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Gender, genetics, and analgesia: understanding the differences in response to pain relief.

ABSTRACT: Genetic variations and gender contribute significantly to the large interpatient variations in opioid-related serious adverse effects and differences in pain relief with other analgesics. Opioids are the most commonly used analgesics to relieve moderate-to-severe postoperative pain. Narrow therapeutic index and unexplained large interpatient variations in opioid-related serious adverse effects and analgesia negatively affect optimal perioperative outcomes. In surgical, experimental, chronic, and neuropathic pain models, females have been reported to have more pain than males. This review focuses on literature evidence of differences in pain relief due to multiple genetic variations and gender of the patient.

SUBMITTER: Packiasabapathy S

PROVIDER: S-EPMC6235329 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Gender, genetics, and analgesia: understanding the differences in response to pain relief.

Packiasabapathy Senthil S Sadhasivam Senthilkumar S

Journal of pain research 20181108

Genetic variations and gender contribute significantly to the large interpatient variations in opioid-related serious adverse effects and differences in pain relief with other analgesics. Opioids are the most commonly used analgesics to relieve moderate-to-severe postoperative pain. Narrow therapeutic index and unexplained large interpatient variations in opioid-related serious adverse effects and analgesia negatively affect optimal perioperative outcomes. In surgical, experimental, chronic, and ...[more]

PMID: 30519077

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Project description:BackgroundListening to preferred music can provide distraction and reduce the feeling of pain and negative emotions associated with an uncomfortable experience. Several studies have examined how music can reduce pain and anxiety related to urological procedures that are not typically performed under anesthesia, such as cystoscopy, cystoscopy with stent pull, and urodynamic studies. To our knowledge, no studies have been done to examine the effect of listening to preferred music generalized across a variety of these procedures. Therefore, we looked to combine multiple factors from prior studies to determine if listening to music of a patient's choice would decrease pain during various outpatient clinic urological procedures, and to examine differences between men and women.MethodsThis was a single investigator series randomized controlled trial with 91 subjects in an academic outpatient urology clinic. After applying exclusion criteria, eligible patients were randomized to a music group or non-music group via coin flip. Fifty-three patients were in the music group (16 men, 37 women) and 38 patients were in the non-music group (16 men, 22 women). Subjects in the music group selected a song to play during the procedure, which was stopped at the conclusion of the procedure. Pre- and post-procedure Visual Analog Pain Scale were completed by the subjects of each group and subsequently analyzed. Where appropriate either Pearson's Chi-Square or Independent-Sample t-test were used to compare the groups as well as randomized-repeated analysis of variance (ANOVA).ResultsFor men, pain scores worsened in both groups, however the music group experienced a statistically significant increase in pain (mean change =1.0, P=0.05), while the non-music group only clinically worsened (mean change =0.38, P=0.459). For women, the music group noticed an improvement in the pain score (mean change =-0.14, P=0.590), while the non-music group significantly worsened (mean change =1.14, P=0.008).ConclusionsWomen who listened to music of their choosing experienced significant improvement in overall perceived pain compared to women who did not listen to music. Women may benefit from music as a novel tool to alleviate pain during outpatient clinic urological procedures.

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.

Dataset Information

Gender, genetics, and analgesia: understanding the differences in response to pain relief.

Publications

Gender, genetics, and analgesia: understanding the differences in response to pain relief.

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