Human Studies

Over 50% of adolescents with chronic pain report comorbid sleep disturbances (e.g., difficulties with falling asleep), which is associated with increased pain-related disability and poorer quality of life. However, limited longitudinal data are available to understand how sleep disturbance may impact response to psychological treatment. Our primary hypothesis was that baseline sleep disturbances would significantly modify how adolescents responded to an internet-delivered psychological intervention for chronic pain in terms of outcome trajectories. The sample included 85 adolescents, 12 to 17 years, with chronic pain recruited from a multidisciplinary pain clinic and headache clinic who received access to an internet-delivered psychological intervention for chronic pain. Baseline sleep assessment included actigraphy monitoring for 7 days and survey measures. Outcomes were assessed at baseline, 8 weeks, and 3 months including core pain-related outcomes, executive functioning, fatigue, positive and negative affect. Results demonstrated that greater baseline insomnia and poorer sleep quality was associated with worse outcome trajectories for pain-related disability, depression, anxiety, fatigue, negative affect, and executive functioning. Findings extend the limited studies that examine how sleep disturbance may modify effectiveness of psychological treatments for adolescent chronic pain and emphasize the importance of treating comorbid sleep disturbance. This trial was registered at clinicaltrials.gov (NCT04043962). Perspective: Our study suggests that sleep deficiency, in particular insomnia and poor sleep quality, may modify the effectiveness of psychological treatments for chronic pain, highlighting the urgent need to screen youth for sleep problems prior to initiating treatment, and to consider implementation of sleep-specific treatments such as cognitive-behavioral therapy for insomnia.

Knee osteoarthritis (OA) is a disease of multiple phenotypes of which a chronic pain phenotype (PP) is known. Previous PP studies have focused on one domain of pain and included heterogenous variables. We sought to identify multidimensional PPs using the IMMPACT recommendations and their relationship to clinical outcomes.

Recent scientific evidence suggests a link between migraine and brain energy metabolism. In fact, migraine is frequently observed in mitochondrial disorders. We studied 46 patients affected by mitochondrial disorders, through a headache-focused semi-structured interview, to evaluate the prevalence of migraine among patients affected by mitochondrial disorders, the possible correlations between migraine and neuromuscular genotype or phenotype, comorbidities, lactate acid levels and brain magnetic resonance spectroscopy. We explored migraine-related disability, analgesic and prophylactic treatments. Diagnoses were achieved according to International Classification of Headache Disorders, 3rd edition. Lifetime prevalence of migraine was 61% (28/46), with high values in both sexes (68% in females, 52% in males) and higher than the values found in both the general population and previous literature. A maternal inheritance pattern was reported in 57% of cases. MIDAS and HIT6 scores revealed a mild migraine-related disability. The high prevalence of migraine across different neuromuscular phenotypes and genotypes suggests that migraine itself may be a common clinical manifestation of brain energy dysfunction. Our results provide new relevant indications in favour of migraine as the result of brain energy unbalance.

Neck pain and forward head posture (FHP) are typical in prolonged smartphone users and need to be targeted for treatment. We aimed to compare the effect of a routine therapeutic program with and without respiratory exercises on smartphone users with FHP and non-specific chronic neck pain (NSCNP). Sixty patients (aged 24.7 ± 2.1 years) with FHP and NSCNP were randomly assigned to the routine therapeutic program (n = 20), combined respiratory exercises with a routine therapeutic program (n = 20), or control (n = 20) groups. At baseline, there was no difference among groups at all variables. Each programme was implemented three times a week for eight weeks. Primary Outcome was pain measured by visual analogue scale (VAS), and secondary ones were forward head angle, the activity of specific muscles, and respiratory patterns, measured by photogrammetry, electromyography and manual, respectively. All outcomes were measured at baseline and eight weeks post-treatment. We used the repeated measures analysis of variance to examine the interaction between time and group, paired t-test for intragroup comparison, one-way analysis of variance for intergroup comparison, and Tukey post hoc test at a significant level 95% was used. There were significant differences in the combined group compared with the routine therapeutic group (P = 0.03) for diaphragm muscle activation, respiratory balance (P = 0.01), and the number of breaths (P = 0.02). There were significant within-group changes from baseline to post-treatment in the combined group for all outcomes above, but no changes in the therapeutic exercise routine group. Despite respiratory pattern, none of the secondary outcomes proved to be superior in the combination group compared to the routine therapeutic program in smartphone users with FHP and NSCNP. Future studies with longer follow-up assessments could strengthen these results.Trial registration: Current Controlled Trials using the IRCT website with ID number of, IRCT20200212046469N1 "Prospectively registered" at 04/03/2020.

With regard to attitudes towards pain, many questionnaires have been developed. Although undoubtedly useful, they were specifically designed for the use in chronic pain and are less suitable for the assessment in the general population. The purpose of the present paper was to develop a measure for the assessment of general attitudes towards pain applicable in the general population, regardless of clinical condition, and to test its psychometric properties.

Central neuropathic pain (CNP) is an excruciating condition, prevalent in up to a third of patients with multiple sclerosis (MS). Identifying CNP among MS patients is particularly challenging considering the ample comorbid chronic pain conditions and sensory disturbances entailed by the disease. The aim was to identify sensory features unique to CNP beyond those of chronic pain and MS.

Pain is a major symptom in adults with Fibrous dysplasia/McCune-Albright Syndrome (FD/MAS) and response to current treatments, including bisphosphonates and standard analgesics (NSAIDs and opiates) is unpredictable. No studies have explored whether the type of pain is variable in this patient group.

Throughout the somatosensory system, neuronal ensembles generate high-frequency signals in the range of several hundred Hertz in response to sensory input. High-frequency signals have been related to neuronal spiking, and could thus help clarify the functional architecture of sensory processing. Recording high-frequency signals from subcortical regions, however, has been limited to clinical pathology whose treatment allows for invasive recordings. Here, we demonstrate the feasibility to record 200-1200 Hz signals from the human spinal cord non-invasively, and in healthy individuals. Using standard electroencephalography equipment in a cervical electrode montage, we observed high-frequency signals between 200 and 1200 Hz in a time window between 8 and 16 ms after electric median nerve stimulation (n=15). These signals overlapped in latency, and, partly, in frequency, with signals obtained via invasive, epidural recordings from the spinal cord in a patient with neuropathic pain. Importantly, the observed high-frequency signals were dissociable from classic spinal evoked responses. A spatial filter that optimized the signal-to-noise ratio of high-frequency signals led to submaximal amplitudes of the evoked response, and vice versa, ruling out the possibility that high-frequency signals are merely a spectral representation of the evoked response. Furthermore, we observed spontaneous fluctuations in the amplitude of high-frequency signals over time, in the absence of any concurrent, systematic change to the evoked response. High-frequency, "spike-like" signals from the human spinal cord thus carry information that is complementary to the evoked response. The possibility to assess these signals non-invasively provides a novel window onto the neurophysiology of the human spinal cord, both in a context of top-down control over perception, as well as in pathology.

Adolescence is a sensitive period for both brain development and the emergence of chronic pain particularly in females. However, the brain mechanisms supporting pain perception during adolescence remain unclear. This study compares perceptual and brain responses to pain in female adolescents and adults to characterize pain processing in the developing brain. Thirty adolescent (ages 13-17 years) and 30 adult (ages 35-55 years) females underwent a functional magnetic resonance imaging scan involving acute pain. Participants received 12 ten-second noxious pressure stimuli that were applied to the left thumbnail at 2.5 and 4 kg/cm2, and rated pain intensity and unpleasantness on a visual analogue scale. We found a significant group-by-stimulus intensity interaction on pain ratings. Compared with adults, adolescents reported greater pain intensity and unpleasantness in response to 2.5 kg/cm2 but not 4 kg/cm2. Adolescents showed greater medial-lateral prefrontal cortex and supramarginal gyrus activation in response to 2.5 kg/cm2 and greater medial prefrontal cortex and rostral anterior cingulate responses to 4 kg/cm2. Adolescents showed greater pain-evoked responses in the neurologic pain signature and greater activation in the default mode and ventral attention networks. Also, the amygdala and associated regions played a stronger role in predicting pain intensity in adolescents, and activity in default mode and ventral attention regions more strongly mediated the relationship between stimulus intensity and pain ratings. This study provides first evidence of greater low-pain sensitivity and pain-evoked brain responses in female adolescents (vs adult women) in regions important for nociceptive, affective, and cognitive processing, which may be associated with differences in peripheral nociception.