The analgesic activity of acetyl-L-carnitine (ALCAR) in neuropathic pain is well established. By contrast, its potential efficacy in the relief of acute pain has not been reported. The antinociceptive effect of ALCAR was, therefore, examined in the mouse hot-plate and abdominal constriction tests, and in the rat paw-pressure test. ALCAR (100 mg kg(-1) s.c. twice daily for seven days) produced an increase of the pain threshold in both mice and rats. ALCAR was also able to reverse hyperalgesia induced by kainic acid and NMDA administration in the mouse hot-plate test. The antinociception produced by ALCAR was prevented by the unselective muscarinic antagonist atropine, the M(1) selective antagonists pirenzepine and S-(-)-ET126, and by the choline uptake inhibitor hemicholinium-3 (HC-3). By contrast the analgesic effect of ALCAR was not prevented by the opioid antagonist naloxone, the GABA(B) antagonist CGP 35348, the monoamine synthesis inhibitor (alpha)-methyl-p-tyrosine, and the Gi-protein inactivator pertussis toxin. Moreover, ALCAR antinociception was abolished by pretreament with an antisense oligonucleotide (aODN) against the M(1) receptor subtype, administered at the dose of 2 nmol per single i.c.v injection. On the basis of the above data, it can be postulated that ALCAR exerted an antinociceptive effect mediated by a central indirect cholinergic mechanism. In the antinociceptive dose-range, ALCAR did not impair mouse performance evaluated by the rota-rod and hole-board tests.

Chronic pain (CP) and posttraumatic stress disorder (PTSD) are both frequent and often comorbid in refugees. To date, few controlled trials have studied the efficacy of treatments targeting this comorbidity; no treatment guidelines yet exist. The authors examined the feasibility and efficacy of short-term cognitive behavioural biofeedback (BF) addressing CP in traumatised refugees. The sample comprised 11 severely traumatised refugees with CP and PTSD (mean age = 36 years, SD = 6), who underwent assessment with the Mini International Neuropsychiatric Interview, Posttraumatic Diagnostic Scale, Pain Disability Index, and Visual Rating Scale. Additionally, coping with pain and psychotherapy tolerance were assessed. Acceptance of BF was high. Pre-post effects were small to medium for increased pain management and associated heart rate reactivity but large for coping with pain. The results encourage further research to confirm whether BF is indicated as a treatment component, but not a stand-alone treatment, for traumatised refugees with comorbid CP and PTSD.

The steam-distilled essential oil of Iranian black cumin seed (Nigella sativa L.) was investigated for its composition and analgesic and antiinflammatory properties. After oil analysis by GC/MS, 20 compounds were identified in the oil, obtained in 0.4% (v/w) yield. Among them, para-cymene (37.3%) and thymoquinone (13.7%) were the major components. Acetic acid-induced writhing, formalin and light tail flick tests were used for assessment of analgesic activity. Antiinflammatory activity was evaluated using carrageenan-induced paw oedema in rats and croton oil-induced ear oedema in mice. Black cumin seed essential oil (BCSEO) was found to produce a significant analgesic effect in acetic acid-induced writhing, formalin and light tail flick tests. Naloxone, an opioid antagonist, could not reverse the analgesic effect observed in the formalin test. Although oral administration of BCSEO at doses of 100, 200 and 400 micro L/kg did not exert a significant antiinflammatory effect in the carrageenan test, i.p. injection of the same doses significantly (p < 0.001) inhibited carrageenan-induced paw oedema. BCSEO at doses of 10 and 20 micro L/ear could also reduce croton oil-induced oedema. It seems that mechanism(s) other than opioid receptors is (are) involved in the analgesic effect of BCSEO since naloxone could not reverse this effect. Both systemic and local administration of BCSEO showed antiinflammatory activity. Thymoquinone, as one of the major components of BCSEO, probably has an important role in these pharmacological effects. Copyright 2004 John Wiley & Sons, Ltd.

This paper explores the potentiality of Bach flower remedies as a means of pain relief through a retrospective case-study analysis to establish how clients suffering with painful conditions responded to the therapy. RESULTS: Of 384 subjects, 41 suffered pain. Of these, 46% felt treatment had relieved their pain; in 49% the physical outcome was unknown. About 88% of all subjects reported an improvement in their emotional outlook. DISCUSSION: The role of placebo and its influence on the study's key features: focus shift from physical pain to emotional outlook, and the importance of the client-practitioner relationship and belief in the therapy. CONCLUSION: The use of Bach flower remedies has brought about positive emotional changes in the majority of clients in this study. Whilst it is difficult to draw a definitive conclusion as to significance of the therapeutic value of these remedies in relation to pain above that of a placebo, the results are encouraging. In particular, relief of negative emotions and promotion of positive thought including how clients opened up about, and dealt with, emotional issues. The indication is that potential for Bach flower remedies as a therapeutic agent in the relief of pain does exist and is worthy of further qualitative and quantitative investigation through robust, purpose-designed studies to replicate and progress the results shown here.

The objective of this study was to calculate the effect of Reiki therapy for pain and anxiety in randomized clinical trials. A systematic search of PubMed, ProQuest, Cochrane, PsychInfo, CINAHL, Web of Science, Global Health, and Medline databases was conducted using the search terms pain, anxiety, and Reiki. The Center for Reiki Research also was examined for articles. Studies that used randomization and a control or usual care group, used Reiki therapy in one arm of the study, were published in 2000 or later in peer-reviewed journals in English, and measured pain or anxiety were included. After removing duplicates, 49 articles were examined and 12 articles received full review. Seven studies met the inclusion criteria: four articles studied cancer patients, one examined post-surgical patients, and two analyzed community dwelling older adults. Effect sizes were calculated for all studies using Cohen's d statistic. Effect sizes for within group differences ranged from d = 0.24 for decrease in anxiety in women undergoing breast biopsy to d = 2.08 for decreased pain in community dwelling adults. The between group differences ranged from d = 0.32 for decrease of pain in a Reiki versus rest intervention for cancer patients to d = 4.5 for decrease in pain in community dwelling adults. Although the number of studies is limited, based on the size Cohen's d statistics calculated in this review, there is evidence to suggest that Reiki therapy may be effective for pain and anxiety. Continued research using Reiki therapy with larger sample sizes, consistently randomized groups, and standardized treatment protocols is recommended.

PURPOSE:The purpose of this study was to examine the effects of aroma hand massage on pain, state anxiety and depression in hospice patients with terminal cancer.

METHODS:This study was a nonequivalent control group pretest-posttest design. The subjects were 58 hospice patients with terminal cancer who were hospitalized. Twenty eight hospice patients with terminal cancer were assigned to the experimental group (aroma hand massage), and 30 hospice patients with terminal cancer were assigned to the control group (general oil hand massage). As for the experimental treatment, the experimental group went through aroma hand massage on each hand for 5 min for 7 days with blended oil-a mixture of Bergamot, Lavender, and Frankincense in the ratio of 1:1:1, which was diluted 1.5% with sweet almond carrier oil 50 ml. The control group went through general oil hand massage by only sweet almond carrier oil-on each hand for 5 min for 7 days.

RESULTS:The aroma hand massage experimental group showed more significant differences in the changes of pain score (t=-3.52, p=.001) and depression (t=-8.99, p=.000) than the control group.

CONCLUSION:Aroma hand massage had a positive effect on pain and depression in hospice patients with terminal cancer.

OBJECTIVE: This study aimed to examine the adjuvant effects of auricular acupres-sure in augmenting intravenous patient-controlled analgesia with morphine and droperidol for postoperative lumbar surgery patients in terms of postoperative pain relief satisfaction, and the incidence of postoperative nausea and vomiting (PONV). METHODS: In this single-blind experimental study, 94 subjects were randomly assigned to the experimental group in which patients received auricular acupressure to six auricular acupoints or a control group without acupressure. Data were collected using the American Pain Society Patient Outcome Questionnaire. Descriptive analyses, t tests, chi(2) tests, Mann-Whitney tests, and the generalized estimating equation model were used. RESULTS: The experimental group had lower average pain scores than the control group, but no between-group difference was found. Analgesic dose and satisfaction were similar in both groups. The incidence of PONV was low and similar in both groups. CONCLUSION: Although this study did not demonstrate adjuvant effects of auricular acupressure on postoperative pain, analgesic dose, analgesic satisfaction and PONV, most subjects were satisfied with the pain management even though they were subjected to moderate pain because of insufficient analgesia. Further studies should reconfirm the effects of auricular acupressure on analgesia provided by intravenous patient-controlled analgesia in postoperative patients, and its influence on the frequency and duration of analgesia administration.

The effects of hypnosis/therapeutic suggestion in connection with intravenous sedation and surgery have been described in many clinical publications; however, few randomized, controlled, and blind studies have been performed in the outpatient area. This study aimed to evaluate the use of hypnosis/therapeutic suggestion as an adjunct to intravenous (IV) sedation in patients having 3rd molar removal in an outpatient setting. The patients were randomly assigned to a treatment (n = 46) or control (n = 54) group. The treatment group listened to a rapid conversational induction and therapeutic suggestions via headphones throughout the entire surgical procedure along with a standard sedation dose of intravenous anesthetic. The control group listened to only music without any hypnotic intervention. Intraoperative Propofol administration, patient postoperative pain ratings, and postoperative prescription pain reliever consumption were all significantly reduced in the treatment compared to the control group. Implications of these results are discussed.

OBJECTIVE:To examine the effectiveness of music listening on pain, anxiety, and vital signs among patients after thoracic surgery in China.

DESIGN AND SETTING:A randomized controlled clinical trial was conducted in the thoracic surgery department of two tertiary hospitals in Wuhan, China. 112 patients were recruited and randomly assigned to either experimental (n=56) or control (n=56) group respectively.

INTERVENTION:The experimental group received standard care and a 30-min soft music intervention for 3 days, while the control group received only standard care. Measures include pain, anxiety, vital signs (blood pressure, heart rate and respiratory rate), patient controlled analgesia, and diclofenac sodium suppository use.

RESULTS:The experimental group showed statistically significant decrease in pain, anxiety, systolic blood pressure and heart rate over time compared to the control group, but no significant difference were identified in diastolic blood pressure, respiratory rate, patient controlled analgesia and diclofenac sodium suppository use.

CONCLUSION:The findings provide further evidence to support the practice of music therapy to reduce postoperative pain and anxiety, and lower systolic blood pressure and heart rate in patients after thoracic surgery in China.

Recently, we reported that Qi-therapy may be beneficial in reducing negative psychological symptoms and increasing melatonin levels, neutrophil function and natural killer cell cytotoxicity in young subjects. However, there is little scientific evidence of its efficacy in elderly subjects. Therefore, this study was designed to investigate the effects of Qi-therapy on anxiety, depression, fatigue, pain and blood pressure in elderly subjects. Ninety-four elderly subjects were randomly assigned to either Qi-therapy (n=47) or mimic therapy (n=47) groups. Both groups received a 10-min intervention period once using similar procedures. The Qi-therapy group exhibited greater reduction in anxiety, depression, fatigue, pain level and blood pressure compared to the placebo group; the difference in anxiety was significant (P=0.014). These results suggest that even a brief application of Qi-therapy may exert a positive psychological and physiological effect. However, further research is necessary in order to fully understand the long-term impact of Qi-therapy on psychological health and the cardiovascular system.

The purpose of this study was to evaluate the effect of Reiki as an alternative and complementary approach to treating community-dwelling older adults who experience pain, depression, and/or anxiety. Participants (N = 20) were randomly assigned to either an experimental or wait list control group. The pre- and posttest measures included the Hamilton Anxiety Scale, Geriatric Depression Scale-Short Form, Faces Pain Scale, and heart rate and blood pressure. The research design included an experimental component to examine changes in these measures and a descriptive component (semi-structured interview) to elicit information about the experience of having Reiki treatments. Significant differences were observed between the experimental and treatment groups on measures of pain, depression, and anxiety; no changes in heart rate and blood pressure were noted. Content analysis of treatment notes and interviews revealed five broad categories of responses: Relaxation; Improved Physical Symptoms, Mood, and Well-Being; Curiosity and a Desire to Learn More; Enhanced Self-Care; and Sensory and Cognitive Responses to Reiki.

OBJECTIVES: Acupuncture, an alternative medical therapy with a long history, is appealing because it can activate endogenous analgesic mechanisms by minimally invasive means. The mechanisms of acupuncture, however, are not well understood yet. The following sentence was removed from our original manuscript. One of the major problems impeding understanding of the acupuncture mechanism is lack of experimental models that mimic various forms of persistent pain that respond to acupuncture in humans. METHODS: In this review, we summarize and discuss previous and recent findings regarding electroacupuncture-induced analgesia in an ankle sprain pain model and the potential underlying mechanisms of acupuncture. RESULTS: A novel model of ankle sprain pain is introduced recently and the mechanism of electroacupuncture-induced analgesia in this model has been explored. The following sentence was removed from our original manuscript. This model provides a reproducible and quantifiable index of persistent pain at the ankle joint in rats. Acupuncture at a remote site produces long-lasting and powerful analgesia. The consistent analgesic effect of acupuncture in this model has allowed us to pursue the underlying neural mechanisms. CONCLUSIONS: These studies provide insight into the mechanisms of acupuncture analgesia in one particular form of persistent pain, and hopefully will allow us to expand our knowledge to other painful conditions.

Integrative approaches such as electroacupuncture, devoid of drug effects are gaining prominence for treating pain. Understanding the mechanisms of electroacupuncture induced analgesia would benefit chronic pain conditions such as sickle cell disease (SCD), for which patients may require opioid analgesics throughout life. Mouse models are instructive in developing a mechanistic understanding of pain, but the anesthesia/restraint required to administer electroacupuncture may alter the underlying mechanisms. To overcome these limitations, we developed a method to perform electroacupuncture in conscious, freely moving, unrestrained mice. Using this technique we demonstrate a significant analgesic effect in transgenic mouse models of SCD and cancer as well as complete Freund's adjuvant-induced pain. We demonstrate a comprehensive antinociceptive effect on mechanical, cold and deep tissue hyperalagesia in both genders. Interestingly, individual mice showed a variable response to electroacupuncture, categorized into high-, moderate-, and non-responders. Mechanistically, electroacupuncture significantly ameliorated inflammatory and nociceptive mediators both peripherally and centrally in sickle mice correlative to the antinociceptive response. Application of sub-optimal doses of morphine in electroacupuncture-treated moderate-responders produced equivalent antinociception as obtained in high-responders. Electroacupuncture in conscious freely moving mice offers an effective approach to develop a mechanism-based understanding of analgesia devoid of the influence of anesthetics or restraints.

OBJECTIVE:This study was designed to evaluate the effectiveness of lavender aromatherapy on pain, anxiety, and level of satisfaction associated with the peripheral venous cannulation (PVC) in patients undergoing surgery.

METHOD:One hundred and six patients undergoing surgery were randomized to receive aromatherapy with lavender essential oil (the lavender group) or a placebo (the control group) during PVC. The patients' pain, anxiety, and satisfaction scores were measured.

RESULTS:There was no statistically significantly difference between the groups in terms of demographic data. After cannulation, the pain and anxiety scores (anxiety 2) of the patients in the lavender group were significantly lower than the control group (for p = 0.01 for pain scores; p < 0.001 for anxiety 2 scores). In addition, patient satisfaction was significantly higher in the lavender group than in the control group (p = 0.003).

CONCLUSION:Lavender aromatherapy had beneficial effects on PVC pain, anxiety, and satisfaction level of patients undergoing surgery.

For the past several decades, papers in the nursing literature have advocated the use of cognitive interventions in clinical practice. Increasing consumer use of complementary therapies, a cost-driven health care system, and the need for evidence-based practice all lend urgency to the validation of the efficacy of these interventions. This review focuses specifically on guided imagery intervention studies identified in the nursing, medical and psychological literature published between 1966 and 1998. Included were 46 studies of the use of guided imagery for management of psychological and physiological symptoms. There is preliminary evidence for the effectiveness of guided imagery in the management of stress, anxiety and depression, and for the reduction of blood pressure, pain and the side effects of chemotherapy. Overall, results of this review demonstrated a need for systematic, well-designed studies, which explore several unanswered questions regarding the use of guided imagery. These include the effects of different imagery language, symptoms for which guided imagery is effective, appropriate and sensitive outcome measures, method of delivery of the intervention and optimum dose and duration of the intervention, and individual factors that influence its effectiveness.

OBJECTIVE:To evaluate the efficacy of Homeopathic Arnica in reducing the morbidity following tonsillectomy.

METHODS:Randomised double blind, placebo controlled trial at a tertiary referral centre. 190 patients over the age of 18 undergoing tonsillectomy were randomised into intervention and control groups receiving either Arnica 30c or identical placebo, 2 tablets 6 times in the first post-operative day and then 2 tablets twice a day for the next 7 days. The primary outcome measure was the change in pain scores (visual analogue scale) recorded by the patient on a questionnaire over 14 days post-operatively; Secondary outcome measures were: analgesia consumption, visits to the GP or hospital, antibiotic usage, the day on which their swallowing returned to normal and the day on which they returned to work.

RESULTS:111 (58.4%) completed questionnaires were available for analysis. The Arnica group had a significantly larger drop in pain score from day 1 to day 14 (28.3) compared to the placebo group (23.8) with p<0.05. The two groups did not differ significantly on analgesic consumption or any of the other secondary outcome measures (number of post-operative visits to GP, use of antibiotics and secondary haemorrhage readmissions).

CONCLUSION:The results of this trial suggest that Arnica montana given after tonsillectomy provides a small, but statistically significant, decrease in pain scores compared to placebo.

Physical complaints, such as pain, can be effectively reduced by placebo effects through induction of positive expectations, or increased by nocebo effects through induction of negative expectations. In the present study, verbally induced nocebo and placebo effects on itch were experimentally investigated for the first time. In part 1, the role of verbal suggestions in inducing nocebo effects on itch and pain was investigated. All subjects received the same somatosensory quantitative sensory testing stimuli, that is, mechanical and electrical stimuli and application of histamine, and verbal suggestions to manipulate expectations regarding the stimuli. The suggestions were designed to produce either high expectations for itch (itch nocebo) or pain (pain nocebo) or low expectations for itch (itch nocebo control) or pain (pain nocebo control). Results showed that high itch and pain expectations resulted in higher levels of itch and pain, respectively. When comparing nocebo effects, induced by verbal suggestions, results were more pronounced for itch than for pain. In part 2, verbal suggestions designed to produce a placebo effect on itch (itch placebo) or pain (pain placebo), or neutral suggestions (itch placebo control and pain placebo control) were given regarding a second application of histamine and compared with the first application applied in part 1. Results of placebo effects only showed a significantly larger decrease in itch in the itch placebo condition than in the pain placebo condition. In conclusion, we showed for the first time that nocebo and possibly placebo responses can be induced on itch by verbal suggestions. Experiments of nocebo and placebo effects on itch and pain demonstrated that particularly nocebo effects can be induced on itch and pain by verbal suggestions.

 L-Acetylcarnitine (LAC, 100 mg/kg, s.c.), a drug commonly used for the treatment of painful neuropathies, substantially reduced mechanical allodynia in rats subjected to monolateral chronic constriction injury (CCI) of the sciatic nerve and also attenuated acute thermal pain in intact rats. In both cases, induction of analgesia required repeated injections of LAC, suggesting that the drug induces plastic changes within the nociceptive pathway. In both CCI- and sham-operated rats, a 24-day treatment with LAC increased the expression of metabotropic glutamate (mGlu) receptors 2 and 3 in the lumbar segment of the spinal cord, without changing the expression of mGlu1a or -5 receptors. A similar up-regulation of mGlu2/3 receptors was detected in the dorsal horns and dorsal root ganglia of intact rats treated with LAC for 5-7 days, a time sufficient for the induction of thermal analgesia. Immunohistochemical analysis showed that LAC treatment enhanced mGlu2/3 immunoreactivity in the inner part of lamina II and in laminae III and IV of the spinal cord. An increased mGlu2/3 receptor expression was also observed in the cerebral cortex but not in the hippocampus or cerebellum of LAC-treated animals. Reverse transcription-polymerase chain reaction combined with Northern blot analysis showed that repeated LAC injections selectively induced mGlu2 mRNA in the dorsal horns and cerebral cortex (but not in the hippocampus). mGlu3 mRNA levels did not change in any brain region of LAC-treated animals. To examine whether the selective up-regulation of mGlu2 receptors had any role in LAC-induced analgesia, we have used the novel compound LY 341495, which is a potent and systemically active mGlu2/3 receptor antagonist. LAC-induced analgesia was largely reduced 45 to 75 min after a single injection of LY 341495 (1 mg/kg, i.p.) in both CCI rats tested for mechanical allodynia and intact rats tested for thermal pain. We conclude that LAC produces analgesia against chronic pain produced not only by peripheral nerve injury but also by acute pain in intact animals and that LAC-induced analgesia is associated with and causally related to a selective up-regulation of mGlu2 receptors. This offers the first example of a selective induction of mGlu2 receptors and discloses a novel mechanism for drug-induced analgesia.