Recent systematic reviews (SRs) came to divergent conclusions on the efficacy and safety of medical marijuana and cannabis-based medicines for chronic pain management. This paper gives an overview and critical appraisal of the methods of recent SRs of randomized controlled trials (RCTs) with cannabis medicines for chronic pain.Selective search of the literature, incorrect data analyses and presentation in favor of cannabis medicines can be detected in both RCTs and SRs. The more detailed the search of literature (e.g. inclusion of so-called grey literature) and the higher the criteria of the inclusion of studies (such as study duration) and of the clinical relevance of the study findings, the more disappointing are the conclusions of SRs on the efficacy and safety of cannabis medicines. There is moderate quality evidence of a moderate relief of neuropathic pain. Cannabis medicines can be regarded to be third-line therapy for chronic neuropathic pain. There are signals of a lack of efficacy for all other chronic pain syndromes.New high-quality RCTs and approaches, such as network meta-analyses combining different treatments and controlled and observational including additional outcomes than pain relief, are necessary to better define the importance of cannabis medicines for chronic pain management.

BACKGROUND:Hyperbaric oxygen (HBO) therapy is proven to attenuate neuropathic pain in rodents. The goal of the present study was to determine the potential involvement of the Kindlin-1/Wnt-10a signaling pathway during astrocyte activation and inflammation in a rodent model of neuropathic pain.

METHODS:Rats were assigned into sham operation, chronic constriction injury (CCI), and CCI + HBO treatment groups. Neuropathic pain developed in rats following CCI of the sciatic nerve. Rats in the CCI + HBO group received HBO treatment for five consecutive days beginning on postoperative day 1. The mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) tests were performed to determine mechanical and heat hypersensitivity of animals, respectively. Kindlin-1, Wnt-10a and β-catenin protein expression was examined by immunohistochemistry and Western blot analysis. Expression of tumor necrosis factor (TNF)-α was also determined by ELISA.

RESULTS:Our findings demonstrated that HBO treatment significantly suppressed mechanical and thermal hypersensitivity in the CCI neuropathic pain model in rats. HBO therapy significantly reversed the up-regulation of Kindlin-1 in dorsal root ganglia (DRG), spinal cord, and hippocampus of CCI rats. CCI-induced astrocyte activation and increased levels of TNF-α were efficiently reversed by HBO (P < 0.05 vs. CCI). HBO also reversed Wnt-10a up-regulation induced by CCI in the DRG, spinal cord, and hippocampus (P < 0.05 vs. CCI).

CONCLUSIONS:Our findings demonstrate that HBO attenuated CCI-induced rat neuropathic pain and inflammatory responses, possibly through regulation of the Kindlin-1/Wnt-10a signaling pathway.

BACKGROUND AND OBJECTIVE:Hyperbaric oxygen therapy (HBOT) is a treatment providing 100% oxygen at a pressure greater than that at sea level. HBOT is becoming increasingly recognized as a potential treatment modality for a broad range of ailments, including chronic pain. In this narrative review, we discuss the current understanding of pathophysiology of nociceptive, inflammatory and neuropathic pain, and the body of animal studies addressing mechanisms by which HBOT may ameliorate these different types of pain. Finally, we review clinical studies suggesting that HBOT may be useful in treating chronic pain syndromes, including chronic headache, fibromyalgia, complex regional pain syndrome, and trigeminal neuralgia.

DATABASE AND DATA TREATMENT:A comprehensive search through MEDLINE, EMBASE, Scopus, and Web of Science for studies relating to HBOT and pain was performed using the following keywords: hyperbaric oxygen therapy or hyperbaric oxygen treatment (HBOT), nociceptive pain, inflammatory pain, neuropathic pain, HBOT AND pain, HBOT AND headache, HBOT AND fibromyalgia, HBOT AND complex regional pain syndrome, and HBOT AND trigeminal neuralgia.

RESULTS:Twenty-five studies examining the role of HBOT in animal models of pain and human clinical trials were found and reviewed for this narrative review.

CONCLUSIONS:HBOT has been shown to reduce pain using animal models. Early clinical research indicates HBOT may also be useful in modulating human pain; however, further studies are required to determine whether HBOT is a safe and efficacious treatment modality for chronic pain conditions.

OBJECTIVE:To assess benefits of mindfulness meditation and cognitive behavioral therapy (CBT)-based intervention for opioid-treated chronic low back pain (CLBP).

DESIGN:26-week parallel-arm pilot randomized controlled trial (Intervention and Usual Care versus Usual Care alone).

SETTING:Outpatient.

SUBJECTS:. Adults with CLBP, prescribed≥30 mg/day of morphine-equivalent dose (MED) for at least 3 months.

METHODS:The intervention comprised eight weekly group sessions (meditation and CLBP-specific CBT components) and 30 minutes/day, 6 days/week of at-home practice. Outcome measures were collected at baseline, 8, and 26 weeks: primary-pain severity (Brief Pain Inventory) and function/disability (Oswestry Disability Index); secondary-pain acceptance, opioid dose, pain sensitivity to thermal stimuli, and serum pain-sensitive biomarkers (Interferon-γ; Tumor Necrosis Factor-α; Interleukins 1ß and 6; C-reactive Protein).

RESULTS:Thirty-five (21 experimental, 14 control) participants were enrolled and completed the study. They were 51.8± 9.7 years old, 80% female, with severe CLBP-related disability (66.7 ± 11.4), moderate pain severity (5.8 ± 1.4), and taking 148.3 ± 129.2 mg/day of MED. Results of the intention-to-treat analysis showed that, compared with controls, the meditation-CBT group reduced pain severity ratings during the study (P = 0.045), with between-group difference in score change reaching 1 point at 26 weeks (95% Confidence Interval: 0.2,1.9; Cohen's d = 0.86), and decreased pain sensitivity to thermal stimuli (P<0.05), without adverse events. Exploratory analyses suggested a relationship between the extent of meditation practice and the magnitude of intervention benefits.

CONCLUSIONS:Meditation-CBT intervention reduced pain severity and sensitivity to experimental thermal pain stimuli in patients with opioid-treated CLBP.

This study examined whether a modified version of biofeedback (ie, Conditioned Biofeedback) that incorporated placebo analgesia-like manipulations could promote antinociception in healthy, pain-free participants. During Conditioned Biofeedback (n = 28), sympathetic arousal level was displayed visually and participants were asked to reduce it while they received painful electric stimulations that were surreptitiously controlled by their arousal level. Thus, electric pain decreased as arousal decreased to associate successful arousal-reduction/relaxation with pain relief, and to promote expectations for future pain relief. A Biofeedback Only group (n = 24) controlled for the general effects of biofeedback/relaxation. A Biofeedback+Shock group (n = 21) controlled for the effects of practicing biofeedback during painful shocks. Nociceptive flexion reflex (NFR) threshold and temporal summation of pain (TS-pain) were used to assess changes in spinal nociception and pain facilitation, respectively. Results indicated all groups showed pre- to postbiofeedback increases in NFR threshold, but only the Conditioned Biofeedback group showed pre- to postbiofeedback reductions in TS-pain. Moreover, Conditioned Biofeedback resulted in a persistent (prebiofeedback) increase in NFR threshold across sessions, whereas Biofeedback Only resulted in a persistent (prebiofeedback) decrease in TS-pain. In sum, Conditioned Biofeedback maypromote antinociception in healthy participants thus reducing risk for chronic pain. The study was registered prospectively on ClinicalTrials.gov (TU1560). PERSPECTIVE: A modified version of biofeedback that employs placebo analgesia manipulations was successful in increasing descending inhibitionand reducing pain facilitation in healthy volunteers. As a result, it may be an effective means of reducing risk of future chronic pain onset by promoting an antinociceptive pain profile.

Epidemic increases in opioid use in the USA and globally highlight the need for effective adjunctive therapies to opioid-based analgesia. Given the shortcomings of behavioral adjuncts to opioid-based pain treatment, an urgent need exists for pain-related behavioral interventions that resonate with broad patient populations, can be delivered confidentially in any environment, and can incorporate new content automatically. Understanding the potential for automated behavioral therapies like music therapy in modulating the experience of pain may unlock methods to transition patients to lower doses of pharmacologic therapy or provide alternatives to opioids during acute exacerbations of pain. This manuscript describes the neurologic mechanism of action, theoretical basis, and potential applications of personalized music as a smartphone-based mHealth intervention for acute and chronic pain management.

Epidemic increases in opioid use in the USA and globally highlight the need for effective adjunctive therapies to opioid-based analgesia. Given the shortcomings of behavioral adjuncts to opioid-based pain treatment, an urgent need exists for pain-related behavioral interventions that resonate with broad patient populations, can be delivered confidentially in any environment, and can incorporate new content automatically. Understanding the potential for automated behavioral therapies like music therapy in modulating the experience of pain may unlock methods to transition patients to lower doses of pharmacologic therapy or provide alternatives to opioids during acute exacerbations of pain. This manuscript describes the neurologic mechanism of action, theoretical basis, and potential applications of personalized music as a smartphone-based mHealth intervention for acute and chronic pain management.

BACKGROUND AND OBJECTIVE:Studies on laser phototherapy for pain relief have used parameters that vary widely and have reported varying outcomes. The purpose of this study was to determine the optimal parameter ranges of laser phototherapy for pain relief by analyzing data aggregated from existing primary literature.

MATERIALS AND METHODS:Original studies were gathered from available sources and were screened to meet the pre-established inclusion criteria. The included articles were then subjected to meta-analysis using Cohen's d statistic for determining treatment effect size. From these studies, ranges of the reported parameters that always resulted into large effect sizes were determined. These optimal ranges were evaluated for their accuracy using leave-one-article-out cross-validation procedure.

RESULTS:A total of 96 articles met the inclusion criteria for meta-analysis and yielded 232 effect sizes. The average effect size was highly significant: d = +1.36 (confidence interval [95% CI] = 1.04-1.68). Among all the parameters, total energy was found to have the greatest effect on pain relief and had the most prominent optimal ranges of 120-162 and 15.36-20.16 J, which always resulted in large effect sizes. The cross-validation accuracy of the optimal ranges for total energy was 68.57% (95% CI = 53.19-83.97). Fewer and less-prominent optimal ranges were obtained for the energy density and duration parameters. None of the remaining parameters was found to be independently related to pain relief outcomes.

CONCLUSIONS:The findings of meta-analysis indicate that laser phototherapy is highly effective for pain relief. Based on the analysis of parameters, total energy can be optimized to yield the largest effect on pain relief.

BACKGROUND AND OBJECTIVE:Studies on laser phototherapy for pain relief have used parameters that vary widely and have reported varying outcomes. The purpose of this study was to determine the optimal parameter ranges of laser phototherapy for pain relief by analyzing data aggregated from existing primary literature.

MATERIALS AND METHODS:Original studies were gathered from available sources and were screened to meet the pre-established inclusion criteria. The included articles were then subjected to meta-analysis using Cohen's d statistic for determining treatment effect size. From these studies, ranges of the reported parameters that always resulted into large effect sizes were determined. These optimal ranges were evaluated for their accuracy using leave-one-article-out cross-validation procedure.

RESULTS:A total of 96 articles met the inclusion criteria for meta-analysis and yielded 232 effect sizes. The average effect size was highly significant: d = +1.36 (confidence interval [95% CI] = 1.04-1.68). Among all the parameters, total energy was found to have the greatest effect on pain relief and had the most prominent optimal ranges of 120-162 and 15.36-20.16 J, which always resulted in large effect sizes. The cross-validation accuracy of the optimal ranges for total energy was 68.57% (95% CI = 53.19-83.97). Fewer and less-prominent optimal ranges were obtained for the energy density and duration parameters. None of the remaining parameters was found to be independently related to pain relief outcomes.

CONCLUSIONS:The findings of meta-analysis indicate that laser phototherapy is highly effective for pain relief. Based on the analysis of parameters, total energy can be optimized to yield the largest effect on pain relief.

BACKGROUND/AIM: It is weel-known that sulphur baths and mud paks demonstrate beneficial effects on patients suffering from degenerative knee and hip osteoarthritis (OA) through the increased activity of protective antioxidant enzymes. The aim of this study was to assess lipid peroxidation level, i.e., malondialdehyde concetration, in individuals with knee and/or hip osteoarthritis (OA), as well as to determine the influence of sulphur baths and mud packs application on the activity of superoxide dismutase (SOD) and catalase (CAT) in order to minimize or eliminate excessive free radical species production (oxidative stress). METHODS: Thirty one patiens with knee and/or hip OA of both sexes were included in the study. All OA patients received mud pack and sulphur bath for 20 minutes a day, for 6 consecutive days a week, over 3 weeks. Blood lipid peroxidation, i.e., malondialdehyde concentration, superoxide dismutase and catalase activity were measured spectrophotometrically, before, on day 5 during the treatment and at the end of spa cure. Healthy volunteers (n=31) were the controls. RESULTS: The sulphur baths and mud packs treatment of OA patients caused a significant decrease in plasma malondialdehyde concentration compared to the controls (p<0.001). The mean SOD activity before the terapy was 1836.24 U/gHb, on day 5 it rose to 1942.15 U/gHb and after the spa cure dropped to 1745.98 U/gHb. Catalase activity before the therapy was 20.56 kU/gHb and at the end of the terapy decreased to 16.16 kU/gHb. The difference in catalase activity before and after the therapy was significant (p<0.001), and also significant as compared to control (p<0.001). At the end of the treatment significant increase of hemoglobin level and significant decrease of pain intensity were noticed. CONCLUSION: A combined 3-week treatment by sulphur bath and mud packs led to a significant decrease of lipid peroxidation in plasma, as well as pain intensity in the patients with OA. These changes were associated with changes in plasma activity of SOD and CAT and a significant increase of hemoglobin level suggesting their role in beneficial effect of spa therapy in the patients with OA.

Periods of deliberate fasting with restriction to intake of solid food are practiced worldwide, mostly based on a traditional, cultural, or religious background. Recent evidence from clinical trials shows that medically supervised modified fasting (200-500 kcal nutritional intake/day) with periods from 7 to 21 days is efficacious in the treatment of rheumatic diseases and chronic pain syndromes. Here, fasting is frequently accompanied by increased alertness and mood enhancement. The beneficial claims of fasting are supported by experimental research, which has found fasting to be associated with increased brain availability of serotonin, endogenous opioids, and endocannabinoids. Fasting-induced neuroendocrine activation and mild cellular stress response with increased production of neurotrophic factors may also contribute to the mood enhancement of fasting. Fasting treatments may be useful as an adjunctive therapeutic approach in chronic pain patients. The mood-enhancing and pain-relieving effect of therapeutic fasting should be further evaluated in randomized clinical trials.

BACKGROUND:Pain may be reported in one-half to three-fourths of children with cancer and other terminal conditions and anxiety in about one-third of them. Pharmacologic methods do not always give satisfactory symptom relief. Complementary therapies such as Reiki may help children manage symptoms.

OBJECTIVE:This pre-post mixed-methods single group pilot study examined feasibility, acceptability, and the outcomes of pain, anxiety, and relaxation using Reiki therapy with children receiving palliative care.

METHODS:A convenience sample of children ages 7 to 16 and their parents were recruited from a palliative care service. Two 24-minute Reiki sessions were completed at the children's home. Paired t tests or Wilcoxon signed-rank tests were calculated to compare change from pre to post for outcome variables. Significance was set at P<.10. Cohen d effect sizes were calculated.

RESULTS:The final sample included 8 verbal and 8 nonverbal children, 16 mothers, and 1 nurse. All mean scores for outcome variables decreased from pre- to posttreatment for both sessions. Significant decreases for pain for treatment 1 in nonverbal children (P = .063) and for respiratory rate for treatment 2 in verbal children (P = .009). Cohen d effect sizes were medium to large for most outcome measures.

DISCUSSION:Decreased mean scores for outcome measures indicate that Reiki therapy did decrease pain, anxiety, heart, and respiratory rates, but small sample size deterred statistical significance. This preliminary work suggests that complementary methods of treatment such as Reiki may be beneficial to support traditional methods to manage pain and anxiety in children receiving palliative care.

The objective of this work was to update the rheumatologic indications of spa therapy, based on clinical practice guidelines published by the French National Authority for Health (HAS) and the European League Against Rheumatism (EULAR), and on the results of randomized clinical trials (RCT)

METHODOLOGY: We first examined the indications for which spa therapy is mentioned and/or recommended in HAS and EULAR guidelines. We then identified RCTs in spa therapy and rheumatology by using the key words spa therapy, balneology, balneotherapy, hydrotherapy, mud therapy and mineral water in the Pubmed, Pascal and Embase databases. Only RCTs including a statistical analysis of between-group outcomes were retained We also examined the possible contribution of RCTs not listed in the bibliography of the guidelines.

RESULTS: RECOMMENDATIONS: spa therapy is recommended by HAS for chronic lower back pain, rank B and for stabilized rheumatoid arthritis, rank C. In ankylosing spondylitis, EULAR classifies spa therapy along with physiotherapy, rank A. In fibromyalgia, EULAR recommends hot-water balneology, an important component of spa therapy, rank B, based on five RCTs, of which three were carried out in thermal springs. Nineteen RCTs that comprised a statistical comparison of between-group outcomes were identified Sixteen studies indicated a persistent improvement (at least twelve weeks) in pain, analgesic and non-steroidal antiinflammatory drug consumption, functional capacity and/or quality of life, in the following indications: chronic lower back pain, knee osteoarthritis, hand osteoarthritis, fibromyalgia, ankylosing spondylitis andrheumatoidarthritis (PR).

CONCLUSION: Spa therapy, or hot-water balneology, appears to be indicated for chronic low back pain, stabilized rheumatoid arthritis, ankylosing spondylitis and fibromyalgia. RCT findings suggest that patients with knee and hand osteoarthritis might also benefit.

Several studies reported that Tai Chi showed potential effects for chronic pain, but its role remains controversial. This review assessed the evidence regarding the effects of Tai Chi for chronic pain conditions. 18 randomized controlled trials were included in our review. The aggregated results have indicated that Tai Chi showed positive evidence on immediate relief of chronic pain from osteoarthritis (standardized mean difference [SMD], -0.54; 95% confidence intervals [CI], -0.77 to -0.30; P < 0.05). The valid duration of Tai Chi practice for osteoarthritis may be more than 5 weeks. And there were some beneficial evidences regarding the effects of Tai Chi on immediate relief of chronic pain from low back pain (SMD, -0.81; 95% CI, -1.11 to -0.52; P < 0.05) and osteoporosis (SMD, -0.83; 95% CI, -1.37 to -0.28; P = 0.003). Therefore, clinicians may consider Tai Chi as a viable complementary and alternative medicine for chronic pain conditions.

Beta-endorphin (betaE) is an important reliever of pain. Various stressors and certain modalities of physiotherapy are potent inducers of the release of endogenous betaE to the blood stream. Most forms of exercise also increase blood betaE level, especially when exercise intensity involves reaching the anaerobic threshold and is associated with the elevation of serum lactate level. Age, gender, and mental activity during exercise also may influence betaE levels. Publications on the potential stimulating effect of manual therapy and massage on betaE release are controversial. Sauna, mud bath, and thermal water increase betaE levels through conveying heat to the tissues. The majority of the techniques for electrical stimulation have a similar effect, which is exerted both centrally and--to a lesser extent--peripherally. However, the parameters of electrotherapy have not yet been standardised. The efficacy of analgesia and the improvement of general well-being do not necessarily correlate with betaE level. Although in addition to blood, increased brain and cerebrospinal fluid betaE levels are also associated with pain, the majority of studies have concerned blood betaE levels. In general, various modalities of physical therapy might influence endorphin levels in the serum or in the cerebrospinal fluid--this is usually manifested by elevation with potential mitigation of pain. However, a causal relationship between the elevation of blood, cerebrospinal fluid or brain betaE levels and the onset of the analgesic action cannot be demonstrated with certainty.

Beta-endorphin (betaE) is an important reliever of pain. Various stressors and certain modalities of physiotherapy are potent inducers of the release of endogenous betaE to the blood stream. Most forms of exercise also increase blood betaE level, especially when exercise intensity involves reaching the anaerobic threshold and is associated with the elevation of serum lactate level. Age, gender, and mental activity during exercise also may influence betaE levels. Publications on the potential stimulating effect of manual therapy and massage on betaE release are controversial. Sauna, mud bath, and thermal water increase betaE levels through conveying heat to the tissues. The majority of the techniques for electrical stimulation have a similar effect, which is exerted both centrally and--to a lesser extent--peripherally. However, the parameters of electrotherapy have not yet been standardised. The efficacy of analgesia and the improvement of general well-being do not necessarily correlate with betaE level. Although in addition to blood, increased brain and cerebrospinal fluid betaE levels are also associated with pain, the majority of studies have concerned blood betaE levels. In general, various modalities of physical therapy might influence endorphin levels in the serum or in the cerebrospinal fluid--this is usually manifested by elevation with potential mitigation of pain. However, a causal relationship between the elevation of blood, cerebrospinal fluid or brain betaE levels and the onset of the analgesic action cannot be demonstrated with certainty.

Beta-endorphin (betaE) is an important reliever of pain. Various stressors and certain modalities of physiotherapy are potent inducers of the release of endogenous betaE to the blood stream. Most forms of exercise also increase blood betaE level, especially when exercise intensity involves reaching the anaerobic threshold and is associated with the elevation of serum lactate level. Age, gender, and mental activity during exercise also may influence betaE levels. Publications on the potential stimulating effect of manual therapy and massage on betaE release are controversial. Sauna, mud bath, and thermal water increase betaE levels through conveying heat to the tissues. The majority of the techniques for electrical stimulation have a similar effect, which is exerted both centrally and--to a lesser extent--peripherally. However, the parameters of electrotherapy have not yet been standardised. The efficacy of analgesia and the improvement of general well-being do not necessarily correlate with betaE level. Although in addition to blood, increased brain and cerebrospinal fluid betaE levels are also associated with pain, the majority of studies have concerned blood betaE levels. In general, various modalities of physical therapy might influence endorphin levels in the serum or in the cerebrospinal fluid--this is usually manifested by elevation with potential mitigation of pain. However, a causal relationship between the elevation of blood, cerebrospinal fluid or brain betaE levels and the onset of the analgesic action cannot be demonstrated with certainty.

AIM:The purpose of this study was to determine the effect of Clinical Pilates exercises on patients with shoulder pain.

MATERIAL AND METHODS:Thirty-three patients, experiencing shoulder pain continuously for at least four weeks were selected as study subjects. The patients were randomly divided into two groups, namely Clinical Pilates exercise (n = 17) group and conventional exercise (n = 16) group. The patients were treated for five days a week, the total treatment being carried out for 10 days. The assessment of pain and disability amongst the patients were done at the baseline and at the end of the treatment sessions, using Visual Analogue Scale (VAS) and Shoulder Pain and Disability Index (SPADI).

RESULTS:The clinical Pilates exercise group showed a significant improvement in all scores used for assessment (p < 0.05), while the conventional exercise group demonstrated a significant improvement only in the SPADI total score (p < 0.05). A comparison of scores for the VAS, SPADI-Pain and SPADI-Total between the two groups, revealed a significant improvement in the Clinical Pilates exercise group (p < 0.05).

CONCLUSION:It was demonstrated by the study that Clinical Pilates exercise is an efficient technique for patients experiencing shoulder pain, as it helps reduce pain and disability among them.

BACKGROUND:Electroacupuncture (EA) is widely applied for pain management, but the analgesic effects of EA have not been fully elucidated. In this study, we investigated the effect of EA on inflammatory pain caused by intraplantar injection of complete Freund's adjuvant (CFA) and apelin/APJ expression in the spinal cord of rats.

METHODS:The study was conducted in 3 parts. In part 1, Sprague-Dawley rats were divided into 4 groups (n = 10): sham, CFA, EA (CFA + 2 Hz EA at acupoints), and NA-EA (CFA + acupuncture without electrical stimulation). The time courses of mechanical and thermal sensitivity were determined. The protein and messenger RNA (mRNA) levels of apelin and APJ in the spinal cord were assayed by Western blotting and real-time polymerase chain reaction, respectively. In part 2, the rats were divided into 5 groups (n = 7-8): sham, CFA, EA, F13A (CFA + intrathecal injection of F13A), and EA-F13A (CFA + EA + intrathecal injection of F13A). In part 3, the rats were divided into 5 groups (n = 8): sham, CFA, EA, apelin-13 (CFA + intrathecal injection of apelin-13), and EA + apelin-13 (CFA + EA + intrathecal injection of apelin-13).

RESULTS:EA treatment exhibited significant antinociceptive effects (mechanical sensitivity: mean difference [99% confidence interval {CI}]: 5.86 [4.96-6.77]; thermal sensitivity: mean difference [99% CI]: 2.45 [0.91-4.00]; EA versus CFA) and mitigated the CFA-induced reduction of apelin and APJ protein and mRNA expression in the spinal cord. Furthermore, intrathecal injection of the apelin/APJ system antagonist F13A blocked the analgesic effect of EA (mechanical sensitivity: mean difference [99% CI]: 8.99 [5.81-12.17]; thermal sensitivity: mean difference [99% CI]: 4.22 [1.33-7.12]; EA versus EA-F13A). When EA was combined with apelin-13 through intrathecal administration, it was more potent in reducing mechanical allodynia (mean difference [99% CI]: 5.98 [2.38-9.57], EA + apelin-13 versus apelin-13; mean difference [99% CI]: 4.29 [0.72-7.87], EA + apelin-13 versus EA) and thermal hyperalgesia (mean difference [99% CI]: 5.23 [2.19-8.28], EA + apelin-13 versus apelin-13; mean difference [99% CI]: 6.43 [3.38-9.48], EA + apelin-13 versus EA).

CONCLUSIONS:EA stimulation could alleviate inflammatory pain, at least in part, by restoring apelin and APJ mRNA and protein expression levels, which are downregulated in the CFA pain model.

This study aimed to investigate the effects of a two-day forest therapy program on individuals with chronic widespread pain. Sixty one employees of a public organization providing building and facilities management services within the Seoul Metropolitan area participated in the study. Participants were assigned to an experimental group (n = 33) who participated in a forest therapy program or a control group (n = 28) on a non-random basis. Pre- and post-measures of heart rate variability (HRV), Natural Killer cell (NK cell) activity, self-reported pain using the visual analog scale (VAS), depression level using the Beck Depression Inventory (BDI), and health-related quality of life measures using the EuroQol Visual Analog Scale (EQ-VAS) were collected in both groups. The results showed that participants in the forest therapy group, as compared to the control group, showed physiological improvement as indicated by a significant increase in some measures of HRV and an increase in immune competence as indicated by NK cell activity. Participants in the forest therapy group also reported significant decreases in pain and depression, and a significant improvement in health-related quality of life. These results support the hypothesis that forest therapy is an effective intervention to relieve pain and associated psychological and physiological symptoms in individuals with chronic widespread pain.