Endogenous opioids in placebo-induced analgesia

2018 ◽  
Author(s):  
Véronique A. Taylor ◽  
Pierre Rainville
Keyword(s):  
Pain Modulation ◽  
Endogenous Opioids ◽  
Anterior Cingulate ◽  
Placebo Analgesia ◽  
Psychological Determinants ◽  
Post Operative Pain ◽  
Conditioned Learning ◽  
Descending Pain Modulation ◽  
Pharmacological Manipulations

Placebos achieve scientifically proven pain-relieving effects yet are inactive substances for the treatment of pain. Levine, Gordon, and Fields were the first to demonstrate the role of endogenous opioids in placebo-induced analgesia during dental post-operative pain. Several studies using pharmacological manipulations and/or neuroimaging techniques confirmed their findings that placebo analgesia is reversible by naloxone, and also identified brain pathways involved in opioidergic neurotransmission during placebo analgesia (prefrontal regions rich in opioid receptors such as the anterior cingulate cortex, presumably initiating descending pain modulation through downstream projections to the brainstem). Fifty years of research in pharmacology and neurobiology have contributed to the identification of physical as well as psychological determinants of placebo analgesia. Expectations of pain relief are maintained by conditioned learning and reward-related processes, reflected by interactions between different neurotransmitters (opioids, dopamine, endocannabinoids) in a variety of brain circuits related to executive/cognitive processes as well as affect and reward.

scholarly journals Different modulation effects of 1 Hz and 20 Hz transcutaneous auricular vagus nerve stimulation on the functional connectivity of the periaqueductal gray in patients with migraine

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jin Cao ◽  
Yue Zhang ◽  
Hui Li ◽  
Zhaoxian Yan ◽  
Xian Liu ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Resting State ◽  
Vagus Nerve Stimulation ◽  
Cingulate Cortex ◽  
Periaqueductal Gray ◽  
Pain Modulation ◽  
Anterior Cingulate ◽  
Descending Pain Modulation

Abstract Background A growing body of evidence suggests that transcutaneous auricular vagus nerve stimulation (taVNS) may relieve symptoms of migraineurs. Frequency is one of the key stimulation parameters. The aim of this study is to investigate the modulation effect of taVNS frequency on the descending pain modulation system (DPMS) in patients with migraine. Methods Twenty-four episodic migraineurs without aura (21 females) were recruited for the single-blind, crossover, functional magnetic resonance imaging (fMRI) study. Each participant attended two separate fMRI scan sessions, one for 1 Hz and another for 20 Hz taVNS, in a random order. Seed-based functional connectivity analysis was applied using the ventrolateral periaqueductal gray (PAG) as the region of interest. Results Compared with the pre-taVNS resting state, continuous 1 Hz taVNS (during) produced a significant increase in functional connectivity between the PAG and the bilateral middle cingulate cortex (MCC), right precuneus, left middle frontal gyrus (MFG), and left cuneus. Compared with 20 Hz taVNS, 1 Hz taVNS produced greater PAG connectivity increases with the MCC, right precuneus/posterior cingulate cortex, left insula, and anterior cingulate cortex (ACC). A significant negative correlation was observed between the number of migraine attacks in the previous 4 weeks and the PAG-MCC functional connectivity in the pre-taVNS resting-state before 1 Hz taVNS. Conclusions Our findings suggest that taVNS with different frequencies may produce different modulation effects on the descending pain modulation system, demonstrating the important role of stimulation frequency in taVNS treatment.

scholarly journals The Role of Descending Pain Modulation in Chronic Primary Pain: Potential Application of Drugs Targeting Serotonergic System

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Zhuo-Ying Tao ◽  
Pei-Xing Wang ◽  
Si-Qi Wei ◽  
Richard J. Traub ◽  
Jin-Feng Li ◽  
...  
Keyword(s):  
Potential Application ◽  
Pain Modulation ◽  
Serotonergic System ◽  
Intractable Pain ◽  
Cost Of Health Care ◽  
Antinociceptive Effects ◽  
Regulation Mechanisms ◽  
Specific Tissue ◽  
Descending Pain Modulation

Chronic primary pain (CPP) is a group of diseases with long-term pain and functional disorders but without structural or specific tissue pathologies. CPP is becoming a serious health problem in clinical practice due to the unknown cause of intractable pain and high cost of health care yet has not been satisfactorily addressed. During the past decades, a significant role for the descending pain modulation and alterations due to specific diseases of CPP has been emphasized. It has been widely established that central sensitization and alterations in neuroplasticity induced by the enhancement of descending pain facilitation and/or the impairment of descending pain inhibition can explain many chronic pain states including CPP. The descending serotonergic neurons in the raphe nuclei target receptors along the descending pain circuits and exert either pro- or antinociceptive effects in different pain conditions. In this review, we summarize the possible underlying descending pain regulation mechanisms in CPP and the role of serotonin, thus providing evidence for potential application of analgesic medications based on the serotonergic system in CPP patients.

Opioids and breathing

1985 ◽  
Vol 59 (6) ◽  
pp. 1675-1685 ◽  
Author(s):  
T. V. Santiago ◽  
N. H. Edelman
Keyword(s):  
Pain Modulation ◽  
Endogenous Opioids ◽  
Opiate Antagonist ◽  
Endogenous Opioid ◽  
Disease States ◽  
Specific Effects ◽  
Neonatal Life ◽  
Opiate Drugs ◽  
Recent Developments

This review summarizes recent developments on the effects of opiate drugs and the various endogenous opioid peptides on breathing. These developments include demonstration of receptors and site-specific effects of application of opioids in the pons and medulla, demonstration of variable tolerance of respiratory responses in addicted individuals as well as their offspring, and demonstration of an endogenous opioid influence on breathing in early neonatal life and in certain physiological settings and disease states. The validity and limitations of using naloxone as a tool to uncover postulated endogenous opioid influences are also discussed as well as the potential problems imposed by the various settings in which this opiate antagonist drug is used. It is concluded that some parallelism exists between the role of endogenous opioids in pain modulation and their role in respiration especially in adults. Although more studies are needed especially with regard to defining specific effects of the various opioid receptors and ligands, it is felt that the effects of endogenous opioids on the control of breathing will probably be one of modulating the responses to drugs or nociceptive respiratory stimuli through inhibitory pathways.

scholarly journals FMRP acts as a key messenger for visceral pain modulation

2020 ◽  
Vol 16 ◽  
pp. 174480692097224
Author(s):  
Liu-kun Yang ◽  
Liang Lu ◽  
Ban Feng ◽  
Xin-shang Wang ◽  
Jiao Yue ◽  
...  
Keyword(s):  
Visceral Pain ◽  
Fragile X ◽  
Glutamate Release ◽  
Mechanical Stretch ◽  
Pain Modulation ◽  
Anterior Cingulate ◽  
Knock Out ◽  
Related Enzyme

Visceral pain is a common clinical symptom, which is caused by mechanical stretch, spasm, ischemia and inflammation. Fragile X syndrome (FXS) with lack of fragile X mental retardation protein (FMRP) protein is an inherited disorder that is characterized by moderate or severe intellectual and developmental disabilities. Previous studies reported that FXS patients have self-injurious behavior, which may be associated with deficits in nociceptive sensitization. However, the role of FMRP in visceral pain is still unclear. In this study, the FMR1 knock out (KO) mice and SH-SY5Y cell line were employed to demonstrate the role of FMRP in the regulation of visceral pain. The data showed that FMR1 KO mice were insensitive to zymosan treatment. Recording in the anterior cingulate cortex (ACC), a structure involved in pain process, showed less presynaptic glutamate release and postsynaptic responses in the FMR1 KO mice as compared to the wild type (WT) mice after zymosan injection. Zymosan treatment caused enhancements of adenylyl cyclase 1 (AC1), a pain-related enzyme, and NMDA GluN2B receptor in the ACC. However, these up-regulations were attenuated in the ACC of FMR1 KO mice. Last, we found that zymosan treatment led to increase of FMRP levels in the ACC. These results were further confirmed in SH-SY5Y cells in vitro. Our findings demonstrate that FMRP is required for NMDA GluN2B and AC1 upregulation, and GluN2B/AC1/FMRP forms a positive feedback loop to modulate visceral pain.

The Pronociceptive Effect of Paradoxical Sleep Deprivation in Rats: Evidence for a Role of Descending Pain Modulation Mechanisms

2015 ◽  
Vol 53 (3) ◽  
pp. 1706-1717 ◽  
Author(s):  
Dabna H. Tomim ◽  
Felipe M. Pontarolla ◽  
Jessica F. Bertolini ◽  
Mauricio Arase ◽  
Glaucia Tobaldini ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Paradoxical Sleep ◽  
Pain Modulation ◽  
Paradoxical Sleep Deprivation ◽  
Descending Pain Modulation

A novel clinical applicable bed-side tool for assessing conditioning pain modulation: proof-of-concept

2020 ◽  
Vol 20 (4) ◽  
pp. 801-807
Author(s):  
Lars Arendt-Nielsen ◽  
Jesper Bie Larsen ◽  
Stine Rasmussen ◽  
Malene Krogh ◽  
Laura Borg ◽  
...  
Keyword(s):  
Pain Modulation ◽  
Clinical Settings ◽  
Proof Of Concept ◽  
Finger Nail ◽  
Tonic Stimulus ◽  
Pressure Pain Thresholds ◽  
Custom Made ◽  
The Individual ◽  
Descending Pain Modulation ◽  
Finger Pressure

AbstractBackground and aimsIn recent years, focus on assessing descending pain modulation or conditioning pain modulation (CPM) has emerged in patients with chronic pain. This requires reliable and simple to use bed-side tools to be applied in the clinic. The aim of the present pilot study was to develop and provide proof-of-concept of a simple clinically applicable bed-side tool for assessing CPM.MethodsA group of 26 healthy volunteers participated in the experiment. Pressure pain thresholds (PPT) were assessed as test stimuli from the lower leg before, during and 5 min after delivering the conditioning tonic painful pressure stimulation. The tonic stimulus was delivered for 2 min by a custom-made spring-loaded finger pressure device applying a fixed pressure (2.2 kg) to the index finger nail. The pain intensity provoked by the tonic stimulus was continuously recorded on a 0–10 cm Visual Analog Scale (VAS).ResultsThe median tonic pain stimulus intensity was 6.7 cm (interquartile range: 4.6–8.4 cm) on the 10 cm VAS. The mean PPT increased significantly (P = 0.034) by 55 ± 126 kPa from 518 ± 173 kPa before to 573 ± 228 kPa during conditioning stimulation. When analyzing the individual CPM responses (increases in PPT), a distribution of positive and negative CPM responders was observed with 69% of the individuals classified as positive CPM responders (increased PPTs = anti-nociceptive) and the rest as negative CPM responders (no or decreased PPTs = Pro-nociceptive). This particular responder distribution explains the large variation in the averaged CPM responses observed in many CPM studies. The strongest positive CPM response was an increase of 418 kPa and the strongest negative CPM response was a decrease of 140 kPa.ConclusionsThe present newly developed conditioning pain stimulator provides a simple, applicable tool for routine CPM assessment in clinical practice. Further, reporting averaged CPM effects should be replaced by categorizing volunteers/patients into anti-nociceptive and pro-nociceptive CPM groups.ImplicationsThe finger pressure device provided moderate-to-high pain intensities and was useful for inducing conditioning stimuli. Therefore, the finger pressure device could be a useful bed-side method for measuring CPM in clinical settings with limited time available. Future bed-side studies involving patient populations are warranted to determine the usefulness of the method.

scholarly journals Psychobiological risk factors for suicidal thoughts and behaviors in adolescence: a consideration of the role of puberty

2021 ◽  
Author(s):  
Tiffany C. Ho ◽  
Anthony J. Gifuni ◽  
Ian H. Gotlib
Keyword(s):  
Pubertal Timing ◽  
Anterior Cingulate ◽  
Neural Systems ◽  
Hormonal Changes ◽  
Suicidal Thoughts ◽  
Social Stressors ◽  
And Behaviors ◽  
Suicidal Thoughts And Behaviors ◽  
Pubertal Transition

AbstractSuicide is the second leading cause of death among adolescents. While clinicians and researchers have begun to recognize the importance of considering multidimensional factors in understanding risk for suicidal thoughts and behaviors (STBs) during this developmental period, the role of puberty has been largely ignored. In this review, we contend that the hormonal events that occur during puberty have significant effects on the organization and development of brain systems implicated in the regulation of social stressors, including amygdala, hippocampus, striatum, medial prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex. Guided by previous experimental work in adults, we also propose that the influence of pubertal hormones and social stressors on neural systems related to risk for STBs is especially critical to consider in adolescents with a neurobiological sensitivity to hormonal changes. Furthermore, facets of the pubertal transition, such as pubertal timing, warrant deeper investigation and may help us gain a more comprehensive understanding of sex differences in the neurobiological and psychosocial mechanisms underlying adolescent STBs. Ultimately, advancing our understanding of the pubertal processes that contribute to suicide risk will improve early detection and facilitate the development of more effective, sex-specific, psychiatric interventions for adolescents.

scholarly journals Dispositional empathy predicts primary somatosensory cortex activity while receiving touch by a hand

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michael Schaefer ◽  
Anja Kühnel ◽  
Franziska Rumpel ◽  
Matti Gärtner
Keyword(s):  
Somatosensory Cortex ◽  
Anterior Cingulate ◽  
Primary Somatosensory Cortex ◽  
Rubber Hand ◽  
Somatosensory Cortices ◽  
Touch Perception ◽  
Trait Empathy ◽  
Human Perceptions ◽  
Dispositional Empathy

AbstractPrevious research revealed an active network of brain areas such as insula and anterior cingulate cortex when witnessing somebody else in pain and feeling empathy. But numerous studies also suggested a role of the somatosensory cortices for state and trait empathy. While recent studies highlight the role of the observer’s primary somatosensory cortex when seeing painful or nonpainful touch, the interaction of somatosensory cortex activity with empathy when receiving touch on the own body is unknown. The current study examines the relationship of touch related somatosensory cortex activity with dispositional empathy by employing an fMRI approach. Participants were touched on the palm of the hand either by the hand of an experimenter or by a rubber hand. We found that the BOLD responses in the primary somatosensory cortex were associated with empathy personality traits personal distress and perspective taking. This relationship was observed when participants were touched both with the experimenter’s real hand or a rubber hand. What is the reason for this link between touch perception and trait empathy? We argue that more empathic individuals may express stronger attention both to other’s human perceptions as well as to the own sensations. In this way, higher dispositional empathy levels might enhance tactile processing by top-down processes. We discuss possible implications of these findings.

scholarly journals Role of the Anterior Cingulate Cortex in Translational Pain Research

2021 ◽  
Vol 37 (3) ◽  
pp. 405-422
Author(s):  
Xiao Xiao ◽  
Ming Ding ◽  
Yu-Qiu Zhang
Keyword(s):  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Pain Research
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