13864c16.
PGS 12/13/04 3:38 PM Page 537
Photomedicine and Laser Surgery
Volume 22, Number 6, 2004
© Mary Ann Liebert, Inc.
Pp. 537–539
A Clinical Study on Serum Prostaglandin E2
with Low-Level Laser Therapy
KAZUHIRO MIZUTANI,1 YOSHIRO MUSYA,1 KOUZABUROU WAKAE,1
TOSHIYUKI KOBAYASHI,1 MASAHIRO TOBE,1 KAZUMASA TAIRA,1 and TAKASHI HARADA2
ABSTRACT
Methods: The subjects of this investigation consisted of 83 female patients that were treated in this depart-
ment during the 2-year period from January 1999 to December 2002. Laser irradiation was applied for 3 min
either every day or every other day for a total of 10 times. A diode semi-conductor laser with a wavelength of
830 nm and a photointensity of 1 W was used. Evaluations were performed before and after the series of 10 ex-
posures to laser irradiation. The evaluation included the measurement of pain using the visual analog scale
(VAS) and serum prostaglandin E2 (pg/mL) measured by RIA-PEG. Results: The analgesic effects were ob-
served in 67 of 83 cases, or 80.7%. The VAS scores for the effective cases decreased after the irradiation series
from 8.5 ± 0.2, to 2.8 ± 0.2 ( p < 0.001). The post-irradiation PGE2 levels were lower than the pre-irradiation
PGE2 levels in the effective cases, which were 5.8 ± 0.3 and 7.1 ± 0.4 pg/mL, respectively ( p < 0.05). The post-
irradiation PGE2 levels for the effective cases were lower than those for the ineffective cases, which were 5.8 ±
0.3 and 7.3 ± 0.9 pg/mL, respectively ( p < 0.05). Conclusions: Based on the above findings, the analgesic effects
of LLLT were found to be valid. The serum PGE2 levels are therefore considered to directly reflect nociceptive
pain.
INTRODUCTION MATERIALS AND METHODS
T HE STIMULATION of mechanical and polymodal nociceptors
by tissue damage leads to the production of bradykinin
(BK). The activation of bradykinin by noxious stimuli leads to
The study sample comprised a total of 83 female patients
who received LLLT at our facility on an out-patient basis be-
tween January 1999 and December 2001. The age distribu-
the production of many kinds of inflammatory mediators such tion ranged from 20 to 79 years, with the mean age being
as prostaglandin E2 (PGE2) and substance P (SP). The percep- 56.3 years. The period of morbidity ranged from 3 days to
tion of pain is mediated by the excitation of nociceptors exist- 3 years before laser exposure, with a mean of 6 months.
ing at the free nerve-endings of nociceptive C and A fibers. Specifically, the gallium aluminium arsenide (GaAlAs) diode
This process plays an important role in the occurrence of pain semi-conductor laser system, Mediator Soft 1000(r), manufac-
and sensitization. tured by the Matsushita Electric Co., Ltd. (Tokyo Japan), was
Few investigations have so far been reported regarding low- selected. This device has a continuous wavelength of 830 nm
level laser therapy (LLLT) and the correlation between pain in- and an output power of 1 W, respectively. Regarding laser expo-
hibition and the serum PGE2 level in clinical disorders. A study sure, the irradiation time per trigger point was 15 sec, with a
was carried out to clarify the efficiency of low-level laser ther- total of 3 min per day. The patients visited the hospital either
apy to attenuate pain in various orthopedic diseases. A statisti- every day or every other day up to a total of 10 times before the
cal analysis was performed to investigate the serum level of last study was performed. No physical or analgesic require-
PGE2 before and after laser irradiation. ments were simultaneously imposed during the treatment.
1Department of 2nd Orthopedic Surgery Toho University, Tokyo, Japan.
2Department of Physical Medicine and Rehabilitation, Toho University, Tokyo, Japan.
537
[Link] 12/13/04 3:38 PM Page 538
538 Mizutani et al.
Three evaluation items were used: (1) the rating of the anal- TABLE 2. SERUM PGE2 (PG/ML) EVALUATION
gesic effect as effective or ineffective according to the patients’ REPRESENTS SIGNIFICANT DIFFERENCE ESPECIALLY
satisfaction or dissatisfaction, (2) an 11-point visual analog IN EFFECTIVE CASES WITH LASER THERAPY
scale (VAS) and (3) the serum prostaglandin E2 (PGE2) level
Group Effective n=57 Ineffective n=14
(pg/mL). All measurements were performed using the RIA-
PEG method (ARC-950g-Counter, Aloka Co., Ltd.). The diag-
Laser exposure N.S.
nosis of the 83 subjects consisted of the following: frozen
shoulder in 45 cases, cervical spondylosis in seven cases, os- Before 7.10.4 6.90.5
teoarthritis of the knee joint in six cases, de Quervain’s disease * N.S.
After 5.80.3 7.30.9
in five cases, Morton’s disease in three cases, pyriformis syn-
drome in two cases, and miscellaneous disease in 15 cases. **
*p<0.05.
RESULTS
The treatment was effective in 67 of 83 patients (80.7%). No (%). The results in the effective group were significantly lower
significant differences in the mean age on morbid period were than those in the ineffective group, which were 2.4 ± 7.7 and
recognized between the effective and ineffective groups. On 31.6 ± 19.9 respectively ( p < 0.001).
the other hand, the treatment was ineffective in 16 patients
(19.3%) (Table 1).
According to the results of a typical VAS evaluation, the DISCUSSION
score recorded after laser exposure was significantly lower
than that recorded before laser exposure in the effective group, Although it has been confirmed that LLLT may be an effec-
which were 2.8 ± 0.2 and 8.5 ± 0.2, respectively ( p < 0.001). tive alternative to conventional analgesics in the treatment of
The score recorded after laser exposure in the effective group debilitating pain entities, its mechanism of action still remains
was also significantly lower than that recorded after laser ex- unknown, no matter what kind of laser application it may be.
posure in the ineffective group, which were 2.8 ± 0.2 and 7.4 ± The efficacy of LLLT in producing pain attenuation has been
0.4, respectively ( p < 0.001). The VAS evaluation results ob- demonstrated in some papers, however, some issues remain
tained before and after laser exposure were compared between controversial.
the two groups in order to calculate the fluctuations in VAS. The pain plasticity of nociception can be subdivided into
The difference in the pre- and post-irradiation VAS scores and acute and chronic pain, and its cause is characterized by noci-
changes in VAS scores for the effective and ineffective cases ceptive and neuropathic entities, which thus suggests a close
were 5.7 ± 0.2 and 1.6 ± 0.3, respectively, indicating that relationship with efficacy assessment by LLLT. Various studies
the decrease in the VAS score for the effective cases was on the characteristics of semiconductor laser with outputs of
greater than that for the ineffective cases ( p < 0.001) (Table 2). 1 W in power have been reported. Kenmotsu1 described that
According to the results of the serum PGE2 (pg/mL) evalua- comparison to a unit with an output of 150 mW, a semiconduc-
tion, the scores recorded after laser exposure were significantly tor laser with a 1-W output emits light at a constant intensity in
lower than those recorded before laser exposure in the effec- tissue specimens over area approximately twice as deep and
tive group, which were 5.8 ± 0.3 and 7.1 ± 0.4, respectively five times as wide. The introduction of optic fibers has enabled
( p < 0.05). The score recorded after laser exposure in the effec- uniform laser irradiation which can cover a more extensive
tive group were also significantly lower than those recorded area. Harada2 also reported that LLLT with an output power of
after laser exposure in the ineffective group, which were 5.8 ± 1 W demonstrated significant pain attenuation ( p < 0.05).
0.3 and 7.3 ± 0.9, respectively ( p < 0.05). The serum PGE2 Many studies have previously described nociceptive pain
levels obtained before and after laser exposure were compared and its relationship with PGE2, bradykinin (BK) and cytokines.
between the two groups in order to calculate the rate of change In 1971, Vane3 reported that the effect of aspirin-like drugs is
due to their ability to inhibit the synthesis of prostaglandins.
Thereafter, many studies clarified correlations among PGE2,
BK, and SP. PGE2 has also been reported to participate in the
TABLE 1. TYPICAL VAS EVALUATION BEFORE AND
AFTER LASER THERAPY SHOWING SIGNIFICANT indirect sensitizing function of inflammatory hyperalgesia.4
IMPROVEMENT IN EFFECTIVE GROUP On the other hand, an experimental hypoalgesic effect has been
emphasized using a high dosage of PGE2 administered to the
Group Effective n=67 Ineffective n=16 brain stem.5 Many findings on the correlation between PGE2
and inflammatory cytokines such as IL-1 and IL-6 have been
Laser exposure N.S. described.6,7 Prostaglandins have been reported to affect the
terminal of C fibers and an elevation in the tissue prostaglandin
Before 8.50.2 9.20.3 levels resulted in a reduction in the threshold for nociceptive
** N.S.
After 2.80.2 7.40.4 pain and vice versa.8 Regarding the conventional LLLT used in
** these experimental studies, Oyamada9 reported that LLLT in-
hibited the arthralgia accompanying rheumatoid arthritis and
**p<0.001. diminished prostaglandin E2 in the synovial fluid.
[Link] 12/13/04 3:38 PM Page 539
Serum PGE2 with LLLT 539
The findings of our study suggest the following: LLLT ini- 3. Vane J.R. (1971). Inhibition of prostaglandin E2 synthesis as a
tially inhibits the arachidonic acid cascade in tissue leading to mechanism of action for aspirin-like drugs. Nat. New Biol. 231,
a decreased PGE2 production. This phenomenon subsequently 232–235.
affects the production of BK and many kinds of inflammatory 4. Ferreira, S.H. (1978). The hyperalgesic effects of prostaglandin and
prostaglandin E2. Postaglandins 16, 31–37.
cytokines. A local increase in the blood flow after LLLT im-
5. Horiguchi, S., et al. (1986). Alterations in nociception after in-
proves acidosis while also promotes the release and removal of tracisternal administration of prostaglandin D2, E2, or F2 to con-
pain-related substances. Finally, the excitation of mechanical scious mice. Eur. J. Pharmacol. 122, 173–179.
and polymodal nociceptors appears to be controlled. 6. Scheweizer, A., et al. (1988). Interleukin-1 enhances pain reflexes.
Agents Action 25, 246–251.
7. Oka, T., et al. (1994). Intracerebroventicular injection of inter-
CONCLUSION leukin-1 enhances nociceptive neuronal responses of the trigeminal
nucleus caudalis in the rat. Brain Res. 656, 236–244.
LLLT, using a device with a 1-W output, effectively attenu- 8. Otsuka, M., et al. (1990). Physiology and pharmacology of pain.
ated clinical pain in 80.7% of patients and significantly im- Tokyo Med. 97, 37–45.
9. Oyamada, Y. (1988). Cases of therapy with He-Ne laser irradiation
proved their VAS levels. LLLT was also closely associated
in rheumatoid diseases. Jpn. Laser Med. Assoc. 9, 17–24.
with a decreased serum level PGE2 leading to an inhibition of
the sensitization to nociceptive pain. Address reprint requests to:
Dr. Kazuhiro Mizutani
Department of 2nd Orthopedic Surgery
REFERENCES Toho University School of Medicine
2-17-6 Ohashi Meguroku
1. Kenmotsu, O. (2000). Guidebook in treatment of pain with semi- 153-8515 Tokyo, Japan
conductor laser. Tokyo: Medical View Co.
2. Harada, T., et al. (1998). A clinical application of the 1 W Ga-Al-As
diode laser—double blind study. J. Phys. Med. 9, 99–103. E-mail: ortho-2@[Link]
