Abstract：
:Genetics studies on the placebo hypoalgesic effect highlight a promising link between single nucleotide polymorphisms (SNPs) in the dopamine, opioid, and endocannabinoid genes and placebo hypoalgesia. However, epistasis and replication studies are missing. In this study, we expanded on previous findings related to the 3 SNPs in the opioid receptor mu subunit (OPRM1 rs1799971), catechol-O-methyltransferase (COMT rs4680), and fatty acid amide hydrolase (FAAH rs324420) genes associated with placebo hypoalgesia and tested the effect of a 3-way interaction on placebo hypoalgesia. Using 2 well-established placebo procedures (verbal suggestion and learning paradigm), we induced significant placebo hypoalgesic effects in 160 healthy participants. We found that individuals with OPRM1 AA combined with FAAH Pro/Pro and those carrying COMT met/met together with FAAH Pro/Pro showed significant placebo effects. Participants with COMT met/val alleles showed significant placebo effects independently of OPRM1 and FAAH allele combinations. Finally, the model that included the placebo procedure and genotypes predicted placebo responsiveness with a higher accuracy (area under the curve, AUC = 0.773) as compared to the SNPs alone indicating that genetic variants can only partially explain the placebo responder status. Our results suggest that the endogenous mu-opioid system with a larger activation in response to pain in the met/val allele carriers as well as the synergism between endogenous mu-opioid system and cannabinoids might play the most relevant role in driving hypoalgesic responses. Future epistasis studies with larger sample sizes will help us to fully understand the complexity of placebo effects and explain the mechanisms that underlie placebo responsiveness.
journal_name
Painjournal_title
Painauthors
Colloca L,Wang Y,Martinez PE,Chang YC,Ryan KA,Hodgkinson C,Goldman D,Dorsey SGdoi
10.1097/j.pain.0000000000001578subject
Has Abstractpub_date
2019-08-01 00:00:00pages
1824-1834issue
8eissn
0304-3959issn
1872-6623pii
00006396-201908000-00015journal_volume
160pub_type
杂志文章相关文献
PAIN文献大全abstract：:The treatment of neuropathic pain remains a clinical challenge because of its unclear mechanisms and broad clinical morbidity. Matrix metalloproteinase (MMP)-9 and MMP-2 have previously been described as key components in neuropathic pain because of their facilitation of inflammatory cytokine maturation and induction ...
journal_title：Pain
pub_type： 杂志文章
doi：10.1097/j.pain.0000000000000575
更新日期：2016-08-01 00:00:00
abstract：:Histamine, substance P, serotonin and bradykinin were applied by iontophoresis to lesional and visually non-lesional skin of 14 patients with atopic dermatitis, and normal skin of 15 healthy volunteers. Itch could be evoked by light stroking of skin with a cotton swab (alloknesis) in all lesional skin sites, but not i...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/j.pain.2006.06.003
更新日期：2006-12-15 00:00:00
abstract：:Nitric oxide (NO), synthesised by different isoforms of nitric oxide synthase (NOS), has been linked with the development and maintenance of nociception. We studied the role of the inducible isoform, iNOS, in two different rat pain models with an inflammatory component. iNOS was immunohistochemically detected locally ...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/j.pain.2005.10.028
更新日期：2006-01-01 00:00:00
abstract：:Chronic complications of traumatic brain injury represent one of the greatest financial burdens and sources of suffering in the society today. A substantial number of these patients suffer from posttraumatic headache (PTH), which is typically associated with tactile allodynia. Unfortunately, this phenomenon has been u...
journal_title：Pain
pub_type： 杂志文章
doi：10.1097/j.pain.0000000000002103
更新日期：2020-10-02 00:00:00
abstract：:Extracellular signal-regulated kinase (ERK), a mitogen-activated protein kinases (MAPK), transduces a broad range of extracellular stimuli into diverse intracellular responses. Recent studies have showed that ERK activation in the supraspinal level involved in the development of drug dependence, especially in psycholo...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/j.pain.2005.09.006
更新日期：2005-12-05 00:00:00
abstract：:The effect of the central grey matter (CG) on pain sensitivity has been investigated in rats. It has been demonstrated that baseline pain thresholds, tested by the hot plate method (HPM) after surgical operation, were significantly greater in CG-lesioned rats than in controls. Baseline tail flick latencies did not dif...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/0304-3959(83)90083-0
更新日期：1983-05-01 00:00:00
abstract：:Trigeminal neuralgia (TN) is a rare form of neuropathic facial pain characterised by severe, paroxysmal pains in the face. Little is known about the decision process in treatment of TN, and management with anti-epileptic drugs or surgical procedures carries risks of side effects, recurrence and complications. One hund...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/j.pain.2007.02.009
更新日期：2007-10-01 00:00:00
abstract：:Movement is changed in pain, but the mechanisms remain unclear. Key questions are unresolved such as whether activation can be inhomogeneously distributed within a muscle in a manner that is specific to the location of noxious input. This study addressed this question using high-density electromyography (EMG) to study...
journal_title：Pain
pub_type： 杂志文章
doi：10.1097/j.pain.0000000000001317
更新日期：2018-11-01 00:00:00
abstract：:Rats and humans manifest elevated response thresholds to aversive stimuli during gestation and parturition. This pregnancy-associated antinociception is mediated, in part, by a spinal cord dynorphin/kappa antinociceptive system. Simulating the maternal pregnancy blood concentration profile (in non-pregnant animals) of...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/0304-3959(95)00092-5
更新日期：1996-01-01 00:00:00
abstract：:Two classes of neurons with distinct responses to opioids have been identified in the rostral ventromedial medulla (RVM), a region with a well-documented role in nociceptive modulation. 'On-cells' are directly inhibited by opioids, and opioids can thus gain access to the modulatory circuitry of the RVM by an action on...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/s0304-3959(97)00226-1
更新日期：1998-04-01 00:00:00
abstract：:In knee osteoarthritis (OA), pain sensitization has been linked to a more severe symptomatology, but the prognostic implications of pain sensitivity in people undergoing conservative treatment such as physiotherapy are not established. This study aimed to prospectively investigate the association between features of p...
journal_title：Pain
pub_type： 杂志文章
doi：10.1097/j.pain.0000000000001288
更新日期：2018-09-01 00:00:00
abstract：:Sendide is a selective and extremely potent antagonist of neurokinin-1 (NK1) receptors in the mouse spinal cord. The antinociceptive activities of sendide, an antagonist of NK1 receptors, and its analogue, [D-Trp7]sendide have been examined after intrathecal (i.t.) administrations in the mouse paw formalin test. Intra...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/0304-3959(94)00107-P
更新日期：1995-02-01 00:00:00
abstract：:Though it is clear that genomic variability plays an integral role in accounting for pain sensitivity, controversy exists over which genes are involved. While recent data suggest a "protective" (i.e., less pain) haplotype in the GTP cyclohydrolase (GCH1) gene, other research has failed to confirm this association. Pos...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/j.pain.2008.10.023
更新日期：2009-01-01 00:00:00
abstract：:The purpose of this study was to assess if the functional activation caused by painful stimuli could be detected with arterial spin labeling (ASL), which is a non-invasive magnetic resonance imaging (MRI) technique for measuring cerebral blood flow (CBF). Because ASL directly measures blood flow, it is well suited to ...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/j.pain.2007.06.021
更新日期：2008-05-01 00:00:00
abstract：:Attenuation of neuropathic manifestations in experimental animals, by lidocaine injection in the rostral ventro-medial medulla (RVM), has been traditionally attributed to selective block of a descending pain facilitatory system. However, the presence of descending fibers carrying this effect and the selective action o...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/j.pain.2010.01.014
更新日期：2010-04-01 00:00:00
abstract：:The purpose of this study was to examine the relationship between a mother's rating of her own and her child's anxiety and their observed behavior during an immunization. Eighty-three preschool children and their mothers were observed in a health screening clinic while the child received an immunization. Each mother w...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/0304-3959(89)90156-5
更新日期：1989-04-01 00:00:00
abstract：:The associative network theory of memory [2] is outlined along with the concepts of mood congruity and state dependent learning. Two experiments are reported which investigate the occurrence of these effects where memory for pain is concerned. In experiment 1 the performance of 25 chronic pain patients was compared wi...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/0304-3959(90)91072-Q
更新日期：1990-11-01 00:00:00
abstract：:Acute zoster infection may be followed by a chronic pain syndrome, i.e., postherpetic neuralgia (PHN). Besides older age, the intensity of pain and neuronal damage within the acutely affected body region are regarded as predictors or risk factors for PHN. As an alternative approach an underlying peripheral polyneuropa...
journal_title：Pain
pub_type： 临床试验,杂志文章
doi：10.1016/S0304-3959(97)00105-X
更新日期：1997-11-01 00:00:00
abstract：:Osteoarthritis (OA) is a major healthcare burden of increasing prevalence. It has been demonstrated that the relationship between pain and sleep produces changes in sleep patterns and pain perception. However, electrophysiological studies in animal models of pain are limited. The current study examined the effect of c...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/j.pain.2008.09.025
更新日期：2008-12-01 00:00:00
abstract：:OnabotulinumtoxinA (onabotA) has shown efficacy in chronic migraine (CM). Its mechanism of action, however, remains obscure. We have analysed whether treatment with onabotA is able to induce changes in interictal plasma calcitonin gene-related peptide (CGRP) concentrations, which have been shown to be increased in pat...
journal_title：Pain
pub_type： 杂志文章
doi：10.1097/j.pain.0000000000000119
更新日期：2015-05-01 00:00:00
abstract：:Pain is a complex human trait. It is likely that the interaction of multiple genes, each with a small individual effect, along with the effect of environmental factors, influences the clinical efficacy of opioids rather than a single gene alone. Polymorphisms in genes coding for the mu-opioid receptor (A118G) and cate...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/j.pain.2006.10.023
更新日期：2007-07-01 00:00:00
abstract：:The GABA(B) receptor-mediated presynaptic inhibition of glycinergic transmission was studied from young rat substantia gelatinosa (SG) neurons using a conventional whole-cell patch clamp technique. Action potential-dependent glycinergic inhibitory postsynaptic currents (IPSCs) were recorded from SG neurons in the pres...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/j.pain.2008.01.005
更新日期：2008-08-31 00:00:00
abstract：ABSTRACT:The purpose of our work was to determine the role of nonopioid peptides derived from opioid prohormones in sensory hypersensitivity characteristics of neuropathic pain and to propose a pharmacological approach to restore the balance of these endogenous opioid systems. Nonopioid peptides may have a pronocicepti...
journal_title：Pain
pub_type： 杂志文章
doi：10.1097/j.pain.0000000000002045
更新日期：2021-02-01 00:00:00
abstract：:A 1-year follow-up of two preadolescent age cohorts with musculoskeletal pain at least once a week was conducted to analyze predictive factors for the persistence of musculoskeletal pain. Of the 564 children with pain at baseline, representing one third of the sample studied, 515 (91.3%) could be followed and 452 (80....
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/S0304-3959(98)00083-9
更新日期：1998-07-01 00:00:00
abstract：:We assessed nimodipine's ability to increase the analgesic effect of morphine in 32 patients suffering from cancer pain in a double-blind, placebo controlled cross-over study. Morphine administration began a few days before the start of the study. The analgesic effects of two combinations were compared: morphine (M) p...
journal_title：Pain
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/s0304-3959(96)03186-7
更新日期：1996-12-01 00:00:00
abstract：:Chronic widespread pain (CWP) is associated with poor health-related quality of life (HRQoL). It is unclear whether pain itself is the cause of poor HRQoL or other factors play a role. We hypothesised that new onset of CWP was associated with poor physical and mental HRQoL but that psychosocial risk markers for CWP on...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/j.pain.2008.10.022
更新日期：2009-01-01 00:00:00
abstract：:The nociceptive flexion reflex (NFR) has been used as a psychophysiological tool to study spinal nociceptive processes in numerous clinical and experimental studies. Despite widespread use of the NFR, few attempts have been made to empirically test and compare different scoring criteria to detect the presence/absence ...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/j.pain.2009.06.022
更新日期：2009-09-01 00:00:00
abstract：:To quantify performance differences between patients with low-back pain (LBP) and a control group during their performance of a repetitive isodynamic lifting task. Case-control study was done. LBP patients were recruited and tested at an outpatient ambulatory chronic pain rehabilitation program before treatment was be...
journal_title：Pain
pub_type： 杂志文章
doi：10.1016/s0304-3959(03)00247-1
更新日期：2003-09-01 00:00:00
abstract：:High-quality information on the potential benefit and harm of a drug is required for patients and clinicians to make informed treatment decisions and to enable cost-effectiveness modeling to be undertaken. This systematic review describes the collection and reporting of adverse event data as presented in published cli...
journal_title：Pain
pub_type： 杂志文章,评审
doi：10.1016/j.pain.2012.08.012
更新日期：2013-02-01 00:00:00
abstract：:This study investigated the effects of a single administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridinyl-4-isoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), a negative allosteric modulator (NAM) of metabotropic glutamate receptor 7 (mGluR7), on pain and on affective and cognitive behavior in neuropathic mice. The activity ...
journal_title：Pain
pub_type： 杂志文章
doi：10.1097/j.pain.0000000000000150
更新日期：2015-06-01 00:00:00
