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Primary somatosensory cortex (S1) is involved in pain processing and thus its suppression using neuromodulatory techniques such as continuous theta burst stimulation (cTBS) might be a potential pain management strategy in patients with neuropathic pain. cTBS over S1 is known to elevate pain threshold in young adults. However, the time course of this after-effect is unknown. Furthermore, the effect of cTBS over S1 on pain threshold might be confounded by changes in the excitability of primary motor cortex (M1), an area known to be involved in pain processing, due to spread of current. Therefore, whether S1 plays a role in pain processing independent of M1 also remains unknown. The corticospinal excitability (CSE) can provide a measure of M1 excitability because cTBS over M1 is known to reduce CSE. Here, we studied the time-course of the effects of MRI-guided cTBS over S1 on electrical pain threshold and CSE. Ten healthy young adults received cTBS over S1 and sham stimulation in counterbalanced sessions at least 5 days apart. Electrical pain threshold (EPT) and CSE were recorded before and following cTBS over S1. We assessed each measure once before stimulation and then every 10 min starting immediately after stimulation until 40 min. cTBS over S1 elevated EPT compared to sham stimulation with the after-effect lasting for 40 min. We observed no change in CSE following cTBS and sham stimulation. Our findings suggest that cTBS over S1 can elevate EPT for 40 minutes without altering M1 excitability.
Learn More >To investigate prognostic factors for physical and emotional functioning following interdisciplinary multimodal pain rehabilitation, by targeting patients' baseline characteristics and health measures.
Learn More >Neck pain and headache are two of the most common complications of whiplash injury. Therefore, we performed a systematic literature search on PubMed and Embase for publications reporting on the prevalence of neck pain and headache following whiplash injury. The literature search identified 2,709 citations of which 44 contained relevant original data. Of these, 27 studies provided data for the quantitative analysis. For non-population-based studies, the present meta-analysis showed that a pooled relative frequency of neck pain was 84% CI (68-95%) and a pooled relative frequency of headache was 60% (46-73%), within 7 days following whiplash injury. At 12 months post-injury, 38% (32-45%) of patients with whiplash still experienced neck pain, while 38% (18-60%) of whiplash patients reported headache at the same time interval post-injury. However, we also found considerable heterogeneity among studies with I-values ranging from 89-98% for the aforementioned meta-analyses. We believe that the considerable heterogeneity among studies underscores the need for clear-cut definitions of whiplash injury and standardized reporting guidelines for post-whiplash sequelae such as neck pain and headache. Future studies should seek to optimize these aspects paving the way for a better understanding of the clinical characteristics and natural course of whiplash-associated sequelae.
Learn More >Chronic pruritus of unknown origin (CPUO) is defined as itching lasting more than 6 weeks in the absence of discernible skin lesions. Pregabalin is used to treat patients with CPUO. In this study, we aimed to investigate differences in the perception threshold of itch sensation between patients with CPUO and healthy individuals and to evaluate the efficacy of pregabalin for CPUO. At baseline, week 2, and week 4 after treatment initiation, the visual analogue scale (VAS) score was measured to assess pruritus severity, and electric current perception threshold (CPT) was measured at 250 and 5 Hz using a NEUROMETER CPT/C stimulator. Twenty healthy individuals and 41 patients with CPUO were enrolled in this study. The patients with CPUO were categorised as those who responded to antihistamines (Antihistamine group), were not improved by antihistamines (Pregabalin group), and were not improved by antihistamines and pregabalin (Refractory group). The baseline CPT values were not significantly different between patients with CPUO and healthy control. Pruritus was improved in 7 of 10 patients in the Pregabalin group after treatment with pregabalin, showing decreased CPT at 5 Hz. The sensitive C-fibres presented a high threshold to detect itch sensation, and this sensitivity decreased in response to treatment with pregabalin.
Learn More >Investigate the potential role of (mu-opioid receptor) and (catechol-O-methyltransferase enzyme) polymorphisms in postoperative acute, chronic and experimental thermal pain. A secondary analysis of 125 adult cardiac surgery patients that were randomized between fentanyl and remifentanil during surgery and genotyped. Patients in the fentanyl group with the high-pain sensitivity haplotype required less postoperative morphine compared with the average-pain sensitivity haplotype (19.4 [16.5; 23.0] vs 34.6 [26.2; 41.4]; p = 0.00768), but not to the low-pain sensitivity group (30.1 [19.1; 37.7]; p = 0.13). No association was found between haplotype and other pain outcomes or polymorphisms and the different pain modalities. haplotype appears to explain part of the variability in acute postoperative pain in adult cardiac surgery patients.
Learn More >Neurons are an integral component of the immune system that functions to coordinate responses to bacterial pathogens. Sensory nociceptive neurons that can detect bacterial pathogens are found throughout the body with dense innervation of the intestinal tract. Here we assessed the role of these nerves in the coordination of host defenses to Citrobacter rodentium. Selective ablation of nociceptive neurons significantly increased bacterial burden 10 days post infection and delayed pathogen clearance. Since the sensory neuropeptide CGRP regulates host-responses during infection of the skin, lung, and small intestine, we assessed the role of CGRP receptor signaling during C. rodentium infection. Although CGRP receptor blockade reduced certain pro-inflammatory gene expression, bacterial burden and Il-22 expression was unaffected. Our data highlight that sensory nociceptive neurons exert a significant host protective role during C. rodentium infection, independent of CGRP receptor signaling.
Learn More >Cortical spreading depression (CSD) is a wave of transient network hyperexcitability leading to long lasting depolarization and block of firing, which initiates focally and slowly propagates in the cerebral cortex. It causes migraine aura and it has been implicated in the generation of migraine headache. Cortical excitability can be modulated by cholinergic actions, leading in neocortical slices to the generation of rhythmic synchronous activities (UP/DOWN states). We investigated the effect of cholinergic activation with the cholinomimetic agonist carbachol on CSD triggered with 130 mM KCl pulse injections in acute mouse neocortical brain slices, hypothesizing that the cholinergic-induced increase of cortical network excitability during UP states could facilitate CSD. We observed instead an inhibitory effect of cholinergic activation on both initiation and propagation of CSD, through the action of muscarinic receptors. In fact, carbachol-induced CSD inhibition was blocked by atropine or by the preferential M1 muscarinic antagonist telenzepine; the preferential M1 muscarinic agonist McN-A-343 inhibited CSD similarly to carbachol, and its effect was blocked by telenzepine. Recordings of spontaneous excitatory and inhibitory post-synaptic currents in pyramidal neurons showed that McN-A-343 induced overall a decrease of the excitatory/inhibitory ratio. This inhibitory action may be targeted for novel pharmacological approaches in the treatment of migraine with muscarinic agonists.
Learn More >Race disparities in pain care are well-documented. Given that the majority of Black patients are treated by White providers, patient-provider racial discordance is one hypothesized contributor to these disparities. Research and theory suggest that providers' trait-level intergroup anxiety impacts their state-level comfort while treating patients, which, in turn, impacts their pain treatment decisions. To test these hypothesized relationships, we conducted a planned secondary analysis of data from a randomized controlled trial of a perspective-taking intervention to reduce pain treatment disparities. Mediation analyses were conducted on treatment decision data from White providers for Black virtual patients with chronic pain. Results indicated that White providers with higher trait-level intergroup anxiety reported lower state-level comfort treating Black patients and were thereby more likely to recommend opioid (indirect effect=0.76, 95% confidence interval [CI]: 0.21,1.51) and pain specialty (indirect effect=0.91, 95% CI: 0.26,1.78) treatments and less likely to recommend non-opioid analgesics (indirect effect=-0.45, 95% CI: -0.94,-0.12). Neither trait-level intergroup anxiety nor state-level comfort significantly influenced provider decisions for physical therapy. This study provides important new information about intra- and inter-personal contributors to race disparities in chronic pain care. These findings suggest that intergroup anxiety and the resulting situational discomfort encroach on the clinical decision-making process by influencing White providers' decisions about which pain treatments to recommend to Black patients. Should these findings be replicated in future studies, they would support interventions to help providers become more aware of their trait-level intergroup anxiety and manage their state-level reactions to patients who are racially/ethnically different from themselves.
Learn More >The attrition of novel analgesic drugs in the clinic can be attributed in the main to two factors: failure of preclinical research findings translating into human pain conditions, and a drop-off of efficacy between proof-of-concept (i.e., Phase II trials) and pivotal, confirmatory (Phase III trials) testing. In order to enhance the efficiency of the clinical drug evaluation process and determine rapidly whether a potential therapeutic candidate gives pain relief, by modulating central pain neurobiology, we propose a 'pre-proof-of-concept' approach, in which an efficacy assessment is performed in a single individual (N-of-1) using subjective clinical pain assessments supported by objective validated functional neuroimaging measures. Using an N-of-1 + i methodology, clinical- and neuroimaging-based metrics can be quantified under conditions of drug versus placebo or drug versus current standard of care conditions.
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