Acupuncture for Reduction of Inflammation
| Status: | Completed |
|---|---|
| Conditions: | Endocrine |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 4/13/2015 |
| Start Date: | March 2013 |
| End Date: | April 2015 |
| Contact: | Dennis Grech, MD |
| Email: | grechgde@umdnj.edu |
| Phone: | 973 972-2929 |
Acupuncture for Reduction of Inflammation in Thyroid and Parathyroid Surgery
This study is being done because the investigators wish to study ways to improve recovery
after surgery. Injury, including surgical injury, causes inflammation. Inflammation is the
body's attempt to protect itself and to start the healing process. Some surgical
complications are related to the body's natural inflammatory response. Although mainly a
healing response, inflammation can also have side effects which delay recovery. The
investigators wish to determine the effect of acupuncture on post-operative surgical pain.
An increase in pain after surgery can cause distress for patients. Acupuncture is an
alternative medicine methodology originating in China that treats patients by manipulating
thin, solid needles that have been inserted into acupuncture points in the skin. Acupuncture
has been used for the reduction of pain. The investigators would like to see if acupuncture
during surgery can provide a lower level of pain, reduced pain medication requirement, and a
lower incidence of nausea and vomiting.
after surgery. Injury, including surgical injury, causes inflammation. Inflammation is the
body's attempt to protect itself and to start the healing process. Some surgical
complications are related to the body's natural inflammatory response. Although mainly a
healing response, inflammation can also have side effects which delay recovery. The
investigators wish to determine the effect of acupuncture on post-operative surgical pain.
An increase in pain after surgery can cause distress for patients. Acupuncture is an
alternative medicine methodology originating in China that treats patients by manipulating
thin, solid needles that have been inserted into acupuncture points in the skin. Acupuncture
has been used for the reduction of pain. The investigators would like to see if acupuncture
during surgery can provide a lower level of pain, reduced pain medication requirement, and a
lower incidence of nausea and vomiting.
Acupuncture has traditionally been used in Asia and is increasingly popular in Western
countries to treat a variety of conditions (1). In recent years, acupuncture is widely used
to assist in improving pain and inflammatory diseases (2). However, the mechanisms
associated with these treatments that influence the immune system are not yet understood.
Cytokines like interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6
(IL-6) are proposed to be proximal mediators in the early stages of inflammation. They
modulate many of the early inflammatory response that is induced by tissue injury,
infection, or an immune stimulus (3, 4). Although the response is a critical first line of
defense against pathogens, when the inflammatory reaction is uncontrolled, it can cause more
damage to the host than the initial stimulus. TNF-α is a pro-inflammatory cytokine that is
very effective in local and systemic inflammations (5). In addition, TNF-α increases the
production of other inflammatory cytokines such as IL-1β, IL-6, and interleukin-18 (IL-18)
during the inflammatory process. Therefore, it initially brings infections under control,
produces coagulation in the damaged tissue, and stimulates tissue improvement. An excessive
increase of TNF-α level causes an extreme immune reaction and contributes to the development
of atherosclerosis, shock, endotoxemia, and chronic inflammatory diseases such as rheumatoid
arthritis, ankylosing spondylitis, and inflammatory bowel disease (5-7). Yim and colleagues
reported a decrease in increased serum TNF-α, IL-6, and interferon gamma levels by arthritis
as a result of electroacupuncture treatment (9). In a rat model for ulcerative colitis,
acupuncture inhibited the expression of IL-1β and IL-6 (10). It has been reported that
acupuncture significantly reduces complete Freund's adjuvant-induced hind paw edema and
mouse air pouch inflammation (11, 12). Acupuncture could also improve immune dysfunction
after surgical stress both in human and animals (13, 14).
Some cytokines are pro-inflammatory, but others are anti-inflammatory (3). The
anti-inflammatory interleukins comprise interleukine-4 (IL-4) and interleukine-10 (IL-10)
and these are considered as mediating the down-regulation of immune-inflammatory conditions.
Acupuncture for treatment of the ulcerative colitis rats is possibly related with the
decrease of IL-1β, a pro-inflammatory cytokine, and the increase of IL-4, an
anti-inflammatory cytokine (15).
Therefore, it is reasonable to expect that the protective action of acupuncture is exerted
by the modulation of pro- and anti-inflammatory cytokines. The restoration of balance
between pro- and anti-inflammatory cytokines by acupuncture gives into the mechanisms
underlying the immune-modulation effect of acupuncture.
Inflammation is associated with pain hypersensitivity that is produced by the release of
inflammatory mediators. The pro-inflammatory cytokines play an essential role in pain
sensitization (16). The peripheral effects of these cytokines on sensitizing nociceptors
have been well documented (16). Post-operative surgical pain can cause significant
physiologic and psychologic distress for patients. An increase in pain duration and
intensity after surgery can contribute to a variety of complications, including delayed
ambulation, pulmonary and thromboembolic complications, increased length of hospital stay,
and generalized distress and anxiety. Effective post-surgical pain relief requires a
multidisciplinary effort and influences patients' satisfaction with care and successful
outcomes (17). Acupuncture has been used for a long time for the reduction of pain. In light
of these factors, the use of acupuncture that may allow a reduction in the dosage of
conventional analgesics is highly valuable because it can lower the incidence of possible
adverse effects. Several trials have demonstrated that patients receiving acupuncture prior
to surgery have a lower level of pain, reduced opioid requirement, a lower incidence of
post-operative nausea and vomiting, and lower sympatho-adrenal responses (18). The local
release of β-endorphin could be responsible for the analgesic effect. β-endorphin may be
interacting with cytokines to reduce pain and acupuncture may amplify the interaction
between β-endorphin and cytokines.
The investigators will ask patients undergoing thyroid and parathyroid surgery to determine
how acupuncture restores a balance of pro- and anti-inflammatory cytokines to reduce pain
and inflammation before, during, and after surgery. The effect of acupuncture on
post-surgical pain will be evaluated.
Protocol A prospective randomized, double-blinded (patient and data collector), study of 30
patients undergoing thyroid or parathyroid surgery under general anesthesia, will be
conducted to compare the effects of acupuncture on the levels of circulating cytokines
between acupuncture group and control group. The control group is to receive the same
anesthetic and surgical techniques without the acupuncture.
The principal investigator will use the Large intestine 4 (LI-4), the Large intestine 11
(LI-11), and the Stomach 36 (ST-36) acupuncture points (acupoints). LI-4 and LI-11 acupoints
lie on the Large intestine meridian (pathway). The Large intestine meridian runs through the
frontal neck region including the thyroid. LI-4 point is located in the middle of the 2nd
metacarpal bone on the radial side and LI-11 point is located at the lateral end of the
transverse cubital crease. Acupuncture on these two acupoints showed increased
immune-modulatory effects including cytotoxicity of leukocytes (19, 20). ST-36 point is
located on the outside of the anterior crest of the tibia and just below the knee. This
point is the most commonly used to reduce general body pain (21). The acupuncture procedures
will be performed by an anesthesiologist licensed to do so.
After cleaning the skin with alcohol swabs, an acupuncture needle (30 Gauge, 0.30X30 mm, Mac
Spring Handle Needle, Korea) will be swiftly inserted approximately 5-10 mm deep bilaterally
at both LI-4 and LI-11 acupoints of each arm and at ST-36 acupoint of each leg.
Electroacupuncture (EA) will be delivered by a stimulator (Digital Electronic Acupunctoscope
4-C, Model AWQ-104L™ Hong Kong, Dist by Lhasa Medical, Weymouth, MA) via electrodes from the
stimulator at 10 Hz frequency with the electrical current of continuous wave. This setting
showed significant anti-hyperalgesic effects in a rat inflammation model (22, 23) and also
inhibited the up-regulation of IL-1β and its mRNA compared to the sham control in a rat
model of bone cancer pain (24). EA is a particularly therapeutic method in which a small
electrical charge is applied to acupuncture needles inserted at the acupoints. EA has the
advantage of combining the stimulation of both needles and electricity compared to manual
acupuncture alone, and may potentiate the effect of the acupuncture treatment along the
meridians. One end of electrode will be attached to the acupuncture needle handle at LI-4
acupoint, and another end will be attached to the acupuncture needle handle at LI-11acupoint
bilaterally. For EA on ST-36, one end of electrode will be attached at the right side ST-36
acupoint and another end will be attached at the left side ST-36 acupoint. A symmetrical
biphasic wave will be delivered to the electrodes so that the electrode will be alternately
positive and negative and the bilateral LI-4, LI-11, and ST-36 acupoints will be stimulated
alternately. Mild muscle twitching will be observed.
The investigator will stimulate the acupoints as follows:
1. EA will be performed for 30 min (a time that is similar to that used in clinical
practice).
2. EA will stop after 30 min of the treatment, but leave the needles on the acupoints.
3. Subsequently, EA will be re-initiated for an additional 30 min.
This advanced EA technique showed more increased nitric oxide production in the second
interval of EA than that of the first interval, and reduced blood pressure at the end of the
second interval in our preliminarily study (25). In addition, this technique increased
transient receptor potential vanilloid type-1 receptor immunoreactivity in the acupoints
compared to that of non-acupoints (26). The advanced EA treatment will be started just
before the beginning of surgery.
At the conclusion of the surgical procedure, the acupuncture needles will be removed. The
subjects will be awakened and after meeting the criteria for extubation will be transferred
to the Post Anesthesia Care Unit (PACU).
Blood Samples A second intravenous line will be placed in the other arm after the induction
of anesthesia and prior to surgical incision to collect blood samples. 15 ml of blood will
be collected at three time points: (1) preinduction, (2) just after the advanced EA
treatment (3) after arrival in PACU and prior to additional medication administration
(approximately 120 minutes post preinduction sample). These specimens will be placed into
vacutainer tubes with no anti-coagulant. Blood will be drawn with a syringe attached
directly to the angiocatheter which has been placed intravenously. To prevent hemolysis,
blood will be transferred without a needle, to a vacutainer whose top has been removed. The
vacutainer top will be replaced and specimens labeled with study name, subject's study ID
number, sample number, and dated. Bloods from the first two time points will be kept
refrigerated until the final sample is obtained postoperatively. Blood samples will be
transported to the Institute for Complementary and Alternative Medicine/School of Health
Related Professions Interprofessional Health Research Laboratory within the Department of
Clinical Lab Sciences (G level, Bergen Building, 65 Bergen St., Newark). They will be
centrifuged, serum removed, aliquoted, and stored at -800C until analysis.
Laboratory Analysis Samples will be analyzed for levels of cortisol, C-reactive proteins,
and cytokines interleukin (IL)-1α, IL-1β, IL-1ra, IL-2, IL-6, IL-8, IL-10, and TNF-α, by
appropriate methods, including ELISA or multiplex fluorescent bead technology. All samples
will be run in duplicate on with plates and reagents of the same lot. Any samples varying
greater than 15% between duplicates will be repeated.
countries to treat a variety of conditions (1). In recent years, acupuncture is widely used
to assist in improving pain and inflammatory diseases (2). However, the mechanisms
associated with these treatments that influence the immune system are not yet understood.
Cytokines like interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6
(IL-6) are proposed to be proximal mediators in the early stages of inflammation. They
modulate many of the early inflammatory response that is induced by tissue injury,
infection, or an immune stimulus (3, 4). Although the response is a critical first line of
defense against pathogens, when the inflammatory reaction is uncontrolled, it can cause more
damage to the host than the initial stimulus. TNF-α is a pro-inflammatory cytokine that is
very effective in local and systemic inflammations (5). In addition, TNF-α increases the
production of other inflammatory cytokines such as IL-1β, IL-6, and interleukin-18 (IL-18)
during the inflammatory process. Therefore, it initially brings infections under control,
produces coagulation in the damaged tissue, and stimulates tissue improvement. An excessive
increase of TNF-α level causes an extreme immune reaction and contributes to the development
of atherosclerosis, shock, endotoxemia, and chronic inflammatory diseases such as rheumatoid
arthritis, ankylosing spondylitis, and inflammatory bowel disease (5-7). Yim and colleagues
reported a decrease in increased serum TNF-α, IL-6, and interferon gamma levels by arthritis
as a result of electroacupuncture treatment (9). In a rat model for ulcerative colitis,
acupuncture inhibited the expression of IL-1β and IL-6 (10). It has been reported that
acupuncture significantly reduces complete Freund's adjuvant-induced hind paw edema and
mouse air pouch inflammation (11, 12). Acupuncture could also improve immune dysfunction
after surgical stress both in human and animals (13, 14).
Some cytokines are pro-inflammatory, but others are anti-inflammatory (3). The
anti-inflammatory interleukins comprise interleukine-4 (IL-4) and interleukine-10 (IL-10)
and these are considered as mediating the down-regulation of immune-inflammatory conditions.
Acupuncture for treatment of the ulcerative colitis rats is possibly related with the
decrease of IL-1β, a pro-inflammatory cytokine, and the increase of IL-4, an
anti-inflammatory cytokine (15).
Therefore, it is reasonable to expect that the protective action of acupuncture is exerted
by the modulation of pro- and anti-inflammatory cytokines. The restoration of balance
between pro- and anti-inflammatory cytokines by acupuncture gives into the mechanisms
underlying the immune-modulation effect of acupuncture.
Inflammation is associated with pain hypersensitivity that is produced by the release of
inflammatory mediators. The pro-inflammatory cytokines play an essential role in pain
sensitization (16). The peripheral effects of these cytokines on sensitizing nociceptors
have been well documented (16). Post-operative surgical pain can cause significant
physiologic and psychologic distress for patients. An increase in pain duration and
intensity after surgery can contribute to a variety of complications, including delayed
ambulation, pulmonary and thromboembolic complications, increased length of hospital stay,
and generalized distress and anxiety. Effective post-surgical pain relief requires a
multidisciplinary effort and influences patients' satisfaction with care and successful
outcomes (17). Acupuncture has been used for a long time for the reduction of pain. In light
of these factors, the use of acupuncture that may allow a reduction in the dosage of
conventional analgesics is highly valuable because it can lower the incidence of possible
adverse effects. Several trials have demonstrated that patients receiving acupuncture prior
to surgery have a lower level of pain, reduced opioid requirement, a lower incidence of
post-operative nausea and vomiting, and lower sympatho-adrenal responses (18). The local
release of β-endorphin could be responsible for the analgesic effect. β-endorphin may be
interacting with cytokines to reduce pain and acupuncture may amplify the interaction
between β-endorphin and cytokines.
The investigators will ask patients undergoing thyroid and parathyroid surgery to determine
how acupuncture restores a balance of pro- and anti-inflammatory cytokines to reduce pain
and inflammation before, during, and after surgery. The effect of acupuncture on
post-surgical pain will be evaluated.
Protocol A prospective randomized, double-blinded (patient and data collector), study of 30
patients undergoing thyroid or parathyroid surgery under general anesthesia, will be
conducted to compare the effects of acupuncture on the levels of circulating cytokines
between acupuncture group and control group. The control group is to receive the same
anesthetic and surgical techniques without the acupuncture.
The principal investigator will use the Large intestine 4 (LI-4), the Large intestine 11
(LI-11), and the Stomach 36 (ST-36) acupuncture points (acupoints). LI-4 and LI-11 acupoints
lie on the Large intestine meridian (pathway). The Large intestine meridian runs through the
frontal neck region including the thyroid. LI-4 point is located in the middle of the 2nd
metacarpal bone on the radial side and LI-11 point is located at the lateral end of the
transverse cubital crease. Acupuncture on these two acupoints showed increased
immune-modulatory effects including cytotoxicity of leukocytes (19, 20). ST-36 point is
located on the outside of the anterior crest of the tibia and just below the knee. This
point is the most commonly used to reduce general body pain (21). The acupuncture procedures
will be performed by an anesthesiologist licensed to do so.
After cleaning the skin with alcohol swabs, an acupuncture needle (30 Gauge, 0.30X30 mm, Mac
Spring Handle Needle, Korea) will be swiftly inserted approximately 5-10 mm deep bilaterally
at both LI-4 and LI-11 acupoints of each arm and at ST-36 acupoint of each leg.
Electroacupuncture (EA) will be delivered by a stimulator (Digital Electronic Acupunctoscope
4-C, Model AWQ-104L™ Hong Kong, Dist by Lhasa Medical, Weymouth, MA) via electrodes from the
stimulator at 10 Hz frequency with the electrical current of continuous wave. This setting
showed significant anti-hyperalgesic effects in a rat inflammation model (22, 23) and also
inhibited the up-regulation of IL-1β and its mRNA compared to the sham control in a rat
model of bone cancer pain (24). EA is a particularly therapeutic method in which a small
electrical charge is applied to acupuncture needles inserted at the acupoints. EA has the
advantage of combining the stimulation of both needles and electricity compared to manual
acupuncture alone, and may potentiate the effect of the acupuncture treatment along the
meridians. One end of electrode will be attached to the acupuncture needle handle at LI-4
acupoint, and another end will be attached to the acupuncture needle handle at LI-11acupoint
bilaterally. For EA on ST-36, one end of electrode will be attached at the right side ST-36
acupoint and another end will be attached at the left side ST-36 acupoint. A symmetrical
biphasic wave will be delivered to the electrodes so that the electrode will be alternately
positive and negative and the bilateral LI-4, LI-11, and ST-36 acupoints will be stimulated
alternately. Mild muscle twitching will be observed.
The investigator will stimulate the acupoints as follows:
1. EA will be performed for 30 min (a time that is similar to that used in clinical
practice).
2. EA will stop after 30 min of the treatment, but leave the needles on the acupoints.
3. Subsequently, EA will be re-initiated for an additional 30 min.
This advanced EA technique showed more increased nitric oxide production in the second
interval of EA than that of the first interval, and reduced blood pressure at the end of the
second interval in our preliminarily study (25). In addition, this technique increased
transient receptor potential vanilloid type-1 receptor immunoreactivity in the acupoints
compared to that of non-acupoints (26). The advanced EA treatment will be started just
before the beginning of surgery.
At the conclusion of the surgical procedure, the acupuncture needles will be removed. The
subjects will be awakened and after meeting the criteria for extubation will be transferred
to the Post Anesthesia Care Unit (PACU).
Blood Samples A second intravenous line will be placed in the other arm after the induction
of anesthesia and prior to surgical incision to collect blood samples. 15 ml of blood will
be collected at three time points: (1) preinduction, (2) just after the advanced EA
treatment (3) after arrival in PACU and prior to additional medication administration
(approximately 120 minutes post preinduction sample). These specimens will be placed into
vacutainer tubes with no anti-coagulant. Blood will be drawn with a syringe attached
directly to the angiocatheter which has been placed intravenously. To prevent hemolysis,
blood will be transferred without a needle, to a vacutainer whose top has been removed. The
vacutainer top will be replaced and specimens labeled with study name, subject's study ID
number, sample number, and dated. Bloods from the first two time points will be kept
refrigerated until the final sample is obtained postoperatively. Blood samples will be
transported to the Institute for Complementary and Alternative Medicine/School of Health
Related Professions Interprofessional Health Research Laboratory within the Department of
Clinical Lab Sciences (G level, Bergen Building, 65 Bergen St., Newark). They will be
centrifuged, serum removed, aliquoted, and stored at -800C until analysis.
Laboratory Analysis Samples will be analyzed for levels of cortisol, C-reactive proteins,
and cytokines interleukin (IL)-1α, IL-1β, IL-1ra, IL-2, IL-6, IL-8, IL-10, and TNF-α, by
appropriate methods, including ELISA or multiplex fluorescent bead technology. All samples
will be run in duplicate on with plates and reagents of the same lot. Any samples varying
greater than 15% between duplicates will be repeated.
Inclusion Criteria:
1. Not currently pregnant or beast feeding
2. American Society of Anesthesiologists physical status of 1, 2, 3 as determined by
your anesthesiologist
3. Patients have a working telephone
Exclusion Criteria:
1. Uncontrolled high blood pressure (systolic > 180mmHg, diastolic>110mmHg
2. Heart block >than first degree
3. Pacemaker
4. Cardiac muscle is at risk for injury
5. not English speaking
6. Acupuncture within the last 30 days
7. If you have taken ibuprofen, advil aleve, motrin or aspirin with 5 days of the
scheduled surgery.
8. Prior history of drug or alcohol dependence
9. If you are unable to feed, dress or bathe yourself
10. If your breathing tube is not removed prior to leaving the operating room.
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