Syfte: Syftet med denna studie var att undersöka hur statisk muskelkontraktion och cold pressor test påverkar kroppsegna smärtreglerande system (”Exercise induced analgesia” (EIA) och ”Conditioned pain modulation” (CPM)) hos patienter med kronisk ländryggssmärta kännetecknad av lumbal myalgi (LM) jämfört med friska kontroller. Försökspersoner och metod: Tjugosex friska köns- och åldersmatchade personer och tjugosex LM-patienter deltog. De utförde standardiserad statisk muskelkontraktion med m. Erector spinae (ME) i form av rygglyft och kontraktion av m. Quadriceps femoris (MQ) i form av knäledsextension. För att bedöma CPM användes sk cold pressor test. Smärttrösklar för tryck (PPTs) mättes över m. Deltoideus (MD), m. Erector spinae (ME) samt över m. Quadriceps (MQ) i vila och under resp. efter kontraktionen/cold pressor test. Under kontraktion mättes PPTs över den arbetande muskeln respektive över de två vilande musklerna. Dessutom undersöktes PPTs och känsligheten för övertrösklig trycksmärta (P7) i vila på 8 olika punkter på kroppen. Resultat: Kvinnliga LM-patienter hade ökad känslighet för trycksmärta (PPT) och övertrösklig trycksmärta (P7) jämfört med köns- och åldermatchade friska kontroller, medan manliga LM-patienter paradoxalt nog hade minskad känslighet för övertrösklig trycksmärta. Beträffande EIA fann vi att LM-patienter och kontroller kunde aktivera lokal EIA under kontraktion med ME. Vi fann dessutom en minskad förmåga hos LM-patienter att rekrytera generaliserad EIA under kontraktion med MQ. Slutligen hade LM-patienterna en normal funktion av CPM. Slutsats: LM-patienter kunde aktivera lokal EIA under kontraktion av ME, men hade mindre effektiv generaliserad EIA jämfört med kontrollerna, trots normal funktion av CPM. Våra resultat tyder på att muskelarbete med smärtande ryggmuskler skulle kunna användas för att minska smärtkänslighet i det drabbade området.

Introdução: As estatinas são drogas amplamente utilizadas na prevenção primária e secundária de doenças cardiovasculares, por reduzirem o nível de colesterol. Porém alguns pacientes podem apresentar elevação da creatinofosfoquinase (CPK) e sintomas musculares relacionados ao seu uso. Além da CPK, outros marcadores de dano muscular podem apresentar alterações. Este estudo analisou a concentração dos marcadores bioquímicos, CKMB e anidrase carbônica III (CAIII) e sua relação com a presença de miosite. Métodos: Foram selecionados pacientes em tratamento com estatinas e com elevação da CPK. Foram realizadas as determinações de CKMB e CAIII e analisadas as variáveis clínicas e laboratoriais destes pacientes. Resultados: Cerca de 10% dos pacientes em tratamento com estatina apresentaram elevações de CPK acima 1x o limite superior de normalidade (LSN). Desses, 50,4% apresentaram sintomas musculares, definido como miosite. O uso de sinvastatina [OR=2,24 (IC95%:1,47-3,42)], o índice de massa corpórea > 28 Kg/m2 [OR=1,06 (IC95%: 1,01-1,10)] e a CKMB > 1xLSN [OR=1,59 (IC95%: 1,02-2,49)] apresentaram-se como preditores independentes para a ocorrência de miosite. A CKMB aumentada foi observada em 36,2% dos pacientes (7,17±4,4 ng/mL). Os pacientes com e sem miosite apresentaram valores semelhantes de CAIII (211,3±93,4pg/mL vs 204,0±84,6pg/mL; p=0,549). Pacientes diabéticos apresentaram elevações significantes de CKMB em relação aos não diabéticos (4,8±4,6ng/mL vs 3,5±2,4ng/mL; p=0,0006) e não apresentaram diferenças quanto à presença de miosite. Conclusão: A CKMB apresentou alteração em parte dos pacientes tratados com estatinas e foi um preditor independente para a presença de miosite. A CAIII não foi considerada um bom marcador de dano muscular na população deste estudo / Introduction: Statins are drugs widely used in primary and secondary prevention of cardiovascular diseases, due to the decreasing effect on cholesterol level. However, some patients may present elevated levels of creatine phosphokinase (CK) and muscle symptoms related to statin use. In addition to CK, other markers of muscle damage may present changes. This study analyzed the concentration of biochemical markers, CKMB and carbonic anhydrase III (CAIII) and related them to the presence of myositis. Methods: Patients on statin therapy and CK elevation were selected. CKMB and (CAIII) assays were performed and the clinical and laboratory variables of these patients were analyzed. Results: About 10% of the patients receiving statin therapy (6692) presented CK elevations above 1x upper reference limit (URL). Muscular symptoms, defined as myositis, were presented in 50.4% of these patients. Use of simvastatin [OR=2,24 (IC95%:1,47-3,42)], a body mass index > 28 kg / m2 [OR = 1.06 (95% CI: 1.01-1, 10)] and a concentration of CKMB > 1x URL [OR = 1.59 (95% CI: 1.02-2.49)] presented as independent predictors for the occurrence of myositis. Increased CKMB was observed in 36.2% of patients (7.17 ± 4.4 ng / mL). Patients with and without myositis had similar CAIII values (211.3 ± 93.4pg / mL vs 204.0 ± 84.6pg / mL, p = 0.549). Diabetic patients showed significant elevations of CKMB compared to non-diabetic patients (4.8 ± 4.6 ng / mL vs. 3.5 ± 2.4 ng / mL, p = 0.0006) and did not present differences regarding the presence of myositis. Conclusion: CKMB level changed in part of the patients treated with statins and this enzyme was an independent predictor for the presence of myositis. CAIII was not considered a good marker of muscle damage in the studied population

SyfteUndersöka påverkan av kronisk orofacial smärta och psykologiska faktorer på sömnkvalitet vid käkmuskelmyalgi.Material och metoderDenna retrospektiva studie omfattade 37 patienter (6 män, 31 kvinnor, medelålder: 49 år) med käkmuskelmyalgi. Sömnkvalitet (Pittsburgh Sleep Quality Index), smärtintensitet och smärtrelaterad funktionsnedsättning (Graded Chronic Pain Scale), depression (Patient Health Questionnaire-9), ångest (General Anxiety Disorder-7), stress (Perceived Stress Scale-10) och katastrofiering (Patient Catastrophizing Scale) undersöktes med varierade formulär. Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) användes för att identifiera patienter med myalgi i käkmuskulatur.Resultat75% av patienterna rapporterade dålig sömnkvalitet, 73% rapporterade minst mild depressionsgrad, 54% rapporterade minst mild ångest, 59% rapporterade måttlig stressnivå och 38% rapporterade kliniskt relevant katastrofiering. Försämrad sömnkvalitet var relaterad till depression (rs = 0.45, n = 37, p = 0.008) ångest (rs = 0.46, n = 37, p = 0.007), stress (rs = 0.43, n = 37, p = 0.014) och katastrofiering (rs = 0.37, n = 37, p = 0.034). Multivariat logistisk regression visade att smärtintensitet, smartrelaterad funktionsnedsättning, depression, ångest, stress, katastrofiering och antal käkmuskler med refererad palpationssmärta förklarade dålig sömnkvalitet signifikant (p = 0.031).KonklusionSömnkvaliteten hos patienter med käkmuskelmyalgi påverkas i hög grad av kronisk smärtintensitet, smärtrelaterad funktionsnedsättning, antal käkmuskler med refererad palpationssmärta och depression samt ångest, stress och katastrofiering. / AimInvestigate the influence of chronic orofacial pain and psychological factors on sleep quality in patients with myalgia of the masticatory muscles.Material and methodsThis retrospective study included 37 patients (6 men, 31 women, mean age: 49 years) with masticatory muscle myalgia. Sleep quality (Pittsburgh Sleep Quality Index), pain intensity and pain-related disability (Graded Chronic Pain Scale), depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), stress (Perceived Stress Scale-10) and catastrophizing (Patient Catastrophizing Scale) were assessed by questionnaires. The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) were used to identify patients with myalgia.Results75% of the patients reported poor sleep quality, 73% reported at least mild depression degree, 54% reported at least mild degree of anxiety, 59% reported at least a moderate stress level and 38% reported a clinically relevant degree of catastrophizing. Impaired sleep quality was related to degree of depression (rs = 0.45, n = 37, p = 0.008), anxiety (rs = 0.46, n = 37, p = 0.007), stress (rs = 0.43, n = 37, p = 0.014) and catastrophizing (rs = 0.37, n = 37, p = 0.034). Multivariate logistic regression showed that characteristic pain intensity, degree of pain-related disability, depression, anxiety, stress, catastrophizing and number of masticatory muscle sites with referred pain significantly explained poor sleep quality (p = 0.031).ConclusionSleep quality in patients with masticatory myalgia is influenced by chronic pain intensity and related disability, number of masticatory muscle sites with referred pain as well as depression, anxiety, stress and catastrophizing.

Indiana University-Purdue University Indianapolis (IUPUI) / Aromatase inhibitors (AIs) are the current standard of care for the treatment of hormone receptor positive breast cancer in postmenopausal women. Nearly one-half of patients receiving AI therapy develop musculoskeletal toxicity that is characterized by joint and/or muscle pain and approximately one-fourth of patients discontinue their therapy as a result of musculoskeletal pain. Since there are no effective strategies for prevention or treatment, insight into the mechanisms of AI-induced pain is critical to improve treatment. However, there are few studies of AI effects in animal models of nociception. To determine whether AIs produce hypersensitivity in animal models of pain, I examined the effects of AI administration on mechanical, thermal, and chemical sensitivity in rats. The results demonstrate that (1) repeated injection of 5 mg/kg letrozole in male rats produces mechanical, but not thermal, hypersensitivity that extinguishes when drug dosing is stopped; (2) administering a single dose of 1 or 5 mg/kg letrozole in ovariectomized (OVX) rats also induces mechanical hypersensitivity, without altering thermal sensitivity and (3) a single dose of 5 mg/kg letrozole or daily dosing of letrozole or exemestane in male rats augments flinching behavior induced by intraplantar ATP injection. To determine whether the effects of AIs on nociceptive behaviors are mediated by activation or sensitization of peptidergic sensory neurons, I determined whether letrozole exposure alters release of calcitonin gene-related peptide (CGRP) from isolated rat sensory neurons and from sensory nerve endings in rat spinal cord slices. No changes in basal, capsaicin-evoked or high extracellular potassium-evoked CGRP release were observed in sensory neuronal cultures acutely or chronically exposed to letrozole. Furthermore, letrozole exposure did not alter the ability of ATP to augment CGRP release from sensory neurons in culture. Finally, chronic letrozole treatment did not augment neuropeptide release from spinal cord slices. Taken together, these results do not support altered release of this neuropeptide into the spinal cord as mediator of letrozole-induced mechanical hypersensitivity and suggest the involvement of other mechanisms. Results from this dissertation provide a new experimental model for AI-induced hypersensitivity that could be beneficial in delineating mechanisms mediating pain during AI therapy.

Indiana University-Purdue University Indianapolis (IUPUI) / Symptoms of post-traumatic stress disorder (PTSD) are a common comorbidity in veterans seeking treatment of chronic musculoskeletal pain (CMP). However, little is known regarding the mutual influence of PTSD and CMP in this population. Using cross-sectional and longitudinal data from a randomized clinical trial evaluating a stepped care intervention for CMP in Iraq/Afghanistan veterans (ESCAPE), this dissertation examined the relationships between PTSD and CMP along with other factors including depression, anxiety, catastrophizing and health-related quality of life. The Classification and Regression Tree (CART) analysis was conducted to identify key factors associated with baseline PTSD besides CMP severity. A series of statistical analyses including logistical regression analysis, mixed model repeated measure analysis, confirmatory factor analysis and cross-lagged panel analysis via structural equation modeling were conducted to test five competing models of PTSD symptom clusters, and to examine the mutual influences of PTSD symptom clusters and CMP outcomes. Results showed baseline pain intensity and pain disability predicted PTSD at 9 months. And baseline PTSD predicted improvement of pain disability at 9 months. Moreover, direct relationships were found between PTSD and the disability component of CMP, and indirect relationships were found between PTSD, CMP and CMP components (intensity and disability) mediated by depression, anxiety and pain catastrophizing. Finally, the coexistence of PTSD and more severe pain was associated with worse SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Together these findings provided empirical support for the mutual maintenance theory.