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The exacerbation of a clinical condition or the occurrence of negative symptoms after an inert substance dispensation or a sham treatment is known as "nocebo effect." Nocebo is the psychobiological effect due to the negative psychosocial context that accompanies a therapy, and it is a direct consequence of negative expectations by the patients and their own personal characteristics. Although the clinical relevance of the phenomenon is now recognized, a small number of studies have tried to ascertain its neural underpinnings (that it means nocebo responses). Moreover, there is no consensus on the brain networks involved in nocebo processes in humans. In particular, nocebo hyperalgesia has attracted almost no research attention. We conducted a mini-review on the few experimental pain functional magnetic resonance imaging (fMRI) studies of nocebo responses to discuss how negative expectancies and conditioning effects engage brain networks to modulate pain experiences. Moreover, we present possible clinical implications considering Alzheimer's disease and behavioral frontotemporal dementia, in which the existence of a hypothetically disrupted neurocognitive anticipatory network-secondary to an endogenous pain modulatory system damage-may be responsible for pain processing alterations.
Learn More >Emerging evidence show that patients with chronic pancreatitis (CP) and abdominal pain have structural and functional alterations in the central nervous system. The aim was to investigate cerebral metabolic signatures in CP and the associations to various risk factors/clinical characteristics and patient outcomes.
Learn More >The primary objective of this systematic review was to identify the characteristics of physicians who prescribe opioids to adults with chronic pain. This review was limited to studies examining fully-trained physicians, as relevant characteristics of resident physicians and non-physician clinicians may differ. A comprehensive search of databases from January 1, 1980 to December 5, 2017 was conducted. Eligible study designs included (1) randomized trials; (2) nonrandomized prospective and retrospective studies; and (3) cross-sectional observational studies. The risk of bias in the included studies was assessed using an adapted version of the Newcastle-Ottawa Scale for cross-sectional studies. A total of 2508 records were screened and 22 studies met inclusion criteria. The majority of studies were cross-sectional (n=20) and the total number of participants was 8433. The risk of bias was high overall. The majority of physicians were confident managing and prescribing opioids for chronic pain but had high levels of dissatisfaction. Physicians reported high awareness of the potential for opioid misuse and were concerned about inadequate prior training in pain management. The majority of physicians were less likely to prescribe for patients with a history of substance abuse and reported major concerns about regulatory scrutiny. This systematic review provides the foundation for the development of prospective studies aimed at further elucidating the constellation of mechanisms that influence physicians who manage pain and prescribe opioids.
Learn More >Two-pore domain K (K) channels generate K leak current, which serves a vital role in controlling and modulating neuronal excitability. This diverse family of K channels exhibit distinct expression and function across neuronal tissues. TWIK-related spinal cord K channel (TRESK) is a K channel with a particularly enriched role in sensory neurons and pain pathways. Here, we explored the role of TRESK across molecularly distinct sensory neuron populations and assessed its contribution to different sensory modalities. We found TRESK mRNA only in select populations of C- and A-δ nociceptors, in addition to low threshold D-hair afferents. Neurons from mice in which TRESK has been ablated demonstrated marked hyperexcitability, which was amplified under inflammatory challenge. Detailed behavioral phenotyping of TRESK knockout mice revealed specific deficits in somatosensory processing of noxious and non-noxious stimuli. These results demonstrate novel roles of TRESK in somatosensory processing and offer important information to those wishing to target the channel for therapeutic means.
Learn More >CGRP has long been suspected as a mediator of arthritis pain, although evidence that CGRP directly mediates human musculoskeletal pain remains circumstantial. This chapter describes in depth the evidence surrounding CGRP's association with pain in musculoskeletal disorders and also summarises evidence for CGRP being a direct cause of pain in other conditions. CGRP-immunoreactive nerves are present in musculoskeletal tissues, and CGRP expression is altered in musculoskeletal pain. CGRP modulates musculoskeletal pain through actions both in the periphery and central nervous system. Human observational studies, research on animal arthritis models and the few reported randomised controlled trials in humans of treatments that target CGRP provide the context of CGRP as a possible pain biomarker or mediator in conditions other than migraine.
Learn More >Certain perceptual measures have been proposed as indirect assays of brain neurochemical status in people with migraine. One such measure is binocular rivalry, however, previous studies have not measured rivalry characteristics and brain neurochemistry together in people with migraine. This study compared spectroscopy-measured levels of GABA and Glx (glutamine and glutamate complex) in visual cortex between 16 people with migraine and 16 non-headache controls, and assessed whether the concentration of these neurochemicals explains, at least partially, inter-individual variability in binocular rivalry perceptual measures. Mean Glx level was significantly reduced in migraineurs relative to controls, whereas mean occipital GABA levels were similar between groups. Neither GABA levels, nor Glx levels correlated with rivalry percept duration. Our results thus suggest that the previously suggested relationship between rivalry percept duration and GABAergic inhibitory neurotransmitter concentration in visual cortex is not strong enough to enable rivalry percept duration to be reliably assumed to be a surrogate for GABA concentration, at least in the context of healthy individuals and those that experience migraine.
Learn More >The determinants and mechanisms contributing to diabetic sensorimotor polyneuropathy (DSPN) remain unclear. Since neuroinflammation and altered nerve regeneration have been implicated in the pathogenesis of both DSPN and neuropathic pain, we hypothesized that the corresponding biomarkers could be associated with DSPN in general and could have the potential to discriminate between the painful and painless DSPN entities.
Learn More >Reliable population-based data on the prevalence and characteristics of primary headache across the lifespan are essential. However, robust data are lacking. We utilized questionnaire data from a random general population sample in Germany, that comprised 2,478 participants aged ≥14 years. A standardized questionnaire addressing headache and headache treatment was filled in during the face-to-face survey. The 6-month prevalence of self-reported headache in the total sample amounted to 39.0% (known diagnosis of migraine 7.2%; tension-type headache 12.4%; another diagnosis or unknown diagnosis 23.4%). Age-specific prevalence rates were 37.9% (14-34 years), 44.6% (35-54 years), 38.5% (55-74 years), and 26.9% (≥75 years). Compared to age group 14-34, participants aged 35-54 were more ( = 1.29, 95%- 1.05-1.60, = 0.018) and those aged ≥75 were less ( = 0.55, 95%- 0.40-0.76, < 0.001) likely to have any headache. Of the participants with headache, 79.5% reported headache on <4 days per month, 15.6% on 4-14 days per month and 4.9% on >14 days per month. The frequency of headache did not differ significantly between age groups in men [ = 1.45, > 0.05], but in women [ = 21.57, < 0.001]: women aged ≥75 years were over-represented in the group reporting 4-14 headache days per month. The analgesic use (days per month) differed significantly between age groups among participants with headache on <4 days per month and on >14 days per month: 1.8 (14-34 years), 2.5 (35-54 years), 3.2 (55-74 years), and 3.4 (≥75 years), respectively 7.9 (14-34 years), 11.4 (35-54 years), 18.4 (55-74 years), and 22.8 (≥75 years). In general, the prevalence of headache decreases with age. However, older women suffer from more frequent attacks and older participants take analgesics on more days per month than younger participants. This might put them at risk of medication overuse which may lead to medication overuse headache. More research is needed to understand these specifics in headache frequency and treatment behavior in older people.
Learn More >The prevalence of neuropathic pain is estimated to be between 7 and 10% in the general population. The efficacy of intravenous (IV) lidocaine has been studied by numerous clinical trials on patients with neuropathic pain. The aim of this systematic review and meta-analysis was to evaluate the efficacy of IV lidocaine compared with a placebo for neuropathic pain and secondly to assess the safety of its administration. A literature search on PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), and Google scholar databases was performed for relevant studies published up to February 2019. Randomized controlled trials (RCTs) evaluating IV lidocaine treatment for pain relief in patients with neuropathic pain were included. 26 articles met the inclusion criteria. Patients with varied etiology of neuropathic pain were among the patient samples of these studies. Fifteen articles were included for quantitative analysis. Lidocaine was superior to a placebo in relieving neuropathic pain in the early post-infusion period [Mean Difference (MD) = -11.9; 95% Confidence interval (CI): -16.8 to -7; < 0.00001]. Multiple infusions of lidocaine over a period of 4 weeks, however, had no significant effect on reliving neuropathic pain (MD = -0.96; 95% CI: -2.02 to 0.11; = 0.08). IV lidocaine was also associated with a significant number of adverse events compared to a placebo [Odds Ratio (OR) = 7.75; 95% CI: 3.18-18.92; < 0.00001]. Our study indicates that while IV lidocaine is effective in pain control among patients with neuropathic pain in the immediate post-infusion period, it does not have a long-lasting, persistent effect. IV infusions of the drug are associated with an increased risk of side effects compared to a placebo. However, the risk of serious adverse events is negligible. Further, well-designed RCTs evaluating the effects of various dosages and infusion periods of IV lidocaine are required to provide clear guidelines on its clinical use.
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