Project description:For over a millennium, mind-body interactions have fascinated scientists and doctors for their abilities to shape human perceptions of the external world 1,2. Placebo effects are striking demonstrations of mind-body interactions in which, in the absence of any treatment, a positive expectation of pain relief can reduce or even abolish the experience of pain 3–6. However, despite widespread recognition of the strength of placebo effects and their impact on everyday human experience and clinical trials for new analgesics, the neural circuit basis of the placebo effect has remained a mystery. Here, we show that analgesia from the expectation of pain relief is mediated by a distinct population of rostral anterior cingulate cortex (rACC) neurons that project to the pontine nuclei (rACC→Pn), a pair of brainstem pre-cerebellar nuclei with no established function in pain processing. To do this, we created a behavioral assay that models placebo analgesia by conditioning mice to expect pain relief when moving from a chamber with a heated floor to a second chamber. In this assay, an expectation of pain relief induces an analgesic effect that, like placebo analgesia in humans, is mediated by endogenous opioids. Calcium imaging of neural activity in freely moving mice and electrophysiological studies in cingulate cortical brain slices showed that expectations of pain relief boost the activity of rACC→Pn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an unusual abundance of opioid receptors in these cells, further suggesting a role in pain modulation. Selective inhibition of either the rACC→Pn pathway or of opioid-receptor-expressing Pn neurons disrupted placebo analgesia and decreased pain thresholds. Finally, a subset of cerebellar Purkinje cells exhibits activity patterns resembling those of rACC→Pn neurons during pain relief expectation, providing cellular-level evidence of a role for the cerebellum in cognitive pain modulation. Altogether, these findings elucidate longstanding mysteries surrounding the placebo effect by identifying a specific neural pathway that mediates expectation-based pain relief. This discovery opens the possibility of targeting this novel pathway with drugs or neurostimulation methods to treat pain. More broadly, our studies provide a framework for investigating the neural circuit basis of other mind-body interactions beyond those involving pain, and point to prefrontocortical-cerebellar communication as a potential basis for such effects.

Project description:Many women experience pain during hysterosalpingogram (HSG). This prospective, randomized, double-blinded, placebo-controlled study assessed whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, parity, pre-procedure oral analgesic use and history of dysmenorrhoea and/or chronic pelvic pain. Median change in pain score from baseline to procedure was 50.6mm (-7.4 to 98.8mm) in the benzocaine group and 70.4mm (19.8 to 100mm) in the placebo group. There was no difference between groups after adjusting for history of dysmenorrhoea. There was no difference in resolution of pain in benzocaine versus placebo groups at 5 min post procedure--median pain score difference -11.1 (-90.1 to 18.5) versus -37.0 (-100 to 1.2)--or at 30 min post procedure. Satisfaction scores did not differ by treatment and did not correlate with pain score during the procedure (rho=0.005). The use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain. Many women experience pain during hysterosalpingogram (HSG), which is a test used to evaluate the uterine cavity and fallopian tube. We conducted a prospective, randomized, double-blinded, placebo-controlled study to assess whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, previous pregnancies, pre-procedure oral analgesic use and history of dysmenorrhoea (painful periods) and/or chronic pelvic pain. There was no difference in pain scores or resolution of pain between the two groups. Satisfaction scores did not differ by treatment group and did not correlate with the pain score during the procedure. We conclude that the use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain.

Project description:BackgroundEpidural analgesia offers greater pain relief compared to systemic opioid-based medications, but its effect on morbidity and mortality is unclear. This review was originally published in 2006 and was updated in 2012 and again in 2016.ObjectivesTo assess the benefits and harms of postoperative epidural analgesia in comparison with postoperative systemic opioid-based analgesia for adults undergoing elective abdominal aortic surgery.Search methodsIn the updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and five trial registers in November 2014, together with reference checking to identify additional studies.Selection criteriaWe included all randomized controlled trials comparing postoperative epidural analgesia and postoperative systemic opioid-based analgesia for adults who underwent elective open abdominal aortic surgery.Data collection and analysisTwo authors independently assessed trial quality and extracted data. We contacted study authors for additional information and data when required. We assessed the level of evidence according to the scale provided by the GRADE working group.Main resultsWe included 15 trials published from 1987 to 2009 with 1498 participants in this updated review. Participants had a mean age between 60.5 and 71.3 years. The percentage of women in the included studies varied from 0% to 28.1%. Adding an epidural to general anaesthesia for people undergoing abdominal aortic repair reduced myocardial infarction (risk ratio (RR) 0.54 (95% confidence interval (CI) 0.30 to 0.97); I(2) statistic = 0%; number needed to treat for one additional beneficial outcome (NNTB) 28 (95% CI 19 to 1423), visual or verbal analogical scale (VAS) scores up to three days after the surgery (mean difference (MD) -1.78 (95% CI -2.32 to -1.25); I(2) statistic = 0% for VAS scores on movement at postoperative day one), time to tracheal extubation (standardized mean difference (SMD) -0.42 (95% CI -0.70 to -0.15); I(2) statistic = 83%; equivalent to a mean reduction of 36 hours), postoperative respiratory failure (RR 0.69 (95% CI 0.56 to 0.85); I(2) statistic = 0%; NNTB 8 (95% CI 6 to 16)), gastrointestinal bleeding (OR 0.20 (95% CI 0.06 to 0.65); I(2) statistic = 0%; NNTB 32 (95% CI 27 to 74)) and time spent in the intensive care unit (SMD -0.23 (95% CI -0.41 to -0.06); I(2) statistic = 0%; equivalent to a mean reduction of six hours). We did not demonstrate a reduction in the mortality rate up to 30 days (RR 1.06 (95% CI 0.60 to 1.86); I(2) statistic = 0%). The level of evidence was low for mortality and time before tracheal extubation; moderate for myocardial infarction, respiratory failure and intensive care unit length of stay; and high for gastrointestinal bleeding and VAS scores.Authors' conclusionsEpidural analgesia provided better pain management, reduced myocardial infarction, time to tracheal extubation, postoperative respiratory failure, gastrointestinal bleeding, and intensive care unit length of stay compared with systemic opioid-based drugs. For mortality, we did not find a difference at 30 days.

Project description:BackgroundPlant extracts with analgesic properties are seldom considered for treatment of acute musculoskeletal pain due to delay in onset of analgesia. Turmeric (Curcuma longa) and boswellia (Boswellia serrata) extracts are well-studied anti-inflammatory compounds gaining in popularity and used as an alternative to conventional treatments for musculoskeletal pain. This study analyzed the analgesic effect of a formulation of turmeric and boswellia extracts in sesame oil (Rhuleave-K, TBF) in reducing exercise-induced acute musculoskeletal pain in healthy participants.MethodsIn this randomized double-blinded placebo-controlled, single-dose, single-day, multicentre study, a total of 232 participants (TBF n = 116; placebo n = 116) having moderate-to-severe exercise-induced acute musculoskeletal pain were randomized in an allocation concealed 1:1 ratio to receive a single dose of 1000 mg of TBF or placebo. The outcome measures were numerical rating scale (NRS), categorical pain relief scale (PRS), onset of analgesia, and short form of McGill questionnaire (SF-MPQ). NRS and PRS were measured from predose to every 30 minutes interval of postdose up to 6 hours at rest, with movement and applying pressure on the affected part. The onset of analgesia was measured from the time of dosage and censored at 6 hours of postdose. The sum of pain intensity difference (SPID6) and total pain relief (TOTPAR6) at 6 hours was, respectively, analyzed from NRS and PRS scores.ResultsTBF showed a significant reduction in pain intensity (SPID6rest) with 97.85% improvement in cumulative responder analysis compared with 2.46% in placebo. The onset of pain relief was fast and highly significant in the TBF group with 99% of participants having a mean perceptible pain relief at 68.5 minutes (95% confidence interval, 59.5-77.4) and 96% of participants having a mean meaningful pain relief at 191.6 minutes (95% confidence interval, 176.7-206.4) compared to the placebo group. Highly significant and continuous improvement in pain relief was observed in the TBF group with 93% of participants having ≥ 50% of maximum TOTPAR6 with a number needed to treat of 1.1 at rest.ConclusionExercise-induced acute musculoskeletal pain can be effectively relieved by TBF (Rhuleave-K) in about 3 hours signifying its strong analgesic activity.

Dataset Information

Neural circuit basis of placebo pain relief.

Publications

Neural circuit basis of placebo pain relief.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets