European Journal of Pain
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Peripheral endothelin A receptor antagonism attenuates carcinoma‐induced pain Abstract In this study we investigated the role of endothelin‐1 (ET‐1) and its peripheral receptor (ET‐A) in carcinoma‐induced pain in a mouse cancer pain model. Tumors were induced in the hind paw of female mice by local injection of cells derived from a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at four days after SCC inoculation and lasted to 28 days, the last day of measurement. Intra‐tumor expression of both ET‐1 mRNA and ET‐1 protein were significantly upregulated compared to normal tissue, and local administration of the ET‐A receptor selective antagonist, BQ‐123 (100μM) significantly elevated withdrawal thresholds, indicating the induction of an antinociceptive effect. These findings support the suggestion that ET‐1 and ET‐A receptors contribute to the severity of carcinoma‐induced soft tissue cancer pain.
European Journal of Pain - Tập 11 - Trang 406-414 - 2007
Cortical processing of mechanical hyperalgesia: A MEG study Abstract Mechanical hyperalgesia may develop following tissue inflammation or nerve injury. Basically, peripheral sensitization leads to primary hyperalgesia at the site of injury, whereas secondary hyperalgesia occurs in the surrounding tissue and results from central sensitization. The present study focuses on the cerebral processing of secondary mechanical hyperalgesia. Primary (S1) and secondary (S2) somatosensory cortices and posterior parietal cortex (PPC) are thought to be involved in cerebral processing of noxious mechanical stimuli. However, their response pattern in the presence of mechanical hyperalgesia remains to be elucidated. Therefore, we investigated the cortical processing of secondary mechanical hyperalgesia using magnetoencephalography (MEG). In 12 healthy subjects mechanoinsensitive c‐nociceptors were repetitively stimulated using transcutaneously applied high‐current electrical stimulation. This procedure resulted in stable areas of secondary mechanical hyperalgesia. Pin‐prick stimuli were applied inside and outside the hyperalgesic area. The corresponding cortical activations were detected and quantified using MEG. We found pin‐prick‐induced sequential activation of contralateral S1, PPC and S2 as well as activation of ipsilateral S2 during both pin‐prick hyperalgesia and normal pin‐prick pain. During pin‐prick hyperalgesia significantly higher activation was detected in contralateral PPC and bilateral S2 but not in S1 compared to normal pin‐prick pain. In contrast to PPC, we found a significant correlation between increases of magnetic field strengths within bilateral S2 with the increase of pain ratings during pin‐prick hyperalgesia. We conclude that the S2 cortex may be involved for the processing of secondary mechanical hyperalgesia in the human brain. PPC activation may reflect higher attentional processing during mechanical hyperalgesia.
European Journal of Pain - Tập 14 - Trang 64-70 - 2010
Preventing pain after breast surgery: A systematic review with meta‐analyses and trial‐sequential analyses Abstract Background and objective The aim of this systematic review was to indirectly compare the efficacy of any intervention, administered perioperatively, on acute and persistent pain after breast surgery. Databases and data treatment We searched for randomized trials comparing analgesic interventions with placebo or no treatment in patients undergoing breast surgery under general anaesthesia. Primary outcome was intensity of acute pain (up to 6 hr postoperatively). Secondary outcomes were cumulative 24‐hr morphine consumption, incidence of postoperative nausea and vomiting (PONV), and chronic pain. We used an original three‐step approach. First, meta‐analyses were performed when data from at least three trials could be combined; secondly, trial sequential analyses were used to separate conclusive from unclear evidence. And thirdly, the quality of evidence was rated with GRADE. Results Seventy‐three trials (5,512 patients) tested loco‐regional blocks (paravertebral, pectoralis), local anaesthetic infiltrations, oral gabapentinoids or intravenous administration of glucocorticoids, lidocaine, N‐methyl‐D‐aspartate antagonists or alpha2 agonists. With paravertebral blocks, pectoralis blocks and glucocorticoids, there was conclusive evidence of a clinically relevant reduction in acute pain (visual analogue scale > 1.0 cm). With pectoralis blocks, and gabapentinoids, there was conclusive evidence of a reduction in the cumulative 24‐hr morphine consumption (> 30%). With paravertebral blocks and glucocorticoids, there was conclusive evidence of a relative reduction in the incidence of PONV of 70%. For chronic pain, insufficient data were available. Conclusions Mainly with loco‐regional blocks, there is conclusive evidence of a reduction in acute pain intensity, morphine consumption and PONV incidence after breast surgery. For rational decision making, data on chronic pain are needed. Significance This quantitative systematic review compares eight interventions, published across 73 trials, to prevent pain after breast surgery, and grades their degree of efficacy. The most efficient interventions are paravertebral blocks, pectoralis blocks and glucocorticoids, with moderate to low evidence for the blocks. Intravenous lidocaine and alpha2 agonists are efficacious to a lesser extent, but with a higher level of evidence. Data for chronic pain are lacking.
European Journal of Pain - Tập 25 Số 1 - Trang 5-22 - 2021
Angiotensin (1–7) prevents angiotensin <scp>II</scp>‐induced nociceptive behaviour via inhibition of p38 <scp>MAPK</scp> phosphorylation mediated through spinal <scp>M</scp>as receptors in mice Abstract Background We have recently demonstrated that intrathecal (i.t.) administration of angiotensin II (A ng II ) induces nociceptive behaviour in mice accompanied by a phosphorylation of p38 mitogen‐activated protein kinase (MAPK ) mediated through A ng II type 1 (AT 1 ) receptors. The N ‐terminal fragment of A ng II , A ng (1–7), plays a pivotal role in counterbalancing many of the well‐established actions induced by A ng II . However, the role of A ng (1–7) in spinal nociceptive transmission remains unclear. Therefore, we examined whether i.t. administration of A ng (1–7) can inhibit the A ng II ‐induced nociceptive behaviour in mice. Methods In the behavioural experiments, the accumulated response time of nociceptive behaviour consisting of scratching, biting and licking in conscious mice was determined during a 25‐min period starting after i.t. injection. The distribution and localization of AT 1 or M as receptors were analysed using a M apA nalyzer and confocal microscope, respectively. Phosphorylation of p38 MAPK in the dorsal spinal cord was measured by Western blotting. Results The nociceptive behaviour induced by A ng II was dose‐dependently inhibited by the co‐administration of A ng (1–7). The inhibitory effect of A ng (1–7) was reversed by the co‐administration of A 779, a M as receptor antagonist. Western blot analysis showed that the increase in spinal p38 MAPK phosphorylation following the i.t. administration of A ng II was also inhibited by A ng (1–7), and the A ng (1–7) induced‐inhibition was prevented by A 779. Conclusions Our data show that the i.t. administration of A ng (1–7) attenuates an A ng II ‐induced nociceptive behaviour and is accompanied by the inhibition of p38 MAPK phosphorylation mediated through M as receptors.
European Journal of Pain - Tập 18 Số 10 - Trang 1471-1479 - 2014
Efficacy, acceptability and safety of guided imagery/hypnosis in fibromyalgia – A systematic review and meta‐analysis of randomized controlled trials Abstract This systematic review aimed at evaluating the efficacy, acceptability and safety of guided imagery/hypnosis (GI /H) in fibromyalgia.
Cochrane Library, MEDLINE , PsycINFO and SCOPUS were screened through February 2016. Randomized controlled trials (RCT s) comparing GI /H with controls were analysed. Primary outcomes were ≥50% pain relief, ≥20% improvement of health‐related quality of life, psychological distress, disability, acceptability and safety at end of therapy and 3‐month follow‐up. Effects were summarized by a random effects model using risk differences (RD ) or standardized mean differences (SMD ) with 95% confidence intervals (CI ).Seven RCT s with 387 subjects were included into a comparison of GI /H versus controls. There was a clinically relevant benefit of GI /H compared to controls on ≥50% pain relief [RD 0.18 (95% CI 0.02, 0.35)] and psychological distress [SMD −0.40 (95% CI −0.70, −0.11)] at the end of therapy. Acceptability at the end of treatment for GI /H was not significantly different to the control. Two RCT s with 95 subjects were included in the comparison of hypnosis combined with cognitive behavioural therapy (CBT ) versus CBT alone. Combined therapy was superior to CBT alone in reducing psychological distress at the end of therapy [SMD −0.50 (95% CI −0.91, −0.09)]. There were no statistically significant differences between combined therapy and CBT alone in other primary outcomes at the end of treatment and follow‐up. No study reported on safety.
GI /H hold promise in a multicomponent management of fibromyalgia. Significance We provide a systematic review with meta‐analysis on guided imagery and hypnosis for fibromyalgia. Current analyses endorse the efficacy and tolerability of guided imagery/hypnosis and of the combination of hypnosis with cognitive–behavioural therapy in reducing key symptoms of fibromyalgia.
European Journal of Pain - Tập 21 Số 2 - Trang 217-227 - 2017
A randomized controlled trial of hypnosis compared with biofeedback for adults with chronic low back pain Abstract Background Chronic low back pain (CLBP ) is common and results in significant costs to individuals, families and society. Although some research supports the efficacy of hypnosis for CLBP , we know little about the minimum dose needed to produce meaningful benefits, the roles of home practice and hypnotizability on outcome, or the maintenance of treatment benefits beyond 3 months. Methods One hundred veterans with CLBP participated in a randomized, four‐group design study. The groups were (1) an eight‐session self‐hypnosis training intervention without audio recordings for home practice; (2) an eight‐session self‐hypnosis training intervention with recordings; (3) a two‐session self‐hypnosis training intervention with recordings and brief weekly reminder telephone calls; and (4) an eight‐session active (biofeedback) control intervention. Results Participants in all four groups reported significant pre‐ to post‐treatment improvements in pain intensity, pain interference and sleep quality. The hypnosis groups combined reported significantly more pain intensity reduction than the control group. There was no significant difference among the three hypnosis conditions. Over half of the participants who received hypnosis reported clinically meaningful (≥30%) reductions in pain intensity, and they maintained these benefits for at least 6 months after treatment. Neither hypnotizability nor amount of home practice was associated significantly with treatment outcome. Conclusions The findings indicate that two sessions of self‐hypnosis training with audio recordings for home practice may be as effective as eight sessions of hypnosis treatment. If replicated in other patient samples, the findings have important implications for the application of hypnosis treatment for chronic pain management.
European Journal of Pain - Tập 19 Số 2 - Trang 271-280 - 2015
Preterm births: Can neonatal pain alter the development of endogenous gating systems? Abstract Prematurity is known to affect the development of various neurophysiological systems, including the maturation of pain and cardiac circuits. The purpose of this study was to see if numerous painful interventions, experienced soon after birth, affect counterirritation‐induced analgesia (triggered using the cold pressor test) later in life. A total of 26 children, between the ages of 7 and 11 participated in the study. Children were divided into three groups, according to their birth status (i.e., term‐born, born preterm and exposed to numerous painful interventions, or born preterm and exposed to few painful interventions). Primary outcome measures were heat pain thresholds, heat sensitivity scores, and cardiac reactivity. Results showed that preterm children and term‐born children had comparable pain thresholds. Exposure to conditioning cold stimulation significantly increased heart rate and significantly decreased the thermal pain sensitivity of term‐born children. These physiological reactions were also observed among preterm children who were only exposed to a few painful interventions at birth. Changes in heart rate and pain sensitivity in response to conditioning cold stimulation were not observed in preterm children that had been exposed to numerous painful procedures during the neonatal period. These results suggest that early pain does not lead to enhanced pain sensitivity when premature babies become children, but that their endogenous pain modulatory mechanisms are not as well developed as those of children not exposed to noxious insult at birth. Greater frequency of painful procedures also dampened the rise in heart rate normally observed when experimental pain is experienced.
European Journal of Pain - Tập 12 Số 7 - Trang 945-951 - 2008
Internalizing behaviours in school‐age children born very preterm are predicted by neonatal pain and morphine exposure Abstract Background Greater neonatal pain is associated with higher internalizing behaviours in very preterm infants at 18 months corrected age, but it is unknown whether this relationship persists to school age. Moreover, it is unclear whether morphine ameliorates or exacerbates the potential influence of neonatal pain/stress on internalizing behaviours. We examined whether neonatal pain‐related stress is associated with internalizing behaviours at age 7 years in children born very preterm, and whether morphine affects this relationship. Methods One hundred one children born very preterm (≤32 weeks gestation) were seen at mean age 7.7 years. A parent completed the Parenting Stress Index and Child Behavior Checklist questionnaires. Neonatal pain‐related stress (the number of skin‐breaking procedures adjusted for clinical factors associated with prematurity) was examined in relation to internalizing behaviour, separately in subjects mechanically ventilated and exposed to both pain and morphine (n = 57) and those never mechanically ventilated, exposed to pain but not morphine (n = 44). Results In the non‐ventilated group, higher skin‐breaking procedures (p = 0.037) and parenting stress (p = 0.004) were related to greater internalizing behaviours. In the ventilated group, greater morphine exposure (p = 0.004) was associated with higher child internalizing scores. Conclusions In very preterm children who undergo mechanical ventilation, judicious use of morphine is important, since morphine may mitigate the negative effects of neonatal pain on nociception but adversely affect internalizing behaviours at school age. Management of procedural pain needs to be addressed in very preterm infants in the neonatal intensive care unit, to prevent long‐term effects on child behaviour.
European Journal of Pain - Tập 18 Số 6 - Trang 844-852 - 2014
Differential effectiveness of psychological interventions for reducing osteoarthritis pain: a comparison of Erickson hypnosis and Jacobson relaxation The present study investigates the effectiveness of Erikson hypnosis and Jacobson relaxation for the reduction of osteoarthritis pain. Participants reporting pain from hip or knee osteoarthritis were randomly assigned to one of the following conditions: (a) hypnosis (i.e. standardized eight‐session hypnosis treatment); (b) relaxation (i.e. standardized eight sessions of Jacobson's relaxation treatment); (c) control (i.e. waiting list). Overall, results show that the two experimental groups had a lower level of subjective pain than the control group and that the level of subjective pain decreased with time. An interaction effect between group treatment and time measurement was also observed in which beneficial effects of treatment appeared more rapidly for the hypnosis group. Results also show that hypnosis and relaxation are effective in reducing the amount of analgesic medication taken by participants. Finally, the present results suggest that individual differences in imagery moderate the effect of the psychological treatment at the 6 month follow‐up but not at previous times of measurement (i.e. after 4 weeks of treatment, after 8 weeks of treatment and at the 3 month follow‐up). The results are interpreted in terms of psychological processes underlying hypnosis, and their implications for the psychological treatment of pain are discussed. © 2002 European Federation of Chapters of the Association for the Study of Pain
European Journal of Pain - Tập 6 - Trang 1-16 - 2002
Scopolamine into the anterior cingulate cortex diminishes nociception in a neuropathic pain model in the rat: an interruption of ‘nociception‐related memory acquisition’? Abstract The cingulate cortex plays a key role in the affective component related to pain perception. This structure receives cholinergic projections and also plays a role in memory processing. Therefore, we propose that the cholinergic system in the anterior cingulate cortex is involved in the nociceptive memory process. We used scopolamine (n =10 each). The vehicle group (saline solution 0.9%, n =14) was microinjected before thermonociception. Chronic nociception was measured by the autotomy score, which onset and incidence were also determined. Group scopolamine—thermonociception–denervation (STD) presented the lowest autotomy score as compared to vehicle and group thermonociception—denervation–scopolamine (TDS) (vehicle vs. STD, p =0.002, STD vs. TDS, p =0.001). Group thermonociception‐scopolamine‐denervation (TSD) showed a diminished autotomy score when compared to TDS (p =0.053). STD group showed a delay in the onset of AB as compared to the rest of the groups. Group TSD presented a significative delay (p =0.048) in AB onset when compared to group TDS. There were no differences in the incidence between groups. The results show that nociception‐related memory processed in the anterior cingulate cortex is susceptible of being modified by the cholinergic transmission blockade. When scopolamine is microinjected prior to the nociceptive stimuli, nociception‐related memory acquisition is prevented. The evidence obtained in this study shows the role of the anterior cingulate cortex in the acquisition of nociception‐related memory.
European Journal of Pain - Tập 7 Số 5 - Trang 425-429 - 2003
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