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Despite growing interest in the role of stress mediators in pain chronicity, the effects of the stress hormone cortisol on acute pain remain incompletely understood. In a randomized, double-blind, placebo-controlled study with N=100 healthy volunteers, we tested the effects of oral hydrocortisone (20 mg) in two widely-used pain models for the visceral and somatic modality.Salivary cortisol was increased in the hydrocortisone group (time x group: p<.001). For the visceral modality, assessed using pressure-controlled rectal distensions, hydrocortisone decreased the pain threshold from pre- to post-treatment (time x group: p=.011), an effect primarily driven by women (time x sex: p=.027). For the somatic modality, cutaneous heat pain thresholds remained unaffected by hydrocortisone. Hydrocortisone did not alter perceived pain intensity or unpleasantness of either modality. Conditioned pain-related fear in response to predictive cues was only observed for the visceral modality (time x modality: p=.026), an effect that was significantly reduced by hydrocortisone compared ot placebo (time x group: p=.028).This is the first psychopharmacological study to support that acutely increased cortisol enhances pain sensitivity and impairs pain-related emotional learning within the visceral, but not the somatic pain modality. Stress-induced visceral hyperalgesia and deficits in emotional pain-related learning could play a role in the pathophysiology of chronic visceral pain.
Learn More >The comorbidity between chronic pain and emotional problems has proven difficult to address with current treatment options. This study addresses the efficacy of a transdiagnostic emotion focused exposure treatment ("hybrid") for chronic pain patients with comorbid emotional problems. Adults (n=115) with chronic musculoskeletal pain, functional and emotional problems were included in a two centre, parallel randomized controlled, open label trial comparing this treatment to an active control condition receiving a guided internet delivered pain management treatment based on CBT principles (iCBT). The hybrid treatment (n=58, 10-16 sessions) integrates exposure in vivo for chronic pain based on the fear-avoidance model with an emotion regulation approach informed by procedures in Dialectical Behavior Therapy. The iCBT (n=57; 8 treatment modules) addresses topics such as pain education, coping strategies, relaxation, problem solving, stress and sleep management using standard CBT techniques. Patient-reported outcomes were assessed pre- and posttreatment as well as at a 9-month primary end point. Across conditions, 78% participants completed post-treatment and 81% follow-up assessment. Intent-to-treat analyses showed that the hybrid had a significantly better post-treatment outcome on pain catastrophizing (d=0.39) and pain interference (d=0.63) and significantly better follow-up outcomes on depression (d=0.43) and pain interference (d=0.51). There were no differences on anxiety and pain intensity. Observed proportions of clinically significant improvement favoured the hybrid on all but one comparison, but no statistically significant differences were observed. We conclude that the hybrid emotion focused treatment may be considered an acceptable, credible and efficacious treatment option for chronic pain patients with comorbid emotional problems.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Learn More >Opioid and neurotensin (NT) receptors are expressed in both central and peripheral nervous systems where they modulate nociceptive responses. Nowadays, opioid analgesics like morphine remain the most prescribed drugs for the treatment of moderate to severe pain. However, despite their daily used, opioids can produce life-threatening side effects, such as constipation or respiratory depression. Besides, NT analogs exert strong opioid-independent analgesia. Here, we thus hypothesized that the combined use of opioid and NT agonists would require lower doses to produce significant analgesic effects, hence decreasing opioid-induced adverse effects. We used isobologram analyses to determine if the combination of a NT brain-penetrant analog, An2-NT(8-13) with morphine results in an inhibitory, synergistic or additive analgesic response. We found that intravenous administration of An2-NT(8-13) reduced by 90% the nocifensive behaviors induced by formalin injection, at the dose of 0.018mg/kg. Likewise, subcutaneous morphine reduced pain by 90% at 1.8mg/kg. Importantly, isobologram analyses revealed that the co-injection of An2-NT(8-13) with morphine induced an additive analgesic response. We finally assessed the effects of morphine and An2-NT(8-13) on the gastrointestinal tract motility using the charcoal meal test. As opposed to morphine which significantly reduced the intestinal motility at the analgesic effective dose of 1.8mg/kg, An2-NT(8-13) did not affect the charcoal meal intestinal transit at 0.018mg/kg. Interestingly, at the dose providing 90% pain relief, the co-administration of morphine with An2-NT(8-13) had a reduced effect on constipation. Altogether, these results suggest that combining NT agonists with morphine may improve its analgesic/adverse effect ratio.
Learn More >Attempts to discontinue opioid therapy to reduce the risk of overdose and adhere to prescribing guidelines may lead patients to be exposed to variability in opioid dosing. Such dose variability may increase the risk of opioid overdose even if therapy discontinuation is associated with a reduction in risk.
Learn More >In persons with migraine, severity of migraine is an important determinant of several health outcomes (e.g., patient quality of life and health care resource utilization). This study investigated how migraine patients rate the severity of their disease and how these ratings correlate with their socio-demographic, clinical, and psycho-social characteristics.
Learn More >The role of onabotulinumtoxinA in headache management was serendipitously found over a decade ago and approved for chronic migraine in 2010 based on pivotal studies. The purpose of this review is to highlight the impact on headache and other health parameters which is critically reviewed, as well as the putative mechanisms of action.
Learn More >The analgesic effect of venlafaxine (VLX), which is a selective serotonin and noradrenaline reuptake inhibitor (SNRI), has been observed on oxaliplatin-induced neuropathic pain in mice. Significant allodynia was shown after oxaliplatin treatment (6 mg/kg, i.p.); acetone and von Frey hair tests were used to assess cold and mechanical allodynia, respectively. Intraperitoneal administration of VLX at 40 and 60 mg/kg, but not 10 mg/kg, significantly alleviated these allodynia. Noradrenaline depletion by pretreatment of -(2-Chloroethyl)–ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg, i.p.) blocked the relieving effect of VLX (40 mg/kg, i.p.) on cold and mechanical allodynia. However, serotonin depletion by three consecutive pretreatments of para-chlorophenylalanine (PCPA, 150 mg/kg/day, i.p.) only blocked the effect of VLX on mechanical allodynia. In cold allodynia, the α₂-adrenergic antagonist idazoxan (10 μg, i.t.), but not the α₁-adrenergic antagonist prazosin (10 μg, i.t.), abolished VLX-induced analgesia. Furthermore, idazoxan and 5-HT₃ receptor antagonist bemesetron (MDL-72222, 15 μg, i.t.), but not prazosin or mixed 5-HT receptor antagonist methysergide (10 μg, i.t.), abolished VLX-induced analgesia in mechanical allodynia. In conclusion, 40 mg/kg of VLX treatment has a potent relieving effect against oxaliplatin-induced neuropathic pain, and α₂-adrenergic receptor, and both α₂-adrenergic and 5-HT₃ receptors are involved in this effect of VLX on cold and mechanical allodynia, respectively.
Learn More >The DSM-5 diagnosis 'opioid use disorder' (OUD) was established to better describe and detect significant impairment or distress related to opioid use. There is no data on rates of OUD in chronic non-cancer pain (CNCP) in European countries. Therefore, our objective was to screen patients in specialised pain centres for signs of OUD.
Learn More >While migraine headaches can be provoked, or predicted by the presence of an aura or premonitory symptoms, the prediction or elicitation of the aura itself is more problematic. Therefore, imaging studies directly examining the aura phenomenon are sparse. There are however interictal imaging studies that can shed light on the pathophysiology of the migraine with aura (MWA) cascade. Here, we review findings pointing to the involvement of cortical spreading depression (CSD) and neuroinflammation in MWA. Whether asymptomatic CSD also happens in some migraine without aura is still under debate. In addition, new evidence points to glial activation in MWA, indicating the involvement of astrocytes in the neuroinflammatory cascade that follows CSD, as well as dural macrophages, supporting the involvement of the trigeminovascular system in migraine pain.
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