Human Studies

Little is understood about differences in resting neural activity among those with spinal cord injury (SCI)-related neuropathic pain. The purpose of this pilot study was to determine resting cerebral blood flow differences in persons with SCI-related neuropathic pain compared to healthy, pain-free able-bodied controls. Five persons with paraplegia and ten able-bodied participants were included in this study. Resting blood flow, as measured by a continuous arterial spin labeling (ASL) method of fMRI, was analyzed via statistical parametric mapping. Persons with SCI-related neuropathic pain had significantly lower resting blood flow in the cerebellum (Crus I/II), rostral ventromedial medulla and left insular cortex. In contrast, greater resting blood flow occurred in the medial orbitofrontal cortex among those with SCI-related neuropathic pain compared to controls. Differences in resting blood flow were observed among those with SCI-related pain, particularly in regions that may be involved in affective-motivational and cognitive-evaluative aspects of pain. Larger ASL studies in addition to functional connectivity studies using fMRI are needed to clarify unique neural patterns in this complex and often intractable form of pain.

To quantify preferences for attributes of potential analgesic treatments for moderate-to-severe pain associated with osteoarthritis (OA) and/or chronic low back pain (CLBP) as relevant to injectable nerve growth factor (NGF)-inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids.

Offset analgesia (OA), a psychophysical test of endogenous pain inhibition, is diminished in many adult chronic pain disorders but OA has not been investigated in youth with chronic pain disorders. The present study assessed OA responses in 30 youth with chronic primary and secondary pain disorders and 32 healthy controls. The OA, control and constant thermal tests were evoked with an individualized noxious heat stimulus of approximately 50/100 mm on a visual analog scale followed by 1°C offset temperature. This study also examined the association of OA responses with two self-report measures of pain sensitivity, the Central Sensitization Inventory (CSI) and Pain Sensitivity Questionnaire (PSQ). Patients exhibited diminished capacity to activate OA with a reduction in ΔeVASc of 53 ± 29% vs. controls 74 ± 24% (P = 0.003) even after multivariate regression adjusting for age, sex and body mass index. Patients also showed decreased ability to habituate to a constant noxious heat stimulus compared to controls (P = 0.021). CSI scores showed excellent predictive accuracy in differentiating patients from controls (AUC= 0.95; 95% CI: 0.91, 0.99) and CSI score ≥ 30 was identified as an optimal cut-off value. PSQ scores did not differentiate patients from controls nor correlate with OA. In this study 60% of youth with chronic pain showed reduced capacity for endogenous pain inhibition.

The small-fiber polyneuropathies (SFN) are a class of diseases in which the small thin myelinated (Aδ) and/or unmyelinated (C) fibers within peripheral nerves malfunction and can degenerate. SFN usually begins in the farthest, most-vulnerable axons, so distal neuropathic pain and symptoms from microvascular dysregulation are common. It is well known in adults, e.g. from diabetes, human immunodeficiency virus, or neurotoxins, but considered extremely rare in children, linked mostly with pathogenic genetic variants in voltage-gated sodium channels. However, increasing evidence suggests that pediatric SFN is not rare, and that dysimmunity is the most common cause. Because most pediatric neurologists are unfamiliar with SFN, we report the diagnosis and management of 5 Swiss children, aged 6-11y, who presented with severe paroxysmal burning pain in the hands and feet temporarily relieved by cooling-the erythromelalgia presentation. Medical evaluations revealed autoimmune diseases in 3 families and 3/5 had preceding or concomitant infections. The standard diagnostic test (PGP9.5-immunolabeled lower-leg skin biopsy) confirmed SFN diagnoses in 3/4, and autonomic function testing (AFT) was abnormal in 2/3. Blood testing for etiology was unrevealing, including genetic testing in 3. Paracetamol and ibuprofen were ineffective. Two children responded to gabapentin plus mexiletine, one to carbamazepine, two to mexiletine plus immunotherapy (methylprednisolone/IVIg). All recovered within 6 months, remaining well for years. These monophasic tempos and therapeutic responses are most consistent with acute post-infectious immune-mediated causality akin to Guillain-Barré large-fiber polyneuropathy. Skin biopsy and AFT for SFN, neuropathic-pain medications and immunotherapy should be considered for acute sporadic pediatric erythromelalgia.

Secondary analysis of an observational cohort study.

Virtual reality (VR) is a promising tool for distraction analgesia. This study aims to compare brain perfusion patterns while patients were undergoing burn wound care in two conditions-VR distraction and control (NoVR).