Πέμπτη 26 Σεπτεμβρίου 2019

To focus on pain or not to focus? WHEN is the question
No abstract available
Getting closer to the other's world
No abstract available
Reading and writing: the evolution of molecular pain genetics
imageNo abstract available
Beyond pain: can antidepressants improve depressive symptoms and quality of life in patients with neuropathic pain? A systematic review and meta-analysis
imageNeuropathic pain can be a predictor of severe emotional distress, up to full-blown depressive states. In these patients, it is important to move beyond the sole treatment of pain, to recognize depressive symptoms, and to ultimately improve the quality of life. We systematically searched for published and unpublished clinical trials assessing the efficacy and tolerability of antidepressants vs placebo on depression, anxiety and quality of life in patients with neuropathic pain, and pooled data in a meta-analysis. A total of 37 studies fulfilled eligibility criteria and 32 provided data for meta-analysis. Antidepressants were more effective than placebo in improving depressive symptoms (standardized mean difference −0.11; 95% confidence interval −0.20 to −0.02), although the magnitude of effect was small, with a number needed to treat of 24. No significant difference emerged between antidepressants and placebo in reducing anxiety. Quality of life seemed improved in patients on antidepressants, as did pain. Acceptability and tolerability were higher in patients on placebo. To the best of our knowledge, this is the first meta-analysis specifically focusing on the effect of antidepressants on psychiatric symptoms and quality of life in patients with neuropathic pain. Our findings suggest that despite their potential benefit in patients with neuropathic pain, antidepressants should be prescribed with particular care because they might be less tolerable in such a fragile population. However, our findings warrant further research to explore how a correct use of antidepressants can help patients to cope with the consequences of neuropathic pain on their psychosocial health and quality of life.
Alterations in evoked and spontaneous activity of dorsal horn wide dynamic range neurons in pathological pain: a systematic review and analysis
imageWide dynamic range (WDR) neurons of the spinal dorsal horn respond to a wide range of innocuous and noxious mechanical stimulation and encode the intensity of mechanical stimuli as changes in firing rate. However, there are inconsistent findings regarding whether WDR neuron stimulus encoding activity is altered in pathological pain states. This inconsistency may arise from differences in the pain models used or in the experimental conditions themselves. In this study, we use a meta-regression approach to examine which variables modulate and determine WDR activity. We pooled data from in vivo electrophysiological studies of WDR activity evoked by von Frey filament stimulation of the hind paw in rats across a number of pathological pain models. We observed that WDR firing rate was better predicted by the calculated pressure of von Frey stimulation rather than applied filament force, as reported in all studies. The pressure-evoked firing rate of WDR neurons was not altered by any experimental pain model except for arthritis and inflammation models, where mechanical stimuli evoked a higher firing rate than controls. Conversely, there was a consistent increase in the spontaneous firing rate of WDR neurons in neuropathic pain, arthritis and inflammation, and chemoneuropathy pain models. Overall, these data indicate that changes in WDR encoding of applied pressure are unlikely to significantly contribute to pathological sensory processing but suggest a possible role for these neurons in spontaneous pain.
Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: mechanism of action in the context of efficacy and safety
imageChronic pain continues to be a significant global burden despite the availability of a variety of nonpharmacologic and pharmacologic treatment options. Thus, there is a need for new analgesics with novel mechanisms of action. In this regard, antibodies directed against nerve growth factor (NGF-Abs) are a new class of agents in development for the treatment of chronic pain conditions such as osteoarthritis and chronic low-back pain. This comprehensive narrative review summarizes evidence supporting pronociceptive functions for NGF that include contributing to peripheral and central sensitization through tropomyosin receptor kinase A activation and stimulation of local neuronal sprouting. The potential role of NGF in osteoarthritis and chronic low-back pain signaling is also examined to provide a mechanistic basis for the observed efficacy of NGF-Abs in clinical trials of these particular pain states. Finally, the safety profile of NGF-Abs in terms of common adverse events, joint safety, and nerve structure/function is discussed.
Pain-related gaze biases and later functioning among adults with chronic pain: a longitudinal eye-tracking study
imageIn previous studies that examined the impact of attention biases (ABs) on later pain outcomes, reaction times (RTs) in response to brief stimulus presentations had been used as measures of attention. Consequently, little is known about effects of ABs assessed during presentations of cues or biases in prolonged attention towards pain stimuli as influences on subsequent functioning. To address these gaps, 89 adults with chronic pain (68 women, 21 men) engaged in a baseline dot-probe task in which visual attention was tracked during injury-neutral (I-N) image pair presentations as well as a 6-month follow-up reassessing pain intensity and interference from pain. Neither RTs to probes after image pair offsets nor biases in initial orienting of gaze towards injury images predicted follow-up outcomes. However, participants who gazed at injury images for longer durations during I-N trials reported significantly more pain and interference at follow-up than did peers who gazed at injury images for less time, even after the impact of other significant baseline predictors had been controlled. In sum, results provided initial evidence for gaze biases reflecting prolonged vigilance towards pain-related information as a potential risk factor for relative elevations in pain and interference from chronic pain.
A randomized controlled trial testing a virtual perspective-taking intervention to reduce race and socioeconomic status disparities in pain care
imageWe conducted a randomized controlled trial of an individually tailored, virtual perspective-taking intervention to reduce race and socioeconomic status (SES) disparities in providers' pain treatment decisions. Physician residents and fellows (n = 436) were recruited from across the United States for this two-part online study. Providers first completed a bias assessment task in which they made treatment decisions for virtual patients with chronic pain who varied by race (black/white) and SES (low/high). Providers who demonstrated a treatment bias were randomized to the intervention or control group. The intervention consisted of personalized feedback about their bias, real-time dynamic interactions with virtual patients, and videos depicting how pain impacts the patients' lives. Treatment bias was re-assessed 1 week later. Compared with the control group, providers who received the tailored intervention had 85% lower odds of demonstrating a treatment bias against black patients and 76% lower odds of demonstrating a treatment bias against low SES patients at follow-up. Providers who received the intervention for racial bias also showed increased compassion for patients compared with providers in the control condition. Group differences did not emerge for provider comfort in treating patients. Results suggest an online intervention that is tailored to providers according to their individual treatment biases, delivers feedback about these biases, and provides opportunities for increased contact with black and low SES patients, can produce substantial changes in providers' treatment decisions, resulting in more equitable pain care. Future studies should examine how these effects translate to real-world patient care and the optimal timing/dose of the intervention.
Structural and functional alterations in the retrosplenial cortex following neuropathic pain
imageHuman and animal imaging studies demonstrated that chronic pain profoundly alters the structure and the functionality of several brain regions. In this article, we conducted a longitudinal and multimodal study to assess how chronic pain affects the brain. Using the spared nerve injury model which promotes both long-lasting mechanical and thermal allodynia/hyperalgesia but also pain-associated comorbidities, we showed that neuropathic pain deeply modified the intrinsic organization of the brain functional network 1 and 2 months after injury. We found that both functional metrics and connectivity of the part A of the retrosplenial granular cortex (RSgA) were significantly correlated with the development of neuropathic pain behaviours. In addition, we found that the functional RSgA connectivity to the subiculum and the prelimbic system are significantly increased in spared nerve injury animals and correlated with peripheral pain thresholds. These brain regions were previously linked to the development of comorbidities associated with neuropathic pain. Using a voxel-based morphometry approach, we showed that neuropathic pain induced a significant increase of the gray matter concentration within the RSgA, associated with a significant activation of both astrocytes and microglial cells. Together, functional and morphological imaging metrics of the RSgA could be used as a predictive biomarker of neuropathic pain.
The contribution of obesity to prescription opioid use in the United States
imageThe prevalence of obesity has grown rapidly over the past several decades and has been accompanied by an increase in the prevalence of chronic pain and prescription opioid use. Obesity, through its association with pain, may represent an important contributor to opioid use. This cross-sectional study investigated the relationship between obesity and prescription opioid use among adults aged 35 to 79 years using data from the National Health and Nutrition Examination Survey (NHANES, 2003-2016). Relative to normal weight, body mass indices in the overweight {odds ratio (OR), 1.11 (confidence interval [CI], 0.88-1.39)}, obese I (OR, 1.26 [CI, 1.01-1.57]), obese II (OR, 1.69 [CI, 1.34-2.12]), and obese III (OR, 2.33 [CI, 1.76-3.08]) categories were associated with elevated odds of prescription opioid use. The association between excess weight and opioid use was stronger for chronic opioid use than for use with a duration of less than 90 days (P-value, <0.001). We estimated that 14% (CI, 9%-19%) of prescription opioid use at the population level was attributable to obesity, suggesting there might have been 1.5 million fewer opioid users per year under the hypothetical scenario where obese individuals were instead nonobese (CI, 0.9-2.0 million users). Back pain, joint pain, and muscle/nerve pain accounted for the largest differences in self-reported reasons for prescription opioid use across obesity status. Although interpretation is limited by the cross-sectional nature of the associations, our findings suggest that the obesity epidemic may be partially responsible for the high prevalence of prescription opioid use in the United States.

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