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17 Articles in Volume 20, Issue #1
20/20 with Lynn Webster, MD
Correspondence: Opioid-Induced Hyperalgesia; Pain Care in Older Adults
Don’t Discount the Role of Diet for Chronic Pain Relief
Editorial: Why Haven’t There Been More Breakthrough Analgesics?
Gasping for Air: Sleep-Disordered Breathing and Chronic Opioids
How can botulinum toxin be used in chronic pain syndromes?
Inside the Potential of Peripheral Kappa Opioid Receptor Agonists
Neurodestructive Interventions for Cancer Pain
Obesity and Pain Care: Multifaceted Considerations for Treatment
Obesity and Rheumatoid Arthritis: What Clinicians Should Know
Sickle Cell Pain Crisis: Clinical Guidelines for the Use of Oxygen
The Complexity of Sickle Cell Pain: An Overview
The Perseverance Loop: The Psychology of Pain and Factors in Pain Perception
The Rapid Rise of Non-Opioid Pain Policies
Treating Pain by Overcoming Communication Barriers
Visual Artists Tackle What Pain Looks Like
Will 2020 Be the Year of Patient Education?

Neurodestructive Interventions for Cancer Pain

Chemical neurolysis, radiofrequency neurotomy, and cordotomy offer appropriate treatments for patients with localized, severe, medically intractable pain.
Pages 58-61

A Practical Application Note

Pain is one of the most common and debilitating components of cancer, with an estimated 50% prevalence among all patients with cancer, and rates as high as 90% in patients with stage IV disease.1,2 While adherence to the WHO analgesic ladder was initially linked to effective pain relief for the majority of these patients, newer data suggest as many as 20% of patients are left with unrelieved pain.3 The inefficacy of conventional analgesics for these patients has opened an opportunity for the increased use of interventional techniques to address cancer pain. In focal or localized pain syndromes, such interventions may provide prompt and durable pain relief with fewer systemic side effects. As cancer pain moves toward a more chronic management strategy, due both to increased life expectancy and cure rates, these interventions may also help to reduce reliance on systemic therapies.

Pain associated with cancer and cancer treatment is a prev- alent part of the cancer care and survivorship continuum. (Image: iStock)

Patient Selection

Appropriate patient selection is crucial when considering neurodestructive interventions, given the varying types, locations, and natures of cancer-
associated pain syndromes. Common selection factors include the following:

  • cancer type and tumor bulk location(s)
  • location and type of pain
  • clinical and imaging findings supportive of structural origin of pain
  • support system
  • psychological status.

Given the invasive nature of these procedures, as well as their side effect profile, appropriate candidates tend to be patients with localized pain syndromes that are severe and medically intractable. Specific to cordotomy, lesioning of the spinothalamic tract can result in paresthesias and dysesthesias on the affected side, although this may be viewed by the patient as an acceptable trade-off for relief of chronic, intractable pain.

Unlike systemic pain management options such as opioid medication or intrathecal therapy, neurodestructive approaches are localized to the sensory distribution of a nerve. In the case of chemical neurolysis or radiofrequency neurotomy, this approach restricts their use to pain syndromes in which the source of pain can be effectively captured with destruction of a single nerve territory. In contrast, cordotomy interrupts the transmission of pain signals along the spinothalamic tract, so it may provide pain relief on one entire side of a patient’s body.

Evaluation of the patient, encompassing clinical and imaging examination as well as consultation with the primary treatment team about planned interventions and prognosis, are central to the identification of neurodestructive targets. Depending on the implicated neural structure, a specific neurodestructive approach can be selected. Details on the indications for specific procedures are outlined below.

Overview of Neurodestructive Techniques

Chemical Neurolysis

Chemical neurolysis of primary afferents or first-order ganglia has been a mainstay of cancer pain therapy for decades. First described in 1926 with the use of phenol for nerve ablation, chemical neurolytics remain in use today.4 Phenol and ethanol act as concentration-dependent denaturants, with phenol demonstrating neurolytic effect at 3 to 12% concentration5 and ethanol at ranges from 50 to 100%.6 Effective minimum concentrations have not been established for either, although data exist demonstrating no difference in efficacy between 2% phenol and local anesthetic.7 Both phenol and ethanol exert their effect by denaturing axonal proteins, causing Sunderland third-degree peripheral nerve injury and Wallerian degeneration.8

As this process does not fully disrupt the neuron or surrounding Schwann cells, axonal regeneration occurs over time with consequent recurrence of pain. Data suggest the average duration of effect of chemical neurolysis is 3 to 6 months.9 Neurolysis may be repeated as needed.

Target Selection. Common targets for chemical neurolysis in cancer pain include the trigeminal nerves for head and neck cancers, splanchnic nerves for abdominal cancers, intercostal nerves for thoracic cancers, and the hypogastric plexus for lower abdominal and pelvic cancers. Additionally, case reporting exists demonstrating efficacy in brachial plexus lesioning for neuropathic pain stemming from local tumor invasion.10 The maximum total dose per session is generally limited to 1 gram, and dysesthesias are a common side effect, more often with ethanol than phenol.

Radiofrequency Neurotomy/Neuroablation

Radiofrequency neurotomy (RFN), also called radiofrequency ablation (RFA), was first described in 1975.11 It has been utilized to provide durable pain relief in the range of 6 to 12 months, through thermal neurolysis. This procedure uses percutaneously inserted probes with electrodes heated to a fixed temperature to deliver thermocoagulation to the target axon or cell body. The resultant scarring interferes with effective signal transmission, delivering pain relief.12 Pathology studies of ablated tissue demonstrate acute inflammation followed by fibrosis and scarring of the nerve tissue. As the procedure does not fully destroy the surrounding Schwann cells and supportive matrix, neuronal regeneration occurs over time with return of symptoms.

Although RFA may also be implemented in the direct lesioning of tumors for pain treatment as well, the scope of this paper focuses on lesioning of nerve ganglia.

Target Selection. Prior to undergoing radiofrequency interventions, patients will usually undergo a diagnostic block of the proposed target ganglion, which can help predict the success of a future RFN. The diagnostic block is done once with 1% or 2% lidocaine and 0.5% bupivacaine, with a positive response measured as 50% or greater reduction in numerical pain score over the first 6 to 12 hours post-procedure.11

Common targets for RFA mirror those selected for chemical ablation as noted above. A recent randomized trial demonstrated superior results with RFA of thoracic splanchnic nerves, versus chemical neurolysis.13 In this study, patients in the radiofrequency ablation arm demonstrated faster onset and longer duration of pain relief.

Traditional vs Pulsed RFN. Previously, it was believed that radiofrequency procedures were selective for smaller C- and Aδ-fibers transmitting pain signals, while larger-diameter motor neurons would be spared. Newer research, however, demonstrated indiscriminate scarring with traditional RFN.14 Pulsed ablation results in a lower net thermal load and area of effect, preserving a higher proportion of adjacent tissue while effecting comparable pain relief.12 This has been demonstrated in several studies for non-cancer indications, though more data in cancer populations is needed.

Complications. Complications from chemical neurolysis or radiofrequency neurotomy are analogous to those of any percutaneous procedures, such as bleeding or site infection, though these are rare. Note that patients with cancer are often immunocompromised, due to their oncologic treatments, and malnourished, owing to a variety of factors related to their cancer and treatment. In light of that, vigilance with surgical site preparation and dressing, as well as post-procedural monitoring, are crucial to reduce the risk of procedure-associated infection.

Additionally, patients may rarely experience dysesthesias or neuropathic pain in the involved territory as the neural structure undergoes degeneration, but this usually resolves in days to weeks following the procedure. Transient masseter weakness and corneal anesthesia are reported after gasserian ganglion RFN,15 given its supply of additional motor and sensory fibers to the face.

Cordotomy

For patients whose pain is refractory to pharmacologic or the above-described local interventional approaches, more durable pain relief can be achieved with ablative neurosurgical approaches. Careful lesioning of the spinothalamic tract (STT) may provide significant and long-lasting pain relief on one entire side of a patient’s body while sparing motor and proprioceptive tracts. Originally, this was done by open technique, with the neurosurgeon performing a hemilaminectomy and dividing the anterolateral quadrant.16

Minimally invasive percutaneous cordotomy is a newer approach to STT ablation using percutaneously inserted radiofrequency electrodes.17 The procedure is performed under fluoroscopic or more recently CT guidance without the need for laminectomy. Using an ablative technique similar to the previously described radiofrequency neurotomy, lesioning of the STT is achieved with thermocoagulation. Additionally, the percutaneous approach allows for performing a test lesion, which can be used to predict the success of the final procedure.

Target Selection. As pain fibers are first carried through the ipsilateral Lissauer’s tract for three to four levels before crossing to the contralateral STT, pain relief by STT ablation via cordotomy will generally begin three to four levels below and contralateral to the lesioned section. Additionally, as the STT also carries fibers for temperature and fine touch, patients will often experience dysesthesia, numbness, or phantom temperature sensation below the level of the lesion. For patients with a terminal diagnosis and intractable pain, this may be a reasonable concession. Given the decreased sensitivity to temperature, appropriate counseling should be provided on safety precautions to prevent burn injuries to the denervated side.

For these reasons, appropriate patients may include individuals with unilateral tumor-associated somatic pain below the C5 (shoulder) level. The pain must be malignant in origin, as studies show that non-malignant pain carries a high risk of recurrence after cordotomy.18 Even pain of reliably malignant origin may recur or present as central neuropathic pain below the level of lesioning, so the procedure is best suited for patients with a predicted lifespan of a few years or less.

Open cordotomy is achieved by hemi- or full laminectomy three to four levels above the symptomatic area to expose the spinal cord. The anterolateral quadrant is then identified and divided surgically. In contrast, percutaneous cordotomy is done at the C1-C2 level using a radiofrequency electrode that is advanced into the anterolateral quadrant under fluoroscopic or CT guidance. The electrode is heated to 80°C for 60 seconds to create the lesion and may be repeated once or twice to ensure complete lesioning. Post-operatively, the patient may be tested for absence of pinprick sensation in the target area.19

Complications. There is a small but significant risk of respiratory depression after cervical cordotomy,20,21 due to the presence of interneurons innervating the respiratory muscles just medial to the STT. Bilateral cervical cordotomy is contraindicated for this reason, and caution must be taken when considering cordotomy in patients on opioid therapy. Additional complications are similarly linked to the presence of other neurons around the STT, and include bladder dysfunction, temporary hemiparesis, ataxia, or loss of proprioception.22 Recurrence of pain symptoms after cordotomy is reported up to 1 year post-procedure.

Additional symptoms related to percutaneous procedures are similar to those noted above for chemical neurolysis and RFN, and special caution should be taken in appropriate skin preparation, surgical technique, and post-procedural vigilance for patients with cancer who may be immunocompromised or malnourished due to oncologic treatment.

Post-Procedural Care. As with all procedural interventions, appropriate anticipatory guidance and counseling are critical to ensuring patients are aware of the timeline of pain reduction and recurrence, as well as possible side effects or complications. Counseling should be provided on the previously noted complications and site care as well.

Conclusion

Pain associated with cancer and cancer treatment is a prevalent part of the cancer care and survivorship continuum. Chemical neurolysis, radiofrequency neurotomy, and cordotomy are mainstays in the treatment of cancer pain. Focal neurodestructive interventions like these can help provide durable and effective pain relief with fewer systemic side effects as compared to pharmacologic therapies. Appropriate patient selection is crucial, as is balancing of risks and benefits. However, for patients with pain intractable to conservative treatment modalities, or who may not be appropriate candidates for implantable therapies, these neurodestructive options can be considered for symptom palliation.

Last updated on: February 4, 2020
Continue Reading:
Managing Cancer Pain in an Era of Modern Oncology
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