Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study

Aims and methods: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. Results: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57-1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82-1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. Conclusions: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf

Phantom headache: pain-memory-emotion hypothesis for chronic daily headache?

The neurobiology of chronic pain, including chronic daily headache (CDH) is not completely understood. “Pain memory” hypothesis is one of the mechanisms for phantom limb pain. We reviewed the literature to delineate a relation of “pain memory” for the development of CDH. There is a direct relation of pain to memory. Patients with poor memory have less chance to develop “pain memory”, hence less possibility to develop chronic pain. Progressive memory impairment may lead to decline in headache prevalence. A similar relation of pain is also noted with emotional or psychiatric symptoms. Literature review suggests that there is marked overlap in the neural network of pain to that of memory and emotions. We speculate that pain, memory, and emotions are interrelated in triangular pattern, and each of these three is related to other two in bidirectional pattern, i.e., stimulation of one of these will stimulate other symptoms/networks and vice versa (triangular theory for chronic pain). Longstanding or recurrent noxious stimuli will strengthen this interrelation, and this may be responsible for chronicity of pain. Reduction of both chronic pain and psychological symptoms by cognitive behavioral therapy or psychological interventions further suggests a bidirectional interrelation between pain and emotion. Longitudinal studies are warranted on the prevalence of headache and other painful conditions in patients with progressive memory impairment to delineate the relation of pain to memory. Interrelation of headache to emotional symptoms should also be explored

Lysergic acid diethylamide (LSD) and Psilocybin for the Management of Patients with Persistent Pain: A Potential Role?

Recently, there has been interest in lysergic acid diethylamide (LSD) and psilocybin for depression, anxiety and fear of death in terminal illness. The aim of this review is to discuss the potential use of LSD and psilocybin for patients with persistent pain. LSD and psilocybin are 5-hydroxytryptamine receptor agonists and may interact with nociceptive and antinociceptive processing. Tentative evidence from a systematic review suggests that LSD (7 studies, 323 participants) and psilocybin (3 studies, 92 participants) may be beneficial for depression and anxiety associated with distress in life-threatening diseases. LSD and psilocybin are generally safe if administered by a healthcare professional, although further investigations are needed to assess their utility for patients with persistent pain, especially associated with terminal illnes

Angiotensin-converting enzyme gene insertion/deletion polymorphism in migraine patients

<p>Abstract</p> <p>Background</p> <p>The main objective of this study was to investigate the angiotensin converting enzyme (<it>ACE</it>) genotype as a possible risk factor for migraine (both with and without aura) compared to controls. We also wanted to examine whether a clinical response to an ACE inhibitor, lisinopril, or an angiotensin II receptor blocker, candesartan, in migraine prophylaxis was related to <it>ACE </it>genotype.</p> <p>Methods</p> <p>347 migraine patients aged 18–68 (155 migraine without aura (MoA), 187 migraine with aura (MwA) and 5 missing aura subgroup data) and 403 healthy non-migrainous controls > 40 years of age were included in the study. A polymerase chain reaction (PCR) was performed on the genomic DNA samples to obtain the <it>ACE </it>insertion (I)/deletion(D) polymorphisms.</p> <p>Results</p> <p>No significant differences between migraine patients and controls were found with regard to <it>ACE </it>genotype and allele distributions. Furthermore, there was no significant difference between the controls and the MwA or MoA subgroups.</p> <p>Conclusion</p> <p>In our sample there is no association between <it>ACE </it>genotype or allele frequency and migraine. In addition, <it>ACE </it>genotype in our experience did not predict the clinical response to lisinopril or candesartan used as migraine prophylactics.</p

Gender differences in sex life issues – A population-based study of migraine sufferers

<p>Abstract</p> <p>Background</p> <p>Migraine is considered to have a negative influence on sex life. The present study was to analyse the perceptions of importance of and satisfaction with sex life as well as the expression of interest in sex among people having migraines in a prospective follow-up mail survey in 1998 and 2003.</p> <p>Methods</p> <p>The random sample was stratified according to gender and age in four age groups (20–24, 30–34, 40–44, and 50–54 years). Altogether 25 898 individuals responded to the baseline and 19 626 to the follow-up questionnaire (75.8% response rate). We examined as to how the perceptions of sex life of those suffering from migraine changed during a 5-year follow-up. Conditional logistic regression was used to analyse the data of the responses on self-reported migraine in the baseline and follow-up surveys (N = 2 977, 79.2% women). Each person with migraine was assigned a gender- and age-matched control in the analysis.</p> <p>Results</p> <p>All three outcome variables tended to decrease in value. Importance of sex life was higher among men with migraine than among their controls. Among women migraine lessened interest in sex life.</p> <p>Conclusion</p> <p>Our findings suggested that migraine has a different impact on sex life among women from that among men.</p

Sleep duration, vital exhaustion and perceived stress among pregnant migraineurs and non-migraineurs

<p>Abstract</p> <p>Background</p> <p>Migraine has been associated with sleep disorders in men and non-pregnant women, but little is known about sleep complaints among pregnant migraineurs.</p> <p>Methods</p> <p>A cohort of 1,334 women was interviewed during early pregnancy. At the time of interview we ascertained participants' migraine diagnosis status and collected information about sleep duration before and during early pregnancy, daytime sleepiness, vital exhaustion and perceived stress during early pregnancy. Multivariable logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of short/long sleep duration, excessive daytime sleepiness, vital exhaustion and elevated perceived stress associated with a history of migraine.</p> <p>Results</p> <p>Approximately 19.4% of the cohort (n = 259) reported having a medical diagnosis of migraine prior to the study pregnancy. Compared with women without migraine, the multivariable-adjusted ORs (95% CI) among migraineurs for short sleep duration before and during early pregnancy were 1.51 (1.09-2.09), and 1.57 (1.11-2.23), respectively. The corresponding OR (95% CI) for long sleep duration before and during pregnancy were 1.33 (0.77-2.31) and 1.31 (0.94-1.83), respectively. A modest and statistically insignificant association between migraine history and excessive daytime sleepiness in early pregnancy was noted (OR = 1.46; 95% CI 0.94-2.26). Migraineurs had an increased risk of vital exhaustion (OR = 2.04; 95% CI 1.52-2.76) and elevated perceived stress (OR = 1.57; 95% CI 1.06-2.31). Observed associations were more pronounced among overweight migraineurs.</p> <p>Conclusions</p> <p>These data support earlier research documenting increased risks of sleep disorders among migraineurs; and extends the literature to include pregnant women. Prospective studies are needed to more thoroughly explore factors that mediate the apparent migraine-sleep comorbidity among pregnant women.</p

Role of Mitochondrial Electron Transport Chain Complexes in Capsaicin Mediated Oxidative Stress Leading to Apoptosis in Pancreatic Cancer Cells

We evaluated the mechanism of capsaicin-mediated ROS generation in pancreatic cancer cells. The generation of ROS was about 4–6 fold more as compared to control and as early as 1 h after capsaicin treatment in BxPC-3 and AsPC-1 cells but not in normal HPDE-6 cells. The generation of ROS was inhibited by catalase and EUK-134. To delineate the mechanism of ROS generation, enzymatic activities of mitochondrial complex-I and complex-III were determined in the pure mitochondria. Our results shows that capsaicin inhibits about 2.5–9% and 5–20% of complex-I activity and 8–75% of complex-III activity in BxPC-3 and AsPC-1 cells respectively, which was attenuable by SOD, catalase and EUK-134. On the other hand, capsaicin treatment failed to inhibit complex-I or complex-III activities in normal HPDE-6 cells. The ATP levels were drastically suppressed by capsaicin treatment in both BxPC-3 and AsPC-1 cells and attenuated by catalase or EUK-134. Oxidation of mitochondria-specific cardiolipin was substantially higher in capsaicin treated cells. BxPC-3 derived ρ0 cells, which lack mitochondrial DNA, were completely resistant to capsaicin mediated ROS generation and apoptosis. Our results reveal that the release of cytochrome c and cleavage of both caspase-9 and caspase-3 due to disruption of mitochondrial membrane potential were significantly blocked by catalase and EUK-134 in BxPC-3 cells. Our results further demonstrate that capsaicin treatment not only inhibit the enzymatic activity and expression of SOD, catalase and glutathione peroxidase but also reduce glutathione level. Over-expression of catalase by transient transfection protected the cells from capsaicin-mediated ROS generation and apoptosis. Furthermore, tumors from mice orally fed with 2.5 mg/kg capsaicin show decreased SOD activity and an increase in GSSG/GSH levels as compared to controls. Taken together, our results suggest the involvement of mitochondrial complex-I and III in capsaicin-mediated ROS generation and decrease in antioxidant levels resulting in severe mitochondrial damage leading to apoptosis in pancreatic cancer cells