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Pain in sickle cell disease (SCD) is severe, variable, and inadequately comprehended. The β2-adrenergic receptor () is critical in mediating neurotransmitter response in the sympathetic nervous system. In this association study, we examined 16 single nucleotide polymorphisms (SNPs) covering 5'-UTR and coding regions of for pain variability in SCD. Subjects recorded their non-crisis, baseline pain experience on a computerized tool from which we obtained chronic pain measurement score- composite pain index (CPI). Regression models yielded significant associations between chronic pain and seven SNPs. Non-synonymous SNP rs1042713 A allele (Arg16) caused a 5.73-fold decrease in CPI ( = 0.002). Allele A of rs12654778 and T of rs17778257 reduced CPI by a fold of 4.52 ( = 0.019), and 4.39 ( = 0.032), respectively. Whereas, in the 5' UTR, allele C of rs1042711, G of rs11168070, C of rs11959427, and C of rs1801704 increased CPI by a fold of 10.86 ( = 0.00049), 5.99 ( = 0.016), 5.69 ( = 0.023), and 5.26 ( = 0.031), respectively. Together, these SNPs accounted for 2-15% of CPI variance after adjusting for covariates. Moreover, these SNPs were in high linkage disequilibrium (LD) showing three LD blocks in our cohort. A 10-marker haplotype increased CPI by 11.5-fold ( = 0.000407). Thus, polymorphisms might contribute to chronic pain severity and heterogeneity in SCD.
Learn More >Placebo effects benefit a wide range of clinical practice, which can be profoundly influenced by expectancy level and personal characteristics. However, research on the issue of whether these factors independently or interdependently affect the placebo effects is still in its infancy. Here, we adopted a 3-day between-subject placebo analgesia paradigm (2-day conditioning and 1-day test) to investigate the influence of expectancy levels (i.e., No, Low, and High) and personal characteristics (i.e., gender, dispositional optimism, and anxiety state) on placebo effects in 120 healthy participants (60 females). Our results showed that the reduction of pain intensity in the test phase was influenced by the interaction between expectancy and gender, as mainly reflected by greater reductions of pain intensity in females at Low expectancy level than females at No/High expectancy levels, and greater reductions of pain intensity in males than in females at High expectancy level. Additionally, the reduction of pain unpleasantness was not only modulated by the interaction between expectancy and gender, but also by the interaction between expectancy and dispositional optimism, as well as the interaction between expectancy and anxiety state. Specifically, participants who were more optimistic in Low expectancy group, or those who were less anxious in High expectancy group showed greater reductions of pain unpleasantness. To sum up, we emphasized on regulating the expectancy level individually based on the assessment of personal characteristics to maximize placebo effects in clinical conditions.
Learn More >Spinal cord stimulation (SCS) relieves pain by delivering doses of electric current to the dorsal column of the spinal cord and has been found to be most effective in the treatment of neuropathic pain. Psychological distress is a significant risk factor for the development of chronic pain and has been found to affect the outcome of SCS. Childhood trauma is a risk factor for chronic pain, but has not previously been studied in SCS patients.
Learn More >At our center in the Netherlands, patients, who very often are treatment resistant to the analgesics recommended in the guidelines, suffering from symmetrical peripheral neuropathic pain are treated exclusively. We have developed a number of compounded topical formulations containing classical co-analgesics such as ketamine, baclofen, amitriptyline, and phenytoin for the treatment of neuropathic pain in treatment-resistant patients. In order to identify putative responders and exclude an (initial) placebo-response, we developed single-blind and double-blind placebo-controlled response tests. The test can be performed when the patient has a symmetrical polyneuropathy with a pain score difference of not more than 1 point on the 11-point numerical rating scale (NRS) between bilateral pain areas. On one area (eg, left foot) the placebo cream and on the other area (eg, right foot) the active cream will be applied. Within a time frame of 30 minutes, patients are considered responders if they rate a pain difference of at least 2 points on the NRS between the bilateral areas on which the active cream and placebo cream are applied. Response tests can be easily conducted during the first consultation. In this paper, we explore the ethical context of using a placebo in clinical practice in a single-blind and double-blind fashion to improve and individualize treatment of neuropathic pain outside a context of a formal clinical trial.
Learn More >The posterior insula (pIns) is a major brain region that receives itch-related signals from the periphery and transfers these signals to broad areas in the brain. Previous brain imaging studies have successfully identified brain regions that respond to itch stimuli. However, it is still unknown which brain regions receive and process itch-related signals from the pIns. Addressing this question is important in identifying key functional networks that process itch. Thus, the present study investigated brain regions with significantly increased functional connectivity with the pIns during itch stimuli with 25 healthy subjects by using functional MRI. Electrical itch stimuli was applied to the left wrist. Similar to previous brain imaging studies, many cortical and subcortical areas were activated by itch stimuli. However, not all of these regions showed significant increments of functional connectivity with the pIns during itch stimuli. While the subjects perceived the itch sensation, functional connectivity was significantly increased between the right pIns and the supplementary motor area (SMA), pre-SMA, anterior midcingulate cortex (aMCC), anterior insula (aIns), secondary somatosensory cortex (SII), and basal ganglia (BG), suggesting that this is a key network in processing itch. In particular, intensity of functional connectivity between the pIns and BG was negatively correlated with itch rating. The functional pIns-BG pathway may play an important role in regulation of subjective itch sensation. This study first identified a key brain network to process itch.
Learn More >Amputation of a sensory peripheral nerve induces severe anatomical and functional changes along the afferent pathway as well as perception alterations and neuropathic pain. In previous studies we showed that electrical stimulation applied to a transected infraorbital nerve protects the somatosensory cortex from the above-mentioned sensory deprivation-related changes. In the present study we focus on the initial tract of the somatosensory pathway and we investigate the way weak electrical stimulation modulates the neuroprotective-neuroregenerative and functional processes of trigeminal ganglia primary sensory neurons by studying the expression of neurotrophins (NTFs) and Glia-Derived Neurotrophic Factors (GDNFs) receptors. Neurostimulation was applied to the proximal stump of a transected left infraorbitary nerve using a neuroprosthetic micro-device 12 h/day for 4 weeks in freely behaving rats. Neurons were studied by hybridization and immunohistochemistry against RET (proto-oncogene tyrosine kinase "rearranged during transfection"), tropomyosin-related kinases (TrkA, TrkB, TrkC) receptors and IB4 (Isolectin B4 from Griffonia simplicifolia). Intra-group (left vs. right ganglia) and inter-group comparisons (between Control, Axotomization and Stimulation-after-axotomization groups) were performed using the mean percentage change of the number of positive cells per section [100(left-right)/right)]. Intra-group differences were studied by paired -tests. For inter-group comparisons ANOVA test followed by LSD test (when < 0.05) were used. Significance level (α) was set to 0.05 in all cases. Results showed that (i) neurostimulation has heterogeneous effects on primary nociceptive and mechanoceptive/proprioceptive neurons; (ii) neurostimulation affects RET-expressing small and large neurons which include thermo-nociceptors and mechanoceptors, as well as on the IB4- and TrkB-positive populations, which mainly correspond to non-peptidergic thermo-nociceptive cells and mechanoceptors respectively. Our results suggest (i) electrical stimulation differentially affects modality-specific primary sensory neurons (ii) artificial input mainly acts on specific nociceptive and mechanoceptive neurons (iii) neuroprosthetic stimulation could be used to modulate peripheral nerve injuries-induced neuropathic pain. These could have important functional implications in both, the design of effective clinical neurostimulation-based protocols and the development of neuroprosthetic devices, controlling primary sensory neurons through selective neurostimulation.
Learn More >Chiropractic maintenance care is effective as secondary/tertiary prevention of non-specific low back pain (LBP), but the potential effect moderation by psychological characteristics is unknown. The objective was to investigate whether patients in specific psychological sub-groups had different responses to MC with regard to the total number of days with bothersome pain and the number of treatments.
Learn More >The local infectious origin and the putative role of Cutibacterium acnes (CA) of a particular subtype of discopathy (Modic 1) are still debated.
Learn More >Exercise can be used as a treatment for depressive symptoms in the general population. However, little is known as to whether exercise has mental health benefits for adults experiencing chronic low back pain (CLBP). The aim of this study was to examine the feasibility of two intervention protocols commonly used in clinical practice for treating chronic low back pain, but with differing exercise dose, on depressive symptoms.
Learn More >Compression of myofascial trigger points (MTrPs) in muscles is reported to reduce chronic musculoskeletal pain. Although the prefrontal cortex (PFC) is implicated in development of chronic pain, the mechanisms of how MTrP compression at low back regions affects PFC activity remain under debate. In this study, we investigated effects of MTrP compression on brain hemodynamics and EEG oscillation in subjects with chronic low back pain.
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