European journal of pain : EJP
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Pain markedly activates the hypothalamic-pituitary-adrenal (HPA) axis and increases plasma corticosterone release interfering significantly with nociceptive behaviour as well as the mechanism of action of analgesic drugs. ⋯ Our data indicate that HPA axis activation in acute and chronic pain models is time dependent and may be dissociated from evoked hyperalgesia. Therefore, HPA-axis activation represents an important variable to be considered when designing experimental assays of persistent pain as well as for interpretation of data.
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Neuropathic pain is strongly associated with mood disorders like anxiety and depression. Corticotropin-releasing factor (CRF) plays a prominent role in these disorders as it is up-regulated in limbic structures such as the amygdala, upon experimentally induced neuropathy. This review discusses recent literature on the role of CRF in pain processing and highlights the amygdala as a potential hot spot in supraspinal descending pain control. ⋯ Here, CRFR2 can be recruited by either high (pharmacological) concentrations of CRF or by endogenous CRFR2 ligands, the urocortins, leading to analgesia (pain termination). This on-off switching of pain is completed by redistribution of the CRF receptors to their initial activity state. We furthermore propose that in neuropathic pain, this mechanism is dysregulated and causes a state of permanent hyperalgesia, and present an integrative (patho)physiological model for the way disturbed CRF receptor signalling in the amygdala could initiate neuropathic pain.
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Randomized Controlled Trial Multicenter Study Comparative Study
Randomized controlled trial of the combined monoaminergic and opioid investigational compound GRT9906 in painful polyneuropathy.
GRT9906 is an investigational novel compound with μ-opioid receptor agonism and inhibition of noradrenalin/serotonin re-uptake. In this randomized, double-blind, placebo-controlled, three-way cross-over trial in painful polyneuropathy, the efficacy and safety of GRT9906 was assessed and compared with tramadol. During 4-week treatment periods, daily oral doses of either GRT9906 120-240 mg, or placebo, or tramadol 200-400 mg were given. ⋯ The most frequently reported adverse events were nausea, fatigue, constipation and sleep disorder for GRT9906 and tramadol. Four patients dropped out due to adverse events during both GRT9906 and tramadol treatment and two dropped out during placebo treatment. In conclusion, in painful polyneuropathy, GRT9906 demonstrated analgesic efficacy with a magnitude of effect comparable with tramadol and was well tolerated.
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The aim of this review was to determine the impact of spinal cord stimulation (SCS) on physical function and sleep quality in individuals with failed back surgery syndrome (FBSS). This review comprised three phases: an electronic database search (PubMed, Cinahl Plus, EMBASE, PsychInfo, Pedro, Cochrane Library) identified potential papers; these were screened for inclusion criteria, with extraction of data from accepted papers and rating of internal validity by two independent reviewers using the Effective Public Health Practice Project quality assessment tool, a tool designed to assess non-RCTs (randomized controlled trials) as well as RCTs. Strength of the evidence was rated using the Agency for Health Care Policy and Research guidelines. ⋯ Improvements in sleep quantity, a reduction in awakenings and a decrease in sleep medication use were also noted (level D). The impact of SCS on cognitive function, i.e., memory and concentration, was also assessed using the same search strategy, no papers fulfilled the inclusion criteria for this study. Spinal cord stimulation effectively addressed many physical function and sleep problems associated with FBSS; however, there is a need for further high-quality objective investigations to support this.
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Randomized Controlled Trial
Attention focus, trait anxiety and pain perception in patients undergoing colposcopy.
Few studies have compared the relative efficacy of attention-focus strategies in reducing clinical pain. Colposcopy, a medical diagnostic examination performed to identify premalignant cervical cell changes, elicits both anxiety and pain in patients, while allowing little or no behavioural control over the event. Employing a multi-group experimental design, the present study sought to investigate how different types of attention-focus strategies impacted upon pain perception, state anxiety and affect, in a sample of 123 colposcopy patients. ⋯ Pre-colposcopy pain expectancy, but not trait anxiety, was found to be positively related to colposcopy-related pain. It was further demonstrated that heightened state anxiety following colposcopy was due to experienced pain and pain unpleasantness, rather than to aspects of the pre-colposcopy prediction of pain. The results have implications for management of acute clinical pain.