Pain Medicine, 2023, 24, 768–774

https://doi.org/10.1093/pm/pnad022
Advance access publication 21 February 2023
Original Research Article

Chemical neurolysis of the genicular nerves for chronic

refractory knee pain: an observational cohort study
Wassi Shaikh, MD,1 Scott Miller, MD,2 Zachary L. McCormick , MD,2 Prachi Milan Patel, MD,1

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Masaru Teramoto, PhD, MPH, PStatV,2 David R. Walega, MD, MSCI1,*
R

1
Department of Anesthesiology, Northwestern Feinberg School of Medicine, Chicago, IL 60611, United States
2
Department of Physical Medicine and Rehabilitation, University of Utah School of Medicine, Salt Lake City, UT 84108, United States
*Corresponding author: Department of Anesthesiology, Northwestern Feinberg School of Medicine, 251 E. Huron St., F5-704, Chicago, IL 60611, USA.
Email: d-walega@northwestern.edu

Abstract
Objective: Evaluate outcomes of genicular nerve chemical neurolysis (GChN) in a real-world population with chronic knee pain.
Design: Restrospective, observational cohort study.
Setting: Tertiary academic medical center.
Subjects: Consecutive patients who had undergone GChN 3 months prior.
Methods: Standardized surveys were collected by telephone and included the numerical rating scale, opioid analgesic use, and Patient Global
Impression of Change. Age, sex, body mass index, duration of pain, history of arthroplasty, lack of effect from previous radiofrequency ablation,
percentage relief from a prognostic block, and volume of phenol used at each injection site were extracted from charts. Descriptive statistics
were calculated, and logistic regression analyses were performed to identify factors influencing treatment outcome.
Results: At the time of follow-up after GChN (mean 6 SD: 9.9 6 6.1 months), 43.5% (95% CI ¼ 33.5–54.1) of participants reported 50% sus-
tained pain reduction. On the Patient Global Impression of Change assessment, 45.9% (95% CI ¼ 35.5–56.7) of participants reported themselves
to be “very much improved” or “much improved.” Of 40 participants taking opioids at baseline, 11 (27.5%; 95% CI ¼ 14.6–43.9) ceased use. Of
participants with a native knee treated, 46.3% reported 50% pain reduction, whereas of participants with an arthroplasty in the treated knee,
33.3% reported this threshold of pain reduction (P ¼ .326). Logistic regression analyses did not reveal associations between treatment success
and any of the factors that we evaluated.
Conclusions: GChN could provide a robust and durable treatment effect in a subset of individuals with chronic knee pain with complicating fac-
tors traditionally associated with poor treatment outcomes, such as those with pain refractory to radiofrequency ablation or those who have
undergone arthroplasty.
Keywords: knee; osteoarthritis; total knee replacement; phenol

Introduction of skin burns, soft tissue injury, hemarthrosis, and septic

Chronic knee pain from osteoarthritis is a problem with an
increasing prevalence in the aging and obese populations.1
Topical and oral analgesic medications, physical therapy,
intra-articular injections, and viscosupplementation are often
used in this population2,3 but with variable success and often
waning pain relief over time as the condition progresses.
Patients who fail medical or injection-based therapy often
undergo total knee arthroplasty (TKA).4 However, there are
significant comorbidities associated with TKA, and 10%–
34% of patients suffer with chronic knee pain after this sur-
gery.5,6 Furthermore, a subset of patients are unable to
undergo TKA because of medical comorbidities.
Image-guided genicular nerve radiofrequency ablation
(GRFA) has been shown to be clinically efficacious in improv-
ing knee pain and function by partially disrupting nociception
from the painful knee.7,8 In a recent systematic review of 33
studies of moderate to high methodological quality (aggregate
of 1512 patients), 65.5% of treated patients reported greater
than 50% reduction in knee pain, as compared with 19.3%
of controls.8 Functional outcomes and patient satisfaction
were also shown to improve significantly. Although rare cases
arthritis events have been reported, GRFA is generally consid-
ered safe.9–13
Despite the favorable safety profile and relative clinical
effectiveness of GRFA in clinical trials, one to two thirds of
patients demonstrate a lack of clinically meaningful pain
relief, depending on the specific knee pain condition, associ-
ated demographic and clinical factors of the study population,
and the GRFA lesioning protocol.14–16 In addition, high pro-
cedure and equipment costs, procedure duration, logistical
challenges with implantable cardiac devices, and procedure-
related pain necessitating conscious sedation make GRFA an
imperfect pain management tool.
Previously, we have described chemical neurolysis as a
method of partial knee joint denervation with specific advan-
tages compared with GRFA.19 Chemical neurolytic agents
generally act by precipitation of cellular proteins and lipids,
which causes degradation of the myelin sheath, axonal
edema, and consequently axonal degeneration over the course
of days.20,21 The clinical effect of neurolysis might not be evi-
dent until 3 to 7 days after the procedure. Both alcohol and
phenol have been used for this purpose, and both are

Received: 13 January 2023. Revised: 10 February 2023. Accepted: 17 February 2023

C The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved.
V
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Pain Medicine, 2023, Vol. 24, No. 7
inexpensive, but phenol provides the advantage of acting as
an anesthetic, whereas alcohol causes pain during tissue infil-
tration and requires tissue anesthesia before its injection. As a
liquid agent, phenol allows a titratable greater volume of neu-
rolysis compared with single or even multiple lesions via
radiofrequency ablation–based technology with fixed lesion
sizes. As such, image-guided chemical neurolysis of the genic-
ular nerves (GChN) might provide a solution for one of the
shortcomings of the GRFA procedure: the ability to efficiently
capture the optimal number of genicular nerves and their
large tissue territory of variability in each unique individ-
ual.3,22–26
Early case reports and small studies of GChN have demon-
strated safety, tolerability, and favorable outcomes.27–30
However, the current literature is underdeveloped and has
not addressed important questions, which include (1) the abil-
ity of this procedure to provide a treatment effect when
GRFA and TKA did not, (2) opioid-sparing effects, and (3)
demographic and clinical factors that could predict treatment
outcome.
Given the encouraging early safety and clinical-
effectiveness data, as well as the potential time, cost, and
patient-comfort advantages proposed to be associated with
GChN, we sought to expand the current outcome literature
through the largest observational cohort study of GChN for
chronic, refractory knee pain to date. The purpose of our
study was to evaluate the treatment outcomes of GChN in a
real-world, challenging clinical population that includes indi-
viduals with a high body mass index (BMI), baseline daily
opioid use, post-TKA pain, and lack of effect from a prior
GRFA procedure.
Methods
Study design and data collection
Institutional review board approval (STU00208296) was
obtained for this single-center observational cohort study of
consecutive patients who underwent GChN for chronic,
refractory knee pain between January 1, 2014, and December
31, 2020. Study participants were identified through a query
of electronic medical records at a single tertiary academic
medical center, with Current Procedural Terminology (CPT)
code 64620 for peripheral neurolysis and the term “phenol”
used as search criteria. A chart review of these patients was
performed, and all patients who had undergone a GChN pro-
cedure for chronic, refractory knee pain and for whom a mini-
mum duration of 3 months had elapsed since their procedure
were eligible. Eligible patients were individually contacted by
telephone. After a verbal informed consent process, outcome
data were collected via a structured telephone interview that
included the numerical rating scale to quantify pain levels,
opioid analgesic use, and the Patient Global Impression of
Change (PGIC) scale to assess overall improvement. Patients
could refuse participation. The following data elements were
also extracted from each individual patient chart to define
demographic, clinical, radiographic, and procedural factors
that might influence treatment outcome: age, sex, BMI, dura-
tion of knee pain, history of total knee replacement, previous
failure of GRFA procedure to provide pain relief, percentage
of relief from a prognostic genicular nerve block, GChN pro-
cedure date, and volume of phenol used at each injection site.
769
Inclusion and exclusion criteria
All patients who had undergone GChN and for whom a mini-
mum of 3 months had elapsed since this treatment were con-
sidered eligible for inclusion. All patients had undergone
prognostic genicular nerve blocks with 0.5–1.0 mL of 0.5%
bupivacaine and documentation of 50% reduction in knee
pain before they underwent GChN. Patients were excluded
from the study if they refused participation or if they could
not be reached after 4 contact attempts via telephone and
email.
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GChN procedure
The patient was positioned supine on the procedure table
with a bolster to maintain knee flexion at 30 to 40 degrees.
The foot and ankle were secured to ensure leg stabilization
for the procedure. Fluoroscopy was used for image guidance.
After local anesthesia with 1% lidocaine to the skin and sub-
cutaneous tissues, 22 g Whitacre needles were placed at the
inflection point of the medial and lateral femoral epicondyles,
as well as at the inflection point of the medial tibial epicon-
dyle, as visualized on an anterior–posterior fluoroscopic view.
On a lateral fluoroscopic view, the needle tips were positioned
at 50% of the anterior-to-posterior diameter of the medial
and lateral femur and at 75% of the anterior-to-posterior
diameter of the tibial epicondyle. These placements were
intended to allow capture of the tissue territory that includes
the (1) superomedial genicular nerve, (2) terminal articular
branches of the nerve to vastus medialis, (3) superolateral gen-
icular nerve, (4) terminal articular branches of the common
fibular nerve, and (5) inferomedial genicular nerve.
In some cases, 0.5 mL Isovue M-300 (Bracco Diagnostics,
Monroe Twp, NJ) contrast dye was injected at each needle
site with live fluoroscopy to rule out intravascular spread
before any phenol injection. In all cases, 0.5–2.5 mL of 6%
aqueous phenol mixed with 0.5 mL Isovue M-300 was
injected at each site under the live fluoroscopy to ensure ideal
spread to anatomic landmarks along the medial and lateral
femur above the condyle, as well as the medial posterior tibia
below the condyle. Needle placement was adjusted to maxi-
mize the surface area of phenol deposition on a case-by-case
basis, at the discretion of the interventionalist. Once injections
were complete, needles were re-styleted and removed, and
adhesive bandages were placed on the injection sites. The
patient was moved to a gurney and transported to a recovery
area and remained recumbent for at least 30 minutes before
discharge.
Data analysis
Descriptive statistics were calculated for demographic varia-
bles, clinical characteristics, procedural characteristics, and
outcome variables. Specifically, means and standard devia-
tions were used for continuous variables, and categorical vari-
ables were summarized with frequencies and proportions.
Furthermore, a 95% confidence interval (CI) was calculated
for each outcome variable. The primary outcome variable of
interest was 50% pain reduction (categorical, dichotomous
variable; yes or no). Secondary outcomes included 2 catego-
ries of PGIC (categorical, dichotomous variable with very
much / much improved [PGIC of 1–2] or minimally improved /
no change / worse [PGIC of 3–7]), as well as changes in opioid
analgesic use from baseline to follow-up. Contingency table
analysis was performed to examine the associations of knee
770 Pain Medicine, 2023, Vol. 24, No. 7

pain duration (<1 year, 1–3 years, or >3 years) and percent- Table 1. Patient demographics and clinical characteristics (n ¼ 85)
age of relief from a prognostic genicular block (<80%, 80%–
Characteristic Value
99%, or 100%) in relation to the primary outcome variable
of 50% pain reduction, as well as the PGIC categories. The Continuous variables
Pearson v2 test or Fisher exact test (in case of low expected Age, years, mean 6 SD 70.1 6 10.5
frequencies) was used to assess statistical significance. As a BMI, kg/m2, mean 6 SD 31.8 6 9.0
Follow-up time, months, mean 6 SD 9.9 6 6.1
sub-analysis, 50% pain reduction and PGIC category, along Phenol volume / site, cc, mean 6 SD 1.7 6 0.8
with opioid use at baseline and follow-up, were summarized Categorical variables
for patients who both had had a prior TKA and also had Gender, n (%)
failed to respond to a GRFA (to treat post-TKA pain). Lastly, Male 22 (25.9)

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logistic regression analysis was performed to examine the Female 63 (74.1)
associations of select covariates to the primary outcome of Pain duration, n (%)
<1 year 8 (9.5)
50% pain reduction, as well as the 2 categories of PGIC and
1–3 years 29 (34.5)
opioid analgesic use at follow-up. In the regression models for >3 years 47 (56.0)
50% pain reduction and PGIC, the covariates of interest Prognostic block % relief, n (%)
were (1) BMI, (2) history of TKA, (3) history of failure to <80% 23 (29.5)
respond to a prior GRFA procedure, (4) percentage relief with 80%–99% 32 (41.0)
the prognostic genicular block, and (5) phenol volume. The 100% 23 (29.5)
History of TKA, n (%)
covariates for the model of opioid analgesic use at follow-up
Yes 18 (21.2)
included (1) opioid analgesic use at baseline, (2) 50% pain No 67 (78.8)
reduction, (3) history of TKA, (4) history of failure to respond GRFA failure, n (%)
to a prior GRFA procedure, (5) percentage relief with the Yes 55 (64.7)
prognostic genicular block, and (6) phenol volume. No 30 (35.3)

Missing data are excluded from summary statistics.

Results
Two hundred thirty-two consecutive patients were identified
who had undergone a GChN procedure. A total of 85
patients had had a minimum duration of 3 months since their
GChN procedure, were reached by telephone, agreed to par-
ticipate, provided follow-up information, and were subse-
quently included in the analysis. Patient demographics and
clinical characteristics are summarized in Table 1. This study
cohort was 74.1% female (n ¼ 63), with a mean age of
70.1 6 10.5 years and a mean BMI of 31.8 6 9.0 kg/m2. More
than 90% of participants endorsed having had knee pain for
more than 1 year before the GChN procedure, and 56.0%
endorsed having pain for more than 3 years. The mean dura-
tion of outcome assessment by telephone survey after the
GChN procedure was 9.9 6 6.1 months (range: 3–
27 months).
Overall, 43.5% (95% CI ¼ 33.5–54.1; n ¼ 37) of partici-
pants reported 50% sustained pain reduction at the time of
outcome assessment after the GChN procedure. On the PGIC
assessment, 45.9% (95% CI ¼ 35.5–56.7; n ¼ 39) of partici-
pants reported themselves to be “very much improved” or
“much improved.” Percent changes in numerical rating scale
score by follow-up period are depicted in the form of tornado
plots (Figure 1A–1D). Contingency tables showing the rela-
tionship between various clinical and procedural characteris-
tics, with the respective outcomes of 50% pain reduction
and PGIC response of “very much improved” or “much
improved,” are shown in Tables 2 and 3. None of the clinical
or procedural characteristics were significantly associated
with 50% pain reduction or a PGIC response of “very
much improved” or “much improved” (P > .05).
At baseline, 47.1% (n ¼ 40) had been taking opioid analge-
sic medications (“opioids”), and this proportion decreased to
35.3% (n ¼ 30) at follow-up (Table 4). Of the 40 participants
taking opioids at baseline, 11 (27.5%; 95% CI ¼ 14.6–43.9)
ceased use by follow-up. One of 45 participants not taking
opioids at baseline started using one by follow-up (Table 5).
The proportion of patients using opioids was significantly
Abbreviations: BMI ¼ body mass index; GRFA ¼ genicular nerve
radiofrequency ablation; TKA ¼ total knee arthroplasty.
lower at follow-up than at baseline (P ¼ .004; odds
ratio ¼ 0.09; 95% CI ¼ 0.01–0.63).
Of the total 85 patients in this study, 9 (10.6%) both had
had a prior TKA and also failed to respond to a GRFA proce-
dure to treat persistent post-TKA pain in that same knee. Of
those 9 patients, 4 (44.4%) reported 50% pain reduction,
and 4 (44.4%) reported a PGIC response of “very much
improved” or “much improved.” Of those 9 patients, 7
(77.8%) used opioid analgesics at baseline, and of those 7
patients, 1 (14.3%) had ceased use by follow-up.
Logistic regression models investigating factors associated
with 50% pain reduction and a PGIC response of “very
much improved” or “much improved” are shown in Table 6.
None of the covariates of interest demonstrated a significant
relationship with these 2 definitions of treatment success
(P > .05). Logistic regression for predicting opioid use at
follow-up is shown in Table 7. Opioid use at baseline was sig-
nificantly associated with opioid use at follow-up (P < .001).
There was a trend that a report of 50% pain reduction after
the GChN procedure was associated with a lower odds of
opioid use at follow-up (P ¼ .068; odds ratio ¼ 0.21,
95% CI ¼ 0.04–1.12).
In a subgroup analysis, 46.3% of participants with a
native knee treated reported 50% pain reduction, whereas
33.3% of participants with a TKA in the treated knee
reported this threshold of pain reduction (P ¼ .326).
Participants who had previously failed to respond to GRFA
demonstrated a 45.5% success rate (50% pain reduction),
compared with 40% of individuals without a history of
GRFA failure (P ¼ .628).
No serious adverse events occurred. Adverse events were
infrequent, minor, and self-limited. The most common event
was “knee swelling,” which was reported in 30% of patients
within the first 2 weeks and 12% at 1 month after the
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Figure 1. (A) Tornado plot for percent changes in numerical rating scale (NRS) at 3–5 months’ follow-up. (B) Tornado plot for percent changes in NRS at
6–11 months’ follow-up. (C) Tornado plot for percent changes in NRS at 12–24 months’ follow-up. (D) Tornado plot for percent changes in NRS at
>24 months’ follow-up.

procedure. There were no new adverse events reported at 1

Table 2. Contingency table on 50% pain reduction by clinical and
procedural characteristics and 6 months after the intervention.

50% pain reduction

Discussion
Yes No P In this observational cohort study of 85 patients who under-
BMI, kg/m2, n (%) .685 went phenol GChN, 43.5% of patients endorsed significant
Normal weight 8 (36.4) 14 (63.6) pain relief (50% pain reduction) at a mean follow-up dura-
Overweight 8 (50.0) 8 (50.0)
tion of nearly 10 months after the procedure and with fre-
Obese 21 (44.7) 26 (55.3)
Pain duration, n (%) .848a quent durability beyond 1 year. A slightly larger proportion
<1 year 4 (50.0) 4 (50.0) of these patients (45.9%) reported themselves to be “very
1–3 years 13 (44.8) 16 (55.2) much improved” or “much improved” on the PGIC. More
>3 years 19 (40.4) 28 (59.6) than 25% of patients who had been taking opioids at baseline
Prognostic block % relief, n (%) .935 had ceased used by the time of follow-up. This is remarkable,
<80% 9 (39.13) 14 (60.9)
80%–99% 14 (43.8) 18 (56.2) given that many prior studies of GRFA have not demon-
100% 10 (43.5) 13 (56.2) strated opioid cessation in a meaningful proportion of partici-
History of TKA, n (%) .326 pants. Notably, no serious adverse events occurred in this
Yes 6 (33.3) 12 (66.7) cohort.19 This is important to note, given the variable but
No 31 (46.3) 36 (53.7) sometimes high volumes of phenol used. These data support
Prior GRFA failure, n (%) .628
Yes 25 (45.5) 30 (54.5) earlier evidence that GChN could be a safe and effective
No 12 (40.0) 18 (60.0) method of treating chronic knee pain.26–28,30
Compared with prior publications,18,19,29 the present
Values are frequency (%); P values from Pearson v2 test, unless specified
otherwise.
cohort represents the largest to date, and the present study
a
From Fisher exact test. used fluoroscopic guidance according to the current updated
Abbreviations: BMI ¼ body mass index; GRFA ¼ genicular nerve neuroanatomy of the knee, as defined by bony/fluoroscopic
radiofrequency ablation; TKA ¼ total knee arthroplasty.
landmarks rather than ultrasound. Certainly, ultrasound
772 Pain Medicine, 2023, Vol. 24, No. 7

Table 3. Contingency table on PGIC by clinical and procedural Table 6. Logistic regression models on 50% pain reduction and PGIC by
characteristics select covariates

PGIC Outcomes and predictors OR (95% CI) P

Minimally Outcome: 50% pain reduction (yes vs. no)a

improved / BMI (kg/m2; vs. normal weight)
Overweight 1.75 (0.39–7.84) .463
Very much / no change /
Obese 1.02 (0.29–3.53) .979
much improveda worseb P
History of TKA (vs. no)
BMI, kg/m2, n (%) .322 Yes 0.67 (0.21–2.12) .492
Normal weight 8 (36.4) 14 (63.6) GRFA failure (vs. no)

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Overweight 6 (37.5) 10 (62.5) Yes 1.04 (0.34–3.19) .947
Obese 25 (53.2) 22 (46.8) Prognostic block % relief (vs. <80%)
Pain duration, n (%) .718c 80%–99% 1.10 (0.33–3.73) .873
<1 year 3 (37.5) 5 (62.5) 100% 1.05 (0.28–3.89) .944
1–3 years 15 (51.7) 14 (48.3) Phenol volume (mL/site) 0.79 (0.36–1.74) .560
> 3 years 20 (42.6) 27 (57.4) Outcome: PGIC (very much / much improvedb
Prognostic block % relief, n (%) .944 vs. minimally improved / no change /
< 80% 11 (47.8) 12 (52.2) worsec)d
80%–99% 14 (43.8) 18 (56.2) BMI (kg/m2; vs. normal weight)
100% 10 (43.5) 13 (56.5) Overweight 1.28 (0.27–5.98) .752
History of TKA, n (%) .229 Obese 1.59 (0.46–5.56) .466
Yes 6 (33.3) 12 (66.7) History of TKR (vs. no)
No 33 (49.3) 34 (50.7) Yes 0.61 (0.19–1.97) .413
Prior GRFA failure, n (%) .422 GRFA failure (vs. no)
Yes 27 (49.1) 28 (50.9) Yes 1.02 (0.33–3.13) .974
No 12 (40.0) 18 (60.0) Diagnostic block % relief (vs. < 80%)
80%–99% 0.79 (0.23–2.70) .712
Values are frequency (%); P values from Pearson v2 test, unless specified 100% 0.76 (0.20–2.82) .680
otherwise.
a Phenol volume (mL/site) 0.72 (0.33–1.57) .411
PGIC of 1–2.
b
PGIC of 3–7. a
c
From Fisher exact test. n ¼ 78; LR v2(7)¼ 1.84; P ¼ .968; Pseudo R2¼ 0.017.
b
Abbreviations: BMI¼ body mass index; GRFA¼ genicular nerve PGIC of 1–2.
c
radiofrequency ablation; PGIC¼ Patient Global Impression of Change; PGIC of 3–7.
d
TKA¼ total knee arthroplasty. n ¼ 78; LR v2(7)¼ 3.79; P ¼ .804; Pseudo R2¼ 0.035.
Abbreviations: BMI¼ body mass index; CI¼ confidence interval; GRFA¼
genicular nerve radiofrequency ablation; LR¼ Likelihood Ratio; OR¼ odds
ratio; PGIC¼ Patient Global Impression of Change; TKA¼ total knee
Table 4. Opioid use (dichotomous category) at baseline and follow-up arthroplasty.

Opioid use Frequency (%)

Table 7. Logistic regression model on opioid use at follow-up by select
Use at baseline, n (%) covariates
No 45 (52.9)
Yes 40 (47.1) Predictor OR (95% CI) P
Use at follow-up, n (%)
No 55 (64.7) Opioid use at baseline (vs. no)
Yes 30 (35.3) Yes 231.38 (16.55–3235.13) <.001
50% pain reduction (vs. no)
Yes 0.21 (0.04–1.12) .068
History of TKA (vs. no)
Table 5. Contingency table on opioid use (dichotomous category) at Yes 2.94 (0.47–18.28) .248
baseline and follow-up GRFA failure (vs. no)
Yes 1.38 (0.20–9.78) .746
Opioid use (follow-up) Prognostic block % relief (vs. <80%)
80%–99% 8.11 (0.99–66.33) .051
Opioid use (baseline) No Yes OR (95% CI)a Pa 100% 1.73 (0.20–15.27) .622
No 44 1 0.09 (0.01–0.63) .004 Phenol volume (mL/site) 0.50 (0.14–1.79) .285
Yes 11 29 n ¼ 78; LR v2(7)¼ 57.04; P < .001; Pseudo R2¼ 0.560.
Abbreviations: CI¼ confidence interval; GRFA¼ genicular nerve
Values are frequency. radiofrequency ablation; LR¼ Likelihood Ratio; OR¼ odds ratio; TKA¼
a
From McNemar’s v2 test. total knee arthroplasties.
Abbreviations: OR¼ odds ratio; CI¼ confidence interval.

guidance for GChN holds promise and would expand
patient access as a bedside procedure. Nevertheless, more
work is needed to validate the accuracy of GChN under
ultrasound guidance versus fluoroscopic guidance in light of
the complexity and variability of innervation to the knee.21
Furthermore, unlike prior literature, our study cohort
included a large number of patients who had previously
demonstrated a lack of treatment response to GRFA despite
positive prognostic blocks, as well as patients with persistent
pain after TKA.
Patients with chronic knee pain refractory to GRFA and
patients with persistent pain after TKA have few treatment
options and are recognized to be highly challenging popula-
tions. Our data demonstrate treatment success rates of 45.5%
in cases of GChN performed after GRFA “failures” and 33%
in patients with post-TKA pain. In the small subcohort of
Pain Medicine, 2023, Vol. 24, No. 7
patients (n ¼ 9) who both had had a prior TKA and also failed
to respond to a GRFA procedure to treat persistent post-TKA
pain in that same knee, 44.4% reported 50% pain reduction
and 44.4% reported a PGIC response of “very much
improved” or “much improved.” Although these rates are far
from 100% in this observational cohort study, it is encourag-
ing that GChN could provide a viable “salvage” effect in a
subset of patients who otherwise have few options. We sus-
pect that this salvage effect is related to the difference in the
tissue region of genicular nerve capture, which is larger during
a GChN procedure than in a comparative GRFA procedure.
Although a territory of tissue capture similar to that in GChN
is theoretically possible through the use of multiple sequential
GRFA lesions, such a GRFA protocol would be time prohibi-
tive. More recent GRFA protocols do call for the capture
of more nerves and greater regions of tissue capture
to account for variable genicular nerve location among indi-
viduals,19,23–25 but even these protocols do not create the
same magnitude of tissue capture as a GChN procedure with
1–2 mL of liquid chemoneurolytic agent injected at each tar-
get site.26
Our study is the first to evaluate whether specific demo-
graphic and clinical characteristics might predict treatment
success after GChN. Contingency tables and regression mod-
els demonstrated no association between the factors examined
and treatment outcome. As such, age, sex, BMI, duration of
knee pain, relief of <80% from a prognostic block, lack of
relief from a prior GRFA, and history of TKA should not pre-
clude physicians from offering this treatment to patients who
are otherwise eligible for GChN. Lack of prognostic value
associated with genicular nerve blocks is consistent with a
prior study related to GRFA.17 Obesity and a history of TKA
have been associated with a reduced likelihood of treatment
success after GRFA, but we did not find this association in
our cohort who underwent GChN.15
As with any retrospective study, there are limitations to the
interpretation of our results. Variability in the duration of
follow-up and recall bias could have influenced the results.
We were not able to assess functional improvements resulting
from phenol GChN, as a validated functional outcome meas-
ure had not been administered to all patients in this cohort
before their procedure. Despite these limitations, the observed
treatment effect of phenol GChN in this real-world popula-
tion is notable and indicates the need for a large, prospective,
randomized controlled trial. Future studies should aim to
delineate the ideal injection volume per treatment site, the
concentration of phenol to be delivered, the long-term dura-
bility of pain and functional improvement via a knee-specific
measure of disability related to pain, and the cost-
effectiveness of this modality in comparison with GRFA and
other nonsurgical treatments for chronic, refractory knee
pain.
Conclusion
We report on the largest cohort of patients to date who have
undergone GChN for chronic, refractory knee pain. The
present data indicate that GChN could provide a robust and
durable treatment effect, as measured by pain reduction,
PGIC, and opioid analgesic cessation in a subset of individu-
als, even with the inclusion of patients who have complicating
factors traditionally associated with poor treatment out-
comes, such as high BMI, pain refractory to GRFA, or pain
773
after TKA. No specific demographic or clinical factors that
we evaluated suggest that GChN should be withheld because
of a lesser likelihood of treatment effect in any subgroup. A
prospective, controlled trial is warranted.
Funding
There were no sources of support for this study.
Conflicts of interest: D.R.W. and Z.L.M. report consulting
Downloaded from https://academic.oup.com/painmedicine/article/24/7/768/7049535 by AAPM Member Access user on 30 July 2023
fees from Saol Therapeutics. There are no other potential con-
flicts of interest to disclose on the part of any of the other
authors.
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