The sensory innervation of the shoulder is complex and there are variations in the branching patterns of the sensory fibres. Articular branches from the axillary nerve to the subacromial bursa are described in more than 50% of investigated shoulders but the isolated contribution of sensory input from the axillary nerve has never been investigated clinically.We hypothesized that a selective block of the axillary nerve would reduce morphine consumption and pain after arthroscopic subacromial decompression.We included 60 patients in a randomized, blinded, placebo-controlled study. Patients were randomized to a preoperative selective ultrasound-guided axillary nerve block with 20 mL ropivacaine (7.5 mg/mL) or 20 mL saline. Primary outcome was intravenous morphine consumption 0–4 h postoperatively. Secondary outcome was postoperative pain evaluated by a visual analogue scale (VAS) score (0–100).P = 0.12)). There was a reduction in postoperative pain: VAS 0–4 h (area under the curve) ), VAS after 8 h ) and VAS after 24 h ). Eight out of 19 patients with a successful selective axillary nerve block needed an interscalene brachial plexus escape block.We analysed data from 50 patients and found no significant difference in 0–4 h postoperative morphine consumption between the two groups . Registered: November 1, 2011.ClinicalTrials.gov ( The most common types of shoulder surgery are hemiarthroplasty, total shoulder arthroplasty, shoulder arthroscopy, subacromial decompression and shoulder stabilizing procedures. Interscalene brachial plexus block (IBPB) block is effective for analgesia in all procedures and for anaesthesia and analgesia in arthroscopic procedures. Very rare but serious complications to the IBPB are often mentioned as the primary concern for using this nerve block –5. An imThe innervation of the shoulder is complex and involves several nerves. The most important nerves are the axillary nerve and the suprascapular nerve but other nerves also contribute to the sensory innervation –9. A selWe hypothesized that a selective block of the axillary nerve would reduce morphine consumption after arthroscopic subacromial decompression (ASD). We chose to study patients scheduled for ASD for two reasons. 1) A cadaver study found articular branches from the axillary nerve to the subacromial bursa in more than 50% of the investigated shoulders  2) A casClinicalTrials.gov (NCT01463865) and approved by the Ethics Committee of the Capital Region of Denmark (H-1-2011-057) and the Danish Data Protection Agency. Our manuscript was reported according to CONSORT  guidelines.This single center, randomized, blinded, placebo-controlled study was performed in compliance with the declaration of Helsinki and its amendments and was conducted according to the principles of Good Clinical Practice . The triFrom November 2011 to December 2013, we screened elective patients scheduled for ASD at Aleris-Hamlet Hospital, Copenhagen, Denmark, for inclusion in the study.− 2, American Society of Anesthesiologist classification (ASA) IV, preoperative opioid use or allergy to drugs used in the study. Patients scheduled for ASD who had a change of procedure intraoperatively were excluded after inclusion . A nurse with no relation to the study prepared the medication. To reduce performance bias, the patients, caregivers, the physicians performing the blocks and investigators were blinded to allocation. Further, to reduce detection bias, the physicians assessing the outcome measurements were blinded to allocation. The randomization list was kept in a sealed envelope and separated from the investigators until data collection was completed and the data was validated.Based on a central computer-generated list, the patients were randomized in a 1:1 ratio and in blocks of 6 to receive either a preoperative SBAN or placebo. Allocation concealment was ensured according to the principles of SNOSE . A health professional with no relation to the study or study location prepared 60 opaque envelopes containing instructions for study medication preparation with either 20 mL isotonic saline or 20 mL ropivacaine, 7.5 mg.mlSBAN: We used a 13–5 MHz linear transducer  to visualize the posterior circumflex humeral artery in the neurovascular space on the posterior aspect of the humeral neck. We chose a transducer position giving the best short axis view of the posterior circumflex humeral artery, where the artery leaves the quadrangular space and winds around the neck of the humerus. The ultrasonographic landmarks were the neck of the humerus, the deltoid muscle, the teres minor muscle, the triceps brachii muscle and the posterior circumflex humeral artery  in the cutaneous area overlying the deltoid muscle and recorded as normal or reduced/absent. Motor function was assessed by maximal voluntary isometric contraction (MVIC) and recorded as normal or reduced/absent deltoid muscle tone. Block success was defined as both reduced/absent sensory and motor function of the axillary nerve. Sensory and motor functions of the musculocutaneous, radial, ulnar and median nerves were tested in a similar way.− 1.min− 1)  followed by a bolus of propofol (2–3 mg.kg− 1) . No volatile agents or neuromuscular blocking agents were used. The patients had a laryngeal airway mask placed and were normoventilated using capnography. Intravenous anaesthesia was maintained with infusions of remifentanil (0.1–0.5 μg.kg− 1.min− 1) and propofol (6–8 mg.kg− 1.h− 1). We gave 4 mg of Ondansetron  intravenously 15 min before end of surgery and gave 0.5 mg of alfentanil . We moved the patients to the recovery room after surgery and connected a PCA pump set to deliver a 2 mL bolus of morphine 1 mg/mL  with a lockout time of 10 min. All patients were instructed to use the PCA pump to reduce their pain to a visual analogue scale (VAS) score (0–100) < 30. The patients could request an extra dose of 5 mg morphine in case the max PCA administration was insufficient up to three times. We performed an ultrasound-guided IBPB escape block with 5 mL ropivacaine 7.5 mg x ml− 1 if the VAS score was above 70 despite PCA and max escape morphine within the first four postoperative hours. After 4 h the patients were discharged. All patients were prescribed a daily oral dose of paracetamol 1 g × 4 , ibuprofen 400 mg × 3  from the day of surgery. For postoperative pain management we added morphine 10 mg × 1  as needed .Arthroscopic surgery was performed through two portals with no use of local anaesthetics (LA) either for intra-articular injection or for local infiltration. General anaesthesia was induced with an infusion of remifentanil (0.1–0.3 μg.kgOutcomes. Primary outcome: Intravenous morphine consumption during the first four postoperative hours (intravenous morphine consumption 0–4 h). Secondary outcomes: 1) Postoperative pain during the first four postoperative hours (VAS 0–4 (AUC)); 2) Postoperative pain after 8 h (VAS 8 h); 3) Postoperative pain after 24 h (VAS 24 h); 4) Accumulated oral morphine consumption during the first 24 postoperative hours; 5) Number of escape blocks during the first four postoperative hours; 6) Vomiting and/or nausea during the first four postoperative hours.The accumulated dose of administered intravenous morphine (in mg) during the first four postoperative hours was registered.VAS 0–4 (AUC): Postoperative pain during the first four postoperative hours was assessed at rest every 30 min by asking the patient to rate the pain from the operated site from 0 to 100 mm on a sliding VAS ruler. Zero corresponded to no pain and 100 to the worst possible pain. The eight pain measurements for each patient were condensed to a single measure as AUC. VAS scores 8 and 24 h postoperatively were obtained in a telephone interview on the following day. The patients had prior to discharge been carefully instructed to register their VAS scores at rest 8 and 24 h postoperatively. The accumulated oral morphine consumption during the first 24 h postoperatively was obtained in the same telephone interview by asking the patient. Prior to discharge the patients were carefully instructed to record their oral morphine consumption during the first 24 h after the operation. Escape blocks during the first four postoperative hours were registered and recorded as yes/no. Vomiting and/or nausea during the first 4 h was registered as yes/no.www.powersamplesize.com). We expected to exclude some patients after randomization due to changes in scheduled surgical procedures after randomization. We therefore included 60 patients for randomization. We performed both intention-to-treat and per-protocol analyses in intravenous morphine consumption 0–4 h. Patients with incomplete or failed SBAN defined as both reduced/absent sensory and motor function of the axillary nerve were removed from the intention-to-treat analysis before performing per-protocol analysis. Patients with escape block were removed from secondary outcome analyses because we did not follow up on VAS score and oral morphine consumption after discharge in these patients. We calculated the AUC by linear extrapolation between each VAS score measured at a fixed interval of 30 min. All continuous/scale data are presented as medians (range) and Mann Whitney u test for non-parametric unpaired statistical tests was used to compare differences between the ropivacaine group and the placebo group. Chi-square test was used to compare dichotomous outcomes. Fractions are presented with corresponding 95% confidence intervals (CI). P < 0.05 was considered statistically significant. We used SPSS software package  for statistical analyses.We chose a reduction in intravenous morphine consumption of 2.5 mg during the first 4 h postoperatively between the placebo group and the ropivacaine group to be clinically significant. This was based on a study with patients undergoing similar surgery where the placebo group had a mean intravenous morphine consumption of 5 mg during the first four postoperative hours . A reducn = 7), missing data (n = 2) and technical problems (n = 1) 50 patients were included in our primary intention-to-treat analyses (27 in the ropivacaine group and 23 in the placebo group) ). Of the 10 escape blocks in the ropivacaine group 8 were performed in patients with a successful SBAN. The SBAN was successful in 19 of the 27 patients in the ropivacaine group . There were no harms or unintended effects reported in any of the groups.We randomized 60 patients. After excluding patients because of change in surgical procedure (lems n =  50 patielems n =  50 patieP = 0.12)). Following standard procedure, all patients should have remained included in our intention to treat analyses of our secondary outcomes. However, we did not follow up on VAS-scores in the patients having an escape block. Thus, because of missing values, we had to exclude all patients with escape block before analysing our secondary outcomes concerning pain assessment. Therefore, our analyses of pain scores were only performed in 36 patients (17 in the ropivacaine group and 19 in the placebo group). All secondary outcomes exploring the pain-relieving effect at rest showed significant differences. VAS 0–4 h (AUC) ), VAS 8 h ) and VAS 24 h ). We found no significant difference in oral morphine consumption ). Nausea and vomiting were similar in the two groups ) and sensory and motor test in the radial, ulnar and median nerves were not affected after the SBAN in any of the patients. Results are listed in Table There was no significant difference in the accumulated intravenous morphine consumption 0–4 h postoperatively between the two groups . FollowP = 0.40).After excluding the 8 patients with failed SBAN from the intention-to-treat analysis our per-protocol analysis of the primary outcome included 42 patients (19 from the ropivacaine group and 23 from the placebo group). There was no difference in the accumulated intravenous morphine consumption 0–4 h postoperatively between the two groups (P = 0.97)).Because of an unexpected large number of escape blocks, numerous patients were excluded from our assessments of secondary outcomes evaluating pain perception. Therefore, we performed a post hock sensitivity analysis where we assumed that the VAS-score of the patients having an escape block would have persisting severe pain if no escape block was performed. The threshold for performing an escape block was a persistent VAS score above 70. Thus, we chose to impute a VAS score of 85 for all patients with missing VAS-values after having an escape block. Re-analysis with the imputed VAS-values as described included 27 patients in the ropivacaine group and 23 patients in the saline group Fig.  and showNo other severe events or uninteded effects were recorded.To our knowledge, this is the first clinical study evaluating the morphine reducing effect of a SBAN after ASD. We found no difference in intravenous morphine consumption between the ropivacaine group and the placebo group 0–4 h postoperatively. We found a small, but statistically significant, reduction in pain scores during the first 24 h in the ropivacaine group compared to the placebo group. One should always be careful when reporting an essentially negative result. This is also the case in the present study. There are several major weaknesses that deserve further scrutiny.First of all, one may argue that the primary end-point was not wisely chosen. If we consider SBAN to last an average of 10–12 h, then it would make more sense to measure the primary end point for 10–12 h. This would also diminish the potential blurring (confounding) effect of recovery from propofol sedation which may result in equal morphine consumption between groups during the first 4 h postoperatively.post hock sensitivity analysis on VAS-score 0–4 h postoperatively, including the patients from our intention-to-treat analysis who had an escape block. The missing VAS-scores were imputed with a value of 85. Analysing data in this way showed no difference in VAS-scores between the two groups at any time point 0–4 h postoperatively. Obviously, this sensitivity analysis is based on an assumption of constant pain during the remainder of the observation period, which may not be the case. Retrospectively, it seems clear that the escape blocks should only have been administered after the first four postoperative hours. However, we did not forecast the extended need of escape blocks. Further, we considered it ethically more correct to offer a block immediately if bolus morphine could not provide sufficient pain relief.We also had an unexpected high number of patients with severe postoperative pain despite intravenous morphine administration. These patients – 10 out of 27 in the ropivacaine group and 4 out of 23 in the saline group - had an interscalene brachial plexus escape block. This is a critical limitation. A substantial number of patients were excluded from secondary outcome analyses because we did not follow up on the patients receiving escape blocks. Therefore, the study may have been underpowered for the secondary outcome measures. Because this group represented the patients with the highest pain scores our pain analyses were compromised and therefore less valid. After escape block the morphine consumption was reduced and this could have compromised our primary outcome measure to some extent. We chose to perform a Actually, the high number of needed escape blocks helps us in the interpretation of the efficacy of the SBAN in the present setting. Eight patients with successful SBAN needed an escape block. The SBAN was therefore far from sufficient for pain relief in a large proportion of the patients (eight out of 19 patients with successful SBAN). It is impossible to know if a higher success rate would have changed the conclusions in favour of a larger pain relieving effect of the SBAN.We had a high number of failed blocks and there are several explanations for this. The steep needle angle, deep nerve localization and limited possibilities for a parallel shift of the transducer make the SBAN a challenging nerve block. The position of the needle tip must be precise to ensure injection into the neurovascular space. Prior to the present study we performed a case series study to test if the surgical procedure was relevant . We alsoBlock success was defined as a combination of sensory and motor block of the axillary nerve. Motor block assessment was performed by palpating the degree of tension in the deltoid muscle during MVIC. It would have been better to actually measure MVIC and predefine a % decrease in MVIC for a successful motor block. However, while it is easy to define the criteria for a successful block, the fulfilment of these criteria does not always translate meaningfully into a clinical context. We might have overestimated the block failure rate because our test of block success partly depended on a simplified manual muscle test. The sensitivity of a manual muscle test is low especially if the muscle force is only decreased by up to 25% . FurtherIt is impossible to know if a higher success rate would have changed our conclusions. However, after performing additional analyses on the data as described above and taking the high number of needed escape blocks into account, we conclude: In this setting, the SBAN has some pain relieving effect, but this effect is unpredictable, variable and far from sufficient in a large proportion of the patients.intention to treat and per protocol analyses to see how the block performs.The shoulder, like the knee, is a region with complex innervation by multiple nerves. It is likely that the clinical effect of a selective nerve block will vary with different surgical interventions. We therefore recommend uniform surgical procedure in future selective nerve blocks studies for shoulder surgery. Further, studies should be designed to maximize the pain signal and reduce noise. This can be accomplished by measuring pain for a longer time period, i.e. the anticipated mean block duration time and by performing the block postoperatively and only include patients with moderate to severe pain. It is also of value to perform both Selective block of the axillary nerve has some pain relieving effect, but in the present setting this effect was unpredictable, variable and far from sufficient in a large proportion of the patients.


Occlusal appliances are still widely used instruments in the management of orofacial pain in dentistry, yet alone or as a part of multimodal therapy. However, some of those modalities have been lacking thorough randomized assessment, and there is a conflicting evidence available. It is hypothesized that pain symptoms might improve faster and in more tangible way due to combined therapy. Also, to our best knowledge, nimesulide was never examined in this aspect, too.  The aim of this study was to compare early effectiveness of routine intervention methods in patients with myofascial pain (MP) after 3 weeks' notice. Three modalities were evaluated: occlusal appliance (OA) with nonsteroidal anti-inflammatory drug (NSAID) therapy (nimesulide), occlusal appliance with dry needling (DN), and occlusal appliance (OA-control group) therapy.  Randomized controlled clinical trial (RCT) in which ninety patients with MP, who met the inclusion criteria, were randomly assigned to one of the three treatment groups. Sealed, opaque envelopes were used.  For evaluation, each patient completed a Visual Analogue Scale (VAS) and Sleep and Pain Activity Questionnaire (SPAQ) twice, first at the beginning of the study and again after 3 weeks (0–3).  Posttreatment test comparison between the control group and both treated groups reveal significant differences between the control and the NSAID + occlusal appliance groups. There were also differences reported between the control and the DN + occlusal appliance groups, but these differences were, however, not statistically significant.  Occlusal appliances in conjunction with NSAID showed better orofacial pain relief after 3 weeks of therapy, compared to the use of occlusal appliances alone or in conjunction with dry needling. Additionally, differences between pain perception and quality of life between OA and DN + OA groups were not found to be statistically significant. Temporomandibular disorder (TMD) is a mutual term embracing numerous health issues that involve the temporomandibular joint (TMJ), masticatory muscles, or both . Its aetThree modalities were evaluated: occlusal appliance with nonsteroid anti-inflammatory drug therapy (OA + NSAID group), occlusal appliance with dry needling (OA + DN group), and occlusal appliance therapy only (control group). Hence, qualitative and quantitative pain measurement options turned out to be contradictory and of limited clinical value in scientific data assessment and as such are still subject to validation . For thiNCT03400462. The study was endorsed by the Bioethics Committee of Pomeranian Medical University in Szczecin  and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice set forth by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). We also ensured that the study conformed to applicable international regulatory authority laws, regulations, and guidelines.The protocol for this single-center clinical trial is registered with This study was a randomized controlled clinical trial (RCT). Among patients reporting to the Prosthetic Outpatient Clinic of Pomeranian Medical University, ninety patients with myofascial pain in the preauricular area were selected. Patients who met the inclusion criteria were randomly assigned to one of the three treatment groups. One examiner performed all clinical examination, splint therapy, and dry needling and controlled the visits of all patients. Another operator, blinded to patients group assignments, performed data acquisition throughout control appointments. The recruitment period lasted from 1st July 2016 till 1st December 2017. Sealed, opaque envelopes were used for randomization as well as for achieving equal number of patients in each group.Inclusion criteria include patients with unilateral pain localized in the TMJ or in the preauricular area, who had no analgesic treatment in the area of the head and neck during the last 12 months, aged 18–65 years, who and had no tooth losses within occlusal support zones.Exclusion criteria include bilateral pain, inflammation in the oral cavity that emerged as myospasm or preventive muscle contraction, earlier splint therapy, pharmacotherapy , systemic diseases , lack of stability in the masticatory organ motor system, masticatory organ injury, pregnancy, patients undergoing orthodontic treatment, other types of inflammation in the oral cavity , and fibromyalgia .This randomized controlled clinical trial included 2 tested groups and a control group of 30 patients each as follows: occlusal appliance (OA) with nonsteroid anti-inflammatory drug (NSAID) therapy (nimesulide), occlusal appliance with dry needling (DN), and occlusal appliance therapy (OA-control group). Participants who met the inclusion criteria completed the Sleep and Pain Activity Questionnaire (SPAQ) twice, first at the beginning of the study and again after 3 weeks of therapy. Groups consisted mostly of women ranging in age from 18 to 65 years old (mean age = 30.73). For evaluation, each patient completed the Visual Analogue Scale (VAS)  and SleeThis is a type of linear scale for the subjective characterization of pain. The patient describes his/her pain intensity as none, mild, moderate, or severe . It is aRecommended VAS interpretation: no pain (0–4 mm), mild pain (5–44 mm), moderate pain (45–74 mm), and severe pain (75–100 mm) .Sleep and Pain Activity Questionnaire comprised Visual Analogue Scale of Pain  and direDry needling is a therapeutic method in which needles can be inserted into, e.g., muscles, ligaments, or scar tissue  for the purpose of reducing pain. Myofascial trigger points are defined as tender nodules inside the muscle that contain hyperalgesic areas . This meSplint therapy is a well-described and efficacious treatment method for TMD patients, e.g., patients with retrodiscitis and patients with muscle pain disorders such as local muscle soreness or chronic myalgia . The occNimesulide has anti-inflammatory and analgesic properties. Like other NSAIDs, it inhibits the action of COX. Without the further synthesis of prostaglandins, there is no factor available to excite local nociceptors. In light of this, the drug must be taken regularly for a minimum of 2 weeks to achieve appropriate blood concentrations. Dosing instructions for NSAID use are as follows: nimesulide 2 × 100 mg/24 h, i.e., one 100 mg pill twice a day for 14 days, which is the most frequently described duration of therapy in myofascial pain control and management , 17. Patp values of the Wilcoxon signed-rank test at the significance level α = 0.05 for each question in all test groups.The null hypothesis was that sample difference comes from a distribution with zero median. The responses, pretreatment and posttreatment of each group, were tested using the Wilcoxon signed-rank test. The same test was used to determine the difference between groups, separately for pretreatment and posttreatment answers. p value = 0.0781 at significance level 0.05). Comparison of pain intensity between control group and both treated groups results in the pretreatment stage shows no significant difference. This states that entry pain intensity levels were comparable. Results are presented at All groups picture significant differences in almost all of the VAS questions (from 1 to 6) when comparing pre- vs posttreatment results. The exception is question 3 where answers show no difference in the DN-treated group  and the DN group (M2) revealed significantly different answers only to questions 7 and 9, when comparing pretreatment and posttreatment responses.Comparison of both examined groups with controls in terms of posttreatment responses regarding question 7 to 10 showed no significant difference. Detailed analysis was performed by using Fisher's exact test while the count in some of categories was less than 5. The results are presented in All groups presented significant differences according to time of sleep in pre-/posttreatment comparison. Assessment of the control group and the NSAID group (M1) in posttreatment shows significance in the Wilcoxon signed-rank test. The results are shown in The average sleep time is presented in N: 26) and placebo group (N: 26). DN was applied using acupuncture needles, whereas sham DN was administered to the placebo group. Pain pressure threshold (PPT) was measured with pressure algometry, pain intensity was rated using a 10 cm Visual Analogue Scale (VAS), and the unassisted jaw opening without pain measurement was performed. Mean algometric values were significantly higher in the study group when compared to the placebo group . There were no differences between the two groups in terms of VAS and unassisted jaw opening without pain values. According to these findings, DN appears to be an effective treatment method in relieving the pain and tenderness of TrPs; however, comparison between different treatment modalities was not scrutinized [p < 0.01) between therapeutic intervention and the improvement of pain and jaw movements, which continued up to 6 months after treatment. When pain reduction was greater, the higher was the intensity of pain at baseline. The authors concluded that further studies are needed; however, their findings suggest that deep dry needling in the trigger point in the external pterygoid muscle can be effective in the management of patients with myofascial pain located in that muscle [p < 0.001) and decrease of TrPs in the masticatory muscles, which was statistically significant . The general outcome of the study by Ozkan et al. is that injection combined with occlusal splint therapy was far more effective in the treatment of myofascial TMD pain for the improvement of signs and symptoms, which is partly consistent with our own findings [Nimesulide is marketed in more than 50 countries. Yet, to the best of our knowledge, this is the first report, evaluating its usage in TMD patients. From our findings, the OA + NSAID group showed greater short-term improvements in myofascial pain located in the preauricular area compared to the OA + DN and OA only (control) groups. These differences were found to be statistically significant while the OA + DN group was not found to be superior over OA only (control group). In addition, statistically important improvement in sleep quality of OP patients was also noted in the OA + NSAID group. Bocanegra et al. evaluated patients with moderate to severe pain after extraction of impacted third molars. In their study, nimesulide and ibuprofen provided effective pain control in first 24 hours after surgery. They concluded that, despite both medicaments were well tolerated, the therapeutic effect of nimesulide had a faster, less than 15 minutes onset, and was stronger (according to patients' opinion) than ibuprofen . In diffutinized . Varoli utinized . These rfindings . The infIn this study, occlusal appliance in conjunction with nimesulide showed superior orofacial pain relief and improvement of sleep quality after 3 weeks of therapy in comparison with occlusal appliance used unaided or in conjunction with DN. As such, it should be considered as an NSAID of choice in the management of TMD pain, mostly due to the faster onset of action and less side effects than diclofenac, celecoxibe, and ibuprofen , 19, 26.


Background: Lifestyle advice is widely considered as an integral component of acupuncture treatment. However, it is unclear whether lifestyle advice and related self-care are important for sustaining benefit over the longer term. In a novel secondary analysis of trial data, this paper explores the nature and impact of acupuncture-related diagnosis, and associated lifestyle advice and self-care, in patients with chronic neck pain.Design: In a three-arm, randomized, controlled multicenter trial with 12 months of follow-up, a total of 517 patients with chronic neck pain were randomized in equal proportions to acupuncture, Alexander technique, or usual care alone.Methods: For each acupuncture patient, practitioners reported treatment components that included an acupuncture-related diagnosis and provision of associated lifestyle advice. Patients reported at baseline, 3, 6, and 12 months on variables related to treatment, which included aspects of self-care, self-efficacy, and lifestyle advice acted upon, as well as pain and disability scores. Congruence between practitioner advice and patient take-up was assessed using chi-squared test. Impact of lifestyle advice and self-efficacy on outcome was evaluated using regression models.Results: Among patients randomized to acupuncture, the most common diagnostic framework involved the Zang–Fu syndromes for 139/160 (87%) patients. Lifestyle advice was provided by practitioners to 134/160 (84%) of patients, most commonly related to exercise, relaxation, diet, rest, and work. Significant congruence with patient take-up was found for diet, rest, and work. Moreover, patients in the acupuncture group improved their ability to use what they had learnt and increased their self-efficacy. In turn, these characteristics were associated with significant reductions in pain and disability scores at 12 months.Conclusion: Acupuncture-related lifestyle advice helped patients improve the way they live and care for themselves and enhanced self-efficacy and ability to use what they had learnt. These changes were associated with reductions in pain and disability at 12 months. In traditional East Asian medicine, acupuncture is usually a more complex intervention because treatment involves multiple components that are guided by the same overarching theoretical perspective, which is designed to impact on outcome.1 As well as needling, these components include the diagnostic process and the related explanations and lifestyle advice to promote and enhance patient self-care.A2 In Europe and China, acupuncture advice provided by practitioners is primarily related to diet  and exercise (50% and 49%).3 Further studies have elaborated on the role of lifestyle advice and self-care within traditional acupuncture consultations4 and the coconstruction of self-care within the context of the therapeutic relationship in a way that is different from that of a conventional medical consultation.5As a consequence, lifestyle advice is widely considered as being integral to treatment by acupuncture practitioners who use the principles of traditional East Asian medicine in routine practice. For example, in the United Kingdom, lifestyle advice relevant to an acupuncture diagnosis is provided by practitioners to 56% of their patients, which rises to 85% of patients of practitioners who provide a predominantly traditional Chinese medical style of treatment.6 have suggested the importance of lifestyle advice8 as well as from trials for irritable bowel syndrome10 and for depression.12 What is needed, however, are quantitative data to establish whether lifestyle advice, when it is an integral component of acupuncture treatment, enhances overall benefit.The question as to whether the lifestyle advice and related self-care actually do impact in terms of helping promote longer-term benefit is important and needs addressing. This question is relevant to the search for explanations of long-term benefits that have been reported in trials of traditional acupuncture, within which the provision of lifestyle advice as a treatment component has been supported. Qualitative data related to the trial of acupuncture for low back pain13 In a population that had experienced chronic neck pain for on average 6 years, we found that there were statistically significant benefits at 6 and 12 months for patients who received either Alexander technique plus usual care or acupuncture plus usual care when compared with those receiving usual care alone. We also found that the self-efficacy of patients in both the acupuncture and the Alexander technique arms improved when compared with usual care at 6 months. Improved patient self-efficacy meant that patients learned and used better strategies for reducing pain without resorting to medication. Moreover, this improvement in self-efficacy was associated with significant reductions in neck pain at 6 and 12 months.This paper expands on the primary results of the ATLAS (Alexander Technique Lessons or Acupuncture Sessions) chronic neck pain trial published previously.There is a need to better understand these longer-term benefits and whether lifestyle advice translates into better self-care and improved self-efficacy. In prespecified secondary analyses, our aim in this paper is to explore whether there were acupuncture-specific diagnostic variables or lifestyle-related factors that might help explain the reported longer-term benefits at 6 and 12 months.14 a percentage-based scale, which was our primary outcome measure. A total of 517 patients were recruited and randomized between March 2012 and April 2013.The design involved a pragmatic three-arm trial with patients randomized in equal proportions to acupuncture, to Alexander technique, or to usual medical care alone. All patients continued to receive usual medical care throughout the trial. Patients were recruited from primary care by first identifying potential participants from GP databases. Patients were invited to return baseline questionnaires and consent forms, which were then screened for eligibility by members of the research team at the University of York. A minimum score of 28% was required on the Northwick Park neck pain and disability questionnaire (NPQ),2 As this was a pragmatic clinical trial, practitioners were encouraged to practice as closely as possible to how they would routinely.15 Acupuncture practiced in this way can be considered a complex intervention,1 and integral to treatment were the acupuncture diagnosis-related components, such as explanations of the diagnosis and diagnosis-specific lifestyle advice.7Those randomized to acupuncture were offered up to 12 sessions and those randomized to Alexander technique were offered up to 20 sessions. To be eligible to provide treatments within the trial, acupuncture practitioners were required to be members of the British Acupuncture Council with at least 3 years postqualification experience and a commitment to continuing professional development. Moreover, they agreed to provide a style of acupuncture based on traditional Chinese medicine principles, the most commonly used approach to the provision of acupuncture in the United Kingdom.Practitioners documented in their logbook data for each patient: their acupuncture-related diagnosis; the points used each session; the auxiliary modalities provided; and the lifestyle advice given over the course of treatment. Using the eight-principle framework, practitioners identified whether the neck pain was an external, an internal, or a mixed internal and external condition. Practitioners assessed whether their patients could be diagnosed as predominantly having had one of two common clusters of Zang–Fu syndromes: predominantly Liver-related syndromes that included Liver Qi Stagnation, Liver Yin Xu, Liver Yang Rising, and Liver Fire and predominantly Spleen-related syndromes that included Spleen Qi and Yang Xu, Kidney Qi and Yang Xu, and Internal Damp. Clustering in this way helped when conducting subsequent analyses. Moreover, practitioners provided a rationale for any lifestyle advice related to acupuncture theory.16 At baseline, 6, and 12 months, self-efficacy was determined by the 5-question pain management subscale of the Chronic Pain Self-Efficacy Scale scored 0 to 8.17 At 6 and 12 months, data were collected on self-care, the extent that it took place, and the extent that it was perceived to be beneficial. Patients responded to the question, “Can you use/apply the things you learned from the treatment/care in everyday life situations to reduce pain?” with responses as never, seldom, occasionally, often, and every day . Patients responded to the question, “To what extent are you able to put into practice the advice or teaching you received?” on an 11-point scale of increments of 1 from 0  to 10 (completely). Using the same 11-point scale, patients responded to the question, “To what extent are the changes you have been making helpful to you?” Patients responded (yes/no) to the question, “During the treatment/care you received in the last 6 months, did you learn to improve the way you live and care for yourself?” Patients also reported whether they made changes related to diet, exercise, relaxation, rest, and work.At baseline, data were collected for each participant on a number of factors, including the duration of their neck pain, age, gender, and home city, as well as GP practice. At baseline, 6, and 12 months, we also assessed patients' perceived stress levels using the four-question Perceived Stress Scale, each item scored 0 to 4 with total scores 0 to 16.Stata Statistical Software: Release 13. College Station, TX: StataCorp LP). All comparisons of acupuncture and usual care were conducted on an intention-to-treat basis, including all patients in the groups to which they were randomized. Descriptives are reported as means and standard deviations for continuous variables and counts and percentages for categorical variables.Analyses were conducted in Stata, version 13, using two-sided significance tests at the 5% significance level .The ability to make improvements in living/self-care and changes in diet, exercise, relaxation, rest, and work at 6 and 12 months were analyzed individually by logistic regression. Patient-reported perceived stress, self-efficacy, ability to use what has been learnt, number of lifestyle changes, extent put into practice advice or teaching, and extent to which changes were helpful at 6 and 12 months were analyzed individually by linear regression. To explore the impact of patient-reported variables measured during the intervention period and changes in NPQ outcomes at 6 and 12 months, linear regression was utilized. NPQ outcomes were analyzed individually at each time point and included the patient-reported variables (or changes in these variables from baseline) as fixed effect covariates in the model. All regression analyses made adjustments for baseline NPQ scores, duration of neck pain, age, gender, and city as a fixed effect, and GP practice as a random effect using robust standard errors (Stata www.liebertpub.com/acm). Other components of treatment are presented below.Of the 173 participants randomized to acupuncture, 162 (94%) received at least one treatment, 125 (72%) attended all 12 sessions, and 11 (6%) did not attend any treatment. Of the 162 patients attending at least one treatment, 2 withdrew from the trial. A total of 1,775 treatments were received, and the average number of sessions attended was 11 . Treatments were provided by 18 acupuncture practitioners , each of whom treated on average 10 patients (range 2 to 22). The acupuncture points used and auxiliary treatments provided are documented in the Practitioners were asked to record their methods of diagnosis within a traditional Chinese medicine theoretical framework . The thrPractitioners reported up to five key symptoms that guided their diagnosis of either the Liver or Spleen clusters. Within the Liver cluster, we found the most commonly reported symptoms to be stress , muscular tension/stiffness , and headache/migraine  . Within Within the protocol for treatment and integral to the provision of acupuncture, practitioners were encouraged to provide lifestyle advice where appropriate, provided that it was linked to traditional acupuncture theory and the patient's diagnosis. Practitioners reported in the logbooks that they gave advice to make lifestyle changes to 134  patients in total. This was most commonly related to advice about exercise , relaxation , diet , rest (47/134: 35%), work , and other advice .The practitioners also reported in the logbooks the reasons for the advice based on traditional acupuncture theories. Advice related to exercise was most commonly to move the Liver Qi Stagnation . Advice related to relaxation was not only predominantly to move the Liver Qi  but also to strengthen Spleen/Kidneys . Dietary advice was predominantly not only to strengthen the Spleen and resolve Damp  but also to tonify the Yin and Blood . Advice regarding work was commonly focused on moving the Liver Qi . The other advice was often to protect the channels from external pathogenic factors and move channel stagnation , and also to advise on a referral .We compared data related to advice from practitioner logbooks with that reported by patients in questionnaires at 6 and 12 months. We found some evidence of a significant or near-significant congruence between advice reported by practitioners and lifestyle changes reported by patients at 12 months related to diet and rest and work .The relationship between practitioner-reported traditional acupuncture medical diagnoses and patient-reported changes in pain (NPQ) scores at 6 and 12 months is presented in The results of the regression analyses are presented in The above changes associated with the interventions at 6 and 12 months were analyzed to see if differences from usual care were also associated with changes in NPQ pain and disability scores . A lesseOur key finding is that lifestyle advice based specifically on acupuncture theory leads to active patient engagement, which in turn is an important contributor to overall benefits over the longer-term. At 12-month follow-up, we found some evidence of congruence between practitioner-reported lifestyle advice and the actual lifestyle changes reported by patients receiving acupuncture related to diet, rest, and work. Compared with the patients receiving usual care alone, we found that patients in the acupuncture group made more lifestyle changes related to diet, exercise, relaxation, rest, and work and improved their self-efficacy, which is their ability to reduce their neck pain without resorting to medication. We found that patients in the acupuncture group improved their ability to use what they had learnt and increased their self-efficacy when compared with usual care alone and, in turn, these characteristics were found to be associated with significant reductions in NPQ pain and disability scores at 12 months. Overall, we have shown that the characteristics of the acupuncture provision in a pragmatic trial of acupuncture for chronic neck pain go well beyond acupuncture needling alone and specifically that pattern-related lifestyle advice has an impact on outcome.As with any secondary analysis of data from a clinical trial that was powered for the main comparison, the desire to establish whether or not there were treatment components mediating outcomes may have been compromised by low statistical power. Moreover, we conducted multiple exploratory analyses, and if the results had been based on chance alone, we would have expected that 1 in 20 would be statistically significant. However, a strength of the study is that we prespecified the analyses that we conducted in a statistical plan, a plan that was finalized before conducting the primary analysis. Nevertheless, our results should be seen as exploratory.Our analyses include both statistically significant and nonsignificant findings. The nonsignificant results are difficult to interpret as it is not clear whether the analyses are underpowered to find a small association or whether it means that no association exists. Further exploration of these relationships in other studies would help put these findings in context.2 we caution against drawing conclusions about acupuncture when practiced using other treatment styles. We also note that there is some evidence of equivalence in outcomes across different styles and/or associated with different characteristics of acupuncture and of acupuncture practitioners.18 We acknowledge that as the trial was conducted in primary care in the United Kingdom, we must generalize with caution to other populations. Moreover, our results are relevant primarily to patients who, when recruited to the trial, had neck pain for an average duration of 6 years and 75% were taking medication (60% related to neck pain).A limitation of our study is that we only recruited acupuncturists who practiced acupuncture according to traditional acupuncture principles. While this might be the predominant style of practice worldwide as well as in the United Kingdom,2 Our data show the way that lifestyle advice is specific to the diagnosis and is also associated with outcome and therefore cannot be labeled nonspecific. This point was made clearly by Paterson and Dieppe1 when they describe explanatory trial designs that attempt to divide an intervention into characteristic (specific) and incidental  elements as being neither meaningful nor feasible when evaluating complex nonpharmaceutical interventions, attempts that may generate false negative results. As an alternative, pragmatic designs can evaluate complex interventions and also prespecify and monitor the key variables that are thought to mediate outcomes. In this way, we can better understand the take up of lifestyle advice by patients and the strategies that might enhance patient benefits. Further research into the reasons why patients might, or might not, take up lifestyle advice and what strategies practitioners could use to enhance compliance with advice could help improve practice.Pragmatic trials are not designed to separate out the extent that any putative benefits might be specific or nonspecific to the intervention. Our data are based on common practice among traditional acupuncture practitioners, whereby needling is one component of treatment, but so too is the provision of lifestyle advice.Our documentation on the reported symptoms of chronic neck pain, using the framework of traditional Chinese medical diagnostic principles, contributes to our understanding of neck pain. In particular, we noted the considerable overlap between physical and affective aspects of chronic neck pain, particularly stress, suggesting that acupuncture might be of special value when mental and emotional symptoms are involved along with physical symptoms. We suggest that it would be useful to extend the focus of acupuncture research beyond the treatment of single conditions and explore the impact of treatment where such comorbidities are common.We have reported in detail the intervention data for acupuncture in the ATLAS trial, including treatment variables that potentially mediated outcome. We have provided evidence that practitioners actively initiate the active engagement by the patient through targeted lifestyle advice, and that this makes a difference in the way patients learn to improve the way they live and care for themselves. This results in enhanced self-efficacy, which in turn is associated with greater reductions in pain and disability at 12 months. These data, when combined, provide a case to consider traditional acupuncture as not just a needle-related intervention but rather as a complex intervention that combines both acupuncture needling and acupuncture-related lifestyle advice that actively engages the patients in their own recovery.


Patients with temporomandibular joint disorder (TMD) often complain of pain in other areas. Several studies have been conducted on spinal pain in TMD patients, but have contained only limited information. Therefore, this study analyzed the relationship between TMD and spinal pain in greater detail by using nationwide data.A total of 12,375 TMD patients from the Korean National Health Insurance Review and Assessment database were analyzed. Controls were selected using propensity score-matching. The McNemar test, chi-square test, and paired t-test were used to compare the prevalence and severity of spinal pain between cases and matched controls. Logistic regression and linear regression models were used to analyze factors affecting the prevalence and severity of spinal pain in patients with TMD.The annual period prevalence of TMD was 1.1%. The prevalence was higher in younger individuals than in individuals of other ages and was higher in women than in men. The medical expenditure for TMD per person was $86. Among TMD patients, 2.5% underwent surgical procedures and 0.3% were hospitalized. The prevalence of spinal pain in patients with TMD was 48%, whereas that in the control group was 34%. Increased severity of TMD was associated with an increased probability of spinal pain. The medical expenditure, mean number of visits, and lengths of treatment for spinal pain were greater for patients with TMD than for controls . Higher TMD grade was associated with greater differences in average medical expenditure, number of visits, and lengths of treatment for spinal pain between cases and controls. Additionally, for women, living in a rural area and having an older age and more severe TMD were associated with a greater probability of spinal pain and higher medical expenditure related to spinal pain.A strong association was observed between the presence of TMD and the presence of spinal pain. The association became stronger as the severity of TMD increased, indicating a positive correlation between the severity of TMD and spinal pain. Temporomandibular joint disorder (TMD) is a disease in which structural and functional disorders occur in the temporomandibular joints and related structures . Major cTMD is often accompanied by headaches, back pain, joint pain, and abdominal pain , 6. PlesSpinal pain is a common and socially important musculoskeletal condition. In the United States, the lifetime prevalence of low back pain is 65 to 80% . In addiSeveral studies have investigated the relationship between TMD and spinal pain. Wiesinger reported that the incidence of spinal pain increased with the frequency and intensity of temporomandibular joint pain . In a USHowever, the evidence of a correlation between TMD and spinal pain has some limitations: first, a number of these previous studies were performed without a control group , 19; secClarifying the correlation between TMD and spinal pain is important, as secondary prevention can be incorporated into the management and treatment guidelines of TMD if the possibility of spinal pain is known . TherefoThe original data were obtained from the 2016 Korean Health Insurance Review and Assessment Service (HIRA) National Patient Sample. Korea uses a single health insurance system, such that 98% of the population is enrolled in National Health Insurance (NHI) . Claims This study was a cross-sectional, retrospective study of patients who used medical services at least once in Korea, from January 2016 to December 2016, who were diagnosed with TMD. There have been few studies using International Statistical Classification of Disease (ICD) codes in administrative data. Here, a TMD case was operationally defined as a patient who was diagnosed according to the ICD-10 code K07.6 (temporomandibular joint disorders) or S03.4 (sprain and strain of the jaw), based on internal discussions among research team members.TMD severity was defined based on the amount of medical services used in relation to the jaw joint. As previous studies have reported that 6 treatments are generally effective , 26, we In this study, the propensity score-matching method was used to select the control group . The proThe first outcome was the presence of spinal pain. This was operationally defined as when a patient used medical services due to spinal pain more than once, during a 1-year period. Based on the code applied in previous studies of spinal pain using administrative data , 36, andThe variables related to the use of medical care for patients with TMD were surgery, hospitalization, medical institution type, and medical specialty. Surgery and hospitalization were classified into yes  or no. Medical institution type included general hospital, hospital, and clinic. In Korea, according to the Medical Law, secondary medical institutions with more than 100 beds, 7 or 9 medical specialties, and specialists dedicated to each medical field are called general hospitals. Medical institution type and medical specialty were counted according to the most-used institution type and medical specialty for TMD; thus, counts were not duplicated.t-test because paired continuous samples were used in this study. A Kolmogorov–Smirnov test revealed the data were not normally distributed, and thus the differences in medical expenditures, numbers of visits, and lengths of treatment among TMD grades were examined using the Kruskal–Wallis test. For post-hoc analysis, Dunnett’s test was performed because the assumption of equal variance was rejected in Levene’s test [Distributions of categorical sociodemographic variables  between cases and controls before matching were compared using standardized differences. In this study, because the control group was matched by using a propensity score, the sample were paired. There is no consensus method for comparing variables after propensity score matching, but as the standardized difference is an accepted method according to some previous studies , 37 we ue’s test .For the logistic regression and linear regression analyses, 3 models were constructed by classifying the factors that affect medical use according to characteristics based on previous studies , 42. TheModel 1: sex, age.Model 2: Model 1 + .Model 3: Model 2 + .Yi1:dummy variable with 1 for spinal pain and 0 for without spinal pain in ‘i’th TMD patients.Yi2: medical expenditure for spinal pain in ‘i’th TMD patients.X1: sex, X2: age, X3: insurance type, X4: region, X5: medical institution type, X6: CCI, X7: TMD grade, X8: surgery, X10: hospitalization.Logistic regression analyses were performed for each model to determine the odds ratio of covariates that influence the prevalence of spinal pain in patients with TMD. Linear regression analyses were performed for each model to examine how covariates influence medical expenditure for spinal pain in patients with TMD. Medical expenditure was log-transformed because its distribution was non-normal and shifted to the left . In the Table Table Table Table Covariates that influenced the prevalence of spinal pain in TMD patients are shown in Table Analysis of factors influencing medical expenses resulting from spinal pain in patients with TMD are show in Table The annual period prevalence of TMD in this study was 1.1%, which was relatively low compared to the findings of previous studies (5–40%) , 44–46. In addition, in the present study, the prevalence of TMD was higher in women and in younger age groups, as in previous studies , 45–47. In this study, we found that there was a positive correlation between TMD and spinal pain. Patients with TMD were more likely to have spinal pain than non-TMD patients; moreover, they were more likely to have greater medical expenditure and an increased number of treatments for spinal pain. In addition, a higher degree of TMD was associated with a greater probability of spinal pain; greater severity of spinal pain was associated with increased cost of medical care and increased length of treatment. The medical service use of TMD patients in 2016 Korea  on the prevalence of spinal pain in TMD patients and the medical expenditure related to spinal pain. Second, we have overcome the limitations of previous studies by using large-scale data that can represent Korea and provide a variety of objective parameters, such as medical expenses and treatment details, as well as by using propensity score-matching methodology. The results of this study provide useful information for the management of TMD and treatment of patients with both TMD and spinal pain. In addition, when spine problems do not continue to improve in general spine treatment, TMD could be considered. In practice, this suggests that consultations with several specialists such as a dentist and neurologist are necessary. The availability of a consultation system can help patients receive quality care and reduce the costs associated with TMD. Further studies to quantify the degree of the correlation between TMD and spinal pain, and to confirm causality, are needed.A strong association was observed between TMD and spinal pain. The association became stronger as severity of TMD increased, indicating a positive correlation between severity of TMD and spinal pain. This information can aid in the management of TMD and treatment of patients with both TMD and spinal pain.Additional file 1: Figure S1. Prevalence of spinal pain in cases and controls according to TMD grade.Additional file 2: Figure S2. Prevalence of spinal pain for each level in cases and controls according to TMD Grade. spinal1, spinal pain grade 1; spinal2, spinal pain grade 2; spinal3, spinal pain grade 3.Additional file 3: Table S1. Medical Service Use of TMD Patients.Additional file 4: Table S2. Post hoc test for outcome differences between TMD grades.


Unfortunately, the use of carbon dioxide  and received our institution’s common postoperative care. Patients in the intervention group were subjected to the same maneuver but were positioned in a Trendelenburg position (20 °) once fully awake and cooperative in the PACU and retained this position for the first 24 h. Numerical rating scale (NRS) was used to assess shoulder pain and nausea upon patient arrival to the PACU, at 4, 6, 12 (primary outcome) and 24 h postoperatively. Time to first rescue pain medication, total rescue pain medications and overall satisfaction with pain control were recorded. 101 patients were included in the final data analysis.p < 0.001), furthermore improvement in postoperative shoulder pain between time of arrival to PACU (time zero) and 12 h postoperatively was significantly higher in patients allocated to the experimental group compared to the control group. Pain scores were significantly lower in patients allocated to the experimental group versus the control group .Both groups were comparable in terms of baseline characteristics. NRS pain scores were significantly lower in the intervention group at 12 h compared to the control group (0 [0–1] versus 5 [1–4], In conclusion, Trendelenburg position is an easy non-pharmacologic intervention that is beneficial in reducing postoperative shoulder pain following gynecologic laparoscopic surgery.NCT04129385,  date of registration: June 28, 2019Retrospectively registered at Clinicaltrials.gov, registration number  Proc mixed test was used to the mixed group and time effect on pain and nausea scores post-operatively. Student’s t-test was used to compare the normally distributed continuous data and Mann-Whitney test was used for ordinal data. Chi-square test or Fisher exact test was used for categorical data.A total of 248 patients were assessed for eligibility and 108 enrolled in the study between June 2016 and June 2018. Seven patients were excluded . 101 patients were included in the final data analysis .Basic demographics, types of the surgical procedures, and procedural duration are presented in Table p < 0.001) respectively , yet the difference was not statistically significant.Time to first analgesic request was longer in the experimental group compared to the control group . However, the total PONV medications used were significantly lower in the experimental group, metoclopramide consumption  and ondansetron consumption .Nausea scores significantly decreased with time in both groups, and was significantly higher in the experimental group Table . Incidenp < 0.001).Non-opioid and opioid consumption showed statistically significant difference between both groups Table . Patientp < 0.001). These patients had a median score of 9.5 compared to a score of 8 in the control patients  as well as the study subjects and the nature and duration of the surgical procedures are different. While this study required that patients be placed in Trendelenburg position for 24 h postoperatively and measured the pain scores at 4, 6, 12 and 24 h, the study by Aydemir et al. placed patients in extreme Trendelenburg position upon reporting shoulder pain for only 10 min at a time, and recorded pain scores 10 min afterwards. The degree of Trendelenburg was not mentioned. Pain scores were statistically significantly improved thereby supporting the theory that Trendelenburg position decreases the phrenic nerve irritation caused by the COAydemir et al. demonstrated that Trendelenburg position is both quick and effective, with improvement in pain scores as early as ten minutes after Trendelenburg positioning. Acute and fast improvement of shoulder pain was supported by our study as the most acute drop in shoulder pain score was noted from 0 to 6 h Fig. . Beyond Many other methods to decrease postoperative shoulder pain have been described in the literature. The most recent Cochrane review by Kaloo et al.  reviewedThis randomized study provides solid evidence that the intervention is beneficial in reducing shoulder pain. One limitation is that although all healthcare providers and patients were blinded to the study intraoperatively, they were not blinded to the patient postoperatively hence patients might have underreported pain when in the Trendelenburg position and there might have been a small bias due to a placebo effect. Another limitation is the duration of the study intervention: Although most patients tolerated Trendelenburg positioning for 24 h, six refused to stay in Trendelenburg for the entire 24 h and hence withdrew from the study, but the rate of dropout between the two groups was not significant and was below the 20% expected level. Moreover, among the advantages of laparoscopic surgery are early or immediate resumption of regular diet, early ambulation and short hospital stay including same day discharge when applicable. Patients in the intervention arm were kept on a clear fluid diet for 12 h postoperatively, could not ambulate immediately postoperatively and were not discharged till after 24 h, thereby limiting some of the advantages of minimally invasive surgery. However, we can suggest to keep this position as much as feasible at home if an earlier discharge can be suggested in the future.In conclusion, Trendelenburg position is an easy non-pharmacologic intervention that is beneficial in reducing postoperative shoulder pain following gynecologic laparoscopic surgery, decreasing the amount of analgesic consumption and improving patients’ overall satisfaction with the surgical experience. Being non-pharmacologic, it can be administered by trained nursing staff and can even be taught to patients and implemented at home by simply elevating the pelvis with the use of pillows. Not only does it have zero cost, it can potentially decrease medical expenses as less analgesics are administered. More importantly, the smaller the amount of analgesic consumption, the lower the risk of medication adverse events such as respiratory depression, nausea, pruritus and ileus which are often encountered with the use of opioids . Additio


Background/Aim: Using a within-subjects, within-wound care design, this pilot study tested for the first time, whether immersive virtual reality (VR) can serve as an adjunctive non-opioid analgesic for children with large severe burn wounds during burn wound cleaning in the ICU, in a regional burn center in the United States, between 2014–2016.Methods: Participants included 48 children from 6 years old to 17 years of age with >10% TBSA burn injuries reporting moderate or higher worst pain during no VR on Day 1. Forty-four of the 48 children were from developing Latin American countries. Patients played adjunctive SnowWorld, an interactive 3D snowy canyon in virtual reality during some portions of wound care, vs. No VR during comparable portions of the same wound care session . Using Graphic Rating scales, children's worst pain ratings during “No VR”  vs. their worst pain during “Yes VR” was measured during at least 1 day of wound care, and was measured for up to 10 study days the patient used VR.Results: VR significantly reduced children's “worst pain” ratings during burn wound cleaning procedures in the ICU on Day 1. Worst pain during No VR = 8.52 (SD = 1.75) vs. during Yes VR = 5.10 (SD = 3.27), t(47) = 7.11, p < 0.001, SD = 3.33, CI = 2.45–4.38, Cohen's d = 1.03 (indicating large effect size). Patients continued to report the predicted pattern of lower pain and more fun during VR, during multiple sessions.Conclusion: Immersive virtual reality can help reduce the pain of children with large severe burn wounds during burn wound cleaning in the Intensive Care Unit. Additional research and development is recommended. In developing countries, access to opioids is very limited. In 2009, more than 90% of worldwide use of opioid analgesics occurred in the USA, Canada, Australia, New Zealand, and several European countries. Use in that year was deemed low in 21 countries and very low in more than 100.” Patients in Latin American often have limited access to opioids for pain control . Yet even in the U.S.A., there are currently shortages of pharmaceutical medical opioid analgesics needed for acute pain control during medical procedures  experience some of the most painful procedures in medicine. During the course of their weeks in the hospital burn center's intensive care unit, children with large severe burns must have their wounds cleaned/scrubbed frequently to prevent infection and speed up healing. Opioid analgesics are widely regarded as effective and essential tools for acute pain management , opioid side effects  are widely used in clinical practice, and can be used in addition to traditional pain medications to help control pain during burn wound care. Some studies show strong benefits of music therapy during burn wound care in patients . As is often the case for patients with such unusually large severe burn injuries, most of the burn patients in our study had head and face burns, preventing them from wearing a conventional commercially available head mounted VR helmet. Furthermore, even when treated with powerful pain medications, pain during burn wound care procedures in the ICU hydrotank is often “severe to excruciating,” which may make it harder for children to concentrate enough to play in VR during wound care. In theory, pain may become so attention grabbing that psychological distraction techniques cannot compete with pain for the patient's limited attention , during adjunctive Yes VR, children will report significant reductions in worst pain ratings. Our secondary hypothesis is that during VR, children will report significant reductions in pain unpleasantness, and will spend less time thinking about pain during burn wound debridement in the ICU hydrotank. We further hypothesize that VR will increase how much fun patients have during wound care, and that patients will be more satisfied with their pain management during VR.www.wma.net). The studies were approved by the IRB from UTMB, and all participants and their parents/legal guardians provided written informed consent/assent in accordance with the Declaration of Helsinki.This research was conducted between Jan 2014 and Dec 2016, in accordance with the Declaration of the World Medical Association  compliant and able to complete subjective evaluations, (2) had no history of previous psychiatric (DSM-III-R Axis I) disorder(s), (3) were not demonstrating delirium, psychosis, or any form of organic brain disorder, (4) were able to communicate verbally in English or Spanish, and (5) had moderate or higher worst pain during no VR on Day 1, (6) were admitted to Shriners Hospitals for Children: Galveston Texas/University of Texas Medical Branch.Children were excluded from the study if (1) they had a burn size <10% TBSA, (2) they were not capable of completing the study measures, (3) if no wound cleaning sessions were required, (4) if they had a history of previous psychiatric (DSM-III-R Axis I) disorder(s), (5) if they were demonstrating delirium, psychosis, or organic brain disorder, (6) if the child was unable to communicate verbally in English or Spanish, (7) if they had a history of significant cardiac, endocrine, neurologic, metabolic, respiratory, gastrointestinal, or genitourinary impairment, (8) if they were receiving prophylaxis for alcohol or drug withdrawal, (9) if they had a developmental disability, (10) if they were younger than 6 years old, (11) if they were older than 17 years old, or (12) if they had burns of eyes, eyelids, or face so severe the burns precluded the use of VR equipment, (13) or if patients reported having a previous history of severe motion sickness.The current study introduced for the first time, a new portable water-friendly VR system customized for the unique needs of pediatric patients with large severe burn injuries during wound care in the intensive care unit hydrotank. As shown in The portable robot-like arm goggle holder was designed by Hoffman and Magula and built by Jeff Magula, an advanced instrument maker at the University of Washington in Seattle. Once finished, the water-friendly VR system was then safety inspected by Clinical Engineering at the University of Washington, and was inspected again by Clinical Engineering at Shriners Hospitals for Children. The equipment was also approved for use in the Intensive Care Unit and the equipment cleanliness was monitored by infection control at Shriners Hospitals for Children. After each use, the VR cart/portable VR system was returned to the Psychology Department at Shriners Galveston, where it was plugged in to recharge the batteries after each use. As shown in After each wound care session, subjects received the following instructions once prior to answering each of five separate questions. “Please indicate how you felt during wound care today by making a mark anywhere on the line. Your response doesn't have to be a whole number.”no pain at all, mild pain, moderate pain, severe pain, and excruciating pain. For pain unpleasantness, the GRS descriptors were not unpleasant at all, mildly unpleasant, moderately unpleasant, severely unpleasant, and excruciatingly unpleasant. For time spent thinking about pain, the GRS descriptors were none of the time, some of the time, half of the time, most of the time, all of the time.For the primary dependent measure, using Graphic Rating Scales (GRS), after the wound care session, patients answered the following GRS ratings. Pain was measured using Graphic Rating Scales (GRS) . To assess whether patients in the upper quartile on catastrophizing showed pain reduction during immersive Virtual Reality, we administered the Pain Catastrophizing Scale for Children (PSC-C) . During the portions of their burn wound care that they received VR, the research staff positioned the VR goggles weightlessly near the patient's eyes, with little or no physical contact between the VR goggles and the patient, using a robot-like-arm goggle holder , patients interacted with snowmen, igloos, penguins, wooly mammoths, and flying fish by throwing snowballs, using a wireless computer mouse to aim and trigger snowballs while keeping their heads and bodies motionless. During VR, patients heard music , and 3D sound effects e.g., ice breaking when a snowball hits a snowman. Mammoths trumpeted angrily when pelted.All patients used SnowWorld see  during aAfter the wound care session was over, patients briefly rated how much pain they had experienced during No VR vs. during Yes VR using graphic rating scales. The patient's burns were rebandaged, the patient was wheeled back to their hospital room and returned to their hospital beds, and the research staff thoroughly cleaned and disinfected the VR equipment.t-test, with alpha = 0.05.IBM SPSS  statistiPatients participated between January 2014 and December 2016. Out of the 62 patients initially screened, 48 pediatric patients met our apriori inclusion criterion of having a moderate or higher “worst pain” rating during No VR on Day 1 . The mean size of the patient's severe burn injuries was 40 percent Total Body Surface Area (TBSA) burned, 28% third degree burns. Patients' ages ranged from 6 to 17 years of age at time of enrollment (Mean age was 12 years old). Seventy-seven percent of the patients had hand burns, 85% had arm burns, 44% had foot burns, 79% had leg burns, 71% had neck/head burns, 79% had trunk/torso burns, and 23% had groin burns. Regarding the (sometimes overlapping) etiology of their burns, 81% had burns involving flame, 6% scalds, 25% electrical, and zero patients had chemical burns.t-test, VR significantly reduced children's “worst pain” ratings during burn wound cleaning procedures in the ICU. On Day 1, worst pain during No VR = 8.52 (SD = 1.75) vs. during Yes VR = 5.10 (SD = 3.27), t(47) = 7.11, p < 0.001, SD = 3.33, CI = 2.45–4.38, Cohen's d = 1.03, indicating a large effect size.The patients GRS pain ratings on Day 1 are shown in On Day 1, the number of patients reporting excruciating pain (worst pain = 10) during wound care was 22 patients, which dropped to only five patients reporting excruciating pain (worst pain = 10) during Yes VR, and Cohen's d showed a strong effect size of VR analgesia. However, many of those patients with pain of 10 during No VR only dropped to 8 during VR .On Day 1, 40% of the 48 patients still reported pain of 7 or higher (severe to excruciating) during VR, despite receiving powerful traditional pharmacologic pain medications combined with immersive virtual reality.t(44) = 2.47, p < 0.05, SD = 9.97, CI =0.67–6.66, e.g., patients could not use VR while having their faces or heads cleaned. On Day 1, 14 of the 48 patients spent exactly the same amount of time during No VR (13.21 min) and during VR (13.21 min). These 14 patients also reported large and statistically significant reductions in pain during VR, worst pain during No VR = 8.50 (SD = 1.83), VR = 4.43 (SD = 3.08), t(13) = 4.56, p < 0.005, SD = 3.34, CI = 2.14–6.00.On average, patients spent mean = 16.56 min of wound care during No VR vs. 12.89 min during VR, t(47) = 7.32, p < 0.001, SD = 2.65, CI = 2.01–3.57, Cohen's d = 1.06, large effect size.The mean number of days that patients rated their pain during Yes VR vs. during No VR was 4 study days. Collapsed across days, VR significantly reduced worst pain: Worst pain during “No VR”  vs. worst pain during “Yes virtual reality” , F = 1.50, p = 0.36, NS.Consistent with the prediction that VR would continue to reduce pain when used day after day, a one-way within-subjects ANOVA comparing worst pain during “No VR” minus worst pain during “Yes VR” difference scores for days 1–7 showed no significant difference in the size of the VR analgesia effect over days 1–7, Wilks' Lamda t(6) = 2.80, p < 0.05, SD = 2.56, CI = 0.34 vs. 5.09. Patients scoring in the lower quartile in the current sample also showed significant VR analgesia, mean worst pain ratings during No VR = 6.00 (SD = 4.04), and during VR = 2.86 (SD = 2.85), t(6) = 4.01, p < 0.01, SD = 1.03, CI = 1.61–6.67.In exploratory analyses, patients scoring in the upper quartile on the children's pain catastrophizing score (PSC-C) in the current sample, showed significant VR analgesia. For patients scoring in the upper quartile on catastrophizing, mean worst pain during No VR = 7.00 (SD = 3.56), vs. VR = 2.86 (SD = 3.63), t-test. The children were significantly more satisfied with their pain management during VR, on average. Patients reported only a moderate illusion of “being there” inside the 3D computer generated world as if it was a place they visited. VR nausea was nearly zero .As shown in The current study included 48 pediatric patients total. As shown in This pilot study provides preliminary evidence that immersive virtual reality can help reduce the pain of children with large severe burn wounds during burn wound cleaning in the Intensive Care Unit. Although using VR in the ICU hydrotank room was challenging and required creating custom equipment, in the current study, on Day 1, patients reported significant reductions in worst pain (pain intensity), children spent less time thinking about their pain during VR, children reported significant reductions in pain unpleasantness, and the children reported 27% higher ratings of fun during wound care during virtual reality. In addition, these pediatric patients were also significantly more satisfied with their pain management during virtual reality, they reported a moderate illusion of presence in VR , and VR nausea was nearly zero . Patients who received VR during more than 1 day of wound care continued to report the predicted pattern of reductions in worst pain during multiple wound care sessions. And patients with a tendency toward negative emotions and pessimistic beliefs about their ability to deal with the upcoming pain , still benefitted from virtual reality distraction.n = 48 patients). Furthermore, in the current study, on average, patients spent over 12 min in VR and over 12 min in No VR, the wound care was conducted in the ICU instead of in the patients hospital beds, and the current study is the first to use a portable water-friendly VR system.The reductions in worst pain ratings in the current study are similar to the pattern of VR analgesia reported in previous studies of 12 U.S. soldiers with combat-related burn injuries (TBSA of 21%) during wound care in their hospital beds. The soldiers spent 6 min in No VR vs. 6 min of wound care during VR  this is the first study ever to attempt to use virtual reality during burn wound care in the intensive care unit, (b) the patients had unusually severe burn injuries much larger than burn injuries treated in any previous burn debridement VR analgesia study, (c) all of the patients were children, and 44 out of the 48 patients were Spanish speaking children from developing Latin American Countries, (d), the current study shows for the first time that children with large severe burns were generally able to play SnowWorld during severely painful medical procedures, and (e) playing SnowWorld in virtual reality significantly reduced worst pain ratings during wound care.In the current study, a custom portable water-friendly VR system was used that did not have to physically contact the patient. The equipment was carefully cleaned with sterilizing cloths after each use, and the equipment was periodically swabbed/tested by the hospitals infection control team to test for the presence of any bacterial or viral pathogens. There was no problem with infection in the current study, using the custom VR system, which minimized or eliminated physical contact between the patient and the VR goggles. For patients with limited ability to wear VR helmets, modified VR systems that reduce contact surfaces  may eventually prove to be “opioid sparing” during hospitalization , where large severe burns and other serious injuries are more common, and powerful pharmacologic analgesics are more scarce or unavailable. Additional research and development of VR analgesia is recommended.The datasets for this study will not be made publicly available because IRB restrictions.www.wma.net). The studies were approved by the IRB from UTMB, and all participants provided written informed consent/assent in accordance with the Declaration of Helsinki.This research was conducted in accordance with the Declaration of the World Medical Association (All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.All authors have completed the ICMJE uniform disclosure and declare support for the submitted work.


Celecoxib is frequently prescribed to treat knee osteoarthritis (KOA), but how celecoxib influences the activity of the central nervous system to alleviate chronic pain remains unclear.One hundred eight patients with KOA will be enrolled in this study. Patients will be allocated randomly to three groups: the celecoxib group, the placebo group, and the waiting list group. The patients in the celecoxib group will orally take celecoxib 200 mg once daily and the patients in placebo group with placebo 200 mg every day for 2 weeks. Functional magnetic resonance imaging scan will be performed on all patients at baseline and the end of interventions to detect the cerebral activity changes. The short form of McGill pain questionnaire and the Visual Analog Scale will be used as the primary endpoints to evaluate the improvement of knee pain. The secondary endpoints include the Western Ontario and McMaster osteoarthritis index (WOMAC), the Attention Test Scale, the Pain Assessment of Sphygmomanometer, the Self-rating Anxiety Scale, the Self-rating Depression Scale, and 12-Item Short Form Health Survey (SF-12).The results will investigate the influence of celecoxib treatment on cerebral activity of patients with KOA and the possible relationship between the cerebral activity changes and improvement of clinical variables so as to explore the central mechanism of celecoxib in treating knee pain.ChiCTR-IOR-17012365. Registered on August 14, 2017.The online version of this article (10.1186/s13063-018-3111-8) contains supplementary material, which is available to authorized users. Non-steroidal anti-inflammatory drugs (NSAIDs), known as cyclooxygenase (COX) inhibitors, are often prescribed for the management of chronic and acute pain worldwide. NSAIDs exert analgesic effects by inhibiting COX activity in the arachidonic acid cascade and thus inhibit prostaglandin (PG) synthesis , which lCelecoxib, as the first COX-2 selective inhibitor, was introduced into clinical practice nearly 20 years ago –9 and wiAs a high prevalence chronic knee pain , the preWith the application of neuroimaging techniques in pain research, investigators not only mapped the brain regions which are involved in the central pathogenesis of chronic pain but also can explore the cerebral responses elicited by analgesics so as to illuminate the central mechanism. With resting-state functional magnetic resonance imaging (rs-fMRI), investigators found that the patients with chronic pain demonstrated the alternations in functional connectivity (FC) of medial prefrontal-default mode network and the regional homogeneity (ReHo) value changes of anterior cingulate cortex –21.These results greatly enhance the understanding of the central mechanism of chronic pain and provide a new approach to the research and development of drugs. For instance, Xiaoyan Chen et al. had shown that acupuncture can regulate the descending pain modulatory system of patients with KOA by enhancing the FC between the right frontoparietal network and medial prefrontal cortex .So this trial aims to (1) investigate the influence of celecoxib treatment on the brain activities of patients with KOA compared with that of placebo treatment and waiting list by fMRI and (2) analyze the possible correlations between the changes of cerebral activity and the improvement of clinical variables in each group so as to explore how the celecoxib manages pain by modulating brain function to treat KOA.This is a clinical neuroimaging study aiming to investigate the central mechanism of how celecoxib alleviates knee pain for treating KOA. A total of 108 patients with KOA will be randomly allocated to three different groups. Each group includes 36 patients with KOA. The three groups are group A , group B , and group C (waiting list). The treatment period will last for 2 weeks. Outcome measurements and MRI scan will be assessed at baseline and at the end of treatment. The changes of clinical variables and cerebral activity of each group will be analyzed after data collection  criteria (1991 revised version)  will be Inclusion criteria require that the patients (1) match the diagnosis criteria for KOA set by ACR in 1991 , (2) arePatients will be excluded if they (1) are alcohol or drug abusers or abuse other medications that may influence brain imaging outcomes; (2) are pregnant or lactating; (3) have psychiatric, neurologic, gastrointestinal, cardiovascular, infectious, immunologic, respiratory, or renal illnesses; (4) have any other chronic pain conditions or a history of head trauma with loss of consciousness; (5) had diagnosed rheumatoid arthritis or other leg-related pain disorders; (6) have MRI contraindications such as claustrophobia, cardiac pacemaker, defibrillator, heart stenting, or intrauterine device; (7) have active peptic ulcer or a history of peptic ulcer; or (8) are allergic to celecoxib.The sample size calculation of neuroimaging study is different from that of classic randomized controlled trials. The neuroimaging study focuses on investigating mechanism but not evaluating efficacy. General speaking, in MRI studies, 12 to 15 patients per group provide a statistical result , 25. OurThis study protocol has been approved by the supervision of the Sichuan Regional Ethics Review Committee on TCM  and been registered at Chinese Clinical Trial Registry (registration number ChiCTR-IOR-17012365). The authors retain full control of the article’s content. All patients will be informed of the random allocation of celecoxib, placebo, or waiting list treatment and the possible risks. They will voluntarily sign an informed consent form before enrollment. The patients will be free to withdraw from the study at any time without a specific reason and without any penalty or loss of benefits. However, we will attempt to understand the reason for withdrawal and encourage the participant to remain in the study if possible.This study will be performed in accordance with the guidance and principles of the Declaration of Helsinki. Adverse events caused by celecoxib, such as nausea, vomiting, or other severe events, will be processed immediately and recorded in detail in the case report forms. Each patient will get paid for study participation. Figure Eligible patients will be randomly assigned in a ratio of 1:1:1 to the celecoxib group, placebo group, and waiting list group with 36 patients in each group. Random number lists will be created in accordance with PROC PLAN of SAS 9.2 . The randomization allocation will use sequentially numbered, opaque, and sealed envelopes by an independent assistant. The celecoxib group and the placebo group will be concealed from the researchers until completion of the statistical analysis.As waiting list group without any medical intervention, while the other two groups will be given celecoxib or placebo 200mg daily, it is impossible to blind the patients, clinicians and investigators totally. Patients and researchers of the celecoxib group and the placebo group will be unaware of the assignments until completion of the statistical analysis. Only an independent researcher in the pharmacy department knows the allocation of the celecoxib and placebo groups. The evaluators and statisticians will be blinded to the group allocation during outcome evaluation and data analysis to reduce the risk of bias.Patients in the celecoxib group will orally take a celecoxib capsule  at a daily dosage of 200 mg for 2 weeks. Patients in the placebo group will receive a placebo capsule  with oral administration at the same dosage as celecoxib capsule once a day for 2 weeks. The placebo capsule is identical in appearance, smell, and texture to the celecoxib capsule. Patients in the waiting list group will be observed for 2 weeks without any medical or other interventions. After 2 weeks’ observation, patients in the waiting list group and placebo group could choose either 2 weeks’ celecoxib treatment or acupuncture treatments free of charge.Patients will be instructed not to take any caffeine (such as tea and coffee) or have any other treatments for KOA during the study. In case of severe knee pain, ibuprofen (300 mg each capsule with sustained release) will be allowed as rescue medication and should be recorded in the knee pain diary. Patients are also asked to record the name, dose, date, and the exact time of the medications used and reported to the researcher if they take any regular medications during the trial.MRI data will be acquired with a 3.0 T magnetic resonance scanner  with an eight-channel phase-array head coil at the MRI Center in University of Electronic Science and Technology of China. Subjects will be asked to stay awake and to keep their heads still during the scan, with their eyes closed and ears plugged. Subjects will be asked to keep relaxed and not think anything particular during the whole scan. MRI scans will be assessed twice at baseline and after 2 weeks’ intervention or observation period for each patient.3 employing an axial fast spoiled gradient recalled sequence . The rs-fMRI images will be obtained with echo-planar imaging . After the rs-fMRI scan, diffusion tensor imaging sequences with single-shot echo planar imaging will be acquired to detect the possible abnormality of the white matter with the following parameters: field of view 256 × 256 mm2, repetition time 8500 ms, echo time minimum, matrix = 128 × 128, slice thickness 2 mm, and 78 continuous axial slices with no gap. Two diffusion-weighted sequences will be acquired by using gradient values b = 0 s/mm2 and b = 1000 s/mm2 with the diffusion-sensitizing gradients applied along 64 non-linear directions.Prior to the rs-fMRI scan, a high-resolution structural image for each subject will be acquired by using a three-dimensional MRI sequence (3DT1) with a voxel size of 1 mmThe clinical evaluations will comprise four components: knee pain, knee function, cognition, and emotion. All evaluations will be performed twice: at baseline and after 2 weeks’ intervention or observation. All evaluations will be evaluated by two trained licensed physicians.The primary outcome measurements are VAS and the short form of the McGill pain questionnaire of average knee pain in the last 2 weeks and the VAS of knee pain during the MRI scan. The short form of the McGill pain questionnaire could measure the sensory and affective component of pain.The secondary outcome measurements are the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) , AttentiThe case report form includes observation time points, scanning time points, outcome measures, adverse events, and safety evaluations. The researchers will be required to follow the requirements of the case report form and fill in the relevant information in a timely and accurate manner. Data collection will be performed by study physician, and the quality of the data will be supervised by two independent experienced clinical researchers.Before the data analyses, the research group will provide a statistical scheme to the statisticians. The scheme will include the required data and processing method. The data will be processed and analyzed by the statisticians in accordance with the scheme.t test will be used to compare the numerical variables in the within-group analyses, including the VAS, short form of the McGill pain questionnaire, WOMAC, ATS, SAS, SDS, Pain Assessment of Sphygmomanometer (PAS), and SF-12. Analysis of variance and the Kruskal–Wallis test will be used for numerical variables in the between-group analyses, including age, height, weight, scores of VAS, short form of the McGill pain questionnaire, WOMAC, ATS, SAS, SDS, PAS, and SF-12. The chi-squared test will be used for categorical variables. A two-sided test is applied for available data, and a P value of less than 0.05 is considered statistically significant.For the clinical data, statistical analyses will be performed with SPSS 21.0 statistics software . The data analysis process will be completed by statisticians who are independent from the research team and blinded to the test settings. A http://www.fil.ion.ucl.ac.uk/spm/) performed on MATLAB 2015b . The preprocessing steps will include slice timing correction, head motion correction, spatial normalization, spatial smoothing, and detrending. After data preprocessing, amplitude of low-frequency fluctuation, ReHo, and FC will be used to investigate the cerebral responses of different study groups. Two-sample t tests will be used to evaluate possible cerebral responses in each group by within-group analysis (post-treatment minus pre-treatment). We will use between-group analysis to compare the difference in cerebral response changes. Correlation analysis will be conducted to investigate changes between fMRI image data and corresponding clinical data in each group.The fMRI scan data will be preprocessed and analyzed by SPM12 software  and cyclooxygenase-2 (COX-2) . Celecoxin vitro . Demb etin vitro . HoweverWith the advantages of high quality of time and spatial resolution, without radiation, quick imaging velocity, and relative lower price , 33, fMRStraight quality control measurements are conducted to avoid bias in this trial to improve the reliability of results. First, at the stage of participant enrollment, we establish rigorous inclusion and exclusion criteria. Not only demographic characteristics such as age, sex, and handedness will be listed in the including criteria, but also factors which possibly influencing cerebral activities, including the drinking coffee or abusing alcohol and drugs, will be taken into consideration. Furthermore, in order to reduce the influence of emotional state on brain activities of patients with KOA, the SAS and SDS will be used to evaluate the patients’ psychological states. Second, at the stage of treatment, the placebo capsule is identical in appearance, odor, dosage, color, and texture to the celecoxib capsule. Third, at the stage of the fMRI scan, the patients will be asked to follow uniform instructions, wear earplugs, close their eyes, and remain relaxed and awake during the scan. The head of the participant will be placed in the head mask and a sponge will be inserted to strengthen the fixation of the head to eliminate possible head motion.In summary, this fMRI trial is designed to investigate the central mechanism of celecoxib in the treatment of KOA by comparing the cerebral responses to celecoxib, placebo, and waiting list and by analyzing the correlation between the cerebral activity changes and clinical variables’ improvement. We expect that our findings can provide a reference for the clinical application of NSAID.The trial is currently in the participant recruitment stage. The trial began recruitment on October 18, 2017 and is expected to be complete on December 31, 2019. This trial is reported in the light of the Standard Protocol Items: Recommendations for Intervention Trials (SPIRIT) guidelines