Magnetic Non-invasive Auricular Acupuncture During Eye-Exam for Retinopathy of Prematurity in Preterm Infants: A Multicentre Randomized Controlled Trial.

Background: Eye exam for Retinopathy of prematurity (ROP) is a painful procedure and pharmacological analgesia might be ineffective. We hypothesized that magnetic auricular acupuncture (MAA) compared to placebo will decrease pain during ROP exam in preterm infants. Methods: Multicentre randomized controlled trial conducted in three hospitals (Australia, Canada, and Malaysia). Eligibility: >32 weeks, ROP exam, not sedated, and parental consent. A total of 100 infants were randomized (1:1) to MAA (n = 50) or placebo (n = 50). MAA stickers or placebo were placed on both ears by an unblinded investigator. Pain was assessed using the Premature Infant Pain Profile. Primary analyses were by intention-to-treat. ClinicalTrials.gov:NCT03650621. Findings: The mean (standard deviation, SD) gestation, birthweight, and postnatal age were (MAA 28(3) vs. placebo 28(2) weeks; MAA 1,057(455) vs. placebo 952(273) g; MAA 7(3) vs. placebo 7(3) weeks. Placebo infants had significantly higher PIPP scores during [mean difference 1.6 points (95%CI 0.1-3.1)] and 1 h mean difference 1.5 points (95%CI 0.7-2.2) after the procedure (p < 0.03). Heart rate was lower (173(22) vs. 184(18)/min) and oxygen saturations were higher (93.8(6.2) vs. 91.7(6.1)%, p = 0.05) in MAA infants. No adverse effects. Interpretation: MAA may reduce physiological pain responses during and after ROP exam in preterm infants. Assessment of long-term effects are warranted. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT03650621.

A Review of Non-Pharmacological Treatments for Pain Management in Newborn Infants.

Pain is a major problem in sick newborn infants, especially for those needing intensive care. Pharmacological pain relief is the most commonly used, but might be ineffective and has side effects, including long-term neurodevelopmental sequelae. The effectiveness and safety of alternative analgesic methods are ambiguous. The objective was to review the effectiveness and safety of non-pharmacological methods of pain relief in newborn infants and to identify those that are the most effective. PubMed and Google Scholar were searched using the terms: "infant", "premature", "pain", "acupuncture", "skin-to-skin contact", "sucrose", "massage", "musical therapy" and 'breastfeeding'. We included 24 studies assessing different methods of non-pharmacological analgesic techniques. Most resulted in some degree of analgesia but many were ineffective and some were even detrimental. Sucrose, for example, was often ineffective but was more effective than music therapy, massage, breast milk (for extremely premature infants) or non-invasive electrical stimulation acupuncture. There were also conflicting results for acupuncture, skin-to-skin care and musical therapy. Most non-pharmacological methods of analgesia provide a modicum of relief for preterm infants, but none are completely effective and there is no clearly superior method. Study is also required to assess potential long-term consequences of any of these methods.

Magnetic noninvasive acupuncture for infant comfort (MAGNIFIC) - a single-blinded randomised controlled pilot trial.

AIM: To determine the safety and feasibility of auricular noninvasive magnetic acupuncture (MA) to decrease infant pain during heel pricks. METHODS: Infants requiring heel pricks for blood collection were randomised to either MA (n = 21) or placebo (P) (n = 19) after parental informed consent. MA or placebo stickers were placed on both ears according to the Battlefield Protocol by an unblinded investigator and left on for 3 days. Pain was assessed with the Premature Infant Pain Profile (PIPP) by blinded clinicians. RESULTS: Mean gestation (MA:34.1, P:34.4 weeks) and age of infants (MA:5.3, P:4.5 days) were similar as were mean (SD) pre (MA:1.7(1.4), P:2.1(1.9)) and post (MA:1.6(1.4), P: 2.1(1.7)) heel prick PIPP scores. PIPP scores were significantly lower in MA infants during heel pricks (MA:5.9(3.7), P: 8.3(4.7), p = 0.04). One-way ANCOVA modelling showed that MA was significantly associated with lower PIPP scores after controlling for analgesic use (p = 0.043). No differences in heart rate, oxygen saturation, analgesic use or adverse effects (e.g. local skin reactions) noted. CONCLUSION: This pilot study shows that auricular MA is feasible in neonates and may reduce PIPP scores during heel pricks. Further study is required to determine the impact of MA on other painful or stressful conditions and on neurodevelopment.

Differential brain effects of laser and needle acupuncture at LR8 using functional MRI.

OBJECTIVE: While needle acupuncture is a well-accepted technique, laser acupuncture is being increasingly used in clinical practice. The differential effects of the two techniques are of interest. We examine this in relation to brain effects of activation of LR8, a putative acupuncture point for depression, using functional MRI (fMRI). METHODS: Sixteen healthy participants were randomised to receive low intensity laser acupuncture to LR8 on one side and needle acupuncture to the contralateral LR8. Stimulation was in an on-off block design and brain patterns were recorded under fMRI. RESULTS: Significant activation occurred in the left precuneus during laser acupuncture compared with needle acupuncture and significant activation occurred in the left precentral gyrus during needle acupuncture compared with laser acupuncture. CONCLUSIONS: Laser and needle acupuncture at LR8 in healthy participants produced different brain patterns. Laser acupuncture activated the precuneus relevant to mood in the posterior default mode network while needle acupuncture activated the parietal cortical region associated with the primary motor cortex. Further investigations are warranted to evaluate the clinical relevance of these effects.

Laser acupuncture for depression: a randomised double blind controlled trial using low intensity laser intervention.

INTRODUCTION: Trials of acupuncture for the treatment of depression have produced mixed results. We examined the effectiveness of laser acupuncture compared with placebo acupuncture for the treatment of major depression. METHODS: A randomised, double blinded, placebo controlled trial was conducted in Sydney, Australia. Participants aged 18-50 years with DSM-IV major depressive disorder were eligible to join the study. Forty-seven participants were randomised to receive laser acupuncture or placebo laser at acupoints LR14, CV14, LR8, HT7 and KI3. The intervention was administered twice a week for 4 weeks and once a week for another four weeks, for a total of 12 sessions. The primary outcome assessed the change in severity of depression using the Hamilton-Depression Rating Scale (HAM-D), and secondary outcomes assessed the change in severity of depression using the Quick Inventory for Depression-Self Reporting (QID-SR), the Quick Inventory for Depression-Clinician (QIDS-CL), with outcomes assessed at eight weeks. The treatment response (greater than 50% improvement in HAM-D) and remission (HAM-D<8) were analysed. RESULTS: At eight weeks participants showed greater improvement in the active laser group on the primary and clinician-rated secondary outcome measures (HAM-D (mean 9.28 (SD 6.55) vs. mean 14.14 (SD 4.78 p<0.001); QIDS-CL (mean 8.12 (SD 6.61 versus 12.68 (mean SD 3.77)) p<0.001). The self-report QIDS-SR scores improved in both groups but did not differ significantly between the groups. In the active laser group, QIDS-SR scores remained significantly lower than baseline at 3 months follow-up. Response rates (active laser, placebo laser) on ITT (intention to treat) analyses were 72.0% and 18.2% (p<0.001), respectively. Remission rates on ITT analyses (active laser, placebo laser) were 56.0% and 4.5% (p<0.001). Transient fatigue was the only adverse effect reported. LIMITATIONS: There was no follow-up for the placebo group at one and 3 months. CONCLUSION: Laser acupuncture showed a clinically and statistically significant benefit with reducing symptoms of depression on objective measures.

The Antidepressant Effect of Laser Acupuncture: A Comparison of the Resting Brain's Default Mode Network in Healthy and Depressed Subjects During Functional Magnetic Resonance Imaging.

BACKGROUND: It has been suggested that the antidepressant effect of laser acupuncture involves modulation of the default mode network (DMN) or resting state network (RSN). In this study, the authors investigated changes in the DMN during laser acupuncture in depressed and nondepressed participants. OBJECTIVE: To aim of this study was to determine if the modulation of the DMN effects by laser acupuncture in depressed participants are different from those of nondepressed participants. DESIGN: Randomized stimulation was performed with laser acupuncture on four putative antidepressant acupoints (LR 14, LR 8, CV 14, and HT 7) in a block on-off design, while the blood oxygenation level-dependent (BOLD) fMRI response was recorded from each subject's whole brain on a 3T scanner. DMN patterns of the participants were identified, using an independent component analysis. The identified DMN components from both the nondepressed group and the depressed group were then analytically compared using SPM5. SETTING: This study took place at a research institute. SUBJECTS: Ten nondepressed participants and 10 depressed participants (DS) as confirmed by the Hamilton Depression Rating Scale (HAM-D) participated in this study. INTERVENTION: Low Intensity Laser Acupuncture. MAIN OUTCOME MEASURES: Significant DMN patterns in one group were greater than those in the other group. RESULTS: The nondepressed participants had significant modulation of DMN in the frontal region at the medial frontal gyrus (verum laser>rest, p<0.001) for three acupoints (LR 14, LR 8, and CV 14). For the depressive participants, the DMN modulation occurred at the inferior parietal cortex and the cerebellum (verum laser>rest, p<0.001). CONCLUSIONS: Laser acupuncture on LR 8, LR 14, and CV 14 stimulated both the anterior and posterior DMN in both the nondepressed and depressed participants. However, in the nondepressed participants, there was consistently outstanding modulation of the anterior DMN at the medial frontal gyrus across all three acupoints. In the depressed participants, there was wider posterior DMN modulation at the parieto-temporal-limbic cortices. This is part of the antidepressant effect of laser acupuncture.

The brain effects of laser acupuncture in healthy individuals: an FMRI investigation.

BACKGROUND: As laser acupuncture is being increasingly used to treat mental disorders, we sought to determine whether it has a biologically plausible effect by using functional magnetic resonance imaging (fMRI) to investigate the cerebral activation patterns from laser stimulation of relevant acupoints. METHODOLOGY/PRINCIPAL FINDINGS: Ten healthy subjects were randomly stimulated with a fibreoptic infrared laser on 4 acupoints (LR14, CV14, LR8 and HT7) used for depression following the principles of Traditional Chinese Medicine (TCM), and 1 control non-acupoint (sham point) in a blocked design (alternating verum laser and placebo laser/rest blocks), while the blood oxygenation level-dependent (BOLD) fMRI response was recorded from the whole brain on a 3T scanner. Many of the acupoint laser stimulation conditions resulted in different patterns of neural activity. Regions with significantly increased activation included the limbic cortex (cingulate) and the frontal lobe (middle and superior frontal gyrus). Laser acupuncture tended to be associated with ipsilateral brain activation and contralateral deactivation that therefore cannot be simply attributed to somatosensory stimulation. CONCLUSIONS/SIGNIFICANCE: We found that laser stimulation of acupoints lead to activation of frontal-limbic-striatal brain regions, with the pattern of neural activity somewhat different for each acupuncture point. This is the first study to investigate laser acupuncture on a group of acupoints useful in the management of depression. Differing activity patterns depending on the acupoint site were demonstrated, suggesting that neurological effects vary with the site of stimulation. The mechanisms of activation and deactivation and their effects on depression warrant further investigation.