Lasers in Surgery and Medicine 48:653–659 (2016)

Photobiomodulation of the Dorsal Root Ganglion for the

Treatment of Low Back Pain: A Pilot Study
Vanessa Milanesi Holanda, MD, MSc,1,2
Maria Cristina Chavantes, MD, PhD,1,3
Daniela Fatima Teixeira Silva, PhD,1 Carlos Vanderlei M. de Holanda, MD,2
Jose
Oswaldo de Oliveira Jr., MD,2,3,4 Xingjia Wu, BS,5 and Juanita J. Anders, PhD5
1
Post Graduate Program in Biophotonics Applied to Health Sciences and in Medicine, University Nove de
Julho–UNINOVE, Sao ~ Paulo, SP 01504-001, Brazil
2
Center of Neurology and Neurosurgery Associates (CENNA), Benefic^ encia Portuguesa of S~
ao Paulo Hospital,
SP 01323-900 Sao~ Paulo, SP 01504-001, Brazil
3
~ Paulo University, Sao
Medical School, Sao ~ Paulo, SP 05402-000, Brazil
4
AC Camargo Cancer Center, Sao~ Paulo, SP 090041-031, Brazil
5
Uniformed Services University of the Health Sciences, Bethesda, MD 20814

Background and Objective: Chronic low back pain is
a worldwide public health issue with high socioeconomic
impact. The aim of this study was to determine the efficacy
of laser irradiation of the dorsal root ganglion of the second
lumbar spinal nerve for chronic axial low back pain
compared to lidocaine injection and radiofrequency
treatment.
Study Design/Materials and Methods: Twenty-eight
patients were randomly divided into three treatment
groups: lidocaine injection, radiofrequency, or laser. The
second intervertebral foramen between the second and
third lumbar vertebrae was accessed by percutaneous
needle puncture bilaterally, guided by fluoroscopy. In the
local anesthetic group, injection of 1 ml lidocaine without
epinephrine was applied through a 20-gauge (G20)
Quincke tip spinal needle inserted in the second lumbar
intervertebral foramen. In the radiofrequency group, the
probe (150 mm long with a 5 mm active tip) was directed
through a G20 needle placed in the second lumbar
intervertebral foramen and neuromodulation was done
with a radiofrequency of Cosman G41 in pulses of 20 ms
with wash-out period of 480 ms, for 300 seconds at 428C. A
single treatment was used. In the laser treatment group, a
continuous wave, 808 nm wavelength diode laser (Photon
Lase III1 DCM, Brazil), with an output power of 100 mW
was used for a single treatment. An 18 gauge needle was
placed in the second lumbar intervertebral foramen guided
by fluoroscopy. Light was delivered through a 600 mm
optical fiber placed in the G18 needle. The tip of the fiber
extended 5 mm beyond the tip of the needle in the second
lumbar intervertebral foramen. The beam spot size was
0.003 cm2, irradiance ¼ 35W/cm2, exposure time ¼ 84 sec-
onds, energy density ¼ 2800J/cm2, total energy was 8.4 J.
The low back pain score was assessed by the visual analog
scale (VAS) and Pain Relief Scale (PRS) pre, post procedure
and in 1 month follow up. Temperature was measured
using a digital thermometer.
Results: All patients in the local anesthetic and laser
treatment groups reported a pain reduction of at least 50%
immediately post-procedure and 10 out of 11 patients in
the radiofrequency group reported a pain reduction of at
least 50%. At 1 month post-treatment, the laser treatment
group had the greatest number of patients who reported
more than 50% pain relief based on PRS (7 out of
10 patients) while only 2 out of 7 patients and 3 out of
11 patients in the lidocaine and radiofrequency treatment
groups respectively reported more than a 50% pain relief.
Conclusion: Laser irradiation caused an immediate
decrease in low back pain post-procedure similar to pain
reduction caused by lidocaine injection. Both lidocaine
injection and laser irradiation were more effective than
radiofrequency treatment for immediate and longer term
(1 month post-treatment) chronic back pain. Lasers Surg.
Med. 48:653–659, 2016. ß 2016 Wiley Periodicals, Inc.
Key words: laser irradiation; photoneuromodulation;
dorsal root ganglion; back pain; lidocaine injection;
radiofrequency treatment
INTRODUCTION
Chronic low back pain is a worldwide public health issue
with high socioeconomic impact. The economic burden on
society from chronic back pain is increasing and recent
numbers demonstrate the financial impact [1]. An increase
Conflict of Interest Disclosures: All authors have completed
and submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest and none were reported.
Contract grant sponsor: CAPES (Coordenaç~ ao de Aperfeiçoa-
mento de Pesquisa de N
ıvel Superior).


Correspondence to: Vanessa Milanesi Holanda, MD, MSc, Rua
Martiniano de Carvalho, 807-suite 705, Bela Vista, S~
ao Paulo, SP,
Brazil 01321-001. E-mail: vanessamila@gmail.com
Accepted 24 March 2016
Published online 2 May 2016 in Wiley Online Library
(wileyonlinelibrary.com).
DOI 10.1002/lsm.22522

ß 2016 Wiley Periodicals, Inc.

654 HOLANDA ET AL.
in the awareness of the prescription opioid drug problem in
the United States has directed scientists and physicians to
identify non-narcotic medications and non-pharmaceutical
interventional options to treat chronic pain [2].
In light of a need for non-addictive therapeutic options, a
number of methods are currently used to control chronic
pain with varied success. These methods target the dorsal
root ganglia (DRG) which is a cluster of pseudounipolar
neurons located between the dorsal root and the spinal
nerve. The DRG is responsible for modulating sensory
afferent inputs and transmitting them to the central
nervous system [3]. Due to the important roles in the
neuromodulation of sensory processing of neuropathic or
nociceptive pain and its anatomic accessible approach
to clinical intervention [4], the DRG is an outstanding
target for pain control.
Anatomical study in rats shows that the majority of the
sensory nerves from the L2 and L5 bodies go through the
paravertebral sympathetic trunks until reach the L2
DRG [5]. Based on this, Nakamura et al. [6] hypothesized
that pain arising from the lower lumbar intervertebral
discs was transmitted mainly through the sympathetic
afferent fibers contained in the L2 spinal nerve root and
described that afferent pathways of discogenic low-back
pain are mainly in the L2 spinal nerve. Many studies have
shown that the lumbar sympathetic afferents play a role in
the transmission of low back pain [7–9]. For this reason,
the second dorsal root ganglion has been chosen as the
target to treat low back pain in this study.
Non-pharmaceutical methods that target the DRG
include: injection of anesthetics [10], pulsed radiofre-
quency (PRF) [11], and laser irradiation (photobiomodu-
lation [PBM]) [12]. The analgesic effect of PBM has been
reported to involve Ad and C fibers [13]. Pulsed radio-
frequency of the DRG is a treatment procedure during
which a heat lesion in placed near to the ganglion to
produce a neuromodulation, the temperature does not
increase over 458C and neither causes protein denatur-
ation nor destroys the ganglion [14]. The DRG is
protected by a permeable surrounding capsular mem-
brane with a rich blood supply, which makes it an
excellent choice for local anesthetic injection [10]. Local
anesthetics, including lidocaine, are commonly used for
regional blockage [14]. Although some studies have
shown good results, pain relief normally last only a few
hours and some patients developed cardiologic or neuro-
logic side effects [15].
PBM has been reported to be an effective therapeutic
modality for the treatment of pain [12]. To date, there
has been no clinical study of the relative effectiveness
of these treatment modalities for chronic back pain.
Furthermore, there is no reported clinical study of the
use of light directly applied to the DRG through an
optical fiber. Therefore, the aim of this research was to
determine the efficacy of laser irradiation on lumbar
DRG for the treatment of chronic low back pain and to
compare laser irradiation to two established treatments
for lumbar pain relief: lidocaine injection and pulsed
radiofrequency.
METHODS
Ethical Approval
All the patients signed a written consent form after
receiving the information about the research protocol,
which was approved by the local research ethics committee
through Brazilian platform CAAE 53123716.3.0000.5511,
which examined the details of the project for patient safety
and privacy. This study protocol was registered in the
Clinical Trials Platform: NCT02529670.
Study Population
Twenty-eight patients were randomly divided into three
treatment groups: lidocaine injection, radiofrequency,
or laser irradiation. There were 7 patients in the lidocaine
injection group, 11 patients in the radiofrequency group,
and 10 patients in the laser irradiation group. The median
age in the laser group was 53, 47 in the lidocaine group
and 57 in the radiofrequency group. There were no
genders differences or differences in the length of the
chronic pain episodes between groups comparing the
pain time lapse (Table 1). The etiology of low back pain
was equivalent between the three trial arms as shown in
Table 2.
Inclusion and Exclusion Criteria
Inclusion parameter was patients with low back pain
during more than 3 months. Exclusion parameters were
cancer in lumbar region, coagulation disturbance, infec-
tion, and neurologic deficits.
Calibration of the Laser
The laser output was measured by a member of the
Post Graduate Program in Biophotonics Applied to Health
Sciences and in Medicine, University Nove de Julho
(UNINOVE), at the start and during the course of the
study. At the end of this study, the laser output was
measured by a member of Uniformed Services University
of the Health Sciences, Bethesda, MD.
STUDY DESIGN
Local Anesthesia Procedure
The patients were placed in the prone position and the
procedure was performed using an aseptic technique.
After performing local skin anesthesia using 1 ml of
lidocaine without epinephrine, a 20-gauge (G20) Quincke
tip spinal needle was inserted in the second lumbar
intervertebral foramen using the Scottie dog technique
(Fig. 1), by percutaneous puncture guided fluoroscopy. A
total of 1 ml of 0.20% lidocaine without epinephrine was
injected into the second lumbar intervertebral foramen,
bilaterally.
Radiofrequency Procedure
After performing local anesthesia of the skin, the same
procedure was used to approach DRG in this group. The
radiofrequency probe (150 mm long with a 5 mm active tip)
 PHOTOBIOMODULATION OF DORSAL ROOT GANGLIA 655

TABLE 1. Demographics of the Patients Enrolled in This Study

Case Sex Age (years) Length of pain (month) Pain localization Treatment

1 M 35 48 Low back and right leg Laser

2 F 74 60 Low back PRF
3 M 82 3 Low back and both legs Lidocaine
4 F 65 36 Low back and right leg PRF
5 F 86 4 Low back and both legs PRF
6 F 54 72 Low back and left leg PRF
7 F 57 60 Low back and both legs PRF
8 F 42 3 Low back and left leg PRF
9 F 65 36 Low back and right leg Laser
10 F 30 12 Low back and left leg PRF
11 F 74 12 Low back and both legs PRF
12 M 53 24 Low back and right leg Laser
13 M 41 18 Low back and both legs Laser
14 M 77 48 Low back and left leg Lidocaine
15 F 45 24 Low back and both legs PRF
16 M 45 144 Low back and both legs PRF
17 M 62 24 Low back PRF
18 M 49 12 Low back and both legs Laser
19 F 47 3 Low back and right leg Lidocaine
20 F 43 36 Low back and both legs Lidocaine
21 F 33 6 Low back Lidocaine
22 F 33 24 Low back and both legs Laser
23 F 63 120 Low back and both legs Laser
24 F 84 36 Low back and right leg Laser
25 F 45 24 Low back and both legs Laser
26 F 54 14 Low back and left leg Laser
27 F 45 12 Low back and both legs Lidocaine
28 M 68 6 Low back Lidocaine

TABLE 2. Etiology of Chronic Low Back Pain

Local
Etiology of low back pain anesthesia Radiofrequency Laser

Lumbar disc herniation 1 1 1

Facet syndrome 1 2 0
Lumbar spinal stenosis þ Facet syndrome 1 2 2
Spondylolisthesis without dynamic instability þ Facet syndrome 1 2 2
Lumbar disc herniation þ Facet syndrome 3 4 5
Total 7 11 10

Fig. 1. Fluoroscopy guided Scottie dog technique to access the intervertebral foramen. In the
oblique view, the needle must be placed in the front of the dog’s neck to access the intervertebral
foramen. In the lateral view, fluoroscopic image confirms the needle position in the second lumbar
intervertebral foramen.
656 HOLANDA ET AL.
was directed through a G20 needle placed in the second
lumbar intervertebral foramen and treatment was done
with a radiofrequency of COSMAN G41 for 300 seconds
at 428C. The optimal location was determined with
electrical sensory stimulation with 50 Hz, less than or
equal 0.6V, and motor (2 Hz) stimulation, less than or
equal to 3V to avoid placement near the anterior nerve
root. The pulsed radiofrequency was applied in pulses of
20 ms with wash-out period of 480 ms for 5 minutes,
through G20 tubes, 150 mm long and 5 mm active tip in
contact with the target, bilaterally. The output was set at
45V, but if the electrode tip temperature exceeded 428C,
the voltage would be decreased. The temperature never
exceeded 428C.
Laser Procedure
The same procedure to perform a transforaminal
approach were applied under fluoroscopic guidance, as
described in previous groups. A continuous wave, 808 nm
wavelength diode laser (Photon Lase III1 DCM, Brazil),
with an output power of 100 mW was used for a single
treatment (Table 3). Light was delivered bilaterally
through a 600 mm optical fiber, that was cleaved at 908,
polished and placed in the G18 needle. The tip of the fiber
extended 5 mm beyond the tip of the needle in the second
lumbar intervertebral foramen.
Evaluation of Pain
The visual analog scale (VAS) was used to assess the
lumbar pain level and the Pain Relief Scale (PRS) was
applied to assess the chronic low back pain relief. These
scales were used pre-operatively and at 5 minutes and
1 month post-operatively. The VAS is a 10 cm long straight
line, marked at each end with labels which anchor the
scale [16]. The Pain Relief Scale (PRS) is a method that
employs the previous intensity of pain as the baseline, and
subsequently measures the percentage of change in pain
intensity after treatment [17]. For PRS assessment, the
patient was instructed to consider the pain pre-procedure
as 100 and to indicate the decrease in the current pain level
5 minutes post-procedure and in the follow up. Both scales
TABLE 3. Laser Parameters
Parameter Infrared laser
Center wavelength [nm] 808
Average radiant power [mW] 100
Aperture diameter [cm] 0.06
Power density [W/cm2] 35
Energy density [J/cm2] 2,800
Exposure time [second] 84
Total radiant energy [J] 8.4
Beam spot size [cm2] 0.003
Application technique Contact
Number of sessions 1 Laser
Operating mode Continuous wave (CW)
Number of points irradiated 1 Radiofrequency
were used for pain evaluation to increase the objectivity of
the chronic pain assessment compared to the use of only
VAS [17].
Evaluation of Temperature
The skin temperature on the dorsum of the lumbar
region was measured using a digital thermometer pre- and
post-operatively.
Follow Up
All patients were evaluated after 1 month. Pain was
assessed using VAS and PRS. The return to daily activities
was inquired.
Statistical Analysis
The VAS score and temperature data were converted
into percentage of relative difference. Thus, there was a
normalization relative to variables measured pre-opera-
tively for each patient. The Kruskal–Wallis statistical test
was used. If differences among the groups were identified,
the Mann–Whitney post-hoc test was used. A value of
P < 0.05 was considered to be statistically significant.
RESULTS
General Pain Improvement Post Treatment
All patients in the anesthetic and laser treatment groups
reported at least a 50% reduction in pain immediately after
the procedure while 10 of the 11 patients in the radio-
frequency group reported at least a 50% diminution of
pain. For the 1 month follow up post-treatment, the laser
treatment group had the greatest number of patients who
reported more than 50% pain relief based on PRS (7 out of
10 patients) while only 2 out 7 patients and 3 out of 11
patients in the lidocaine and radiofrequency treatment
groups respectively reported more than a 50% pain relief
(Table 4).
The laser and lidocaine treatment groups had a 100%
reported decrease in pain, assessed by VAS, while the
radiofrequency treatment group reduced by 62.50%, when
the relative difference between pre- and post-treatment
values were determined. Seventy percent of the patients
treated with the laser returned to work and their daily
activities compared to 30% in the lidocaine and radio-
frequency treatment groups.
When the relative differences between post- and pre-
treatment and 1 month follow up were compared evaluat-
ing VAS data, the laser group had a decrease in pain by
TABLE 4. Comparison of the Number of Patients Who
Obtained More Than 50% in the Pain Relief Scale (PRS)
Immediately 1 month
post-treatment follow up
10/10 7/10
Lidocaine 7/7 2/7
10/11 3/11
 PHOTOBIOMODULATION OF DORSAL ROOT GANGLIA
Fig. 2. Relative differences of Visual Analog Scale (VAS) between
pre- and post- treatment and 1 month follow up. The interquartile
range (IQR) for the VAS (post-pre) are 28.13 for laser, 0.00 for
lidocaine and 50.00 for radiofrequency. In the VAS (1m-pre) are
59.52 for laser, 55.00 for lidocaine and 50.00 for radiofrequency.
55.00%, the lidocaine group by 62.50% and the radio-
frequency group only 20.00%. There was no statistically
significant difference between the laser and lidocaine
treatment groups (Fig. 2).
Temperature Measurements
In radiofrequency treatment group, there was a 28C
increase (2.86% increase) in the skin temperature on the
dorsum of the lumbar region between pre- and post-
treatment temperature, while there was no change in
temperature in the laser and lidocaine groups.
Adverse Effects of Therapy
During the procedure, patients experienced no pain or
only mild discomfort. There were no infections or other
side-effects seen during the 1 month follow up period.
DISCUSSION
To the best of our knowledge, this is the first prospective
clinical study to explore the use of PBM of the dorsal root
ganglion as an alternative therapy to treat low back pain.
These results demonstrate that laser irradiation dimin-
ished the pain as quickly as lidocaine injection and
maintained a 50% decrease in pain for 1 month period of
follow up in most of patients compared to the lidocaine or
radiofrequency groups.
A randomized prospective clinical study suggests that
pulsed radiofrequency at 428C is a safe and effective
modality when applied to the DRG for radicular neuro-
pathic pain treatment [18]. The mechanism of pulsed
radiofrequency is not completely described. An in vivo
study showed a thermic-like effect consisting in the
impairment of the myelinated fibers with the consequent
swelling of pericytes [19]. Upregulation of glial cell
line-derived neurotrophic factor (GDNF) expression was
657
showed in dorsal root ganglia rat cells after exposure to
pulsed radiofrequency [20]. This upregulation can signifi-
cantly relieve neurophatic pain [21]. Many studies have
described changes in dorsal horn neuronal activity, and
increased cellular stress in small and medium caliber
neurons after pulsed radiofrequency in the DRG [22–27].
The same mechanisms may be involved in laser irradiation
of the DRG.
In dorsal root ganglia culture, lidocaine has been showed
to depolarize the mitochondrial membrane potential by
intracellular alkalization that may induce morphological
changes, apoptosis, and neurotoxicity [28]. In the 1 month
follow up, lidocaine infiltration of DRG produced sustained
pain relief. However, long-term exposure to lidocaine
produces irreversible damage to mitochondria [28]. Pro-
longed analgesia had been described in some patients post-
lidocaine infiltration [29]. The same mechanism of the
DRG neural blockade may cause long-term altered
nociception in laser irradiation of the DRG with no
neurotoxicity.
This prospective, randomized study provides evidence of
100 mW, 808 nm laser in the treatment of chronic low back
pain in only one session, with the laser treated group
demonstrating a statistically significant and clinically
relevant improvement in the primary outcome measure-
ments, VAS and PRS. Many studies provided evidence of
efficacy of PBM in the range of painful conditions [30–32].
Photoneuromodulation is the neuromodulation of
pain through the use of laser. The effectiveness of
photoneuromodulation depends on the dose used, as shown
an in vivo study previously [32]. It is able to modulate the
neuronal activity in the nervous system, due to changes
into Naþ, Kþ, and Caþþ ion channels and ion current flux,
resulting from injury and inflammation that lead to
increased excitability of the peripheral neurons, DRG
and spinal cord [3]. Laser irradiation modulates the
Caþþ pump function and expression, causing increase in
intracellular calcium that triggers degranulation and
endocytic release of ATP [33], this may be one of the
mechanistic basis of photoneuromodulation.
An in vitro study demonstrated that PBM disturbs fast
axonal transport, causing perturbation of microtubule
arrays by reducing ATP synthesis in axonal mitochondria
of small diameter neurons in rat dorsal ganglia culture [34].
In vivo study has shown that PBM inhibits Ad and C fibers
transmission [35]. The same mechanism may be involved
in PBM of the DRG.
A prospective randomized controlled clinical study
reported that an 830 nm wavelength laser (300 mW)
applied transcutaneously provided a clinically relevant
benefit in the management of chronic neck pain [36]. In
this study, the vicinity of the DRG was irradiated by
delivering the light through a 600 mm optical fiber. This
method of light delivery was chosen so that the treatment
approach was similar to the approach used for the lidocaine
injection. Currently, cadaver measurements are being
done to determine the irradiance at the target and dose
that would be required to transcutaneously deliver the
effective irradiance to the lumbar DRG.
658 HOLANDA ET AL.
Mechanistically, the light may also alter the local
inflammatory response since PBM acts by anti-inflamma-
tory effects [37–39] and increasing the production of
endogenous opioids [40]. The additional ability of the light
to alter cellular response to pain may explain why laser
irradiation was more effective than lidocaine injection
and radiofrequency in long term pain reduction (1 month
follow up).
CONCLUSIONS
In our study, both lidocaine injection and laser irradia-
tion were more effective than radiofrequency treatment for
immediate and longer term (post 1 month) chronic back
pain relief. It is possible to state that Lasertherapy caused
an immediate reduction in low back pain post-procedure
due to photoneuromodulation effect in DRG.
ACKNOWLEDGMENTS
We are grateful for all patients who gave their consent to
participate in this study, for the residents and employees
of the Center of Neurology and Neurosurgery Associates
(CENNA) for the excellent treatment of each patient.
This study was funded in part by CAPES (Coordenaç~ ao de
Aperfeiçoamento de Pesquisa de N
ıvel Superior). This
work was presented at ASLMS 2015 and the first author
received a travel grant and the best photobiomodulation
resident/fellow award.
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