Exploring the Efficacy and

Complications of Cordotomy in
Cancer Pain Relief
Introduction
Pain is a universally feared symptom in cancer patients, as well as one of the common
signs leading to the discovery of cancer. With reported prevalence of around 70% in
advanced, metastatic stage patients (van den Beuken-van et al,.. 2016), it forms a grave
challenge to both palliative care providers and clinical practitioner.

Severe pain from malignancy is often debilitating, and could lead to various harmful side-
effects such as sleep impairment (Chen et al,. 2018), fatigue (Matias et al,. 2019) and
emotional or psychological distress (Gagliano-Jucá et al,. 2018). Thus, the management of
pain has been a key part of cancer treatment and care.

Cancer Pain

In the case of cancer, both nociceptive and neuropathic pain were reported. The
nociceptive pain, while varying between different types of cancer, are most caused by
inflammation, tissue damage, structural compression, or Ischemia (Russo & Sundaramurthi
et al,., 2019). Nociceptive pains are generally categorized into two types: somatic and
visceral (table 1). The neuropathic pain, while refractory to opioids, is of lower prevalence
overall (Grond et al¸1996; Rayment et al,. 2013; Smith et al,. 2007). The two types of pain
can and do often co-exist, posing a greater threat to the wellbeing of cancer patients.

Classification Location Affected organ Localization

Somatic pain superficial Skin, bone, joints Well-localized, focal
Visceral pain Within body cavity Internal organs Poorly localized, diffuse
Table 1: Table presents the classification of nociceptive pain, their location, affected organs/structure,
and how well the patients can localize the pain in a pain evaluation.

Assessment tools for pain

Naturally, the quantification of pain is invaluable for the analysis of pain or pain reduction.
To this end, numerous pain scales and testing protocols were developed and used both
clinically and in research. These pain assessments can generally be divided into two types:
patient-reported or clinically tested.

Patient-reported questionnaires are the most common form of pain assessment tools due
to its convenience. Example of a simple questionnaire can be the Numeric Rating Scale
(NRS), which essentially ask the patients to rate their perceived pain from 0 (no pain) to 10
(worst pain imaginable). A more complex questionnaire that is commonly used is the Brief
Pain Inventory (BPI), which comes in a short or long form, asking a series of clinically
relevant questions such as maximum/minimum pain and interference of pain with daily
activities. While these questionnaires are a good indication of perceived pain, they can be
affected by factors such as emotions, fear of consequences (e.g: altered treatment) or even
cognitive impairment. Nevertheless, they prove immensely valuable in both palliative care
and clinical settings, serving as reliable tools to assess the life quality of patients
experiencing chronic pain (Tan et al,. 2004; Shi et al,. 2017).

Pain testing procedurals are physiological or psychophysical examinations performed

clinically or in laboratory by a certified professional. They generally offer higher consistency,
less bias and are better controlled. These tests come in a variety of forms, each measuring
different physiological parameters. For instance, inflammatory markers such as C-reactive
protein can be measured to determine overall inflammatory response, which is associated
with nociceptive pain (Gagliano-Jucá et al,. 2018). A commonly used test in cancer is the
Quantitative Sensory Testing (QST), which measures patient’s sensitivity to heat and
mechanical stimulus. It enables quantification of somatosensory sensitivity, and can be used
to assess the desensitization of patient’s nociception after treatments (Rolke et al,. 2005;
Scott et al,. 2012).

Cancer Pain Relief: Focusing on Cordotomy

In addressing the intricate and challenging situation of cancer pain, numerous therapeutic
modalities and interventions have been developed and explored, each having their own
strengths. The conventional opioid therapy under “WHO Pain Ladder” standard has been
proven effective in reducing nociceptive pain significantly in most patients (Carlson et al,.,
2016;WHO, 2018). The WHO Pain Ladder is a guideline for treating pain with minimum
adverse effect, achieved by progressively increasing dosage and strength of analgesics as the
pain progresses. However, a fraction of the patients still experiences refractory pain under
optimal opioids medication, together with the adverse effect caused by with analgesics
(Berger et al,., 2020; van den Beuken-van et al,., 2016). Thus, several other therapies have
been developed and employed, including neuromodulatory treatments such as morphine
pump, and interventional surgeries such as Cordotomy.

Cordotomy is a minimally invasive surgery that produces a lesion on one or both sides of
the spinothalamic tract --- the major afferent pathway in spinal cord that transmit
somatosensory signals to the brain. The disconnection of lateral spinothalamic tract at C1-C2
level severs the relay of nociceptive signals from somatic nociceptors to the thalamus, thus
alleviating somatic pain on the contralateral side. Cases of recent CT-guided cordotomy
reported an improvement on safety and effectiveness from earlier non CT-guided cordotomy
(Lahuerta et al,., 1994; Viswanathan et al,., 2019). As such, cordotomy is understood to be a
potentially complementary therapy in treating refractory cancer pain, and an overview of its
efficacy is vital for its integrated use in clinical and palliative settings.

Cordotomy Efficacy and Complications

Prospective and Retrospective Evidence of Efficacy

While minimally invasive, cordotomy still remains an irreversible ablative procedural,

hence it is far from being a first-line treatment and is only offered rarely. Among the
relatively limited clinical reports, a recent prospective clinical study by Viswanathan et al in
2019 has provided valuable insight to cordotomy’s effectiveness.

In this clinical study, a group of 16 patients with various pain location was randomized and
allocated to either receive cordotomy (n=7) or continue with comprehensive palliative care
(n=9). After 1 week, seven patients in the palliative care group opted to undergo cordotomy.
The results of the cordotomy group showed significant reduction of pain with different pain
assessment tools.
 85.7% of the patients had a 33% reduction in pain
intensity measured by NRS, with median pain
intensity reducing from 7 (6-10) to 1(0-6).
BPI was also recorded: Worst Pain score (WPS) and
Pain Interference score (PIS) both underwent
immediate and significant decrease post-surgery.
Monthly follow-ups at 1-6 months further suggested
a relatively maintained effect over time (Figure 1):
only three cases of pain resurgence were reported in
6 months, and they were still weaker and less
interfering than the original pain. On the contrary,
palliative patients only received insignificant Figure 1. Outcomes for cordotomy
decrease in both NPR (p=0.097) and BPI (p=0.2) after 7 patient, follow-ups at 1-6 months
confirmed a consistent reduction of WPS
days.
and PIS according to BPI. Figure adapted
from Viswanathan et al,. 2019.

Concurrently, QTS was used to examine the somatic sensitivity of patients pre and post-
surgery. Results reported immediate significant increases in the threshold for pinprick
sensation, sharpness detection and heat pain perception in the area of maximum pain post-
surgery (table 2). Which provided evidence for desensitisation of somatic nociception
following cordotomy.

Additionally, the median mean morphine equivalent daily dosage (MEDD) --- a parameter
that reflect on perceived pain and interference of patients --- also showed a significant
decrease post-operative week 1, from 234 to 90 (p=0.0027), forming a stark contrast with
the MEDD for palliative group, which remained at 210 post-operatively.

Pinprick at area of max. Sharpness on foot in Heat at area of max. pain in

pain in grams (min, max) grams (min, max) Celsius (min, max)
Median pre-op. 19.6 (8-128) 34 (12.6-128) 44.3 (37.2-49.7)
threshold
Median post-op. 64 (18.7-128) 96 (16-128) 47.8 (40.3 -52)
threshold
Δ p value 0.0027 0.003 0.0002
Table 2. Statistically significant outcomes of the QST on patients who underwent cordotomy (n=14)

To further validate and support the results from the said prospective study, a number of
retrospective analyses were also examined: an analysis based on UK national data in 2020 by
Poolman et al. have reported a comparable decrease of pain: NRS decreased from 6 to 2
(p<0.001, n=159) and from 9 to 3(p<0.001) for average pain and worst pain respectively in
patients underwent cordotomy. The consistency of its effect overtime post-operatively was
further supported by a study from Bain et al in 2013, where follow-ups at day 28 post-
operatively suggested maintained low pain level (NRS) in 45 patients.

The overall efficacy of cordotomy, as well as the consistency of its efficacy post-operatively
is supported by a number of primary researches (Bain et al,. 2013; Berger et al,. 2020; Crul
et al,. 2005; Viswanathan et al,. 2019; Lahuerta et al,. 1994), and a conclusion can be drawn
that it is effective in treating unilateral somatic sensory pain in advanced stage cancer
patients.

Clinical Complications

The complications associated with CT-guided cordotomy are shown to be mild. Most
complications were reported to be recoverable, including fatigue, motor weakness, urinary
detention, and dysesthesia, with recovery period from 1 to 2 weeks (Bain et al,. 2013; Higaki
et al,. 2015; Poolman et al., 2020; Viswanathan et al,. 2019;). Notably, a study from Higaki et
al in 2015 pointed out a significant reduction in clinical complications following CT-guided
cordotomy as opposed to the traditional fluoroscopic guided method.

New pain or increased pain are the most consistently reported persistent complications
post-surgery (Bain et al,. 2013; Higaki et al,. 2015). New pain is a pain occurring immediately
after bilateral cordotomy on the contralateral to the original pain. Increased pain refers to
the enhancement of existing pain contralateral to the original pain after unilateral
cordotomy.

New Pain and Increased Pain: A Purposed model

While these two pains are generally weaker than the original pain and can be managed by
analgesics better, the exact mechanism of its formation is relatively unexplored, and poorly
explained. Higaki et al in their study in 2015 purposed a novel mechanism explaining both
complications.

Abbreviations
ALC:
Anterolateral column
SPP:
subsidiary pathway
rFI/lFI:
reflected/local feedback
inhibition
FON/SON:
First/second order neuron
DHN
dorsal horn neuron

Figure 2. Diagrams showing the proposed mechanism of increased pain and new pain after unilateral
or bilateral cordotomy in patients with bilateral pain. A show the normal nociceptive pathway, where
a weaker stimuli “b” and stronger stimuli “a” are located on each side of the body, severity indicated
by the size of the spark. B demonstrate the pathway after unilateral cordotomy, the spinothalamic
tract contralateral to stimuli “a” is severed, and pain signal from a is unable to reach the thalamus,
thus alleviating pain on “a”. However, the SSP on the ipsilateral side is disinhibited and passes the
input from a to the contralateral DHNs corresponding to “b”, increasing perceived pain at b. C show
the pathway after bilateral cordotomy, where normal relay of both “a” and “b” are severed. The
bilaterally disinhibited SSP then pass the signal upwards, eventually converging on the most caudally
located DHNs. The converged signal from both “a” and “b” at the new DHN thus create a new
perceived pain “c”. Figure adapted from Higaki et al, 2015.

Higaki et al’s study suggests the involvement of a subsidiary pathway located in the dorsal
horns, which is constitutively inhibited by local or reflected feedback inhibition. When lesion
is made unilaterally at the spinothalamic tract, feedback inhibition for SSP on one side is
lifted, and it carry the noxious impulses from the ipsilateral side to the contralateral side
across the midline, thus increasing pain at the contralateral side. While in the case of
bilateral cordotomy, bilateral ablation of feedback inhibition promotes the SSP to pass
noxious impulses to the immediate cranial spinal level, and inducing a referred pain just
above the site of original pain (figure 2).

While the clinical observations from the study above (Higaki et al,. 2015) is consistent with
this purposed mechanism. Considering that this is a relatively new model, and that research
on new pain and increased pain mechanism are limited, empirical evidence supporting this
hypothesis is lacking. Nevertheless, it stands as the sole attempt to explain the mechanism
new or increased pain, and may in future contribute to their resolution.

Discussion
Current Limitation

While examining clinical studies on cordotomy, it is identified that most studies are
retrospective or observational in nature. Retrospective studies are lacking in that they do not
have a control group, and are thus unable to draw more definitive conclusions. They are
further disadvantaged when it comes to data collection, as clinical collection of data is less
well-controlled, and are limited in their form --- it is challenging to enact a series of relatively
complex experimental testing (such as QTS) universally. This is made more sophisticated
considering the number of patients undergoing cordotomy is already limited, thus collective
data from several hospitals, or in the case of Poolman et al’s research, the entire nation, is
needed for drawing a strong conclusion.
 Conclusion

In summary, multiple present studies have clearly supported the effectiveness of

cordotomy in treating cancer-induced pain. Associated clinical complications are also shown
to be acceptable. This review thus supports the role of cordotomy as a complementary
treatment in the arsenal of interventions against cancer pain. Conversely, it should be
stressed that prospective research with adequate sample size on cordotomy is relatively
lacking, and mirror pain and increased pain --- a potential complication of cordotomy --- is
still poorly understood.
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