Evidence for the improvement of fatigue in fibromyalgia: a 4-week left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation randomised-controlled trial

Abstract

Background

Fibromyalgia is a complex chronic disorder with few effective treatments currently available. One promising treatment option is repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive brain stimulation technique that has shown promise in disorders effecting the central nervous system.

Methods

We assessed the efficacy of a course of high-frequency (10Hz) left-hemisphere dorsolateral prefrontal cortex (DLPFC) rTMS in 26 patients (14 active; 12 sham) with a diagnosis of fibromyalgia. Participants underwent a double-blind stimulation protocol of daily (Monday-Friday) rTMS sessions over 4 consecutive weeks (total of 20 sessions; 75 x 4-second 10Hz trains at 120% resting motor threshold). Assessments were conducted at baseline, 4 weeks and at 1 month follow-up.

Results

Using mixed-model analysis we did not identify a group difference for our primary outcome measures. However, we found that patients in the active compared to sham treatment group had significantly greater improvement in the Physical Fatigue (p = .045) and General Fatigue (p = .023) scales of the Multidimensional Fatigue Iventory-20 at the 1 month follow up. In a responder analysis, we also found the active group was significantly more likely (2.84 times) to achieve a minimum 30% improvement in pain intensity ratings. (p = .024).

Conclusions

High-frequency rTMS applied daily for 4 weeks to the left DLPFC induces significant relief from fatigue and a greater chance of clinically meaningful improvement in pain intensity in patients with fibromyalgia. These results suggest DLPFC rTMS may be a relevant therapy for fibromyalgia.

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The association between patient-professional partnerships and self-management of chronic back pain: a mixed methods study

Abstract

Background

Self-management is recommended for patients with chronic back pain. Health professionals’ support for self-management can be more effective when working in partnership with patients. The aim of this study was to investigate the associations between patient-professional partnerships and the self-management of chronic back pain.

Methods

An explanatory sequential mixed methods study was undertaken. Adults with chronic back pain referred to pain management clinics participated at baseline and three-month follow-up. Their pain severity, partnerships with health professionals and self-management ability were measured. Hierarchical linear regression was undertaken to examine the strength of the associations between partnerships and self-management. A subsample was interviewed about experiences of the impact of patient-professional partnerships on their self-management ability, using a grounded theory approach.

Results

A total of 147 patients were recruited and 103 (70%) patients completed the follow-up. A strong association (p<0.001) was detected between patient-professional partnerships and all dimensions of self-management ability. This was validated by interviews with a subsample of 26 patients. Four themes emerged: connecting with health professionals, being supported through partnerships, feeling positive and making progress towards self-management, and acknowledging the impact but feeling no difference.

Conclusions

Developing a partnership in care may improve patients’ ability to gain knowledge, manage side effects and symptoms and adhere to treatment. It helped strengthen health professionals’ support and produce a sense of safety for patients. Guiding health professionals in building partnerships where expectations are acknowledged and tailored information and support are provided could be considered as part of the standard education and training.

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Clinical testing of three novel transient receptor potential cation channel subfamily V member 1 (TRPV1) antagonists in a pharmacodynamic intradermal capsaicin model

Abstract

Background

The transient receptor potential cation channel subfamily V 1 (TRPV1) is involved in nociception and has thus been of interest for drug developers, as a target for novel analgesics. However, several oral TRPV1 antagonists have failed in development, and novel approaches to target TRPV1 with innovative chemistry are needed.

Method

This work describes an intradermal microdosing approach in humans for pharmacodynamic deductions and pharmacological profiling of compounds. First, a human capsaicin model was developed, to generate pharmacodynamic translational data (Study Part A, n=24). Then, three small molecule TRPV1 antagonists (AZ11760788, AZ12048189 and AZ12099548) were investigated in healthy volunteers (Study Part B, n=36), applying the established model. Pain and flare were assessed by Visual Analogue Score and laser doppler, respectively.

Results

The developed model proved useful for pharmacologic deductions; all compounds caused a dose dependent inhibition of capsaicin-induced pain and flare responses, with a rank order potency of AZ11760788 > AZ12048189 >> AZ12099548. In addition, the dose-response data showed that the minimal antagonist concentrations needed to inhibit TRPV1 was ≥ 6-7 times the equilibrium dissociation constant for each compound.

Conclusion

With careful design of a pharmacodynamic translational human pain model, it was possible to rank order TRPV1 efficacy among three investigational TRPV1 antagonists, and to estimate human efficacious concentrations.

Significance

This fast and cost-effective translational approach allows for generation of human target engagement information early in drug development. This could be of value for other development programs where pharmacological targets are expressed in peripheral sensory nerves.

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Authors’ reply to the comment by Kendall et al

Abstract

We would like to thank for the opportunity to reply to the important questions raised by Kendall et al. and also would like to thank the authors of that letter for their kind words. Our results indeed seem contrary to previous results about opioid-induced hyperalgesia (OIH), but on a detailed look there is not necessarily a contradiction. Until now no direct link between the short-lasting OIH and long-term pain has been shown in humans.

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Catastrophizing, pain and traumatic stress symptoms following burns: A prospective study

Abstract

Background

Pain and PTSD symptoms are significant problems in the aftermath of a burn injury and they often co-occur. Catastrophizing has been linked to both phenomena. The aim of this study was to investigate the underlying role of catastrophizing in PTSD symptoms and pain following burns.

Methods

This prospective study included 216 patients with burns. PTSD symptoms and pain were measured during hospitalization (T1) and 6 (T2) and 12 months (T3) postburn. The Impact of Event Scale-Revised (IES-R) indexed PTSD symptoms. Acute pain (T1) was the mean pain during the first two weeks of hospitalization measured using an 11-point graphic numeric rating scale. Chronic pain was indexed using the single item ‘average’ pain from the Brief Pain Inventory (BPI). Catastrophizing was measured at T1 and T2 using the Cognitive Emotion Regulation Questionnaire (CERQ). Data were analyzed using structural equation modeling (SEM).

Results

The results showed that T2 catastrophizing mediated between acute and chronic PTSD symptoms, and T3 pain. Furthermore, the study revealed significant associations between catastrophizing, PTSD symptoms and pain at the respective measurements, and significant longitudinal associations between the constructs.

Conclusion

A negative cognitive-affective response to a burn event, such as catastrophizing, mediated the relationship acute and chronic PTSD symptoms and later chronic pain. Screening for catastrophizing and acute PTSD symptoms is recommended to identify persons at risk for chronic PTSD symptoms and pain.

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Anterior insular volume decrease is associated with dysfunction of the reward system in patients with chronic pain

Abstract

Background

Chronification of pain is associated with both anatomical and functional alterations of the brain. Alteration in regional gray matter volume might potentially be associated with modified activity of specific brain networks. In this cross-sectional, observational study, we sought to identify brain regions with gray matter volume changes in patients with chronic pain and to reveal its significance by analysing alteration in functional connectivity from those regions. We further explored relevance of such alterations with psychometrics of chronic pain.

Methods

We recruited 23 patients with chronic pain and 17 age-, gender-matched healthy control subjects. After completing multiple psychophysical questionnaires, each subject underwent resting-state functional magnetic resonance imaging and 3-dimensional anatomical imaging on a 3 Tesla magnetic resonance imaging scanner.

Results

Patients with chronic pain showed significant volume decrease at the right anterior insular cortex (p<0.001) and the left middle cingulate cortex (p<0.001) compared with healthy controls. They also showed decreased connectivity between the right anterior insular cortex and the left nucleus accumbens in negative association with the Pain Catastrophizing Scale (R²=0.20, p=0.046) and the Beck's Depression Inventory scores (R²=0.24, p=0.017).

Conclusions

Decreased gray matter volumes of those core regions for affective processing of pain might be a common cerebral feature shared by, at least some of, different aetiologies of chronic pain. Dysfunctional network between the anterior insular cortex and the nucleus accumbens might reflect affective and motivational disability involved in chronic pain. Such anatomical and functional profiles could potentially be part of a cerebral signature for chronification of pain.

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Effects of a Standard American Diet and an Anti-inflammatory Diet in Male and Female Mice

Abstract

Significance

Obesity may increase susceptibility to chronic pain often due to poor diet. Diet has potential to be used as treatment for pain. The current study investigates the use of a novel translatable diet to act as a preventative (i.e., prior to surgery) or an intervention (i.e., following an injury).

Background

Obesity and chronic pain are prevalent concerns. Pain is frequently experienced in weight bearing joints, but is common in other areas of the body as well, suggesting other factors. Poor diet often contributes to obesity and can directly influence the immune system. We have shown that poor diet prolongs recovery from inflammatory injury. Therefore, our goal was to determine if poor-quality diet-induced consequences could be prevented or reversed by an anti-inflammatory diet.

Methods

A Standard American Diet (SAD) was developed to investigate the effects of poor diet on pain. The SAD includes amounts of refined sugar, carbohydrates and fats that better model the typical American diet, as compared to high-fat diets. We developed an Anti-inflammatory Diet (AID) to explore whether the effects of the SAD could reversed or whether the AID would enhance recovery prophylactically. The AID was developed using ingredients (EGCG, sulforaphane, resveratrol, curcumin, and ginseng) with known anti-inflammatory properties. Following 15 weeks of diet (SAD, AID or regular (REG)) exposure, male and female mice underwent inflammatory injury, at which point some animals had their diets switched for the remainder of the study.

Results

Animals who consumed the SAD showed longer recovery compared to the AID and REG-fed animals. Animals switched off the SAD had faster recovery times, with AID-fed animals recovering as fast as REG-fed animals.

Conclusions

Poor diet prolonged recovery from inflammatory injury. Substitution of SAD with AID or REG promoted faster recovery. These findings suggest diet can be used as a non-pharmacological intervention following injury.

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Randomized double-blind controlled study of bedtime low dose amitriptyline in chronic neck pain

Abstract

Background

Amitriptyline has well-established efficacy in several chronic pain conditions. While optimal treatment for chronic neck pain (CNP) remains controversial, amitriptyline was not tested for CNP. We evaluated the effect of bedtime amitriptyline in the management of CNP.

Methods

220 patients suffering from idiopathic CNP were randomized to receive either placebo pill (n = 108) or 5 mg of amitriptyline (n = 112) at bedtime for two months. Primary outcome measure was visual analog scale (VAS) for pain. Secondary outcome measures were Neck pain Disability Index (NPDI), Bergen Insomnia Score (BIS), and Hospital Anxiety and Depression Scale (HAD), measured before and at the end of two months of treatment, with the percentage of patient satisfaction measured at the end of follow-up only.

Results

8/112 patients (7.14%) in the amitriptyline group withdrew from the study because of intolerance. Amitriptyline group showed significantly lower VAS scores than placebo group (3.34 ± 1.45 versus 6.12 ± 0.92; p < 0.0001), which corresponds to a 53.06 ± 20.29% of improvement from baseline pain as compared to 14.41 ± 11.05%, respectively (p < 0.0001). Similar significant improvements were observed with lesser extents for secondary outcome measures: NPDI, BIS, HAD-A, HAD-D and percentage of patient satisfaction.

Conclusion

Low-dose amitriptyline is effective for the management of idiopathic CNP with few side effects and high patients’ satisfaction.

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Assessing neuropathic pain in patients with low back-related leg pain: Comparing the painDETECT Questionnaire with the 2016 NeuPSIG grading system

Abstract

Background

Low back-related leg pain with nerve root involvement is conceptually regarded as a neuropathic condition. However, it is uncertain to what extent patients with this condition can be formally classified with neuropathic pain.

Method

First, we used the 2016 revision of the IASP Special Interest Group on Neuropathic Pain (NeuPSIG) grading system for neuropathic pain to grade patients suffering from low back-related leg pain and a corresponding disc herniation with either unlikely, possible, probable or definite neuropathic pain. Examination included bedside quantitative sensory testing. Next, we used the clinical classification based on the 2016 NeuPSIG grading system as a reference standard to assess the ability of the painDETECT Questionnaire to identify patients with neuropathic pain.

Results

Of the 50 included patients, 6 (12%) fulfilled the clinical classification criteria for probable and 44 (88%) for definite neuropathic pain, while none were graded unlikely or possible. According to painDETECT, 23 patients (46%) was classified with unlikely neuropathic pain, 18 patients (36%) had an uncertain condition, and in 9 patients (18%) neuropathic pain was likely. Among the 44 patients graded as having definite neuropathic pain by the clinical classification, 8 were classified as likely neuropathic pain by painDETECT, resulting in an agreement of 18%. Of these 44 patients graded with definite neuropathic pain, painDETECT classified 21 patients (48%) as unlikely and 15 (34%) as uncertain.

Conclusion

Our results do not support the use of painDETECT as a screening tool to classify or grade neuropathic components in patients with low back-related leg pain.

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The impact of a short educational movie on promoting chronic pain health literacy in school: a feasibility study

Abstract

Background

School-based health education programs on chronic pain providing information about the proper management of recurrent and chronic pain may increase health literacy in terms of pain knowledge and may thereby prevent dysfunctional coping and may decrease the risk of pain chronification. The aim of the present feasibility study was to evaluate the effectiveness of an educational movie on recurrent and chronic pain in increasing pain knowledge among students.

Methods

N=95 adolescent students provided demographic and pain-related information and completed a pain knowledge questionnaire before and after viewing an educational movie on recurrent and chronic pain. Participants were classified as experiencing frequent pain if they reported pain at least once a week in the last three months.

Results

One-third of the participants experienced frequent pain. There was a significant increase in pain knowledge for all participants (η_p ²=0.544). Students with frequent pain had a stronger knowledge increase regarding the management of chronic and recurrent pain than those without frequent pain (η_p ²=0.087). Sex did not moderate the gain in pain knowledge.

Conclusions

This feasibility study provides first evidence that a short educational movie on recurrent and chronic pain may increase chronic pain health literacy in students. Future studies should investigate the long-term retention of pain knowledge and any associated effects on behavior change. Due to barriers to implementation of interventional studies in the school setting, these studies should use a waitlist control group design and online data collection.

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Cumulative effects of multiple pains sites in youth with chronic pain

Abstract

Background

The experience of persistent pain in multiple locations is common in youth. Based on current literature, youth with multiple pain sites (MPS) are at risk of experiencing poorer emotional outcomes and a spread of symptoms into late adolescence and adulthood. Little is known regarding the association between MPS with physical and school functioning domains, particularly after initiation of multidisciplinary pain treatment. Therefore, the objective of this study was to examine the association of MPS with disability and school functioning among youth with chronic pain.

Methods

A total of 195 patients with chronic pain, aged 8-17, and their parents completed measures assessing patient distress and functioning at a multidisciplinary pain clinic evaluation and at 4-month follow-up.

Results

At evaluation, 63% of patients presented with MPS; 25% reporting MPS endorsed pain in five or more locations. When controlling for relevant demographic and emotional distress factors, MPS was associated with lower school functioning at evaluation with a persistent trend at follow-up. Although MPS was not a significant predictor of pain-related disability at evaluation, it emerged as significant at follow-up.

Conclusions

Potentially due to the MPS load and the inverse effects that such a pain state has on function, such patients may be at-risk for poorer health and school-related outcomes. The mechanisms influencing these relationships appear to extend beyond psychological/emotional factors and warrant further investigation in order to aid in our understanding of youth with MPS.

Significance

Youth with MPS may be at risk for experiencing poorer physical and school functioning in comparison to single-site peers, despite treatment initiation. Further research is warranted in order to inform assessment and treatment approaches for this subgroup of patients.

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Thermal pain tolerance and pain rating in normal subjects: Gender and age effects

Abstract

Background

Thermal detection thresholds and thermal pain thresholds are important in quantitative sensory testing. Although they have been well studied for assessing somatosensory function, the investigation of thermal pain tolerance has been insufficient. The aim of this study was to explore the characteristics of thermal pain tolerance and pain ratings in healthy subjects.

Methods

Cold pain tolerance (CPTol) and heat pain tolerance (HPTol) were tested in 213 healthy adults aged 18–81 years recruited from the local community. The thermal detection and thermal pain thresholds were also tested to investigate the association with pain tolerance. The visual analogue scale (VAS) was used for assessing pain severity immediately after the thermal pain and tolerance tests.

Results

The normality of the CPTol and HPTol was acceptable. Most participants rated the pain induced by the CPTol and HPTol testing as moderate. HPTol was lower in women than in men (p = 0.001), but CPTol did not differ between sexes. The pain ratings of CPTol and HPTol did not differ between sexes, but significant age effects were observed. The association of the tolerance temperature with pain ratings was weak, while those of pain ratings for CPTol and HPTol were strong (r = 0.87).

Conclusions

Women were more sensitive to tolerance heat pain stimuli. Younger participants reported more pain for thermal pain and tolerance tests.

Significance

Thermal pain tolerance and pain rating for the thermal pain tolerance temperature depend on gender and age. Women are more sensitive to heat temperatures, young people rate more pain, and the pain ratings of heat and cold are strongly correlated.

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Validation of the Pain Coping Questionnaire in Finnish

Abstract

Objective

The Pain Coping Questionnaire (PCQ), the first validated pain coping measurement developed specifically for children, has lacked proper validation in Finnish. The original PCQ by Reid et al. (Pain 1998; 76; 83–96) comprises eight-first-order and three higher-order scales. The aim herein was to determine the factor structure and validity of the Finnish PCQ translation in Finnish children.

Methods

Exploratory factor analysis was used for the first-order and higher-order classification of 91 recruited patients aged 8–15. Cronbach's alpha was used for reliability. Relationships between the Children's Depression Inventory, patient-reported pain frequency and pain coping strategies were examined.

Results

Analyses were executed with 38 items; one was excluded. A structure of eight-first-order (Internalizing/Catastrophizing [IC], Positive Self-Statements [PSS], Information Seeking [IS], Seeking Social Support [SSS], Cognitive Distraction [CD], Externalizing [EXT], Behavioural Distraction [BD], Problem Solving [PS]) and three higher-order scales (Approach [APP], Emotion-Focused Avoidance [EFA], Distraction [DIS]) proved the most consistent. Four first-order scales (PSS, CD, EXT, BD) emerged as identical to the original solution. Internal consistency reliability coefficients for all individual first- and second-order scales were satisfactory. A higher CDI score was positively related to EFA and negatively to DIS, and pain frequency positively related to APP and EFA.

Conclusion

The exploratory factor analysis of the PCQ provided a both culturally and statistically satisfactory structure in the Finnish translation. This supports the reliability and validity of the PCQ in future national use and the value of the questionnaire also outside English-speaking countries.

Significance

This study showed both culturally and statistically satisfactory factor structure of PCQ in the Finnish translation. This result supports reliability and validity of the PCQ in the national use in the future. The result shows that the PCQ is a reliable method to be used in different linguistic and cultural surroundings and, thus, encourages using it in various countries. The data consist of two patient groups, adolescents with JIA and musculoskeletal pain. Pain and specifically coping with pain are important aspects of clinical work. A valid pain coping scale may enhance distinguishing vulnerable pain coping style in children and adolescent before pain becomes chronic.

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Pain-relieving effectiveness, quality of life and tolerability of repeated capsaicin 8% patch treatment of peripheral neuropathic pain in Scandinavian clinical practice

Abstract

Context

Clinical trials have demonstrated the efficacy and safety of the capsaicin 8% patch in patients with peripheral neuropathic pain (PNP); however, few studies have assessed this treatment in a clinical practice.

Objective

To determine whether treatment and re-treatment with the capsaicin 8% patch reduce PNP intensity in clinical practice.

Methods

Three non-interventional, observational studies were concurrently conducted in Denmark, Norway and Sweden. Patients with probable or definite PNP received one or two treatments with the capsaicin 8% patch according to usual clinical practice. All analyses were performed on combined data.

Results

Overall, 382 and 181 patients received treatment and re-treatment, respectively, with the capsaicin 8% patch. At the group level, a significant reduction in mean level of ‘usual pain’ intensity (Numerical Pain Rating Scale) over the last 24 h’ score was observed from baseline to Weeks 2 through 8 [−1.05 (95% confidence interval: −1.27, 0.82); p < 0.001] with 28% and 31% of patients reporting a ≥30% reduction in pain after first treatment and re-treatment, respectively. Improvements in health-related quality of life (EQ-5D-3L index) and overall health status (Patient Global Impression of Change) were observed early (Week 1) and throughout the treatment periods. Most application site reactions subsided within a week after treatment. Following treatment and re-treatment, 57% and 71% of patients, respectively, were willing to undergo further treatment with the capsaicin 8% patch.

Conclusion

In Scandinavian clinical practice, capsaicin 8% patch treatment was associated with significant reductions in pain intensity and was well tolerated with over half of patients willing to undergo re-treatment.

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Effect of local wound infiltration with ketamine versus dexmedetomidine on postoperative pain and stress after abdominal hysterectomy, a randomized trial

Abstract

Background and Objectives

Postoperative pain and stress elicit hormonal changes. We aimed at comparing the effects of wound infiltration with ketamine versus dexmedetomidine on postoperative pain and stress response.

Methods

This double-blinded study included ninety patients scheduled for total abdominal hysterectomy and were randomly assigned into three groups to receive local wound infiltration with 40 mL of 0.25% bupivacaine (group C), plus 2 mg/kg ketamine (group K) or 2 μg/kg dexmedetomidine (group D). Primary outcome was postoperative morphine consumption; secondary outcomes included first request of analgesia, VAS scores at rest and movement (VAS–R/M) and side effects. Serum cortisol, prolactin and glucose levels at baseline, pre-infiltration, 6 and 24 h postoperatively were measured.

Results

Rescue analgesia was less in K (6.80 ± 3.19 mg) and D (8.39 ± 3.86 mg) compared to C (13.33 ± 4.01 mg) (p < 0.05). First request of analgesia was delayed in K (7.60 ± 4.16 h) and D (6.00 ± 3.73 h) compared to C (4.20 ± 1.13 h) (p < 0.05). Both VAS and R/M were significantly lower in K (all over 24 h) and D (for 8 and 4 h, respectively) compared to C. Stress markers were significantly lower in K and D compared to C at 6 and 24 h, and in K compared to D at 24 h (p < 0.05).

Conclusions

Local wound infiltration with ketamine or dexmedetomidine added to bupivacaine had an opioid-sparing effect, delayed first request of rescue analgesia, and attenuated postoperative stress response, especially with ketamine in patients underwent total abdominal hysterectomy.

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Medical cannabis: A forward vision for the clinician

Abstract

Medical cannabis has entered mainstream medicine and is here to stay. Propelled by public advocacy, the media and mostly anecdote rather than sound scientific study, patients worldwide are exploring marijuana use for a vast array of medical conditions including management of chronic pain. Contrary to the usual path of drug approval, medical cannabis has bypassed traditional evidence-based study and has been legalized as a therapeutic product by legislative bodies in various countries. While there is a wealth of basic science and preclinical studies demonstrating effects of cannabinoids in neurobiological systems, especially those pertaining to pain and inflammation, clinical study remains limited. Cannabinoids may hold promise for relief of symptoms in a vast array of conditions, but with many questions as yet unanswered. Rigorous study is needed to examine the true evidence for benefits and risks for various conditions and in various patient populations, the specific molecular effects, ideal methods of administration, and interaction with other medications and substances. In the context of prevalent use, there is an urgency to gather pertinent clinical information about the therapeutic effects as well as risks. Even with considerable uncertainties, the health care community must adhere to the guiding principle of clinical care ‘primum non nocere’ and continue to provide empathetic patient care while exercising prudence and caution. The health care community must strongly advocate for sound scientific evidence regarding cannabis as a therapy.

Significance

Legalization of medical cannabis has bypassed usual drug regulatory procedures in jurisdictions worldwide. Pending sound evidence for effect in many conditions, physicians must continue to provide competent empathetic care with attention to harm reduction. A vision to navigate the current challenges of medical cannabis is outlined.

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Dipyrone is the preferred non-opioid analgesic for the treatment of acute and chronic pain. A survey of clinical practice in German speaking countries

Abstract

Purpose

Non-opioid analgesics are frequently used for the treatment of acute and chronic pain. Dipyrone is an alternative to NSAIDs and paracetamol, however, data on the frequency of its usage by anaesthesiologists in the perioperative and chronic pain setting are lacking and its adverse reactions are a matter of debate.

Methods

The link to a questionnaire on the use of non-opioid analgesics (NSAIDs, COX2 inhibitors, paracetamol, dipyrone) and the safety of dipyrone in the perioperative and chronic pain setting was mailed to anaesthesiologists and pain physicians.

Results

A total of 2237 responses were analysed. 97.4% of the respondents used non-opioid analgesics for the treatment of acute pain, with 93.8% administering dipyrone, 54.0% NSAIDs, 41.8% COX2-inhibitors and 49.2% paracetamol. Non-opioid analgesics were administered preoperatively by 22.3%, intraoperatively by 86.1% and postoperatively by 73% of the respondents. For chronic pain management, 76.7% of the respondents prescribed oral dipyrone in combination with other non-opioid analgesics. 19.9% used dipyrone as sole non-opioid, whereas 2.9% denied its use. Cases of dipyrone associated agranulocytosis were observed by 3.5% of the respondents of the acute and 1.5% of the chronic pain questionnaire, respectively. The majority of respondents (acute pain: 73.0%, chronic pain 59.3%) performed no blood cell counts to monitor dipyrone therapy. Patients were rarely informed about possible adverse drug reactions.

Conclusions

Dipyrone is the preferred non-opioid analgesic in the perioperative and chronic pain setting. Although cases of agranulocytosis occur, benefits apparently outweigh the risks according to anaesthesiologists. Measures like patient information may improve safety.

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Gene transfer of a naked plasmid (pUDK-HGF) encoding human hepatocyte growth factor attenuates skin/muscle incision and retraction-induced chronic post-surgical pain in rats

Abstract

Background

Chronic post-surgical pain (CPSP) remains a major clinical problem and is often refractory to current treatments. New analgesic medications and strategies for pain relief are needed. Hepatocyte growth factor (HGF) is known to be a multi-functional growth factor and regulates various biological activities.

Methods

We investigated the analgesic effect and underlying mechanism of plasmid pUDK-HGF encoding human HGF gene on CPSP induced by skin/muscle incision and retraction (SMIR) in rats. The possible changes of inflammatory factors, glial cell activation and pain sensitivity after pUDK-HGF administration were investigated by ELISA, western blot and Von Frey tests, respectively.

Results

In behavioural assays, we found that a single intramuscular or intrathecal injection of pUDK-HGF significantly attenuated mechanical hypersensitivity to von Frey stimulation of plantar ipsilateral hind paw after SMIR. Intramuscular injection of pUDK-HGF promoted blood flow and proliferation of satellite cells and inhibited inflammatory cells recruitment, collagen accumulation and expression of pronociceptive factors. Intrathecal injection of pUDK-HGF inhibited activation of spinal glial cells and production of inflammatory mediators induced by SMIR.

Conclusions

pUDK-HGF has a strong analgesic potency and efficacy in CPSP induced by SMIR in rats. This study highlights a new strategy for the treatment of CPSP.

Significance

The CPSP occurs following various surgical procedures and remains a major clinical problem due to the lack of study on the mechanisms of CPSP. Our findings provide the first evidence that pUDK-HGF attenuates SMIR-induced pain behaviuors through peripheral or central mechanisms. The peripheral analgesic effect of pUDK-HGF is associated with promoting tissue repair and inhibiting inflammatory response; furthermore, pUDK-HGF inhibits activation of spinal glial cells and overexpression of inflammatory mediators in spinal cord. Therefore, naked pUDK-HGF may be a potential therapeutic strategy for treatment of CPSP in clinic.

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Blockade of dopamine D2 receptors disrupts intrahippocampal connectivity and enhances pain-related working memory deficits in neuropathic pain rats

Abstract

Background

Dopamine (DA) is thought to be important to local hippocampal networks integrity during spatial working memory (sWM) processing. Chronic pain may contribute to deficient dopaminergic signalling, which may in turn affect cognition. However, the neural mechanisms that determine this impairment are poorly understood. Here, we evaluated whether the sWM impairment characteristic of animal models of chronic pain is dependent on DA D2 receptor (D2r) activity.

Methods

To address this issue, we implanted multichannel arrays of electrodes in the dorsal and ventral hippocampal CA1 field (dvCA1) of rats and recorded the neuronal activity during a classical delayed food-reinforced T-maze sWM task. Within-subject behavioural performance and patterns of dorsoventral neural activity were assessed before and after the onset of persistent neuropathic pain using the spared nerve injury (SNI) model.

Results

Our results show that the peripheral nerve lesion caused a disruption in sWM and hippocampus spike activity and that disruption was maximized by the systemic administration of the D2r antagonist raclopride. These deficits are strictly correlated with a selective disruption of hippocampal theta-oscillations. Particularly, we found a significant decrease in intrahippocampal CA1 field connectivity level.

Conclusions

Together, these results suggest that disruption of the dopaminergic balance in the intrahippocampal networks may be important for the development of cognitive deficits experienced during painful conditions.

Significance

This study provides new insights into the role of D2r in the manifestation of pain-related sWM deficits. Our findings support that selective blockade of D2r produces a significant decrease in intrahippocampal connectivity mediated by theta-oscillations, and amplifies pain-related sWM deficits. These results suggest that further characterization of intrahippocampal dopaminergic modulation may be clinically relevant for the understanding of cognitive impairments that accompanies nociceptive stressful conditions.

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Reciprocal associations of pain and post-traumatic stress symptoms after whiplash injury: A longitudinal, cross-lagged study

Abstract

Background

The objectives of the current study were to investigate (1) the longitudinal, reciprocal associations between pain and post-traumatic stress symptoms as proposed by the mutual maintenance model, and (2)  to assess the predictive value of the three clusters of post-traumatic stress, where the model revealed that post-traumatic stress symptoms maintained pain in a consecutive cohort of whiplash-injured.

Methods

Participants (n = 253; 66.4% women) were people with WAD grades I–III following motor vehicle crashes in Australia. Pain and post-traumatic stress symptoms were assessed by questionnaires over the course of a year (at baseline (<4 weeks), 3, 6 and 12 months post-injury). The objectives were tested using auto-regressive cross-lagged modelling and two additional structural equation models.

Results

The analyses revealed that post-traumatic stress symptoms at baseline predicted an increase in pain between baseline and 3 months and that post-traumatic stress symptoms at 6 months predicted an increase in pain between 6 and 12 months, beyond the stability of pain over time. Furthermore, hyperarousal at baseline significantly predicted pain at 3 months and hyperarousal at 6 months significantly predicted pain at 12 months with 16 and 30% explained variance, respectively.

Conclusions

The results point to a temporal main effect of post-traumatic stress symptoms on pain over and above the stability of pain itself within the first 3 months post-injury and again in the chronic phase from 6 to 12 months with hyperarousal symptoms driving these effects. From 3 to 6 months, there was a slip in the maintenance patterns with no cross-lagged effects.

Significance

Investigating mutual maintenance of pain and PTSS in whiplash, the present study found evidence suggesting a maintaining effect of PTSS on pain within the first 3 months post-injury and from 6 to 12 months driven by hyperarousal, highlighting the importance of addressing PTSS.

from European Journal of Pain http://ift.tt/2BuLkQd
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