Acupuncture in Patients with Diabetic Peripheral Neuropathy-Related Complaints: A Randomized Controlled Clinical Trial.

Background: Diabetic polyneuropathy (DPN) is a common complication of diabetes, which presents with a loss of sensorimotor function or pain. This study assessed the effectiveness and safety of acupuncture as a treatment for DPN-related complaints. Methods: In this randomized controlled trial, patients with type II diabetes and symptoms of neuropathy in the lower limbs were included. A total of 12 acupuncture treatments were administered over 8 weeks. The waitlist control group received the same acupuncture treatment starting at week 16 (after baseline). Results: A total of 62 patients were randomized (acupuncture group n = 31; control group n = 31). The primary outcome was overall complaints, and it was reduced with a significant difference of 24.7 on a VAS (CI 95% 14.8;34.7, p < 0.001) between both groups in favor of acupuncture. Reductions were recorded for the secondary outcomes VAS pain, neuropathic pain symptom inventory (NPSI), emotional dimensions of pain, SF-12, and diabetic peripheral neuropathic pain impact (DPNPI) after the intervention and at the follow-ups in the acupuncture group. Adverse reactions were minor and transient. Conclusions: Acupuncture leads to a significant and lasting reduction in DPN-related complaints when compared to routine care and is well tolerated, with minor side effects.

Acupuncture in diabetic peripheral neuropathy-neurological outcomes of the randomized acupuncture in diabetic peripheral neuropathy trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus and can lead to serious complications. Therapeutic strategies for pain control are available but there are few approaches that influence neurological deficits such as numbness. AIM: To investigate the effectiveness of acupuncture on improving neurological deficits in patients suffering from type 2 DPN. METHODS: The acupuncture in DPN (ACUDPN) study was a two-armed, randomized, controlled, parallel group, open, multicenter clinical trial. Patients were randomized in a 1:1 ratio into two groups: The acupuncture group received 12 acupuncture treatments over 8 wk, and the control group was on a waiting list during the first 16 wk, before it received the same treatment as the other group. Both groups received routine care. Outcome parameters were evaluated after 8, 16 and 24 wk and included neurological scores, such as an 11-point numeric rating scale (NRS) 11 for hypesthesia, neuropathic pain symptom inventory (NPSI), neuropathy deficit score (NDS), neuropathy symptom score (NSS); nerve conduction studies (NCS) were assessed with a handheld point-of-care device. RESULTS: Sixty-two participants were included. The NRS for numbness showed a difference of 2.3 (P < 0.001) in favor of the acupuncture group, the effect persisted until week 16 with a difference of 2.2 (P < 0.001) between groups and 1.8 points at week 24 compared to baseline. The NPSI was improved in the acupuncture group by 12.6 points (P < 0.001) at week 8, the NSS score at week 8 with a difference of 1.3 (P < 0.001); the NDS and the TNSc score improved for the acupuncture group in week 8, with a difference of 2.0 points (P < 0.001) compared to the control group. Effects were persistent in week 16 with a difference of 1.8 points (P < 0.05). The NCS showed no meaningful changes. In both groups only minor side effects were reported. CONCLUSION: Study results suggest that acupuncture may be beneficial in type 2 diabetic DPN and seems to lead to a reduction in neurological deficits. No serious adverse events were recorded and the adherence to treatment was high. Confirmatory randomized sham-controlled clinical studies with adequate patient numbers are needed to confirm the results.

Acupuncture improves chemotherapy-induced neuropathy explored by neurophysiological and clinical outcomes - The randomized, controlled, cross-over ACUCIN trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is recognized as the second commonest side effect after chemotherapy. Besides neurological deficits and pain, it is a potential reason for terminating chemotherapy. Effective curative treatments of neurodegeneration are lacking. Hitherto, no randomized controlled study used nerve conduction studies (NCS), the gold standard diagnostic tool for peripheral neuropathy, as the primary outcome parameter for evaluating acupuncture for CIPN, which can also measure structural changes. METHODS: The study was carried out at the HanseMerkur Center for TCM at the University Medical Center, Hamburg-Eppendorf. Sixty patients with CIPN were included in the study after physical examination, subjective evaluation and quantitative evaluation by NCS. Subsequently, the patients were randomly assigned to Group 1 (30 patients), which received, in the first period, needle acupuncture and to Group 2 (30 patients), which was assigned to the waiting list in the first period. Group 1 received a standard 10-week bilateral treatment of ST34 (Liangqiu), EX-LE12 (Qiduan) and EX-LE8 (Bafeng). After 14 weeks, both groups were re-evaluated. Using a cross-over design, the patients of Group 2 received the same treatment procedure as Group 1 in the first period. Patients of Group 1 were assigned to the waiting list for the second period. After 28 weeks both groups were re-evaluated. Wilcoxon test was used as a pre-test to rule out carryover effects and to test for differences between acupuncture and the waiting list. Group assignment was not exposed to the statistician and the neurologist. RESULTS: Sural sensory nerve amplitude, and sural nerve conduction velocity, were significantly improved (p < 0.01, effect size (f) 0.55 and 0.49) compared to measurements in the waiting period. Change of NCS of the tibial nerve did not significantly differ in group comparison. Patients reported subjective improvement during acupuncture treatment superior to the waiting period for burning pain, cramps, numbness, frequency of symptoms (all p < 0.01) and unsteadiness of gait (p < 0.05). On physical examination, blind walking, heel-to-toe walking, distal pallhypesthesia (both p < 0.01), and the neuropathy deficit score (p < 0.05) were significantly improved during acupuncture treatment compared to the waiting period. CONCLUSION: Acupuncture can enhance structural regeneration in CIPN as measured by NCS, which is manifested in subjective improvement and neurological findings.

Electrophysiologically verified effects of acupuncture on diabetic peripheral neuropathy in type 2 diabetes: The randomized, partially double-blinded, controlled ACUDIN trial.

BACKGROUND: Acupuncture is commonly used in Traditional Chinese Medicine for treatment of diabetic peripheral neuropathy (DPN), but data from randomized controlled trials are rare. METHODS: This randomized, placebo-controlled, partially double-blinded clinical trial randomly assigned adults with confirmed type 2 diabetes-induced DPN to receive 10 sessions of needle acupuncture, laser acupuncture, or placebo laser acupuncture for 10 consecutive weeks. Treatment was provided at bilateral acupoints Ex-LE-10 (Bafeng), Ex-LE-12 (Qiduan), and ST-34 (Lianqiu). Neurological assessments, including nerve conduction studies (NCS) of sural and tibial nerves, were performed at baseline and weeks 6 and 15. Primary outcome was delta of sural sensory nerve action potential (SNAP). Secondary outcomes included further NCS values, clinical scores, and patient-reported outcome measures (PROMs). RESULTS: Of 180 participants, 172 completed the study. Sural SNAP and sural and tibial nerve conduction velocities improved significantly after 10 treatments when comparing needle acupuncture to placebo. Needle acupuncture showed earlier onset of action than laser acupuncture. PROMs showed larger improvements following needle and laser acupuncture than placebo, reaching significant differences for hyperesthesia and cramps following needle acupuncture and for heat sensation following laser acupuncture. CONCLUSIONS: Classical needle acupuncture had significant effects on DPN. Improvement in NCS values presumably indicates structural neuroregeneration following acupuncture.

ACUDIN - ACUpuncture and laser acupuncture for treatment of DIabetic peripheral Neuropathy: a randomized, placebo-controlled, partially double-blinded trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus with significant clinical sequelae that can affect a patient's quality of life. Metabolic and microvascular factors are responsible for nerve damage, causing loss of nerve function, numbness, painful sensory symptoms, and muscle weakness. Therapy is limited to anti-convulsant or anti-depressant drugs for neuropathic pain and paresthesia. However, reduced sensation, balance and gait problems are insufficiently covered by this treatment. Previous data suggests that acupuncture, which has been in use in Traditional Chinese Medicine for many years, may potentially complement the treatment options for peripheral neuropathy. Nevertheless, more objective data on clinical outcome is necessary to generally recommend acupuncture to the public. METHODS: We developed a study design for a prospective, randomized (RCT), placebo-controlled, partially double-blinded trial for investigating the effect of acupuncture on DPN as determined by nerve conduction studies (NCS) with the sural sensory nerve action potential amplitude as the primary outcome. The sural sensory nerve conduction velocity, tibial motor nerve action potential amplitude, tibial motor nerve conduction velocity, the neuropathy deficit score, neuropathy symptom score, and numeric rating scale questionnaires are defined as secondary outcomes. One hundred and eighty patients with type 2 diabetes mellitus will be randomized into three groups (needle acupuncture, verum laser acupuncture, and placebo laser acupuncture). We hypothesize that needle and laser acupuncture have beneficial effects on electrophysiological parameters and clinical and subjective symptoms in relation to DPN in comparison with placebo. DISCUSSION: The ACUDIN trial aims at investigating whether classical needle acupuncture and/or laser acupuncture are efficacious in the treatment of DPN. For the purpose of an objective parameter, NCS were chosen as outcome measures. Acupuncture treatment may potentially improve patients' quality of life and reduce the socio-economic burden caused by DPN. TRIAL REGISTRATION: German Clinical Trial Register (DRKS), No. DRKS00008562 , trial search portal of the WHO ( http://apps.who.int/trialsearch/ ).

Acupuncture analgesia involves modulation of pain-induced gamma oscillations and cortical network connectivity.

Recent studies support the view that cortical sensory, limbic and executive networks and the autonomic nervous system might interact in distinct manners under the influence of acupuncture to modulate pain. We performed a double-blind crossover design study to investigate subjective ratings, EEG and ECG following experimental laser pain under the influence of sham and verum acupuncture in 26 healthy volunteers. We analyzed neuronal oscillations and inter-regional coherence in the gamma band of 128-channel-EEG recordings as well as heart rate variability (HRV) on two experimental days. Pain ratings and pain-induced gamma oscillations together with vagally-mediated power in the high-frequency bandwidth (vmHF) of HRV decreased significantly stronger during verum than sham acupuncture. Gamma oscillations were localized in the prefrontal cortex (PFC), mid-cingulate cortex (MCC), primary somatosensory cortex and insula. Reductions of pain ratings and vmHF-power were significantly correlated with increase of connectivity between the insula and MCC. In contrast, connectivity between left and right PFC and between PFC and insula correlated positively with vmHF-power without a relationship to acupuncture analgesia. Overall, these findings highlight the influence of the insula in integrating activity in limbic-saliency networks with vagally mediated homeostatic control to mediate antinociception under the influence of acupuncture.

Immediate Pain Relief in Adhesive Capsulitis by Acupuncture-A Randomized Controlled Double-Blinded Study.

OBJECTIVE: Primary adhesive capsulitis (AC), or frozen shoulder, is an insidious and idiopathic disease. Severe pain is predominant in the first two of the three stages of the condition, which can last up to 21 months. DESIGN, SETTING, AND SUBJECTS: Sixty volunteers with primary AC were randomly assigned to acupuncture with press tack needles compared with press tack placebos in a patient- and observer-blinded placebo-controlled study. The participants were subsequently offered classical needle acupuncture in an open follow-up clinical application. Thirty-four volunteers received conservative therapy, including 10 classical needle acupuncture treatments over 10 weeks, 13 volunteers received conservative therapy without classical needle acupuncture. All subjects agreed to follow-up after one year. METHODS: Acupuncture treatment was performed using a specific distal needling concept, using reflex areas on distant extremities avoiding local treatment. RESULTS: An immediate improvement of 3.3 ± 3.2 points in Constant-Murley Shoulder Score (CMS) pain subscore was seen in the press tack needles group and of 1.6 ± 2.8 points in the press tack placebos group (P <0.02). Conservative therapy including classical needle acupuncture significantly improved the pain subscore within 14.9 ± 15.9 weeks compared with 30.9 ± 15.8 weeks with only conservative therapy (P < 0.001). CONCLUSION: The efficiency of distal needling acupuncture on immediate pain reduction was demonstrated in patients with AC and confirmed the applicability of press tack needles and press tack placebos for double-blind studies in acupuncture. Subsequent clinical application observation proved that results obtained with press tack needles/press tack placebos can be transferred to classical needle acupuncture. Integrating acupuncture with conservative therapy showed superior effectiveness with respect to the time course of the recovery process in AC compared with conservative therapy alone.

Low level laser therapy for the treatment of diabetic foot ulcers: a critical survey.

Diabetic foot ulcers as one of the most common complications of diabetes mellitus are defined as nonhealing or long-lasting chronic skin ulcers in diabetic patients. Multidisciplinary care for the diabetic foot is common, but treatment results are often unsatisfactory. Low level laser therapy (LLLT) on wound areas as well as on acupuncture points, as a noninvasive, pain-free method with minor side effects, has been considered as a possible treatment option for the diabetic foot syndrome. A systematic literature review identified 1764 articles on this topic. Finally, we adopted 22 eligible references; 8 of them were cell studies, 6 were animal studies, and 8 were clinical trials. Cell studies and animal studies gave evidence of cellular migration, viability, and proliferation of fibroblast cells, quicker reepithelization and reformed connective tissue, enhancement of microcirculation, and anti-inflammatory effects by inhibition of prostaglandine, interleukin, and cytokine as well as direct antibacterial effects by induction of reactive oxygen species (ROS). The transferral of these data into clinical medicine is under debate. The majority of clinical studies show a potential benefit of LLLT in wound healing of diabetic ulcers. But there are a lot of aspects in these studies limiting final evidence about the actual output of this kind of treatment method. In summary, all studies give enough evidence to continue research on laser therapy for diabetic ulcers, but clinical trials using human models do not provide sufficient evidence to establish the usefulness of LLLT as an effective tool in wound care regimes at present. Further well designed research trials are required to determine the true value of LLLT in routine wound care.

A survey of chinese medicinal herbal treatment for chemotherapy-induced oral mucositis.

Oral mucositis is one of the common side effects of chemotherapy treatment with potentially severe implications. Despite several treatment approaches by conventional and complementary western medicine, the therapeutic outcome is often not satisfactory. Traditional Chinese Medicine (TCM) offers empirical herbal formulas for the treatment of oral ulceration which are used in adaptation to chemotherapy-induced mucositis. While standard concepts for TCM treatment do not exist and acceptance by conventional oncologists is still low, we conducted a review to examine the evidence of Chinese herbal treatment in oral mucositis. Eighteen relevant studies on 4 single herbs, 2 combinations of 2 herbs, and 11 multiherbal prescriptions involving 3 or more compounds were included. Corresponding molecular mechanisms were investigated. The knowledge about detailed herbal mechanisms, especially in multi-herbal prescriptions is still limited. The quality of clinical trials needs further improvement. Meta-analysis on the existent database is not possible but molecular findings on Chinese medicinal herbs indicate that further research is still promising for the treatment of chemotherapy-induced oral mucositis.

Can medical herbs stimulate regeneration or neuroprotection and treat neuropathic pain in chemotherapy-induced peripheral neuropathy?

Chemotherapy-induced neuropathy (CIPN) has a relevant impact on the quality of life of cancer patients. There are no curative conventional treatments, so further options have to be investigated. We conducted a systematic review in English and Chinese language databases to illuminate the role of medical herbs. 26 relevant studies on 5 single herbs, one extract, one receptor-agonist, and 8 combinations of herbs were identified focusing on the single herbs Acorus calamus rhizoma, Cannabis sativa fructus, Chamomilla matricaria, Ginkgo biloba, Salvia officinalis, Sweet bee venom, Fritillaria cirrhosae bulbus, and the herbal combinations Bu Yang Huan Wu, modified Bu Yang Huan Wu plus Liuwei Di Huang, modified Chai Hu Long Gu Mu Li Wan, Geranii herba plus Aconiti lateralis praeparata radix , Niu Che Sen Qi Wan (Goshajinkigan), Gui Zhi Jia Shu Fu Tang (Keishikajutsubuto), Huang Qi Wu Wu Tang (Ogikeishigomotsuto), and Shao Yao Gan Cao Tang (Shakuyakukanzoto). The knowledge of mechanism of action is still limited, the quality of clinical trials needs further improvement, and studies have not yielded enough evidence to establish a standard practice, but a lot of promising substances have been identified. While CIPN has multiple mechanisms of neuronal degeneration, a combination of herbs or substances might deal with multiple targets for the aim of neuroprotection or neuroregeneration in CIPN.

An acupuncture research protocol developed from historical writings by mathematical reflections: a rational individualized acupoint selection method for immediate pain relief.

While balancing yin and yang is one basic principle of Chinese medicine, balancing methods for combination of meridians and acupoints had been described throughout the history of Chinese medicine. We have identified six historical systems for combinations of acupuncture points in historical writings. All of them represent symmetrical combinations which are defined by the steps in the Chinese Clock. Taking the historical systems as a basis, we calculated the possible combinations that fit into these systems they revealed, leading to a total of 19 systems offering new balancing combinations. Merging the data of these 19 systems, there are 7 combinatorial options for every meridian. On the basis of this data, we calculated 4-meridian combinations with an ideal balance pattern, which is given when all meridians balance each other. We identified 5 of these patterns for every meridian, so we end up with 60 patterns for all the 12 meridians but we find multiple overlapping. Finally, 15 distinct patterns remain. By combining this theoretical concept with the Image and Mirror Concept, we developed an acupuncture research protocol. This protocol potentially solves some problems of acupuncture trials because it represents a rational reproducible procedure independent of examiner experience, but the resulting treatment is individualized.

Mathematical reflections on acupoint combinations in the traditional meridian systems.

The meridian system is a systematic order of empirical knowledge functioning as a rational ground for a balanced treatment by combining meridians. In TCM theory, a continuous circulation of Qi through 12 meridians is postulated, described as the Chinese clock (CC). On this basis, combinations of meridians and acupoints had been described in historical writings. The most common is the interior/exterior system beside the neighbouring system, the opposite clock system, and three systems, developed out of the theory of the six stages. All of these represent symmetrical combinations, which were defined by the steps in the CC. We calculated the possible combinations that fit into the systematics of the historical descriptions, leading to 19 systems. Merging the data of the 19 systems, possible steps in the CC clock for balancing a meridian are 1, 2, 3, and 6. Step 4 is not possible. Step 5 is a combinatory possibility but has no widespread tradition except for activating the yin extraordinary vessels. These possibilities can be plotted on the CC as a powerful tool for daily practice. Only two meridians might be excluded as potentially balancing meridians, so it seems almost impossible to define noneffective acupuncture points as controls in clinical trials.

Acupuncture for chemotherapy-induced peripheral neuropathy (CIPN): a pilot study using neurography.

OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) can produce severe neurological deficits and neuropathic pain and is a potential reason for terminating or suspending chemotherapy treatments. Specific and effective curative treatments are lacking. METHODS: A pilot study was conducted to evaluate the therapeutic effect of acupuncture on CIPN as measured by changes in nerve conduction studies (NCS) in six patients treated with acupuncture for 10 weeks in addition to best medical care and five control patients who received the best medical care but no specific treatment for CIPN. RESULTS: In five of the six patients treated with acupuncture, NCS improved after treatment. In the control group, three of five patients did not show any difference in NCS, one patient improved and one showed impaired NCS. CONCLUSION: The data suggest that acupuncture has a positive effect on CIPN. The encouraging results of this pilot study justify a randomised controlled trial of acupuncture in CIPN on the basis of NCS.