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Small-fiber neuropathy (SFN) has been traditionally considered as a pure disorder of peripheral nervous system, characterized by neuropathic pain and degeneration of small-diameter nerve fibers in the skin. Previous functional MRI studies revealed abnormal activations of pain networks, but the structural basis underlying such maladaptive functional alterations remains elusive. We applied diffusion tensor imaging (DTI) to explore the influences of SFN on brain microstructures. Forty-one pathology-proven SFN patients with reduced skin innervation were recruited. White matter connectivity with the thalamus as the seed was assessed using probabilistic tractography of DTI. SFN patients had reduced thalamic connectivity with the insular cortex and the sensorimotor areas including the postcentral and precentral gyri. Furthermore, the degree of skin nerve degeneration, measured by intraepidermal nerve fiber density (IENFd), was associated with the reduction of connectivity between the thalamus and pain-related areas according to different neuropathic pain phenotypes, specifically, the frontal, cingulate, motor, and limbic areas for burning, electrical shocks, tingling, mechanical allodynia, and numbness. Despite altered white matter connectivity, there was no change in white matter integrity assessed with fractional anisotropy. Our findings indicate that alterations in structural connectivity may serve as a biomarker of maladaptive brain plasticity that contributes to neuropathic pain after peripheral nerve degeneration.
Learn More >Dorsal root ganglion neurostimulation (DRG-S) is effective in treating various refractory chronic pain syndromes. In preclinical studies, DRG-S at very low frequencies (<5 Hz) reduces excitatory output in the superficial dorsal horn. Clinically, we have also observed the effectiveness of DRG-S at low frequencies. We conducted a case series to describe the effect of very low-frequency DRG-S stimulation on clinical outcomes.
Learn More >Trajectory studies suggest considerable stability of persistent or recurrent pain in adolescence. This points to the first decade of life as an important aetiologic window for shaping future pain, where the potential for prevention may be optimised.
Learn More >In the field of pain, virtual reality (VR) technology has been increasingly common in the context of procedural pain management. As an interactive technology tool, VR has the potential to be extended beyond acute pain management to chronic pain rehabilitation with a focus on increasing engagement with painful or avoided movements.
Learn More >Poorly controlled chronic pain can lead to non-prescription use of opiates, which is a growing crisis in our communities. Transcranial magnetic stimulation (TMS) is a non-invasive therapeutic tool which has emerged as a potential treatment option for these patients. It is still unclear, however, if the dorsolateral prefrontal cortex (DLPFC) or the motor cortex (MC) is a more effective treatment location. The purpose of this study was to directly compare the effects of DLPFC versus MC TMS on pain severity and the urge to use opiates among chronic pain patients.
Learn More >Disturbed sleep and use of opioid pain medication are common among individuals with chronic pain. Anecdotally, opioids are thought to promote sleep by relieving pain. This study aimed to determine whether opioid use is associated with daily sleep parameters (and vice versa) among adults with comorbid symptoms of insomnia and fibromyalgia.
Learn More >Cluster headache is characterized by recurrent, unilateral attacks of excruciating pain associated with ipsilateral cranial autonomic symptoms. Although a wide array of clinical, anatomical, physiological, and genetic data have informed multiple theories about the underlying pathophysiology, the lack of a comprehensive mechanistic understanding has inhibited, on the one hand, the development of new treatments and, on the other, the identification of features predictive of response to established ones. The first-line drug, verapamil, is found to be effective in only half of all patients, and after several weeks of dose escalation, rendering therapeutic selection both uncertain and slow. Here we use high-dimensional modelling of routinely acquired phenotypic and MRI data to quantify the predictability of verapamil responsiveness and to illuminate its neural dependants, across a cohort of 708 patients evaluated for cluster headache at the National Hospital for Neurology and Neurosurgery between 2007 and 2017. We derive a succinct latent representation of cluster headache from non-linear dimensionality reduction of structured clinical features, revealing novel phenotypic clusters. In a subset of patients, we show that individually predictive models based on gradient boosting machines can predict verapamil responsiveness from clinical (410 patients) and imaging (194 patients) features. Models combining clinical and imaging data establish the first benchmark for predicting verapamil responsiveness, with an area under the receiver operating characteristic curve of 0.689 on cross-validation (95% confidence interval: 0.651 to 0.710) and 0.621 on held-out data. In the imaged patients, voxel-based morphometry revealed a grey matter cluster in lobule VI of the cerebellum (-4, -66, -20) exhibiting enhanced grey matter concentrations in verapamil non-responders compared with responders (familywise error-corrected P = 0.008, 29 voxels). We propose a mechanism for the therapeutic effect of verapamil that draws on the neuroanatomy and neurochemistry of the identified region. Our results reveal previously unrecognized high-dimensional structure within the phenotypic landscape of cluster headache that enables prediction of treatment response with modest fidelity. An analogous approach applied to larger, globally representative datasets could facilitate data-driven redefinition of diagnostic criteria and stronger, more generalizable predictive models of treatment responsiveness.
Learn More >Recurrent pain is a common experience in childhood and adolescence and can result in significant disability in youth, including poor quality of life, school absences, and reduced social activities. Evidence has linked adolescent risk and resilience factors with treatment outcomes. However, less research has focused on examining risk and resilience factors that may influence or predict adolescents' compliance to treatment within an interdisciplinary pediatric chronic pain management program. Participants included 64 adolescents ( = 15.00 ± 1.69 years); 85.9% female, 84.4% Caucasian who presented to an initial evaluation in an interdisciplinary pediatric pain management program with their caregiver. Youth completed a series of questionnaires at the initial evaluation targeting pain acceptance, self-efficacy, pain catastrophizing, parental responses, pain intensity, and functional disability. Treatment compliance was measured at 3 and 6 months post-intake. Findings indicated that higher levels of adolescent-reported self-efficacy predict decreased treatment session attendance, whereas lower levels of acceptance and parental encouragement/monitoring of symptoms predict increased treatment compliance overall. Several adolescent-reported risk factors were associated with increased functional impairment among this sample. Results highlight the unique importance of risk and resilience factors within the developmental context of adolescence, while also emphasizing the need for further investigation of other relevant influences towards treatment compliance and functional impairment.
Learn More >Among youth with chronic non-cancer pain, 50% have parents with chronic pain. These youth report significantly more pain interference and posttraumatic stress symptoms (PTSS), and worse health-related quality of life (HRQL) than youth whose parents do not have chronic pain. Additionally, parent chronic pain is linked to increased child anxiety and depressive symptoms. Survivors of childhood cancer (SCCs) are at risk of pain and negative psychosocial outcomes and therefore may be especially vulnerable if their parents have chronic pain. Thus, the aims of the current study were to (1) identify rates of chronic pain among parents of SCCs, (2) test group differences in psychological symptoms in parents with chronic pain versus without, and (3) test group differences in pain interference, HRQL, anxiety, depression, and PTSS in SCCs with parents with chronic pain versus without.
Learn More >Low intensity, high-frequency transcranial alternating current stimulation (tACS) applied over the motor cortex decreases the amplitude of motor evoked potentials. This double-blind, placebo-controlled parallel group study aimed to test the efficacy of this method for acute management of migraines. The patients received either active (0.4 mA, 140 Hz) or sham stimulation for 15 min over the visual cortex with the number of terminated attacks two hours post-stimulation as the primary endpoint, as a home therapy option. They were advised to treat a maximum of five migraine attacks over the course of six weeks. From forty patients, twenty-five completed the study, sixteen in the active and nine in the sham group with a total of 102 treated migraine attacks. The percentage of terminated migraine attacks not requiring acute rescue medication was significantly higher in the active (21.5%) than in the sham group (0%), and the perceived pain after active stimulation was significantly less for 2-4 h post-stimulation than after sham stimulation. tACS over the visual cortex has the potential to terminate migraine attacks. Nevertheless, the high drop-out rate due to compliance problems suggests that this method is impeded by its complexity and time-consuming setup.
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