bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health care utilization in chronic pain—A population based study
Authors: Jonsdottir Thorbjörg , Jonsdottir Helga , Gunnarsdottir Sigridur , Lindal Eirikur 
Published: October 2013

Abstract

Aims
To investigate health care utilization in relation to chronic pain.

Methods
In this cross-sectional study postal questionnaires, measuring sociodemographic characteristics, pain, health related quality of life (HRQoL), attitudes to pain and health care utilization past six months, were sent to 4500 individuals aged 20–70 years, randomly drawn from the Icelandic National Registry.

Results
Total response rate was 36.9% (n = 1589) and was higher among older individuals and women. Nearly one half of respondents (47.5%, n = 754) reported chronic pain (≥3 months) with mean duration of 9.3 years (median = 6.0 years, SD = 10.0) and 57.5% of them had consulted health care service for their pain past six months. Use of pain related health care was significantly related to attitudes towards pain and individuals with pain in chest, upper extremities, hips and lower extremities consulted health care for their pain significantly more often than people with other pain locations. Pain related health care utilization was not significantly related to sociodemographic characteristics. There was a significant difference in both Physical (PCS) and Mental (MCS) component HRQoL scales as well as nature of pain (severity, interference, spread and pattern), between individuals who had consulted health care for their pain and those who had not. However, when these relationships were tested by using logistic regression models, only PCS and pain interference remained significant in this relationship.

Conclusions
Chronic pain related health care utilization is related to several pain characteristics and its influence on daily life, where interference and physical components of HRQoL are most important.
Pain treatment in rural Ghana—A qualitative study
Authors: Ayim-Aboagye Desmond , Gordh Torsten 
Published: October 2013

Abstract

Aims
We investigated how treatment of pain was functioning among a rural population in African context.

Methods
The investigation employed the observation approach and in-depth interview approach in a rural population of about 5000 inhabitants. However, at the zenith of the study 10 patients were selected for the in-depth interview, having serious conditions, which had rendered them immobile, received a major focus in the study. With qualitative methods, we were capable of procuring rich information through narratives.

Results
The patients employ both biomedical practitioners and traditional practitioners in the culture who have potent knowledge of culture specific disabilities. Even when patients had received satisfactory treatments leading to pain relief from the former practitioners, they still cherish some psychological pain, which demand that they consult other practitioners in the culture for further treatments. Those that only receive help from the mainstream hospitals or speciality clinics show improvement, but usually assailed by fear and excessive worry that their pains will not disappear entirely. While the younger generation patients are reluctant to reveal these consultations with traditional practitioners openly, the older group felt more positive about it and brag of having endured their ordeal because of these consultations with those who could offer them additional protection.

Conclusion
The employment of different practitioners’ treatments alleviated these patients’ pain disabilities and psychological symptoms, which were that of pain relief, psychological pain, and death fear. Traditional treatment of pain has a social function, and therefore must be given attention to and recognition by biomedical-trained doctors.
Pain psychology specialist training 2012–2014
Authors: Soini P. , Valjakka A. , Tuurinkoski S. , Elomaa M. , Väänänen T. , Hägg V. 
Published: October 2013

Abstract

Aims
The training includes learning the practical skills related to the psychological examination, treatment and rehabilitation of pain patients. The completion of the training prepares for work in multiprofessional teams as a specialist in pain psychology. A joint project of the Finnish Association of the Study of Pain and the Psychology Institute since 2008.

Participants
Psychologists working in public, private or occupational health care, in rehabilitation or psychiatric clinics. The fourth training group of 20 psychologists started in the spring of 2012. More than 40 psychologists have already been trained in 1998-2010.

The structure and content of the training: Seminars
Eight seminars include 12 days of training on the topics of pain as a psychosocial phenomenon, psychological assessment, treatment and rehabilitation of pain patients, interaction and multiprofessional teamwork.

Tutorial groups
Eight tutorial meetings of 5 students and one tutor in each group gather together in different parts of Finland to discuss selected scientific articles, work on their professional identity as pain psychologists and receive supervision of clinical and diploma work.

Literature
Getting acquainted with scientific research reports on pain psychology and with vocational literature.

Diploma work
Written article or a short research report on a development project, experiment or a phenomenon related to pain psychology.

Optional studies
Giving a lecture or training on the topic of pain psychology to other professionals or patients, participating in a pain education organized by others, writing a report on a research, treatment or rehabilitation experiment or a book review to be published
Pain assessment, documentation, and management in a university hospital
Authors: Zoёga S. , Aspelund T. , Sigurdsson G. , Ward S.E. , Sveinsdóttir H. , Gunnarsdóttir S. 
Published: October 2013

Abstract

Aims
To determine if pain is assessed, documented, and treated in a university hospital according to recommended practice.

Methods
A cross-sectional descriptive study, conducted in 23 medical and surgical wards in a university hospital. Participants were patients hospitalized for at least 24hours, ≥18 years of age, and able to participate. Data were collected from patients with a questionnaire (APS-POQ-R), from their medical records, and from Therapy®, the hospital medication system.

Results
The response rate was 73%. Participants (N =308) mean age was 67.5 years (SD = 17.4), 50.5% were women. Pain prevalence in the past 24 h was 83.1% and severe pain was experienced by 34.5%. Descriptions of pain were documented for 60.7%. Standardized methods of assessment were used in 11.6% of patients, other forms of documentation included descriptions as “no pain-complaints”, and “patient received 2 Panodil”. The majority of patients (66.8%) were prescribed pain medications and 34.0% of patients used non-pharmacological methods to treat their pain. The pain management index (PMI = prescribed pain medication – worst pain severity) was negative for 38.6% indicating insufficient treatment. The PMI was more favorable in surgical compared to medical patients, x
2(6, N = 306) = 17.81, p = 0.007.

Conclusions
Pain was both prevalent and severe. Although some form of documentation of pain was recorded for the majority of patients, pain was rarely assessed with standardized methods. Many patients did not receive adequate treatment. There is a need to improve the pain management practices in the hospital, with an initial emphasis on pain assessment.
Promising effects of donepezil when added to patients treated with gabapentin for neuropathic pain
Authors: Basnet A. , Butler S. , Hartvig Honoré P. , Butler M. , Gordh T.E. , Kristensen K. , Bjerrum O.J. 
Published: October 2013

Abstract

Aims
The clinical relevance of adding the acetylcholinesterase inhibitor donepezil to existing gabapentin treatment in patients with post-traumatic neuropathic pain was explored in this open-label study. The two drugs have previously shown synergism following co-administration in nerve-injured rats [1,2].

Methods
The study comprised two consecutive periods of minimum six weeks: (1) titration of gabapentin until highest tolerable dose or maximum 24GG mg daily; and (2) addition of donepezil 5 mg once daily to the fixed gabapentin dose. Efficacy and tolerability were assessed by ratings of pain intensity, questionnaires for pain and health-related quality of life, and reporting of adverse events and analgesic rescue medication. Pain scores were also analyzed using mixed-effects analysis (i.e. incorporating inter-subject variability) with the software NONMEM.

Results
Eight patients commenced treatment with donepezil upon the gabapentin titration period, of which two withdrew due to adverse events. Addition of donepezil reduced pain by >35% in four of six patients compared to gabapentin monotherapy. Mixed-effects analysis revealed that pain scores were significantly lower during co-administration (p < 0.05 combination vs. monotherapy). Donepezil was well tolerated in combination with gabapentin. At the end of study, three patients wished to continue combination therapy with gabapentin and donepezil.

Conclusions
Donepezil may provide additional analgesia to neuropathic pain patients with insufficient pain relief from gabapentin as monotherapy. Further confirmation in controlled clinical trials is justified. Mixed-effects analysis was sensitive enough to detect statistically significant effects, showing its usefulness in small-scale trials and/or when data is associated with high variability.
Proteomic analysis of cerebrospinal fluid gives insight into the pain relief of spinal cord stimulation
Authors: Lind Anne-Li , Wetterhall Magnus , Sjödin Marcus , Gordh Torsten 
Published: October 2013

Abstract

Aims
Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system affecting approximately 2% of the population. Current pharmacological treatments are ineffective for more than 50% of the patients and often give much adverse effects. Spinal cord stimulation (SCS) is an alternative cost-effective treatment with high efficacy, prolonged pain relief, few side effects. We have compared the cerebrospinal fluid (CSF) proteomes from neuropathic pain patients during pain relief induced by SCS and during pain sensation without SCS, to gain further insights into the mechanisms behind the obtained analgesia.

Methods
Paired CSF samples were taken from SCS-responsive neuropathic pain patients after the SCS had been turned off for 48 h and when the SCS had been used normally for three weeks. Thus, each patient acted as their own control. The corresponding proteomes for each patient were relatively quantified using a mass spectrometry based shotgun approach.

Results
In total, 419 unique proteins were simultaneously identified and relatively quantified. A panel consisting of seven proteins, 5 up-regulated and 2 down, were found to be significantly regulated by SCS in two complementary statistical tests (P ≤ 0.01). The most up-regulated protein in the SCS linked panel is a known modulator of nicotinic acetylcholine (ACh) receptor activity. Interestingly, it has a striking tertiary structural similarity and biological functionality as pain modulating prototoxins found in snake venoms.

Conclusions
Our findings reveal possible insights into the mechanism of spinal cord stimulation and the obtained pain relief.
The DQB1(*)03:02 HLA haplotype is associated with increased risk of chronic pain after inguinal hernia surgery and lumbar disc herniation
Authors: Dominguez C.A. , Kalliomäki M. , Gunnarsson U. , Moen A. , Sandblom G. , Kockum I. , Lavant E. , Olsson T. , Nyberg F. , Rygh L.J. , Røe C. , Gjerstad J. , Gordh T. , Piehl F. 
Published: October 2013

Abstract
Neuropathic pain conditions are common after nerve injuries and are suggested to be regulated in part by genetic factors. We have previously demonstrated a strong genetic influence of the rat major histocompatibility complex on development of neuropathic pain behavior after peripheral nerve injury. In order to study if the corresponding human leukocyte antigen complex (HLA) also influences susceptibility to pain, we performed an association study in patients that had undergone surgery for inguinal hernia (n = 189). One group had developed a chronic pain state following the surgical procedure, while the control group had undergone the same type of operation, without any persistent pain. HLA DRB1genotyping revealed a significantly increased proportion of patients in the pain group carrying DRB1(*)04 compared to patients in the pain-free group. Additional typing of the DQB1 gene further strengthened the association; carriers of the DQB1(*)03:02 allele together with DRB1(*)04 displayed an increased risk of postsurgery pain with an odds risk of 3.16 (1.61-6.22) compared to noncarriers. This finding was subsequently replicated in the clinical material of patients with lumbar disc herniation (n = 258), where carriers of the DQB1(*)03:02 allele displayed a slower recovery and increased pain. In conclusion, we here for the first time demonstrate that there is an HLA-dependent risk of developing pain after surgery or lumbar disc herniation; mediated by the DRB1(*)04-DQB1(*)03:02 haplotype. Further experimental and clinical studies are needed to fine-map the HLA effect and to address underlying mechanisms.
On the pharmacological effects of two lidocaine concentrations tested on spontaneous and evoked pain in human painful neuroma: A new clinical model of neuropathic pain
Authors: Miclescu Adriana , Hägglöf Björn , Schmelz Martin , Gordh Torsten 
Published: October 2013

Abstract

Aims
Spontaneous and evoked pains are key symptoms of patients with neuropathic pain and there is a current discussion on the predictive value of evoked pain read outs for the reduction of spontaneous pain. Here we describe a new clinical model of neuropathic pain that may be useful for evaluation of new drugs. We also report the effects of lidocaine in this model as reference values.

Methods
In a randomized double-blind experiment, the analgesic effects of local lidocaine were investigated separately for spontaneous pain and for stimulus-evoked allodynia and hyperalgesia in sixteen patients with painful neuromas after traumatic nerve injuries in the upper extremities. The patterns of sensory changes were compared before and after treatment with lidocaine (0.1% or 0.5%, 1 ml), with 1–2 weeks interval, injected close to the neuroma. Spontaneous and evoked pains were assessed using a visual analogue scale (VAS) and quantitative/qualitative sensory testing.

Results
Lidocaine dose-dependently reduced spontaneous and evoked pain scores by more than 90% with maximum effects between 1 and 5 min for evoked pain and between 3 and 15 min for spontaneous pain. While evoked pain normalized rapidly reaching about 50% of the control level 20 minutes after the injection spontaneous pain levels were lower than 25% at this time. Moreover, in 4 patients the reduction of ongoing pain lasted 24 h whereas evoked pain had returned to baseline levels in all the patients after 1 h.

Conclusion
Differential analgesic effects of local lidocaine on spontaneous and evoked pain suggest that different mechanism underlie these two key clinical symptoms. Thus, clinical trials assessing localized traumatic neuropathic pain should investigate both aspects of pain separately with the proposed model allowing testing of new drugs systemically or locally administered.
The mineralocorticoid receptor antagonist spironolactone enhances morphine antinociception
Authors: Jokinen Viljami , Lilius Tuomas O. , Neuvonen Mikko S. , Väänänen Antti J. , Niemi Mikko O. , Rauhala Pekka V. , Kalso Eija A. 
Published: October 2013

Abstract

Aims
Spironolactone, an antimineralocorticoid, has been reported to potentiate the cataleptic effect of morphine in the rat. Since no previous research exists on the matter and the interaction might be clinically significant, the effects of spironolactone on morphine antinociception and pharmacokinetics in the rat were investigated.

Methods
Male SD rats were used to assess the effects of spironolactone on acute morphine-induced antinociception, development of morphine tolerance, and established morphine tolerance in the tail-flick and hot plate tests. Spironolactone was also administered with loperamide to assess whether spironolactone enhances the brain distribution of the acknowledged P-glycoprotein substrate across the blood-brain barrier.

Results
Spironolactone had no antinociceptive effects of its own but when co-administrated with morphine the antinociceptive effect of morphine was greatly enhanced. Morphine concentrations in the brain were increased fourfold in the spironolactone co-administrated group. Spironolactone did not inhibit the formation of pro-nociceptive morphine-3-glucuronide, nor did inhibit the development of tolerance. The peripherally restricted opioid, loperamide, had no antinociceptive effects by itself, but co-administration with spironolactone produced a clear change in the hot plate test.

Conclusions
Although mineralocorticoids have been proposed to take part in pain signaling, in our setting spironolactone did not have antinociceptive properties of its own. The increased antinociceptive effect of morphine is apparently caused by the increased morphine brain concentrations. We suggest this to be due to P-glycoprotein inhibition, as indicated by the loperamide assay. The clinical relevance of P-glycoprotein inhibition by spironolactone should be studied.
Expression of calcium/calmodulin-dependent protein kinase II in dorsal root ganglia in diabetic rats 6 months and 1 year after diabetes induction
Authors: Ferhatovic L. , Jelicic A. , Boric M. , Banozic A. , Sapunar D. , Puljak L. 
Published: October 2013

Abstract

Aim
The aim of this study was to compare expression of total calcium/calmodulin-dependent protein kinase II (tCaMKII) and its α, β, γ and δ isoforms in dorsal root ganglion (DRG) in rat models of diabetes mellitus type I (DM1), 6 months and 1 year after diabetes induction.

Methods
A total of 45 male Sprague-Dawley rats weighing 160-200 g were assigned into four experimental groups: 6-months DM1 and its control group, 1-year and its control group. For the induction of DM1, after overnight fasting animals were injected intraperitonealy with 55 mg/kg of the streptozotocine (STZ). Rats were sacrificed 6 months and 1 year after the diabetes induction. The L4 and L5 ganglions were removed, fixed, embedded in freezing medium and sectioned on a cryostat. Immunofluorescence analysis was performed for detection of tCaMKII and its α, β, γ and δ isoforms. Image J software was used for analysis of immunofluorescence.

Results
The diabetes was successfully induced as confirmed by measurement of glucose levels and weight increase. Analysis of tCaMKII expression in DRGs revealed no differences between DM1 and control animals after 6 and 12 months. In diabetic animals, the expression of α and β isoforms decreased significantly after 6 months, compared to the controls, while decrease of γ and δ was observed after one year of diabetes in diabetic animals.

Conclusions
The observed changes in the expression of CaMKII isoforms reveal plastic changes of this enzyme during the chronic diabetic state and may be involved in the chronic neuropathic pain development.
Pronociceptive effects of a TRPA1 channel agonist methylglyoxal in healthy control and diabetic animals
Authors: Viisanen Hanna , Lasierra Maria , Wei Hong , Koivisto Ari , Åkerman Karl E. , Pertovaara Antti 
Published: October 2013

Abstract

Aims
Methylglyoxal (MG), a reactive carbonyl compound generated in diabetes mellitus (DM), activates the TRPA1 ion channel. Here we studied whether MG induces mechanical hypersensitivity or ongoing pain and whether the pronociceptive effect of MG is changed following its sustained endogenous release in DM.

Methods
DM was induced by streptozotocin (50-60 mg/kg i.p.) in the rat. MG and Chembridge-5861528 (CHEM), a selective TRPA1 channel antagonist, were administered intraplantarly (i.pl.) in control and diabetic animals. Limb withdrawal to monofilaments was used as an index of hypersensitivity, and observation of sustained pain-like behavior and conditioned place-avoidance test were used to assess ongoing pain. In vitro calcium imaging was used to study whether MG induces sustained activation of dorsal root ganglion (DRG) neurons of diabetic as well as control animals.

Results
MG produced mechanical hypersensitivity and ongoing pain behavior in control animals, which effects were reduced in diabetic animals. CHEM treatment at a dose suppressing the MG-induced mechanical hypersensitivity failed to suppress the MG-induced ongoing pain behavior. MG was able to produce sustained calcium inflow in DRG neurons of DM as well as control animals.

Conclusions
The results suggest that MG induces hypersensitivity and ongoing pain that are reduced in diabetes mellitus, possibly due to changes caused by the DM-induced sustained endogenous release of MG. Moreover, the MG-induced mechanical hypersensitivity can be more effectively reversed by a TRPA1 antagonist than the MG-induced ongoing pain behavior.
Human inducible pluripotent stem cell-derived sensory neurons express multiple functional ion channels and GPCRs
Authors: Saarnilehto M. , Pekkanen-Mattila M. , Aalto-Setälä K. , Silvennoinen O. , Koivisto A. 
Published: October 2013

Abstract

Aims
Aim of the study was to characterize functional ion channel and GPCR responses by using selective pharmacological tools and intracellular calcium imaging from human inducible pluripotent stem cell-derived sensory neurons.

Methods
Sensory neurons were generated from human keratinocytes that were reprogrammed to inducible pluripotent stem cells by using standard Yamanaka factors. Inducible pluripotent stem cells were differentiated into sensory neurons by using 2 differentiation protocols (small molecule and PA6 co-culture). Sensory neurons were loaded with intracellular calcium dye Fluo-4. Single-cell calcium imaging was performed with Photometrics Evolve EM-CCD camera at physiological temperature. Cells were perfused with a Ringer solution at 2–3 ml/min into which pharmacological compounds were dissolved. Data was analyzed with Till Photonics Offline Analysis program.

Results
Most of the results were obtained from PA6 differentiated neurons. 50 s application of 50 mM KCl solution was used as diagnostic tool to activate voltage-gated calcium channels and thereby evoke intracellular calcium elevation. Functional ASIC, NMDA, kainate and TRPA1 ion channels were present in a subset of sensory neurons. Majority of sensory neurons showed robust responses to purinergic stimulation with ATP and histaminergic stimulation with histamine, but not to subtype selective histamine H1, H2 or H4 stimulation suggesting the presence of H3 receptor subtype All cells responded strongly to protease-activated receptor stimulation with a low dose of trypsin. Interestingly, at single-cell level notable heterogeneity of ion channel and GPCR responses was observed.

Conclusions
Our results suggest that iPS-derived sensory neurons will be valuable in further pharmacological studies as well as sensory neuropathy disease modeling.