Frontiers in pain research (Lausanne, Switzerland)最新文献

Objectives: We determined whether adding cannabis to oxycodone for chronic non-cancer pain management could reduce treatment-related adverse effects (AEs) while maintaining effective analgesia.

Methods: In this open-label study, fibromyalgia patients aged ≥18 years were randomized to receive 5 mg oxycodone tablets (max. four times/day), 150 mg of inhaled cannabis containing 6.3% Δ⁹-tetrahydrocannabinol and 8% cannabidiol (max. times inhalation sessions/day), or a combination of both for 6 weeks. The primary endpoint was treatment-related adverse events, assessed using a 10-point composite adverse event (cAE) score; additionally, we recorded daily reported pain relief and daily tablet and cannabis consumption.

Results: In total, 23 patients were treated with oxycodone, 29 with cannabis, and 29 with the oxycodone/cannabis combination. Three patients from the oxycodone group (13%) and 18 patients from the cannabis groups (31%, 9 in each group) withdrew from the trial within 2-3 weeks because of the severity of AEs. There were no differences in treatment-related cAE scores among the three groups that completed the study (p = 0.70). The analgesic responder rate showed a ≥1- point reduction in pain in 50% and a ≥2-point reduction in 20% of patients, while 50% of patients experienced no treatment benefit. The combination treatment reduced oxycodone tablet consumption by 35% (p = 0.02), but it did not affect the number of cannabis inhalation sessions.

Conclusions: Cannabis combined with oxycodone offered no advantage over either treatment alone, except for a reduction in opioid tablet intake; however, the overall drug load was the highest in the combination group. Moreover, cannabis was poorly tolerated and led to treatment discontinuation in one-third of participants treated with cannabis.

Clinical trial registration: The trial was registered at the WHO International Clinical Trials Registry Platform (trialsearch.who.int) on July 26, 2019, identifier NL7902.

Background: Sickle cell disease (SCD) disrupts oxygen transport due to the abnormal shape and rigidity of red blood cells, leading to hemolysis. Hemolysis, a major co-morbidity in SCD, is indicated by elevated levels of lactate dehydrogenase (LDH). Arginine depletion, which is essential for nitric oxide (NO) synthesis, contributes to various complications in SCD. L-arginine supplementation may increase NO levels and reduce oxidative stress. Research on its benefits in SCD, which is prevalent in sub-Saharan Africa, is limited. This study evaluates the effect of arginine supplementation on LDH levels in patients with steady state SCD.

Methods: In a retrospective study, we evaluated the effect of arginine supplementation on LDH levels in a cohort of 31 patients. We divided the study into three phases: pre-HU treatment, HU treatment, and combined HU and arginine supplementation.

Results: The cohort had a median age of 12 years, ranging from 2 to 43 years. Throughout all three phases of the study, lactate dehydrogenase (LDH) levels were consistently above the established normal ranges, with elevations of 216.7%, 220.3% and 176.6% above the normative values for baseline, Phase 1 (HU) and Phase 2 (HU + Arg), respectively. Specifically, LDH levels were 649.7 ± 364.2 U/L in Baseline Phase, 661.6 ± 367 U/L in Phase 1, and 529.9 ± 346.3 U/L in Phase 2. When comparing these discrete study intervals, it is noteworthy that LDH levels were significantly lower in Phase 2 compared to the previous phases (p = 0.002).

Conclusion: Preliminary findings revealed a significant lower LDH levels among sickle cell patients receiving combined arginine supplementation and hydroxyurea (HU). Although these findings are promising, their credibility and applicability require further and more extensive research.

Introduction: The new ICD-11 code for chronic pain indicates a direction to divide chronic pain into two categories: chronic secondary pain, which has a clear underlying disease, and chronic primary pain, which is associated with significant emotional distress or functional disability and cannot be explained by another chronic condition. Until now, epidemiological studies have been hampered by the lack of a clear classification, but we believe that this new code system will provide a new perspective on the diagnosis and treatment of chronic pain, and we have begun work on this code system.

Methods: We studied 2,360 patients at Aichi Medical University, the largest pain center in Japan, and asked them to answer questionnaires on pain severity (NRS), pain-related functional impairment (PDAS, Locomo25), quality of life (EQ-5D), and psychological state and pain cognition (HADS, PCS, PSEQ, AIS) while their attending physicians were giving diagnoses according to ICD-11 and the results of the study were used to determine the coding of pain severity.

Results and discussion: The ratio of primary to chronic secondary pain was almost 50%, and the group of patients with MG30.01 classification, which included fibromyalgia, had the highest severity among chronic primary pain. The MG30.01 classification of patients was also found to experience more severe pain compared to other classifications of chronic primary pain patients. The classification of patients with a major psychiatric component was not always clear, and some patients in the secondary category also had a clear psychiatric component, suggesting the need to develop complementary tools to support pain diagnosis.

While distinct, pain and stress share complex biological and psychological mechanisms that-despite their protective functions-can lead to clinically maladaptive changes requiring therapeutic intervention when they recur or persist. Recognized as "worldwide epidemics" of modern life, both conditions significantly affect an individual's quality of life, functioning, and well-being; without timely intervention, they can become chronic, leading to substantial economic costs via healthcare expenses, lost wages, and reduced productivity. Evidence suggests that pain and stress not only feed into but exacerbate each other through a "vicious cycle," driven by overlapping physiological, cognitive, and social mechanisms, indicating mutually reinforcing dynamics between pain and stress. In this review, we highlight the importance of recognizing the overlapping mechanisms that promote the persistence of pain and stress: (1) key physiological processes like maladaptive neuroplasticity, neuroendocrine dysfunction, and chronic inflammation; (2) cognitive and behavioral patterns such as fear avoidance, hypervigilance, and catastrophizing; along with (3) social, lifestyle, and environmental influences, such as socioeconomic status, lack of social support, and lifestyle choices. Through a case study, we illustrate the real-world implications of this vicious cycle perpetuating both conditions. We call for a paradigm shift in pain and stress management, advocating for a holistic management strategy encompassing pharmacological, psychological, and lifestyle interventions that address the underlying biopsychosocial factors. By fostering greater awareness among primary care practitioners and healthcare professionals, it is possible to better support individuals in breaking the cycle of pain and stress, thereby enhancing their quality of life and overall well-being.

Introduction: Shoulder pain is the third leading cause of musculoskeletal complaints in primary care clinics. Its prevalence varies from 14% to 34%. Among all the structures that can cause shoulder pain, the most vulnerable to injury is the tendon of the supraspinatus muscle. The ideal management protocol is still unknown. To date, little is known in the literature about the use of ultrasound-guided suprascapular nerve block as a treatment for supraspinatus muscle tendinitis. Our objective was to assess the effects of the association of a single ultrasound-guided suprascapular nerve block combined with home-based rotator cuff exercises to reduce pain and improve shoulder functioning in patients with supraspinatus tendinitis.

Methods: We evaluated the effect of a single ultrasound-guided suprascapular nerve block on pain and functioning of people with supraspinatus tendinitis. Diagnosis was performed using the positive Jobe test. Due to large disparity between clinical and radiological findings, only clinical diagnostic criteria were used to select patients. This was a double-blind, randomized, controlled, clinical study in which patients in the intervention group (n = 42) received a single injection of 5 ml of 2% lidocaine, while in the control group (n = 41) patients underwent the same procedure receiving saline solution 0.9%. All patients received face to face instructions by an experienced physiotherapist and a leaflet explaining home-based exercises. Pain and functioning were assessed using the Shoulder Pain and Disability Index (SPADI) questionnaire before the procedure, one week and 12 weeks after the procedure.

Results: Patients in both groups improved significantly since the initial evaluation until the 12th week. Intervention group SPADI (pre, 1 week, 12 weeks): 75.80 ± 18.96, 56.25 ± 31.37, 46.31 ± 31.41 (p < 0.001); Control group SPADI: 75.49 ± 16.67, 50.51 ± 27.58, 49.37 ± 30.90 (p < 0.001). However, there were no significant differences between groups (p = 0.291).

Discussion/conclusion: We concluded that both lidocaine and saline ultrasound-guided suprascapular nerve blocks reduce pain and improve shoulder functioning in patients with supraspinatus tendinitis. Unexpectedly, the same block performed with saline showed similar results and effects.

Clinical trial registration: ClinicalTrials.gov, identifier [NCT02495818].

Introduction: Chronic low back pain (CLBP) is the leading cause of disability in the United States and is associated with a steadily increasing burden of healthcare expenditures. Given this trend, it is essential to evaluate interventions aimed at reducing disability and optimizing healthcare utilization (HCU) in affected populations. This study investigates the impact of prior spinal surgery on functional outcomes and HCU patterns following high-frequency (10 kHz) spinal cord stimulation (SCS) therapy.

Methods: This retrospective observational study included 160 subjects who underwent implantation of a 10 kHz SCS device. Participants were divided into surgical and non-surgical cohorts for comparative analysis. Pain relief was assessed using the Numeric Rating Scale (NRS), while disability levels were evaluated using the Oswestry Disability Index (ODI). HCU was examined through the frequency of emergency department (ED) visits, outpatient visits for interventional pain procedures, and opioid consumption measured in morphine milliequivalents (MME).

Results: No statistically significant differences were observed between the surgical and non-surgical groups regarding pain relief and disability outcomes. Additionally, ED visits and outpatient visits for interventional pain procedures did not show significant differences between the two cohorts.

Discussion: This study represents the first comparative analysis of pain, disability, and HCU trends between surgical and non-surgical populations following 10 kHz SCS therapy. The results suggest that prior spinal surgery may not substantially affect the efficacy of 10 kHz SCS therapy in terms of pain relief, disability reduction, or HCU patterns.

Background: Peripherally inserted central catheter (PICC) are a necessary procedure for preterm newborns care. Despite the use of analgesic treatments, its insertion can be painful. Our objective was to study the effect of maternal voice on pain during PICC insertion.

Method: We conducted a pre post study for 2 years. Pain was compared between the two groups (with/without maternal presence) using a neonatal pain scale (FANS). Infection rate, procedure time, number of failures, mothers' anxiety and caregivers'anxiety were compared between the two groups.

Results: Ninety neonates were eligible. Finally, 63 neonates were included. Thirty-four placements were realized without maternal voice (first period) and 29 with maternal voice (second period). Mean FANS during PICC placement was lower in the maternal voice group than in the control group (1.15 ± 1.27 vs. 1.41 ± 1.49, p = 0.033). The FANS was also lower in the maternal voice group during the time of the first cutaneous effraction (p = 0.032). There was no significant difference between the two groups concerning the other outcomes.

Conclusion: Maternal voice added to conventional care decreased acute pain during PICC insertion without increasing infection rate, number of failures or procedure time.

Background: Identifying distinct mechanisms and biomarkers for painful diabetic peripheral neuropathy (DPN) is required for advancing the treatment of this major global unmet clinical need. We previously provided evidence in calf skin biopsies that disproportion between reduced sensory small nerve fibers and increased blood vessels may distinguish painful from non-painful DPN. We proposed that overexposure of the reduced nerve fibers in DPN to increased hypoxemia-induced vasculature and related algogenic factors, e.g., nerve growth factor (NGF), leads to neuropathic pain. To further investigate this proposed mechanism, we have now studied more proximal thigh skin biopsies, to see if the same disproportion between increased vasculature and decreased nerve fibers generally differentiates painful DPN from painless DPN.

Methods: A total of 28 subjects with type 2 diabetes (T2DM) and 13 healthy volunteers (HV) underwent detailed clinical and neurophysiological assessments, based on the neuropathy composite score of the lower limbs [NIS(LL)] plus 7 tests. T2DM subjects were subsequently divided into three groups: painful DPN (n = 15), painless DPN (n = 7), and no DPN (n = 6). All subjects underwent skin punch biopsy from the upper lateral thigh 20 cm below the anterior iliac spine.

Results: Skin biopsies showed decreased PGP 9.5-positive intraepidermal nerve fiber (IENF) density in both painful DPN (p < 0.0001) and painless DPN (p = 0.001). Vascular marker von Willebrand Factor (vWF) density was markedly increased in painful DPN vs. other groups, including painless DPN (p = 0.01). There was a resulting significant decrease in the ratio of intraepidermal nerve fiber density to vasculature and PGP9.5 to vWF, in painful DPN vs. painless DPN (p = 0.05). These results were similar in pattern to those observed in these HV and T2DM groups previously in distal calf biopsies; however, the increase in vWF was much higher and nerve fiber density much lower in the calf than thigh for painful DPN. Thigh skin vWF density was significantly correlated with several metabolic (waist/hip ratio, HbA1c), clinical (e.g., pain score), and neurophysiological measures.

Conclusion: This study supports our proposal that increased dermal vasculature, and its disproportionate ratio to reduced nociceptors, may help differentiate painful DPN from painless DPN. This disproportion is greater in the distal calf than the proximal thigh skin; hence, neuropathic pain in DPN is length-dependent and first localized to the distal lower limbs, mainly feet.

Study objective was to evaluate whether the application of a lip twitch could be proposed as conditioning stimulus in the context of a novel Conditioned Pain Modulation (CPM) assessment paradigm for use in horses. The study was a prospective, experimental, randomized trial. Twelve healthy horses were evaluated in two experimental sessions. The lip twitch was used as the conditioning stimulus in both sessions; electrical stimulation was used as the test stimulus in one session, while mechanical and thermal stimulations were used in the other. Differences between thresholds recorded before and during twitching (Δ) as well as their percent (%) change were computed for each stimulation modality as a measure of CPM. Heart rate and respiratory rate were recorded throughout the experiments to monitor physiological reactions, while the general level of stress and aversiveness toward twitching were scored using ad hoc behavioural scales. Based on these scores, interruption criteria were defined. Ten and seven horses completed the electrical and mechanical/thermal experimental sessions respectively. For electrical stimulation, median (IQR) Δ was -2.8 (-3.9, -1.1) mA and% change 87.9 (65.7-118.2)%; for mechanical stimulation, Δ was -18.2 (-6.4, -21.4) N and% change 343.5 (140, 365.3)%; for thermal stimulation, Δ was -3.1 (-9.2, -2.1)°C, while% change was not calculated. Heart rate and respiratory rates varied significantly over time, with higher values recorded during twitching. Median stress and aversion scores did not differ between the two sessions. As lip twitching consistently affected thresholds to all stimulation modalities, it can be proposed as effective conditioning method for CPM assessment in horses. The exclusion of subjects due to severe aversion shows that this paradigm cannot be indistinctively applied to all horses and that stringent interruption criteria are necessary to guarantee adequate welfare during testing.