homeopathy
    2. Acupuncture
    3. Music therapy etc.

Interventional Pain Management:

The use of neurolytic substances has been used for many decades but has found a niche in the treatment of pain related to abdominal and pelvic cancers. Simple, percutaneous injections of alcohol or phenol can provide much needed pain relief for patients with pancreatic, colon, or gynecologic cancers. The percutaneous placement of catheters for the chronic infusion of spinal analgesics can provide pain relief for virtually any part of the body. Internal or external infusion pumps can be well managed at home, improving quality of life. The physician treating the pain should be aware of these and other interventional pain management techniques to provide alternative therapies to patients with refractory cancer pain. (28)

There are a variety of techniques used by interventional pain physicians, which may be grossly divided into modalities affecting the spinal canal (e.g., intrathecal or epidural space), called neuraxial techniques and those that target individual nerves or nerve bundles, termed neurolytic techniques. (29)

It has been proved undoubtedly in recent times that interventional pain management is a very important component of pain management services for cancer pain, particularly when non-invasive pharmacotherapy fails to give adequate pain relief. (28-32) But, can it be administered without a trial of WHO analgesic protocol?  There are debates, controversies and differences in opinion. Some recent publications are proving that in some situations like upper abdominal malignancies interventional pain management is better in terms of quality of life and amount of pain relief. (33)

These situations where interventions might be administered at first going beyond WHO ladder may be summarized as follows:

  1. Well-localized pain.
  1. Nociceptive pain.
  1. No distant metastasis.
  1. Adequate survival possibility in months.
  1. Good pain relief with diagnostic local anaesthetic block.
  1. Non-availability of morphine.
  1. Certain types of malignancies like pancreatic cancer.

If these criterions are fulfilled one should think beyond WHO ladder and interventional pain management procedures may be the better alternative to opioids.

Classification of Interventional Pain Management procedures in cancer:

  1. Neurolytic block (Neurolysis)
    • Peripheral nerve block
    • Sympathetic nerve block
  2. Central (neuroaxial) nerve block

Neurolysis in Interventional Pain Management:

It is a procedure by which nerve fibre carrying nociception (pain sensation) is irreversibly destroyed to obtain permanent pain relief.

Methods of neurolysis:

  1. Using neurolytic agents:

Advantages of neurolysis:

  1. Longer duration of pain relief.
  2. Instruments and medicines are inexpensive
  3. Repeated visits to pain clinic or hospital is not required.
  4. Prolonged hospital stay is not required.
  5. Patients can remain at home pain free even where medical help is scarce.

Disadvantages of neurolysis:

  1. Blocks are occasionally unpredictable
  2. Motor loss, loss of control bladder & bowel may occur in 5% of cases
  3. Blocks may have to be repeated 8 to 12 weeks intervals
  4. Failure to obtain pain relief in 30%
  5. Preferably patients to be kept in hospital for 1/2 days

Diagnostic local anaesthetic block:

Diagnostic local anaesthetic block should be performed before neurolytic block.

n Distinguishes pain of somatic, sympathetic or of psychological origin.

n Have a predictive value of subsequent neurolytic block.

n Should always be done before neurolytic blocks

n Should be done on subsequent day

Specific interventional pain management procedures in cancer

1. Peripheral nerve block (for head & neck pain):

n Trigeminal nerve at Gasserian ganglion  or at its branches for facial pain.

n Glossopharyngeal and/or vagus nerve block in case of pain from base of tongue, pharynx, throat.

n Para-vertebral block of 2nd or 3rd cervical nerve root can be done in pain in angle of the jaw or neck.

n Phrenic nerve block for intractable hiccup when conservative measure has failed.

2. Peripheral nerve block (for chest & abdominal wall pain):

n Intercostal nerve block or thoracic/lumber paravertebral nerve block can be done in pain of chest and abdominal wall pain or from pleura/peritoneum.

3. Peripheral nerve block (for upper and lower extremity):

n Brachial plexus and its branch blocked for pain of upper extremity.

n Nerves of lower extremity or root block can be done for pain of lower extremity .

Problems of peripheral neurolysis

n Some degree motor loss and numbness is common with chemical neurolysis. So it should only be done when patient is ready to accept these in exchange of pain.

n Pulsed radio-frequency is a better choice to avoid motor/sensory loss.

n Local anaesthetic block should be done before neurolysis to assess the benefits of neurolysis.

n Precise localization of the nerve should be done with the help of nerve stimulator and imaging.

Sympathetic nerve block

n Considered in visceral pain and in dysesthetic neuropathic pain (causalgia) of the limbs.

n Not associated with sensory or motor loss.

n Long lasting benefit than somatic nerve block

<>n Can be done with LA & depo-steroid also.

Stellate ganglion block

n Sympathetically mediated pain of face, neck and upper extremity.

n Examples: post-mastectomy pain and edema of hand; carcinoma of larynx, pharynx, base of tongue.

n May done with alcohol, phenol or repeated block with LA & steroid.

Coeliac plexus block

n Relieves pain from malignancies of foregut and its derivatives i.e. stomach, liver (primary & secondary), pancreas, gall bladder etc.

n Though less effective may be tried in other abdominal malignancies.

Superior hypogastric nerve block

n Effective in the treatment of pain due malignancies of lower abdomen and pelvis.

n Examples: carcinoma of vagina, cervix, uterus, prostate, U. bladder, rectum, perineum and vulva.

Ganglion Impar block

n Relatively easier technique.

n Effectively relieves pain of carcinoma of perineum, vulva, and anus.

Lumber sympathetic block

n Sympathetically mediated pain and causalgia of lower extremity.

Neuroaxial block

n Intrathecal or subarachnoid block using phenol or alcohol does not require any radiologic guidance and can be done as a day care procedure.

n Epidural phenol neurolysis can also be performed depending on the area of pain.

Problems of neuroaxial block:

n Loss of other somatic nerve leading to muscle weakness and numbness.

n Loss of bowel and bladder control.

n Failure to obtain pain relief.

n Repetition of block within three month.

n Complications in judicially administered block is less than 5%.

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