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Back to Table of Contents Part III: Adjuvants, Adverse Effects, Barriers

Adjuvant Analgesics
Neuropathic Pain Management

• Management of Burning, Tingling Neuropathic Pain
• Management of Shooting, Stabbing Neuropathic Pain
• Management of Complex Neuropathic Pain
• Case Example

Bone Pain

• What is Bone Pain and What Causes It?
• Management of Bone Pain
• Case Example

Pain from Bowel Obstruction

• What is Pain from Bowel Obstruction and What Causes It?
• Management of Pain from Bowel Obstruction

Corticosteroids in Pain Management

Adjuvant Analgesics

• Adjuvant analgesics (or coanalgesics) are medications that, when added to primary analgesics, further improve pain control

• They may themselves also be primary analgesics (e.g., tricyclic antidepressant medications for postherpetic neuralgia)

• They can be added into the pain management plan at any step in the WHO ladder

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Neuropathic Pain Management

Management of Burning, Tingling Neuropathic Pain

• Neuropathic pain often requires an adjuvant analgesic in addition to an opioid to adequately manage the pain

• For patients who describe their neuropathic pain as "burning" or "tingling" with or without associated numbness, the first choice is usually:

• Tricyclic Antidepressant or
• Gabapentin

• The SSRIs (selective serotonin reuptake inhibitors):

• Have shown disappointing clinical efficacy as analgesics
• Are less effective as adjuvants to manage neuropathic pain than the tricyclic antidepressants

Amitryptiline - Advantages

• Amitriptyline is the most extensively studied of the tricyclic antidepressants


• In contrast to its antidepressant effects, low doses beginning at 10 to 25 mg orally at bedtime may be effective in only a few days


• The dose may be escalated every 4 to 7 days until pain relief or adverse effects intervene
• It may take high doses and a few weeks to control the pain

Amitryptiline - Adverse Effects

• Increased risk of toxicity at doses greater than 100 mg/24 hours
• Need to monitor plasma drug levels to watch for toxicity


• Prominent anticholinergic activity


• Risk of cardiac toxicity


• Sedating effect
• May be helpful to the patient who is also having difficulty sleeping
• Limits its use in many frail and elderly patients

Amitryptiline Alternatives

Desipramine

• Minimal anticholinergic or sedating adverse effects
• Dosing is the same as for amitriptyline
• Its adverse effect profile may make it the tricyclic of choice, particularly in the frail and seriously ill

Nortriptyline

• May also be effective in pain management
• Has less adverse effects than amitriptyline

Gabapentin for Burning Pain

• Gabapentin, a new anticonvulsant, appears to be quite effective as an adjuvant for all types of neuropathic pain


• Its site and mode of action are not clear


• Most clinicians:
• Begin at low doses (100 mg po q d to tid)
• Dose escalate every 1 to 2 days by 100 mg po tid to effect


• Usual effective dose 900–1800 mg/day
• Some patients require doses of more than 3600 mg/day


• Adverse effects appear to be minimal


• While some patients experience drowsiness with dose escalation, tolerance appears to develop within a few days if the dose remains stable

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Managment of Shooting, Stabbing Neuropathic Pain

• For episodic shooting, stabbing, electrical pain, the anticonvulsants gabapentin, carbamazepine, and valproic acid are the most widely used adjuvant medications

• Gabapentin

• Start at 100 mg po q d to tid
• Increase by 100 mg every 1 to 2 days to effect

• Carbamazepine

• Start at 100 mg po bid to tid
• Increase by 100 to 200 mg every 5 to 7 days to effect

• Valproic acid

• Start at 250 mg po q hs
• Increase by 250 mg every 7 days in divided doses to effect

• As doses escalate, monitoring carbamazepine or valproic acid plasma levels may help to predict increasing risk of adverse effects

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Management of Complex Neuropathic Pain

• As nerve damage evolves, the resulting pain can become mixed and very complex to manage

• Nerve damage and chronic pain can lead to:

• Primary neuronal death
• Loss of myelin sheath
• Central sensitization
• Changes in the effective neurotransmitters and neuroreceptors
• Sensory neuronal death

• Over time:

• Opioid receptors may be down-regulated, making opioids much less effective


• NMDA (N-methyl d-aspartate) receptors may become much more important as glutamate becomes a significant neurotransmitter

• While opioids may continue to be partially effective, adjuvant analgesic medications may be required, including:

• Oral antiarrhythmics
• Alpha-2 adrenergic agonists
• NMDA receptor antagonists
• Corticosteroids

• Consider consulting with a pain management expert early to minimize patient suffering and the risk of further damage from pain itself

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Problem Solving: Neuropathic Pain Case Example (Case 7)

John is a 40-year-old accountant with AIDS (acquired immunodeficiency syndrome). His most recent T4 count is 34. He has noted a burning pain in his hands and feet for the past 2 years. It initially appeared after he began zalcitabine (ddC) in addition to zidovudine (AZT) and resolved when the ddC was discontinued. However, over the past 6 months the pain has returned. It is severe, keeps him awake at night, and is associated with numbness of his feet. He has trouble buttoning his shirt. How would you manage John’s pain?

Click here for the answer

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Bone Pain

What is Bone Pain and What Causes It?

• Bone pain is a frequently occurring problem that may be:

• Constant at rest
• Much worse with movement

• It is frequently the result of mechanical changes due to metastases, compression or pathologic fracture, etc.

• Prostaglandins produced by concurrent inflammation and/or metastases may increase bone pain severity

• Cord compression should always be considered when there is significant back pain in the patient with metastatic cancer

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Management of Bone Pain

• Opioids remain the mainstay of bone pain management

• Significant additional relief may be provided by:

• NSAIDs
• corticosteroids
• bisphosphonates (e.g., alendronate, pamidronate)
• calcitonin
• radiopharmaceuticals (e.g., strontium, samarium)
• external beam radiation

• When definitive orthopedic interventions are not possible, external mechanical supports (splints, braces, etc) may provide relief from movement-related pain

• Consultation with a pain management expert may be necessary to achieve adequate relief

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Problem Solving: Bone Pain Case Example (Case 8)

Sarah is a 73-year-old attorney who has breast cancer with metastases to bone. She was treated with three cycles of AC (Adriamycin, cyclophosphamide) without response. Pain persists, even after 2 months of tamoxifen. How would you manage Sarah’s pain?

Click here for the answer

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Pain From Bowel Obstruction

What is Pain from Bowel Obstruction and What Causes It?

• Mechanical bowel obstruction can lead to significant abdominal pain as the bowel wall is stretched or inflamed

• May be caused by:

• Internal blockage from constipation
• External compression by tumor or scars

• The pain is frequently described as constant, sharp, and cramping

• It may be associated with other unpleasant symptoms including:

• Bloating
• Distention
• Gas
• Nausea/vomiting

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Management of Pain from Bowel Obstruction

• In some cases, definitive intervention may be possible, such as:

• Relief of constipation (see Module 10: Common Physical Symptoms)
• Surgical removal or bypass of external blockages

• While some people will find opioids sufficient to manage this pain, many will need adjuvant medications to effectively relieve their discomfort. Consider using adjuvants such as:

• Corticosteroids
• NSAIDs

• Anticholinergic medications (e.g., scopolamine) or octreotide will reduce the volume of fluid entering the intestine, thus relieving the bowel wall stretch and the pain

• Early consultation with a pain management expert can reduce patient distress even when awaiting definitive intervention

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