Intra- and interindividual attack frequency variability of chronic cluster headache.

BACKGROUND: The lack of knowledge about the intra- and interindividual attack frequency variability in chronic cluster headache complicates power and sample size calculations for baseline periods of trials, and consensus on their most optimal duration. METHODS: We analyzed the 12-week baseline of the ICON trial (occipital nerve stimulation in medically intractable chronic cluster headache) for: (i) weekly vs. instantaneous recording of attack frequency; (ii) intra-individual and seasonal variability of attack frequency; and (iii) the smallest number of weeks to obtain a reliable estimate of baseline attack frequency. RESULTS: Weekly median (14.4 [8.2-24.0]) and instantaneous (14.2 [8.0-24.5]) attack frequency recordings were similar (p = 0.20; Bland-Altman plot). Median weekly attack frequency was 15.3 (range 4.2-140) and highest during spring (p = 0.001) compared to the other seasons. Relative attack frequency variability decreased with increasing attack frequency (p = 0.010). We tabulated the weekly attack frequency estimation accuracies compared to, and the associated deviations from, the 12-week gold standard for different lengths of the observation period. CONCLUSION: Weekly retrospective attack frequency recording is as good as instantaneous recording and more convenient. Attack frequency is highest in spring. Participants with ≥3 daily attacks show less attack frequency variability than those with <3 daily attacks. An optimal balance between 90% accuracy and feasibility is achieved at a baseline period of seven weeks.The ICON trial is registered in ClinicalTrials.gov under number NCT01151631.

Honorary authorship in high-impact journals in anaesthesia and pain medicine.

Enlisting an author on a published paper, whose input was insufficient, is called honorary authorship. The aim of this study is to assess the proportion of honorary authorship in the field of pain medicine. Data were collected from seven high-impact journals. Corresponding authors were sent a survey regarding their awareness on authorship guidelines, the decision-making in authorship and specific contributions made to the surveyed article. We identified two types of honorary authorship: (1) self-perceived honorary authorship, which is measured by asking the corresponding author if honorary authorship was present according to their opinion and (2) International Committee of Medical Journal Editors (ICMJE)-defined honorary authorship, which is honorary authorship based on the guidelines. In total, 1051 mails were sent and 231 responded, leading to a response rate of 22.0%. 81.3% of the respondents were familiar with the ICMJE authorship guidelines, while 59.6% were aware of the issue of honorary authorship. 13.3% of the respondents were employed at a department in which the senior member is automatically included on all manuscripts. The ICMJE-defined honorary authorship was 40%, while self-perceived honorary authorship was 13.5%. There seems to be a high awareness of the ICMJE guidelines among corresponding authors in the field of Pain Medicine. Despite this high awareness, a high proportion of journal articles had honorary authorship, suggesting that authorship guidelines fail to be applied in a significant proportion of the literature.

Cutaneous tactile allodynia associated with microvascular dysfunction in muscle.

BACKGROUND: Cutaneous tactile allodynia, or painful hypersensitivity to mechanical stimulation of the skin, is typically associated with neuropathic pain, although also present in chronic pain patients who do not have evidence of nerve injury. We examine whether deep tissue microvascular dysfunction, a feature common in chronic non-neuropathic pain, contributes to allodynia. RESULTS: Persistent cutaneous allodynia is produced in rats following a hind paw ischemia-reperfusion injury that induces microvascular dysfunction, including arterial vasospasms and capillary slow flow/no-reflow, in muscle. Microvascular dysfunction leads to persistent muscle ischemia, a reduction of intraepidermal nerve fibers, and allodynia correlated with muscle ischemia, but not with skin nerve loss. The affected hind paw muscle shows lipid peroxidation, an upregulation of nuclear factor kappa B, and enhanced pro-inflammatory cytokines, while allodynia is relieved by agents that inhibit these alterations. Allodynia is increased, along with hind paw muscle lactate, when these rats exercise, and is reduced by an acid sensing ion channel antagonist. CONCLUSION: Our results demonstrate how microvascular dysfunction and ischemia in muscle can play a critical role in the development of cutaneous allodynia, and encourage the study of how these mechanisms contribute to chronic pain. We anticipate that focus on the pain mechanisms associated with microvascular dysfunction in muscle will provide new effective treatments for chronic pain patients with cutaneous tactile allodynia.

Multiplex bead array assay for detection of 25 soluble cytokines in blister fluid of patients with complex regional pain syndrome type 1.

Inflammatory processes are known to be involved at least in the early phase of complex regional pain syndrome type 1 (CRPS1). Blister fluid obtained from the involved extremities displayed increased amounts of proinflammatory cytokines IL-6 and TNFalpha compared with the noninvolved extremities. The aim of this paper is to investigate the involvement of mediators by measurement of several other cytokines using new detection techniques that enable multiple cytokine measurement in small samples. The use of a multiplex-25 bead array cytokine assay and Luminex technology enabled simultaneous measurement of representative (1) proinflammatory cytokines such as GM-CSF, IL-1beta, IL-1RA, IL-6, IL-8, and TNF-alpha; (2) Th1/Th2 distinguishing cytokines IFN-gamma, IL-2, IL-2R, IL-4, IL-5, and IL-10; (3) nonspecific acting cytokines IFN-alpha, IL-7, IL-12p40/p70, IL-13, IL-15, and IL-17; and (4) chemokines eotaxin, IP-10, MCP-1, MIP-1alpha, MIP-1beta, MIG, and RANTES. Although minimal detection levels are significantly higher in the bead array system than those in common ELISA assays, in blister fluid, IL-1RA, IL-6, IL-8, TNF-alpha, IL-12p40/p70, MCP-1, and MIP-1beta were detectable and increased in CRPS1 affected extremities. Levels of IL-6 and TNF-alpha simultaneously measured by ELISA (Sanquin Compact kit) and by multiplex-25 bead array assay (Biosource) were highly correlated (r = 0.85, P < .001 for IL-6 and r = 0.88, P < .001 for TNF-alpha). Furthermore, IP-10 and eotaxin were detectable but diminished in CRPS1, whereas detectable amounts of IL-10 were similar in involved and noninvolved extremities. Multiplex bead array assays are useful systems to establish the involvement of cytokines in inflammatory processes by measurements in blister fluids of CRPS1. Ten representative cytokines were detectable. However, detection levels and amounts measured are at least 3 times higher in the multiplex-25 array assay than in the ELISA assays used simultaneously for the measurement of cytokines.