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

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

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

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version

Tadalafil and vardenafil vs sildenafil: a review of patient-preference studies

The immediate objective of phosphodiesterase type 5 (PDE5) inhibitor treatment is to restore the ability of a man to achieve and/or maintain an erection adequate for sexual intercourse. As erectile dysfunction (ED) generally develops in the second half of life, the ultimate objective generally is not procreation, but quality of sexual life. Indeed, ED is known to impair quality of life considerably; two-thirds of men report that ED has impaired their self-esteem and nearly a third claim that it has damaged the relationship with their partner. It follows that the therapeutic success of PDE5 inhibition has an important subjective component, which is compounded by the subjective nature and complexity of sexual life in humans. This makes it very difficult for physicians to be certain that they have selected the optimal therapy for a couple, even after a thorough evaluation. The 2007 European Association of Urology Guidelines stress the importance of educating the patient and claim that 'the patient will choose the final drug after his own experience'. However, PDE5 inhibitors are typically used twice a week, so a patient would have to spend approximate to 3 months trying the various compounds and dosages to achieve adequate exposure to all three PDE5 inhibitors; this would seem an unrealistic strategy in normal clinical practice. The acknowledgement that the patient has an important role in therapeutic decisions for ED has fuelled interest in the concept of patient preference. It has been established that patient preference depends on three factors, i.e. personal characteristics, e. g. age, duration of ED, frequency and dynamics of sexual relations, and the characteristics of their partners, e. g. age, menopausal status and level of interest in sexual activity and medication profile. Medication features of interest include efficacy in terms of quality of erection, consistency of effects, rapid onset of action, long duration of action, side-effect profile and route of administration; drug costs must also be considered if the medicinal product is not reimbursed

Tadalafil and vardenafil vs sildenafil: a review of patient-preference studies

The immediate objective of phosphodiesterase type 5 (PDE5) inhibitor treatment is to restore the ability of a man to achieve and/or maintain an erection adequate for sexual intercourse. As erectile dysfunction (ED) generally develops in the second half of life, the ultimate objective generally is not procreation, but quality of sexual life. Indeed, ED is known to impair quality of life considerably; two-thirds of men report that ED has impaired their self-esteem and nearly a third claim that it has damaged the relationship with their partner. It follows that the therapeutic success of PDE5 inhibition has an important subjective component, which is compounded by the subjective nature and complexity of sexual life in humans. This makes it very difficult for physicians to be certain that they have selected the optimal therapy for a couple, even after a thorough evaluation. The 2007 European Association of Urology Guidelines stress the importance of educating the patient and claim that 'the patient will choose the final drug after his own experience'. However, PDE5 inhibitors are typically used twice a week, so a patient would have to spend approximate to 3 months trying the various compounds and dosages to achieve adequate exposure to all three PDE5 inhibitors; this would seem an unrealistic strategy in normal clinical practice. The acknowledgement that the patient has an important role in therapeutic decisions for ED has fuelled interest in the concept of patient preference. It has been established that patient preference depends on three factors, i.e. personal characteristics, e. g. age, duration of ED, frequency and dynamics of sexual relations, and the characteristics of their partners, e. g. age, menopausal status and level of interest in sexual activity and medication profile. Medication features of interest include efficacy in terms of quality of erection, consistency of effects, rapid onset of action, long duration of action, side-effect profile and route of administration; drug costs must also be considered if the medicinal product is not reimbursed

Painful Diabetic Polyneuropathy: Approach to Diagnosis and Management

OBJECTIVES:: To provide a current overview of the diagnostic work-up and management of painful diabetic polyneuropathy (PDPN). METHODS:: A review covering the literature from 2004 to 2011, which describes the tools designed to diagnose neuropathic pain and assess its severity, including self-administered questionnaires, validated laboratory tests and simple handheld screening devices, and the evidence-based therapeutic approaches to PDPN. RESULTS:: The clinical aspects, pathogenesis, and comorbidities of PDPN, as well as its impact on health related quality of life (HR-QoL), are the main drivers for the management of patients with suspected PDPN. PDPN treatment consists first of all in improving glycemic control and lifestyle intervention. A number of symptomatic pharmacological agents are available for pain control: tricyclic antidepressants and selective serotonin norepinephrine reuptake inhibitors (venlafaxine and duloxetine), α2-delta ligands (gabapentin and pregabalin), opioid analgesics (tramadol and oxycodone), and agents for topical use, such as lidocaine patch and capsaicin cream. With the exception of transcutaneous electrical nerve stimulation, physical treatment is not supported by adequate evidence. DISCUSSION:: As efficacy and tolerability of current therapy for PDPN are not ideal, the need for a better approach in management further exists. Novel compounds should be developed for the treatment of PDPN