European Journal of Pain最新文献

Background

In Europe, opioid use has surged, largely due to prescriptions for chronic non-malignant pain (CNMP). General practitioners (GPs) and community pharmacists (CPs) play a major role in opioid prescribing for non-malignant pain. Exploring their personal beliefs and practices might reveal underlying mechanisms to identify measures that could halt the further escalation of opioid use.

Methods

Guided by the health belief model, a survey was designed and distributed nationwide to examine the practices and beliefs of GPs and CPs in the domains: threats, benefits, barriers and self-efficacy. The results of GPs and CPs were compared at the statement level using chi-square analysis.

Results

Of 214 GPs and 212 CPs who completed the survey, the majority agreed that too many opioids are used in the treatment of chronic non-malignant pain (66.8% GPs and 66.5% CPs). Furthermore, they were concerned about the addictive potential of opioids (83.1% GPs and 71.7% CPs). In general, both professions have concerns about opioid use. GPs report a slightly higher degree of self-efficacy and perceive fewer benefits from opioids in treating CNMP. GPs and CPs valued the recommended measures to reduce opioid prescribing, yet less than half actively implement these strategies in their clinics.

Conclusion

GPs and CPs believe that opioids are being used too frequently to treat CNMP. However, both professions lack the actions to improve opioid-related care. GPs and CPs require education, collaboration and tools to implement guidelines on non-malignant pain and opioids.

Significance

This study, guided by the health belief model, reveals that general practitioners and community pharmacists have serious concerns about opioid use in chronic non-malignant pain. Despite shared concerns, both professions differ in their beliefs about opioid benefits and perceived self-efficacy. Both professions have in common that they value recommended measures to reduce opioid prescribing. Also, they both struggle to implement strategies, emphasizing the urgent need for education, collaboration and tools to align practices with guidelines on non-malignant pain and opioids.

Background

Migraine is a genetically determined disorder that predisposes to recurrent episodes of headache. Interleukin (IL)-18 is a pro-inflammatory cytokine that seems to play a role in migraine pathophysiology, and its genetic variants could potentially impact susceptibility to migraine.

Objective

To investigate the association between IL18 rs360717 and rs187238 genetic variants with migraine diagnosis and its clinical characteristics.

Methods

A case-control study was conducted with 152 people with migraine and 155 healthy controls, matched by sex, age, ethnicity, and body mass index. Clinical characteristics of migraine, as well as validated questionnaires regarding disability and impact of migraine, presence of allodynia, anxiety, depression, and hyperacusis were collected. Genotyping for IL18 rs360717 and rs187238 variants was performed using real-time polymerase chain reaction (qPCR) and TaqMan™ method.

Results

The IL18 rs360717A and rs187238G alleles were associated with increased chance of being diagnosed with migraine (OR = 1.53, 95%CI 1.05–2.24, p = 0.028 and OR = 1.46, 95%CI 1.00–2.14, p = 0.049, respectively). In the dominant model, the rs360717GA + AA genotypes were also associated with a higher chance of migraine than the GG genotype (OR = 1.69, 95%CI 1.05–2.73, p = 0.030). In women, in addition to the previous associations, there was also an effect of the variants on the chance of migraine in the codominant models and dominant models. Furthermore, among women, there was an influence on the prevalence of postdrome perception with rs360717GA + AA (OR = 3.04, 95%CI 1.10–8.42, p = 0.032) and rs187238CG + GG (OR = 2.97, 95%CI 1.08–8.21, p = 0.035).

Conclusion

IL18 rs360717 and rs187238 variants were associated with migraine diagnosis and postdrome symptoms, especially in women.

Significance

This study has demonstrated that IL18 rs360717 and rs187238 variants play a role in migraine, influencing the chance of being diagnosed with migraine, particularly among women. There are prospects that IL18 variants could be considered potential genetic biomarkers for migraine.

Background

The TRPV1 receptor is a key molecule in pain generation. Previous development of oral TRPV1-antagonists was halted due to systemic heat insensitivity and body temperature alterations. The present Phase 1b study investigated the efficacy, safety and plasma exposure of a topically administered TRPV1-antagonist (ACD440 Gel) in healthy subjects.

Methods

The study comprised two parts.

In part 1, 24 healthy subjects were included in this randomized double-blind, placebo-controlled, crossover trial. ACD440 Gel or Placebo was applied once daily and wiped off after 1 h, for 5 consecutive days. Assessments were done in normal skin, skin optimized for penetration (by stripping and occlusive gel application) and UVB-irradiated skin. Pain induced by thermo-nociceptive CO₂ laser impulses generated laser-evoked potentials (LEPs), with readouts of peak-to-peak (PtP) amplitude in vertex-EEG and pain assessments by VAS (0–100). Endpoints include effects at 1 hour post-dose, AUC(Days 1–5) and AUC_{(0–24, Day 4)}. In UVB-irradiated skin, also pain on pinprick and skin redness were assessed.

Part 2 explored the plasma pharmacokinetics of ACD440.

Results

ACD440 Gel reduced LEP PtP amplitude and VAS pain, p < 0.001, in all skin conditions, versus placebo. In UVB-irradiated skin, pinprick pain was also reduced, p = 0.047. Effects were significant after 1 h, maintaining for at least 9 h. There were no adverse events or drug-induced erythema. Plasma exposures of ACD440 were too low to establish an elimination half-life of ACD400.

Conclusions

Topical ACD440 Gel demonstrated a significant analgesic effect on LEP, VAS score and pinprick pain, with low systemic exposures, supporting further clinical development.

Significance

This study demonstrates that the topical administration of a TRPV1-antagonist, ACD440 Gel, has potential as a new treatment for painful conditions affecting the skin, such as chronic peripheral neuropathic pain, without any local or systemic side effects.

Background

Migraine is a common and burdensome neurological disorder. The causal relationship between sedentary behaviours (SBs) and migraine remains instinct. We aimed to evaluate the roles of SBs including watching TV, using computer and driving in the risk of migraine.

Methods

We conducted a univariable and multivariable Mendelian randomization (MR) study based on summary datasets of large genome-wide association studies. The inverse variance weighted method was utilized as the primary analytical tool. Cochran's Q, MR-Egger intercept test, MR pleiotropy residual sum and outlier and leave-one-out were conducted as sensitivity analysis. Additionally, we performed a meta-analysis to combine the causal estimates.

Results

In the discovery analysis, we identified causal associations between time spent watching TV and an increased risk of migraine (p = 0.015) and migraine without aura (MO) (p = 0.002). Such causalities with increasing risk of migraine (p = 0.005), and MO (p = 0.006) were further verified using summary datasets from another study in the replication analysis. There was no significant causal association found between time spent using computer, driving and migraine or its two subtypes. The meta-analysis and multivariable MR analysis also strongly supported the causal relationships between time spent watching TV and an increased risk of migraine (p = 0.0003 and p = 0.034), as well as MO (p < 0.0001 and p = 0.0004), respectively. These findings were robust under all sensitivity analysis.

Conclusions

Our study suggested that time spent watching TV may be causally associated with an increased risk of migraine, particularly MO. Large-scale and well-designed cohort studies may be warranted for further validation.

Significance Statement

This study represents the first attempt to investigate whether a causal relationship exists between SBs and migraine. Utilizing MR analysis helps mitigate reverse causation bias and confounding factors commonly encountered in observational cohorts, thereby enhancing the robustness of derived causal associations. Our MR analysis revealed that time spent watching TV may serve as a potential risk factor for migraine, particularly MO.