Background: For some patients with serious illness, usual analgesic therapies do not achieve adequate pain relief or are associated with intolerable side effects (1). For example, nearly 10% of patients with advanced cancer develop intractable pain despite standard analgesic therapies (2). Interventional/ neuromodulating therapies such as intrathecal (IT) pain pumps (see Fast Fact #98), indwelling epidural catheters (see Fast Fact #85), and sympathetic nerve blocks (see Fast Fact #97) all have a role for select patients with refractory pain. Yet, some may have too short a life expectancy (less than 12 months), are too cachectic to tolerate an implant, find that managing a device would be too burdensome, or have pain that is too widespread and/or at a high-level distribution to make neuromodulating therapies feasible. Neuroablative analgesic procedures utilize surgical or non-surgical strategies to disrupt targeted anatomic locations along the pain signaling pathways (3). They may be considered if an experienced clinician is available (3). In this Fast Fact we will highlight common neuroablative procedures for refractory pain. Of note, few high-quality clinical trials have evaluated these procedures; supporting evidence is based primarily on small studies, case reports, and expert opinion for cancer-related pain (4).

Cingulotomy: For decades, palliative cingulotomy has been performed for refractory pain and is a relatively low-risk procedure that ablates an anatomic region within the medial aspect of the cerebral hemisphere called the anterior cingulate cortex. This region is felt to modulate attention or emotional reaction to pain (3,5). The standard surgical procedure is performed by neurosurgeons under local anesthesia, usually requiring a brief inpatient stay of 1-4 days (2,6,7). Non-surgical cingulotomies have been described utilizing radiation oncologists to target the cingulate cortex via radiosurgery (SRS) (8). Availability and cost varies widely and is institution-dependent (9).

Evidence: Two systematic reviews noted immediate and significant reductions in pain and opioid dosage in 32-83% of patients (4,5). Most exhibited adequate pain relief 3 months post-op (2,4,5,7). A non-controlled study of 13 patients with refractory pain from cancer and an average preoperative Visual Analog Scale (VAS) score of 9 reported a median VAS score reduction of 5 points as well as significant improvements in Karnofsky Performance Status (KPS) scores (10).

Patient selection: widespread pain, a life expectancy < 12 months, and unlikely to benefit from other neuromodulator-based interventions.

Adverse effects: headache, nausea, vomiting, confusion, urinary incontinence, and gait disorders have been reported. Serious adverse events are rare and include post-operative spasticity, hemiparesis, bleeding, seizures, decreased memory, and personality changes such as apathy and decreased spontaneity (3,7,11). Most patients do not show significant cognitive changes (7).

Cordotomy: This procedure targets nociceptive pathways in the anterolateral column of the spinal cord, specifically the spinothalamic pathway. By targeting this anatomic site, fine touch and proprioception should be preserved while the transmission of pain and temperature perception is blocked on the contralateral side of the surgical lesion (12). Neurosurgeons can utilize a variety of techniques depending on the site of pain (open, endoscopic, trans-discal, percutaneous/image-guided) using radiofrequency lesioning. It can be an inpatient or outpatient procedure (13). Availability and cost ($10,000-20,000) of each procedure is institution-dependent (14).

Evidence: like cingulotomy, pain relief is often rapid and may occur in up to 80% of patients (12). Improvements in KPS scores have been noted (15).

Patient selection: cordotomy is best for patients with nociceptive pain that is localized, unilateral, and below the C4-C5 dermatome (2). Since analgesia rarely lasts more than 2 years, this procedure is usually reserved for patients with a shorter prognosis (16).

Adverse effects: ataxia, paresis, sympathetic dysfunction, bladder dysfunction, acquired sleep apnea, or Horner syndrome have been described, primarily due to unintentional ablation of the nearby spinal cord (12). Some patients may develop “mirror” post-procedure pain on the contralateral side of the initial site of pain, which is an unmasking of pre-existing pain that becomes more perceptible after the previously dominant pain subsides (12).

Myelotomy: Myelotomy is less commonly performed compared with cingulotomy and cordotomy. With this procedure, neurosurgeons target one of two locations. For a commissural myelotomy, the spinothalamic tract fibers are sectioned as they cross at the anterior commissure of the spinal cord to target bilateral visceral midline pain (17). A punctate midline myelotomy targets the dorsal column and to treat visceral type pain (17). Studies suggest approximately 90% of patients who undergo myelotomy achieve early pain relief, but pain tends to recur. Bladder, bowel, and sexual dysfunction are common, so it usually is reserved for patients with pre-existing bowel, bladder, or sexual dysfunction (17). It can be done as an inpatient or outpatient; availability is varied and cost ranges from $50,000-100,000 (18).

Mesencephalotomy: This procedure, also performed by neurosurgeons usually via a stereotactic approach, targets pain pathways within the midbrain and is considered for patients with refractory cancer pain located in an anatomic region too high for other interventions (e.g., head or neck) (16). While the use of mesencephalotomies has significantly diminished over the past few decades, it still may have a limited role for inpatients with unilateral pain syndromes above the C4 level. The procedure’s cost is $10,000-30,000 and is institution-dependent (9).

Limitations: Even though guidelines for neuroablative procedures in cancer pain have been developed by the American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) (4), several relevant factors contribute to their relative underutilization for refractory cancer pain including the ignominious history of psychosurgery, aversion to neurosurgical lesioning procedures, concern for adverse effects, hospice enrollment barriers, prognostic uncertainty, and the relative paucity of trained surgeons able and willing to perform these procedures (3,19).

References:

1. Berger A, Tellem R, Arad M, Hochberg U, Gonen T, Strauss I. Neurosurgical interventions for intractable oncological pain. Harefuah. 2018 Feb;157(2):108-111. Hebrew. PMID: 29484867

2. Strauss I, Berger A, Ben Moshe S, et al. Double Anterior Stereotactic Cingulotomy for Intractable Oncological Pain. Stereotact Funct Neurosurg. 2017;95(6):400-408. doi:10.1159/000484613

3. Sagher O, Levin E, Pilitsis J. Pain Neurosurgery: Cingulotomy for Intractable Pain. Oxford University Press. 2019. Pgs 141-148.

4. Raslan AM, Ben-Haim S, Falowski SM, et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Neuroablative Procedures for Patients With Cancer Pain. Neurosurgery. 2021;88(3):437-442. doi:10.1093/neuros/nyaa527

5. Sharim J, Pouratian N. Anterior Cingulotomy for the Treatment of Chronic Intractable Pain: A Systematic Review. Pain Physician. 2016;19(8):537-550

6. Patel NV, Agarwal N, Mammis A, Danish SF. Frameless stereotactic magnetic resonance imaging-guided laser interstitial thermal therapy to perform bilateral anterior cingulotomy for intractable pain: feasibility, technical aspects, and initial experience in 3 patients. Oper Neurosurg (Hagerstown). 2015;11 Suppl 2:17-25. doi:10.1227/NEU.0000000000000581

7. Viswanathan A, Harsh V, Pereira EA, Aziz TZ. Cingulotomy for medically refractory cancer pain. Neurosurg Focus. 2013;35(3):E1. doi:10.3171/2013.6.FOCUS13236

8. American Association of Neurological Surgeons. Stereotactic Radiosurgery. Website. Accessed February 17, 2021. https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Stereotactic-Radiosurgery

9. Kumar KK, Bhati MT, Ravikumar VK, Ghanouni P, Stein SC, Halpern CH. MR-Guided Focused Ultrasound Versus Radiofrequency Capsulotomy for Treatment-Refractory Obsessive-Compulsive Disorder: A Cost-Effectiveness Threshold Analysis. Front Neurosci. 2019;13:66. Published 2019 Feb 7. doi:10.3389/fnins.2019.00066

10. Strauss I, Berger A, Ben Moshe S, Arad M, Hochberg U, Gonen T, Tellem R. Double Anterior Stereotactic Cingulotomy for Intractable Oncological Pain. Stereotact Funct Neurosurg. 2017;95(6):400-408. doi: 10.1159/000484613. Epub 2018 Jan 10.

11. Cosgrove GR, Rauch SL. Stereotactic cingulotomy. Neurosurg Clin N Am. 2003;14:225-235

12. Javed S, Viswanathan A, Abdi S. Cordotomy for Intractable Cancer Pain: A Narrative Review. Pain Physician. 2020;23(3):283-292

13. Tandon N and Slavin K. Epilepsy, Functional, and Pain Neurosurgery. Goodman’s Neurosurgery Oral Board Review 2nd Edition. Oxford University Press. 2020. Pgs 139-160

14. Aljuboori Z, Burke W, Meyer K, Williams B. Cost analysis of cordotomy and intrathecal pain pump placement for refractory cancer pain. Surg Neurol Int. 2020;11:72. Published 2020 Apr 18. doi:10.25259/SNI_15_2020

15. Kanpolat Y, Ugur HC, Ayten M, Elhan AH. Computed tomography-guided percutaneous cordotomy for intractable pain in malignancy. Neurosurgery. 2009;64(3 Suppl):ons187-ons194. doi:10.1227/01.NEU.0000335645.67282.03

16. Giller CA. The Neurosurgical Treatment of Pain. Arch Neurol. 2003;60(11):1537–1540. doi:10.1001/archneur.60.11.1537

17. Sather MD, Follett KA. Chapter 19 – Neurosurgical Management of Pain. Editor(s): Honorio T. Benzon, James P. Rathmell, Christopher L. Wu, Dennis C. Turk, Charles E. Argoff, Raj’s Practical Management of Pain (Fourth Edition). Mosby 2008. Pages 401-411. ISBN 9780323041843. https://doi.org/10.1016/B978-032304184-3.50022-4

18. Aljuboori Z, Meyer K, Sharma M, Ball T, Nauta H. Cost comparison among punctate midline myelotomy, intrathecal pain pump, and spinal cord epidural stimulator. Surg Neurol Int. 2020;11:25. Published 2020 Feb 18. doi:10.25259/SNI_16_2020

19. Berger A, Hochberg U, Zegerman A, Tellem R, Strauss I. Neurosurgical ablative procedures for intractable cancer pain [published online ahead of print, 2019 May 10]. J Neurosurg. 2019;1-8. doi:10.3171/2019.2.JNS18315

Author Affiliations: Veterans Affairs Medical Center and the Vanderbilt University Medical Center; Nashville TN.

Conflicts of Interest: None to report

Version History: first electronically published in April 2021, originally edited by Sean Marks MD