Human Studies

Functional tests are widely used to measure performance in patients with chronic musculoskeletal pain. Our objective was to determine the Minimal Clinically Important Differences (MCID) for the 6-min walk test (6MWT), the Steep Ramp Test (SRT), the 1-min stair climbing test (1MSCT), the sit-to-stand test (STS), the Jamar dynamometer test (JAM) and the lumbar Progressive Isoinertial Lifting Evaluation (PILE) in chronic musculoskeletal pain patients.

Prescription opioids are involved in 40% of all deaths from opioid overdose in the United States and are commonly the first opioids encountered by individuals with opioid use disorder. It is unclear whether the pharmaceutical industry marketing of opioids to physicians is associated with mortality from overdoses.

In light of growing concerns about opioid analgesics, developing new non-pharmacologic pain control techniques has become a high priority. Adjunctive virtual reality can help reduce acute pain during painful medical procedures. However, for some especially painful medical procedures such as burn wound cleaning, clinical researchers recommend that more distracting versions of virtual reality are needed, to further amplify the potency of virtual reality analgesia. The current study with healthy volunteers explores for the first time whether interacting with virtual objects in Virtual Reality (VR) via "hands free" eye-tracking technology integrated into the VR helmet makes VR more effective/powerful than non-interactive/passive VR (no eye-tracking) for reducing pain during brief thermal pain stimuli.

Chronic low back pain (CLBP) is characterized by an alteration in pain processing by the central nervous system that may affect autonomic nervous system (ANS) balance. Heart rate variability (HRV) reflects the balance of parasympathetic and sympathetic ANS activation. In particular, respiratory sinus arrhythmia (RSA) solely reflects parasympathetic input and is reduced in CLBP patients. Yet, it remains unknown if non-invasive brain stimulation can alter ANS balance in CLBP patients.

: Central neuropathic pain represents one of the most common symptoms in multiple sclerosis (MS) and it seriously affects quality of life. Spinal mechanisms may contribute to the pathogenesis of neuropathic pain in MS. Converging evidence from animal models and neurophysiological and clinical studies in humans suggests a potential effect of transcranial direct current stimulation (tc-DCS) on neuropathic pain. Spinal application of DCS, i.e., transcutaneous spinal DCS (ts-DCS), may modulate nociception through inhibition of spinal reflexes. Therefore, ts-DCS could represents an effective, safe and well-tolerated treatment for neuropathic pain in MS, a largely unexplored topic. This study is a pilot randomized double-blind sham-controlled trial to evaluate the efficacy of ts-DCS on central neuropathic pain in MS patients. : Thirty-three MS patients with central neuropathic pain were enrolled and randomly assigned to two groups in a double-blind sham-controlled design: anodal ts-DCS group ( = 19, 10 daily 20-min sessions, 2 mA) or sham ts-DCS group ( = 14, 10 daily 20-min sessions, 0 mA). The following clinical outcomes were evaluated before ts-DCS treatment (T0), after 10 days of treatment (T1) and 1 month after the end of treatment (T2): neuropathic pain symptoms inventory (NPSI), Ashworth Scale (AS) for spasticity and Fatigue Severity Scale (FSS). A subgroup of patients treated with anodal ts-DCS ( = 12) and sham ts-DCS ( = 11) also underwent a parallel neurophysiological study of the nociceptive withdrawal reflex (NWR) and the NWR temporal summation threshold (TST), two objective markers of pain processing at spinal level. : Anodal ts-DCS group showed a significant improvement in NPSI at T1, which persisted at T2, while we did not detect any significant change in AS and FSS. Sham ts-DCS group did not show any significant change in clinical scales. We observed a non-significant trend towards an inhibition of NWR responses in the anodal ts-DCS group at T1 and T2 when compared to baseline. : Anodal ts-DCS seems to have an early and persisting (i.e., 1 month after treatment) clinical efficacy on central neuropathic pain in MS patients, probably through modulation of spinal nociception. www.ClinicalTrials.gov, identifier #NCT02331654.

The mechanisms by which noninvasive vagal nerve stimulation (nVNS) affect central and peripheral neural circuits that subserve pain and autonomic physiology are not clear, and thus remain an area of intense investigation. Effects of nVNS vs sham stimulation on subject responses to five noxious thermal stimuli (applied to left lower extremity), were measured in 30 healthy subjects (n = 15 sham and n = 15 nVNS), with fMRI and physiological galvanic skin response (GSR). With repeated noxious thermal stimuli a group × time analysis showed a significantly (p < .001) decreased response with nVNS in bilateral primary and secondary somatosensory cortices (SI and SII), left dorsoposterior insular cortex, bilateral paracentral lobule, bilateral medial dorsal thalamus, right anterior cingulate cortex, and right orbitofrontal cortex. A group × time × GSR analysis showed a significantly decreased response in the nVNS group (p < .0005) bilaterally in SI, lower and mid medullary brainstem, and inferior occipital cortex. Finally, nVNS treatment showed decreased activity in pronociceptive brainstem nuclei (e.g. the reticular nucleus and rostral ventromedial medulla) and key autonomic integration nuclei (e.g. the rostroventrolateral medulla, nucleus ambiguous, and dorsal motor nucleus of the vagus nerve). In aggregate, noninvasive vagal nerve stimulation reduced the physiological response to noxious thermal stimuli and impacted neural circuits important for pain processing and autonomic output.

Chronic headache is one of the most common pain conditions, often leading to symptomatic drug overuse. The aim of this study was to provide data on symptomatic drug consumption in an Italian outpatient population and to describe how the clinical picture of headache may change after headache experts take charge of the care of affected individuals. A total of 199 adults complaining of chronic headache were recruited through 32 pharmacies in the Pavia health district. Participants underwent four evaluations: a baseline assessment (T0) and three follow-up evaluations performed by a neurologist at 3, 6, and 12 months (T3, T6, and T12, respectively). On each occasion, they underwent a complete neurological assessment and received therapeutic adjustments to achieve better management of their headache. On the basis of a preliminary telephone interview, the prevalence rates of chronic headache and medication overuse headache (MOH) were 16 and 12%, respectively. At 12 months of follow-up, we observed a significant decrease in the frequency of attacks (T0: 9 ± 9/month vs. T12: 2 ± 2/month; < 0.001), in the number of days/month with headache (T0: 11 ± 9 vs. T12: 4 ± 4; < 0.001) and in single attack duration (T0: 34 ± 30 h vs. T12: 10 ± 19 h; < 0.001). Careful headache management resulted in a significant decrease in analgesic consumption (T0: 12 ± 16 vs. T12: 4 ± 6 doses/month; = 0.014) and a significant increase in quality of life, measured using the Migraine Disability Assessment Scale (MIDAS) and Headache Under-Response to Treatment (HURT) scales ( < 0.001). Headache management by a specialist is more effective than self-treatment, resulting in an overall benefit for headache patients.