Neuroimaging of pleasantness and unpleasantness induced by thermal stimuli.

Functional brain imaging techniques provide unique insight into the process of human thermal regulation and its associated hedonics. Similar neuroimaging techniques have predominantly focused on the neural characterization of thermal response separately from hedonics. In this instance, there is a gap in the understanding of hedonics related to regional brain activations. Responses to localized, thermal stimuli are yet to be characterized, but it would appear that thermoregulatory regions are widely distributed throughout the hemispheres of the human brain. The distributed nature of neural activations related to temperature responses is consistent with multiple related functions contributing to thermoregulation. Estimating hedonics of thermal stimulation includes a cognitive process that could potentially interfere with identifying activation specific to hedonics. A future challenge for brain imaging studies is to more accurately dissect the functional neuroanatomy of thermoregulation and related hedonics in hemispheric regions.

Neuroticism and pain catastrophizing aggravate response to pain in healthy adults: an experimental study.

BACKGROUND: The aim of this study was to investigate the association between neuroticism, pain catastrophizing, and experimentally induced pain threshold and pain tolerance in a healthy adult sample from two regions of the country of Croatia: the island of Korcula and city of Split. METHODS: A total of 1,322 participants were enrolled from the Island of Korcula (n = 824) and the city of Split (n = 498). Participants completed a self-reported personality measure Eysenck Personality Questionnaire (EPQ) and pain catastrophizing questionnaire Pain Catastrophizing Scale (PCS), followed by a mechanical pain pressure threshold and tolerance test. We have explored the mediating role of catastrophizing in the relationship between neuroticism and pain intensity. RESULTS: The results showed that pain catastrophizing partially mediated the relationship between neuroticism and pain intensity, suggesting the importance of pain catastrophizing in increasing vulnerability to pain. The results also indicated gender-related differences, marked by the higher pain threshold and tolerance in men. CONCLUSIONS: This study adds to the understanding of the complex interplay between personality and pain, by providing a better understanding of such mechanisms in healthy adults.

Risk factors associated with postoperative pain after ophthalmic surgery: a prospective study.

BACKGROUND: Risk factors associated with postoperative pain intensity and duration, as well as consumption of analgesics after ophthalmic surgery are poorly understood. METHODS: A prospective study was conducted among adults (N=226) who underwent eye surgery at the University Hospital Split, Croatia. A day before the surgery, the patients filled out questionnaires assessing personality, anxiety, pain catastrophizing, sociodemographics and were given details about the procedure, anesthesia, and analgesia for each postoperative day. All scales were previously used for the Croatian population. The intensity of pain was measured using a numerical rating scale from 0 to 10, where 0 was no pain and 10 was the worst imaginable pain. The intensity of pain was measured before the surgery and then 1 hour, 3 hours, 6 hours, and 24 hours after surgery, and then once a day until discharge from the hospital. Univariate and multivariate analyses were performed. RESULTS: A multivariate analysis indicated that independent predictors of average pain intensity after the surgery were: absence of premedication before surgery, surgery in general anesthesia, higher pain intensity before surgery and pain catastrophizing level. Independent predictors of postoperative pain duration were intensity of pain before surgery, type of anesthesia, and self-assessment of health. Independent predictors of pain intensity ≥5 during the first 6 hours after the procedure were the type of procedure, self-assessment of health, premedication, and the level of pain catastrophizing. CONCLUSION: Awareness about independent predictors associated with average postoperative pain intensity, postoperative pain duration, and occurrence of intensive pain after surgery may help health workers to improve postoperative pain management in ophthalmic surgery.

Excitability of contralateral and ipsilateral projections of corticobulbar pathways recorded as corticobulbar motor evoked potentials of the cricothyroid muscles.

OBJECTIVE: The objective of this study was to evaluate the excitability of contralateral and ipsilateral corticobulbar pathways, using the methodologies of navigated transcranial magnetic stimulation (nTMS) and transcranial electrical stimulation (TES). METHODS: In 11 healthy subjects, the primary motor cortex (M1) for laryngeal muscles was mapped with nTMS in both hemispheres and the corticobulbar motor evoked potentials (CoMEPs) were recorded from the right cricothyroid muscle. In 15 patients undergoing left craniotomy, CoMEPs were obtained from cricothyroid muscles bilaterally, using TES over C3/Cz and C4/Cz. RESULTS: In five out of 11 healthy subjects, both contralateral and ipsilateral CoMEPs were recorded from the right cricothyroid muscle. In eight out of 15 patients, contralateral and ipsilateral CoMEPs were elicited with TES over C3/Cz, while in five out of 15 patients contralateral and ipsilateral CoMEPs were elicited with TES over C4/Cz. Contralateral CoMEP amplitude responses were significantly larger compared to ipsilateral CoMEP amplitudes in both groups. CONCLUSION: We obtained significantly larger amplitude responses of contralateral CoMEPs from cricothyroid muscles compared to ipsilateral CoMEP amplitude using nTMS in healthy subjects and TES in patients. This confirms the bilateral nature of corticobulbar pathway projections for laryngeal muscles, with contralateral domination. SIGNIFICANCE: These findings will influence recording of CoMEPs during preoperative and intraoperative mapping of M1 for laryngeal muscle representation, and they facilitate the pathophysiologic research of motor speech disorders.

Dental fear and anxiety in older children: an association with parental dental anxiety and effective pain coping strategies.

An association between dental fear and anxiety (DFA) has been confirmed for children younger than 8 years, but this association in older children is less clear. The aim of this study was to fill this knowledge gap by studying DFA in older children and their parents with validated measures. This cross-sectional study, conducted at Community Health Centre Mostar, Bosnia and Herzegovina, included 114 children and their parents. DFA, coping, and sociodemographic variables were studied using Corah Dental Anxiety Questionnaire (CDAS), Dental Subscale of the Children's Fear Survey Schedule (CFSS-DS), Dental Cope Questionnaire, and sociodemographic questionnaire. Maternal CDAS scores had significant positive correlation with child DFA measured with CFSS-DS (r=0.35, P<0.001) and CDAS (r=0.32, P<0.001). Fathers' CDAS scores were not associated with child CFSS-DS, but showed a moderate correlation with child CDAS (r=0.19, P<0.05). There were no significant differences in children's fear and anxiety based on age, sex, or socioeconomic variables. Children used internal coping strategies most frequently and external coping strategies were rated by the children as the most effective. We did not find differences in number and type of effective coping strategies in children with high DFA compared with children with low DFA. In conclusion, there is evidence of the coexistence of dental fear in parents and older children. These findings may help to devise interventions that will prevent or alleviate children's DFA.

Behavioral changes following experimentally-induced acute myocardial infarction in rats.

Rats with experimentally-induced acute myocardial infarction (AMI) have proven to be a clinically relevant model for visceral pain. As there are no behavioral data available on rats in the postinfarction period, we aimed to identify specific pain-related behavioral changes following AMI to increase the validity of the model. AMI was induced by left coronary artery ligation and pain-related behavior was analyzed using the open field test (OFT) and elevated plus maze (EPM). Morphine was applied following AMI induction to differentiate pain-related changes from those related to nonspecific global changes in responsiveness. AMI was histologically confirmed. Hypolocomotion was consistently evident in all behavioral tests for both the infarcted group and sham group. In the OFT, both AMI and sham rats exhibited less exploratory behavior and less activity. A similar pattern of behavior was observed in EPM, where both surgical groups showed fewer entries to the open arms and spent less time in the open arms. The sham group with an intact pericardium showed the same pattern of activity as control rats. The reduction in activity and rearing observed following AMI was successfully reversed following morphine injection. This effect was abolished after naloxone application allowing us to attribute observed changes specifically to pain.This study demonstrates that pain-related behavior in the acute postinfarction period is generally characterized by reduced mobility and explorative behavior. Our results showed that cardiac ischemia as a consequence of experimentally-induced infarction is a less important source of pain behavior than manipulation of the pericardium.

Reduced epidermal thickness, nerve degeneration and increased pain-related behavior in rats with diabetes type 1 and 2.

To examine the mechanisms contributing to pain genesis in diabetic neuropathy, we investigated epidermal thickness and number of intraepidermal nerve fibers in rat foot pad of the animal model of diabetes type 1 and type 2 in relation to pain-related behavior. Male Sprague-Dawley rats were used. Diabetes type 1 was induced with intraperitoneal injection of streptozotocin (STZ) and diabetes type 2 was induced with a combination of STZ and high-fat diet. Control group for diabetes type 1 was fed with regular laboratory chow, while control group for diabetes type 2 received high-fat diet. Body weights and blood glucose levels were monitored to confirm induction of diabetes. Pain-related behavior was analyzed using thermal (hot, cold) and mechanical stimuli (von Frey fibers, number of hyperalgesic responses). Two months after induction of diabetes, glabrous skin samples from plantar surface of the both hind paws were collected. Epidermal thickness was evaluated with hematoxylin and eosin staining. Intraepidermal nerve fibers quantification was performed after staining skin with polyclonal antiserum against protein gene product 9.5. We found that induction of diabetes type 1 and type 2 causes significant epidermal thinning and loss of intraepidermal nerve fibers in a rat model, and both changes were more pronounced in diabetes type 1 model. Significant increase of pain-related behavior two months after induction of diabetes was observed only in a model of diabetes type 1. In conclusion, animal models of diabetes type 1 and diabetes type 2 could be used in pharmacological studies, where cutaneous changes could be used as outcome measures for predegenerative markers of neuropathies.

Intrathecal inhibition of calcium/calmodulin-dependent protein kinase II in diabetic neuropathy adversely affects pain-related behavior.

Calcium/calmodulin-dependent protein kinase II (CaMKII) is considered an important enzyme contributing to the pathogenesis of persistent pain. The aim of this study was to test whether intrathecal injection of CaMKII inhibitors may reduce pain-related behavior in diabetic rats. Male Sprague-Dawley rats were used. Diabetes was induced with intraperitoneal injection of 55mg/kg streptozotocin. Two weeks after diabetes induction, CaMKII inhibitor myristoil-AIP or KN-93 was injected intrathecally. Behavioral testing with mechanical and thermal stimuli was performed before induction of diabetes, the day preceding the injection, as well as 2h and 24h after the intrathecal injection. The expression of total CaMKII and its alpha isoform in dorsal horn was quantified using immunohistochemistry. Intrathecal injection of mAIP and KN-93 resulted in significant decrease in expression of total CaMKII and CaMKII alpha isoform activity. Also, mAIP and KN93 injection significantly increased sensitivity to a mechanical stimulus 24h after i.t. injection. Intrathecal inhibition of CaMKII reduced the expression of total CaMKII and its CaMKII alpha isoform activity in diabetic dorsal horn, which was accompanied with an increase in pain-related behavior. Further studies about the intrathecal inhibition of CaMKII should elucidate its role in nociceptive processes of diabetic neuropathy.

Impact of extended course duration and stricter study organization on attrition and academic performance of medical students.

AIM: To assess whether extended medical school duration, block/modular structure of subjects, not allowing students to transfer exams into the higher course year, and curriculum implementation in line with the Bologna Accord are associated with lower attrition and better academic outcomes of medical students. METHODS: We retrospectively investigated curricula at the University of Split School of Medicine and academic outcomes of 2301 medical students during a 33-year period (1979-2011). The following data were obtained: grade point average (GPA) at the end of the studies, duration of studies, graduation on time, and whether the student graduated or not. RESULTS: After extension of medical curriculum from 5 to 6 years, students had significantly better grades (3.35 vs 3.68; P<0.001), shorter study duration (7.0 vs 6.0 years; P<0.001), and more students graduated on time (6.5% vs 57%; P<0.001). Changes in the 6-year curriculum, such as stricter study regulations and adoption of Bologna Accord, were associated with better indicators of students' academic success. The lowest attrition and the highest grades during the studied period were observed after the implementation of the Bologna Accord in 2005. CONCLUSION: Introduction of a longer medical curriculum, block/modular subject structure, stricter regulations of exam transfer, and curriculum in line with the Bologna Accord may contribute to better academic outcomes and lower attrition of medical students.

Pain catastrophizing changes during the menstrual cycle.

Pain catastrophizing is an important predictor of pain intensity and pain-related outcomes. Many studies have shown that the level of this phenomenon is higher in women compared to men. The aim of this study was to investigate whether there is a difference in pain catastrophizing in women during the different phases of their menstrual cycle and whether there is a difference in pain catastrophizing depending on the history of childbirth and dysmenorrhea. A prospective study was conducted among 149 healthy women aged 18-35, with a regular menstrual cycle, 80 of which were nulliparous. The participants filled a sociodemographic questionnaire at the enrollment and the Pain Catastrophizing Scale on the 1st, 12th, and 20th day of the menstrual cycle. Pain catastrophizing scores, including all the subscales, significantly varied throughout the menstrual cycle, being highest on the first day of menstrual cycle and declining subsequently. Pain catastrophizing scores were higher in nulliparous than in parous women. Higher pain catastrophizing scores on the first day of the menstrual cycle were found in dysmehorrhoic women and women who regularly use analgesics for dysmenorrhea. Knowing that pain catastrophizing varies throughout the menstrual cycle may help in creating interventions for pain prevention and treatment in cycling women.

Adherence to pharmacological treatment of chronic nonmalignant pain in individuals aged 65 and older.

BACKGROUND: Medication nonadherence is a frequent problem in the treatment of chronic conditions. OBJECTIVE: To study the adherence to pharmacological treatment of chronic nonmalignant pain, as well as factors and patient attitudes related to nonadherence in patients aged ≥65 years. METHODS: The cross-sectional study was conducted with a self-administered questionnaire among 100 patients aged ≥65 years by five family physicians at the Health Care Centre Mostar, Bosnia and Herzegovina. RESULTS: According to their own statements, 57% of the patients were nonadherent, while 84% exhibited some form of nonadherence on the Morisky scale. The patients reported a mean pain intensity of 6.6 ± 2.2 on a visual analog scale. The most common deviation from the prescribed therapy was self-adjustment of the dose and medical regimen based on the severity of pain. Polymedication correlated positively with nonadherence. Nonsteroidal anti-inflammatory drugs were the most frequently prescribed medications. The majority of the participants (59%) believed that higher pain intensity indicates progression of the disease, and half of the participants believed that one can easily become addicted to pain medications. Nonadherence was associated with patient attitudes about addiction to analgesics and ability of analgesics to control pain. CONCLUSION.: High pain intensity and nonadherence found in this study suggest that physicians should monitor older patients with chronic nonmalignant pain more closely and pay more attention to patients' beliefs regarding analgesics to ensure better adherence to pharmacological therapy.

Expression of calcium/calmodulin-dependent protein kinase II and pain-related behavior in rat models of type 1 and type 2 diabetes.

BACKGROUND: Abnormalities in peripheral nerves and dorsal root ganglia are noticed in the early stage of experimentally provoked diabetic neuropathy. Enzyme calcium/calmodulin-dependent protein kinase II (CaMKII) may have a modulating role in diabetic neuropathy because of its role in calcium homeostasis. METHODS: A model of type 1 diabetes mellitus (DM1) was induced with 55 mg/kg of the streptozotocin and for DM2 induction a combination of high-fat diet and low-dose streptozotocin (35 mg/kg) was used. Pain-related behavior was analyzed using thermal and mechanical stimuli. Two weeks and 2 months after induction of diabetes rats were euthanized, and the expression of CaMKII and its isoforms in the dorsal root ganglia were analyzed using immunofluorescence. RESULTS: Both types of diabetes were successfully induced, as confirmed by hyperglycemia. Increased pain-related behavior became evident in DM1 rats in 2 weeks after diabetes induction, but not in DM2 rats. The expression of total CaMKII and the phosphorylated α isoform of CaMKII increased in DM1 animals concurrently with pain-related behavior. Expression of α, ß, γ, and δ isoforms in DM1 animals and expression of total CaMKII and all of its analyzed isoforms in DM2 animals remained unchanged. CONCLUSIONS: Our findings may indicate involvement of CaMKII in transmission of nociceptive input early in DM1, but not in DM2. CaMKII may be a suitable pharmacological target for diabetic neuropathy.

Physicians' attitudes about interprofessional treatment of chronic pain: family physicians are considered the most important collaborators.

AIMS AND OBJECTIVES: Interprofessional collaboration is the process in which different professional groups work together to positively impact health care. We aimed to explore physicians' attitudes toward interprofessional collaboration in the context of chronic pain management with the implication that if attitudes are not positive, appropriate interventions could be developed. DESIGN: A quantitative attitudes study. ETHICAL ISSUES: The ethical committee approved the study. METHODS: A web-based survey about interprofessional treatment of chronic pain was administered to physicians. Outcome measures were as follows: physicians' demographic and workplace information, previous experience of working within an interprofessional team, and attitudes towards interprofessional collaboration in chronic pain management. RESULTS: There were 90 physicians who responded to the survey. Physicians had positive attitudes towards team work in the context of chronic pain, but they were undecided about sharing their role within an interprofessional team. The family physician was singled out as the most important as well as the most common collaborator in chronic pain treatment. Interprofessional educational seminars and workshops were suggested as methods for improving interprofessional collaboration. CONCLUSIONS: Interprofessional collaboration may be enhanced with continuing medical education that will bring together different healthcare professionals, enable them to exchange experiences and learn about their potential roles within a team.

Sex differences in pain-related behavior and expression of calcium/calmodulin-dependent protein kinase II in dorsal root ganglia of rats with diabetes type 1 and type 2.

Sex differences in pain-related behavior and expression of calcium/calmodulin dependent protein kinase II (CaMKII) in dorsal root ganglia were studied in rat models of Diabetes mellitus type 1 (DM1) and type 2 (DM2). DM1 was induced with 55mg/kg streptozotocin, and DM2 with a combination of high-fat diet and 35mg/kg of streptozotocin. Pain-related behavior was analyzed using thermal and mechanical stimuli. The expression of CaMKII was analyzed with immunofluorescence. Sexual dimorphism in glycemia, and expression of CaMKII was observed in the rat model of DM1, but not in DM2 animals. Increased expression of total CaMKII (tCaMKII) in small-diameter dorsal root ganglia neurons, which are associated with nociception, was found only in male DM1 rats. None of the animals showed increased expression of the phosphorylated alpha CaMKII isoform in small-diameter neurons. The expression of gamma and delta isoforms of CaMKII remained unchanged in all analyzed animal groups. Different patterns of glycemia and tCaMKII expression in male and female model of DM1 were not associated with sexual dimorphism in pain-related behavior. The present findings do not suggest sex-related differences in diabetic painful peripheral neuropathy in male and female diabetic rats.

Predictors of attrition and academic success of medical students: a 30-year retrospective study.

AIM: To determine attrition and predictors of academic success among medical students at University of Split, Croatia. METHODS: We analysed academic records of 2054 students enrolled during 1979-2008 period. RESULTS: We found that 26% (533/2054) of enrolled students did not graduate. The most common reasons for attrition were 'personal' (36.4%), transfer to another medical school (35.6%), and dismissal due to unsatisfactory academic record (21.2%). Grade point average (GPA) and study duration of attrition students were significantly associated with parental education. There were 1126 graduates, 395 men and 731 women. Their average graduation GPA was 3.67±0.53 and study duration 7.6±2.44 years. During 5-year curriculum only 6.4% (42/654) of students graduated in time, and 55% (240/472) of students graduated in time after curriculum was extended to 6 years. Variables predicting whether a student will graduate or not were high school grades, entrance exam score and year of enrollment. Significant predictors of graduation grades were high school grades and entrance exam score. Entrance exam score predicted length of studying. CONCLUSION: Preadmission academic qualifications and year of enrollment predict academic success in medical school. More attention should be devoted to high attrition.

Dorsal root ganglion - a potential new therapeutic target for neuropathic pain.

A regional approach can protect our patients from often unacceptable adverse effects produced by systematically applied drugs. Regional therapeutic approaches, as well as interventions at the level of the peripheral nervous system and particularly the dorsal root ganglion (DRG), represent an alternative to the systemic application of therapeutic agents. This article provides an overview of DRG anatomical peculiarities, explains why the DRG is an important therapeutic target, and how animal models of targeted drug delivery can help us in the translation of basic research into clinical practice.

Parents' pain catastrophizing is related to pain catastrophizing of their adult children.

BACKGROUND: Parents' pain behavior is associated with the way their children experience and express pain. PURPOSE: We hypothesized that there is a positive association between levels of pain catastrophizing in parents and their adult children. METHOD: Study included 285 participants, 100 patients, 85 spouses, and 100 adult children from 100 families. Pain catastrophizing was assessed with the Croatian version of Pain Catastrophizing Scale. Patients' pain intensity was measured with the visual analogue scale. RESULTS: Significant positive correlation was found between pain catastrophizing of adult children and both of their parents. Regression analysis was conducted to test for the role of parents' pain catastrophizing scores in explaining pain catastrophizing in their adult children. The results showed that parents' pain catastrophizing scores explain results of their adult children, accounting for 20% of the variance. CONCLUSION: The results from the present study indicate that there is a positive association between levels of pain catastrophizing in parents and their adult children. A family may have a specific cognitive style for coping with pain, which is associated to a child's responses to pain experiences.