Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene.


: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 catechol-O-methyl transferase (Val158Met) may be important modulators of opioid efficacy. We assessed joint effects of the OPRM1 and COMT genes in predicting morphine dose for cancer pain relief. We used genotype and clinical data from a pharmacokinetic study of morphine in 207 inpatients treated with stable morphine dose for at least 3 days by Palliative Medicine Specialists. Results showed significant variation in morphine dose requirement by genotype groups: carriers of COMT Val/Val and Val/Met genotype required 63% and 23%, respectively, higher morphine dose compared to carriers of Met/Met genotype (p=0.02). Carriers of OPRM1 GG genotype required 93% higher morphine dose compared to carriers of AA genotypes (p=0.012). When we explored for joint effects, we found that carriers of the OPRM1 AA and COMT Met/Met genotype required the lowest morphine dose to achieve pain relief (87 mg/24 h; 95%CI=57,116) and those with neither Met/Met nor AA genotype needed the highest morphine dose (147 mg/24 h; 95%CI=100,180). The significant joint effects for the Met/Met and AA genotypes (p<0.012) persisted, even after controlling for demographic and clinical variables in the multivariable analyses. Future studies are needed to further characterize the joint effects of multiple genes, along with demographic and clinical variables, in predicting opioid dose.






Reyes-Gibby CC,Shete S,Rakvåg T,Bhat SV,Skorpen F,Bruera E,Kaasa S,Klepstad P




Has Abstract


2007-07-01 00:00:00
















  • Modality-specific effects of aversive expectancy in the anterior insula and medial prefrontal cortex.

    abstract::Expectations modulate the subjective experience of pain by increasing sensitivity to nociceptive inputs, an effect mediated by brain regions such as the insula. However, it is still unknown whether the neural structures underlying pain expectancy hold sensory-specific information or, alternatively, code for modality-i...


    pub_type: 杂志文章


    authors: Sharvit G,Corradi-DellʼAcqua C,Vuilleumier P

    更新日期:2018-08-01 00:00:00

  • The bee venom test: a new tonic-pain test.

    abstract::The present study describes a new test of tonic pain to be used as an animal model of persistent pain. First, pain responses and edema produced by subcutaneous injection of increasing doses of honey bee venom into the hind paw of the rat were quantified. Second, the effect of morphine and aspirin on the pain responses...


    pub_type: 杂志文章


    authors: Lariviere WR,Melzack R

    更新日期:1996-08-01 00:00:00

  • New approach for investigating neuropathic allodynia by optogenetics.

    abstract::Mechanical allodynia is pain caused by normally innocuous mechanical stimuli and is a cardinal and intractable symptom of neuropathic pain. Roles of low-threshold mechanoreceptors (LTMRs), including Aβ fibers, in mechanical allodynia have previously been proposed, but the necessity and sufficiency of LTMRs in allodyni...


    pub_type: 杂志文章,评审


    authors: Tsuda M

    更新日期:2019-05-01 00:00:00

  • Differential expression of systemic inflammatory mediators in amputees with chronic residual limb pain.

    abstract::Chronic postsurgical pain impacts most amputees, with more than half experiencing neuralgic residual limb pain. The transition from normal acute postamputation pain to chronic residual limb pain likely involves both peripheral and central inflammatory mechanisms. As part of the Veterans Integrated Pain Evaluation Rese...


    pub_type: 杂志文章


    authors: Chamessian A,Van de Ven T,Buchheit T,Hsia HL,McDuffie M,Gamazon ER,Walsh C,Bruehl S,Buckenmaier C' 3rd,Shaw A

    更新日期:2017-01-01 00:00:00

  • Maternal family history of hypertension attenuates neonatal pain response.

    abstract::Reduced sensitivity to naturally occurring and laboratory pain stimuli has been observed in individuals with hypertension, high-normal blood pressure, and a family history of hypertension. The present study sought to extend these findings by examining the relationship between familial history of hypertension and pain ...


    pub_type: 杂志文章,随机对照试验


    authors: France CR,Taddio A,Shah VS,Pagé GM,Katz J

    更新日期:2009-04-01 00:00:00

  • Characteristics of labor pain at two stages of cervical dilation.

    abstract::This study characterized the pain reported in a selected group of obstetrical patients in labor and compared the pain experienced at 2 stages of dilation, dilation of 2-5 cm and of 6-10 cm. Pain was defined as the perception of an unpleasant sensory and emotional experience with multidimensional factors that evoke beh...


    pub_type: 杂志文章


    authors: Brown ST,Campbell D,Kurtz A

    更新日期:1989-09-01 00:00:00

  • Pain affect without pain sensation in a patient with a postcentral lesion.

    abstract::We report findings from clinical examination and cutaneous laser stimulation in a 57-year-old male, who suffered from a right-sided postcentral stroke. In this patient, we were able to demonstrate (i) a dissociation of discriminative and affective components of pain perception and, for the first time in humans, (ii) t...


    pub_type: 杂志文章


    authors: Ploner M,Freund HJ,Schnitzler A

    更新日期:1999-05-01 00:00:00

  • N of 1 randomised controlled trials of oral ketamine in patients with chronic pain.

    abstract::Anecdotal reports suggest that the general anaesthetic drug ketamine, taken orally in low doses, can give rise to some extra analgesia in patients with refractory neuropathic pain. This study was designed to determine the proportion of patients with chronic neuropathic pain responding to oral ketamine, and then to sep...


    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Haines DR,Gaines SP

    更新日期:1999-11-01 00:00:00

  • Emotional modulation of muscle pain is associated with polymorphisms in the serotonin transporter gene.

    abstract::The perception of pain is determined by a combination of genetic, neurobiological, cultural, and emotional factors. Recent studies have demonstrated an association between specific genotypes and pain perception. Particular focus has been given to the triallelic polymorphism in the promoter region of the serotonin tran...


    pub_type: 杂志文章


    authors: Horjales-Araujo E,Demontis D,Lund EK,Vase L,Finnerup NB,Børglum AD,Jensen TS,Svensson P

    更新日期:2013-08-01 00:00:00

  • Substance P, calcitonin gene related peptide and PGE2 co-released from the mouse colon: a new model to study nociceptive and inflammatory responses in viscera, in vitro.

    abstract::Visceral inflammation is thought to play an important role in the sensitization of low and high threshold mechanosensory and polymodal afferents and to recruit silent nociceptors. Yet, little is known about the potential role of the mediators involved in nociceptor sensitization to mechanical stimulation as compared t...


    pub_type: 杂志文章


    authors: Roza C,Reeh PW

    更新日期:2001-09-01 00:00:00

  • GABA(B) receptor-mediated presynaptic inhibition of glycinergic transmission onto substantia gelatinosa neurons in the rat spinal cord.

    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...


    pub_type: 杂志文章


    authors: Choi IS,Cho JH,Jeong SG,Hong JS,Kim SJ,Kim J,Lee MG,Choi BJ,Jang IS

    更新日期:2008-08-31 00:00:00

  • Functional differences between neurochemically defined populations of inhibitory interneurons in the rat spinal dorsal horn.

    abstract::In order to understand how nociceptive information is processed in the spinal dorsal horn we need to unravel the complex synaptic circuits involving interneurons, which constitute the vast majority of the neurons in laminae I-III. The main limitation has been the difficulty in defining functional populations among the...


    pub_type: 杂志文章


    authors: Polgár E,Sardella TCP,Tiong SYX,Locke S,Watanabe M,Todd AJ

    更新日期:2013-12-01 00:00:00

  • Autonomic indices and reactive pain reports on the McGill Pain Questionnaire.

    abstract::Skin conductance and heart rate measures obtained from subjects previous to, during, and after their performance of the cold pressor task were correlated with their responses to the McGill Pain Questionnaire administered immediately after the completion of the cold pressor task. A reliable relationship between skin co...


    pub_type: 杂志文章


    authors: Dowling J

    更新日期:1982-01-01 00:00:00

  • Hemibody pain relieved by microvascular decompression of the contralateral caudal medulla: case report.

    abstract::Microvascular decompression (MVD) of cranial nerves has become an established treatment for trigeminal and (vago)glossopharyngeal neuralgia and for hemifacial spasm. The authors present the case of a 64-year-old man who had a 3.5-year history of severe, drug-resistant hemibody pain with sensory and autonomic disturban...


    pub_type: 杂志文章


    authors: Simpson BA,Amato-Watkins A,Hourihan MD

    更新日期:2014-08-01 00:00:00

  • Retigabine, the specific KCNQ channel opener, blocks ectopic discharges in axotomized sensory fibres.

    abstract::The M-current has been proposed as a potential target for analgesia under neuropathic pain conditions. M-currents and/or their molecular correlates, KCNQ proteins, have been demonstrated in key elements of the nociceptive system including spinal and dorsal root ganglion neurons. Here we demonstrate that retigabine, a ...


    pub_type: 杂志文章


    authors: Roza C,Lopez-Garcia JA

    更新日期:2008-09-15 00:00:00

  • Intrathecal delivery of hydromorphone vs morphine for refractory cancer pain: a multicenter, randomized, single-blind, controlled noninferiority trial.

    abstract::Hydromorphone is an alternative to morphine for intrathecal drug delivery system to treat refractory cancer pain; however, there is not enough clinical evidence to prove it. In our study, 233 patients from 12 different pain management centers across China were enrolled, 121 and 112 in the intrathecal hydromorphone (IT...


    pub_type: 杂志文章


    authors: Ma K,Jin Y,Wang L,Feng ZY,Song T,Yang XQ,Chen FQ,Duan BL,Huang YQ,Xie GL,Bao HG,Wang K,Xu JT,Lu Y,Liu YQ

    更新日期:2020-11-01 00:00:00

  • A phase III placebo- and oxycodone-controlled study of tanezumab in adults with osteoarthritis pain of the hip or knee.

    abstract::Tanezumab is a humanized monoclonal antinerve growth factor antibody in development for treatment of chronic pain. In a phase III, placebo- and active-controlled study, we investigated the efficacy and safety of tanezumab for osteoarthritis (OA) hip or knee pain. Patients (N=610) received up to 2 doses of intravenous ...


    pub_type: 杂志文章,随机对照试验


    authors: Spierings ELH,Fidelholtz J,Wolfram G,Smith MD,Brown MT,West CR

    更新日期:2013-09-01 00:00:00

  • Variation in reporting of pain and other subjective health complaints in a working population and limitations of single sample measurements.

    abstract::Measuring health complaints by administrating a single report is common. Our aim was to assess variation in pain and other subjective complaints over an extended period, whether a single-sample produces representative data, and determine associations between complaints. Health-complaint reports were collected from pos...


    pub_type: 杂志文章


    authors: Steingrímsdóttir OA,Vøllestad NK,Røe C,Knardahl S

    更新日期:2004-07-01 00:00:00

  • Nortriptyline and fluphenazine in the symptomatic treatment of diabetic neuropathy. A double-blind cross-over study.

    abstract::A controlled clinical trial on the efficacy of a nortriptyline-fluphenazine combination was carried out in patients with painful diabetic polyneuropathy. A visual analog scale was used to evaluate the relief of pain or paresthesia. Significant relief of both pain and paresthesia was obtained with this combination. The...


    pub_type: 临床试验,杂志文章


    authors: Gomez-Perez FJ,Rull JA,Dies H,Rodriguez-Rivera GJ,Gonzalez-Barranco J,Lozano-Castañeda O

    更新日期:1985-12-01 00:00:00

  • Cortical excitability changes after high-frequency repetitive transcranial magnetic stimulation for central poststroke pain.

    abstract::Central poststroke pain (CPSP) is one of the most refractory chronic pain syndromes. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been demonstrated to provide moderate pain relief for CPSP. However, the mechanism underlying the pain relief remains unclear. The objective of this s...


    pub_type: 杂志文章


    authors: Hosomi K,Kishima H,Oshino S,Hirata M,Tani N,Maruo T,Yorifuji S,Yoshimine T,Saitoh Y

    更新日期:2013-08-01 00:00:00

  • Pain sensitization associated with nonresponse after physiotherapy in people with knee osteoarthritis.

    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...


    pub_type: 杂志文章


    authors: OʼLeary H,Smart KM,Moloney NA,Blake C,Doody CM

    更新日期:2018-09-01 00:00:00

  • Evaluating persistent pain in long term care residents: what role for pain maps?

    abstract::The purpose of this study was to examine the utility of the pain map as a pain assessment tool in frail nursing home residents. The study was conducted in two phases. In Phase 1, nursing home staff's knowledge of the locations of resident pain complaints was examined. We found significant deficiencies in this knowledg...


    pub_type: 临床试验,杂志文章


    authors: Weiner D,Peterson B,Keefe F

    更新日期:1998-05-01 00:00:00

  • Psychophysical evidence for a neuropathic component of chronic neck pain.

    abstract::Recent studies into the common complaint of chronic neck pain have focused on its anatomical origin, identifying especially the cervical zygapophysial joints. However the pathophysiology of chronic neck pain remains poorly understood. In this psychophysical study, responses to electrocutaneous stimulation in subjects ...


    pub_type: 杂志文章


    authors: Sheather-Reid RB,Cohen ML

    更新日期:1998-04-01 00:00:00

  • Comparable dose-dependent inhibition of AP-7 sensitive strychnine-induced allodynia and paw pinch-induced nociception by mexiletine in the rat.

    abstract::The blockade of spinal glycine receptors with intrathecal (i.t.) strychnine produces segmentally-localized allodynia in the rat; a reversible and highly reproducible effect that is attained without peripheral or central nerve injury. We investigated the effect of i.v. mexiletine, an orally active congener of lidocaine...


    pub_type: 杂志文章


    authors: Khandwala H,Hodge E,Loomis CW

    更新日期:1997-09-01 00:00:00

  • Adrenal medullary implants in the rat spinal cord reduce nociception in a chronic pain model.

    abstract::Previous work in this laboratory has indicated that the transplantation of adrenal medullary tissue into the subarachnoid space of the rat spinal cord can reduce pain sensitivity to acute noxious stimuli, particularly following stimulation by nicotine. This most likely results from the stimulated release of opioid pep...


    pub_type: 杂志文章


    authors: Sagen J,Wang H,Pappas GD

    更新日期:1990-07-01 00:00:00

  • Pain, frailty and comorbidity on older men: the CHAMP study.

    abstract::Intrusive pain is likely to have a serious impact on older people with limited ability to respond to additional stressors. Frailty is conceptualised as a functional and biological pattern of decline accumulating across multiple physiological systems, resulting in a decreased capacity to respond to additional stressors...


    pub_type: 杂志文章


    authors: Blyth FM,Rochat S,Cumming RG,Creasey H,Handelsman DJ,Couteur DGL,Naganathan V,Sambrook PN,Seibel MJ,Waite LM

    更新日期:2008-11-15 00:00:00

  • Effects of capsaicin applied locally to adult peripheral nerve. II. Anatomy and enzyme and peptide chemistry of peripheral nerve and spinal cord.

    abstract::(1) Capsaicin solution was applied for 15 min around a 1 cm length of sciatic nerve in the mid upper leg of adult rats. (2) Electron microscopic examinations of the nerve in the treated region after 14 days shows no signs of degeneration of either myelinated or unmyelinated fibres attributable to the capsaicin. (3) Fl...


    pub_type: 杂志文章


    authors: Ainsworth A,Hall P,Wall PD,Allt G,MacKenzie ML,Gibson S,Polak JM

    更新日期:1981-12-01 00:00:00

  • High-threshold primary afferent supply of spinal lamina X neurons.

    abstract::The spinal gray matter region around the central canal, lamina X, is critically involved in somatosensory processing and visceral nociception. Although several classes of primary afferent fibers terminate or decussate in this area, little is known about organization and functional significance of the afferent supply o...


    pub_type: 杂志文章


    authors: Krotov V,Tokhtamysh A,Safronov BV,Belan P,Voitenko N

    更新日期:2019-09-01 00:00:00

  • Distinct functions of soluble guanylyl cyclase isoforms NO-GC1 and NO-GC2 in inflammatory and neuropathic pain processing.

    abstract::A large body of evidence indicates that nitric oxide (NO)/cGMP signaling essentially contributes to the processing of chronic pain. In general, NO-induced cGMP formation is catalyzed by 2 isoforms of guanylyl cyclase, NO-sensitive guanylyl cyclase 1 (NO-GC1) and 2 (NO-GC2). However, the specific functions of the 2 iso...


    pub_type: 杂志文章


    authors: Petersen J,Mergia E,Kennel L,Drees O,Steubing RD,Real CI,Kallenborn-Gerhardt W,Lu R,Friebe A,Koesling D,Schmidtko A

    更新日期:2019-03-01 00:00:00

  • The analgesic effect of amitriptyline on chronic facial pain.

    abstract::The efficacy of amitriptyline was evaluated in 28 patients with chronic oral-facial pain. Most of the patients had evidence of musculoskeletal pain while some had a history suggesting pain of neurogenic origin. Two patients had mixed elements of neurogenic and musculoskeletal pain. Amitriptyline was more effective tha...


    pub_type: 临床试验,杂志文章


    authors: Sharav Y,Singer E,Schmidt E,Dionne RA,Dubner R

    更新日期:1987-11-01 00:00:00