Oral combined hormonal contraceptive associated with protection against allodynia in migraine in a cross-sectional study.

INTRODUCTION: For the most part, migraine afflicts young women who often need to use the hormonal contraceptive method. OBJECTIVE: To evaluate the effects of using exogenous estrogen, present in combined hormonal contraceptives (CHC) and progestin-only methods on the prevalence of allodynia in women with migraine. METHODS: Study comprising women diagnosed with migraine, with or without aura, who were not pregnant, breastfeeding, or menopausal. The study was conducted via the digital platform. Data were collected relating to demographics, contraceptive method, anthropometric information, smoking habits, and migraine-related symptoms. The participants then answered the following validated, self-administered questionnaires: Migraine Disability Assessment (MIDAS), Allodynia Symptom Checklist, Generalized Anxiety Disorder (GAD-7), and Beck's Depression Inventory (BDI). In order to determine the variables associated with allodynia, two binary logistic regression models were used. RESULTS: Four hundred eighty-six women took part in the study. Of these, 205 used CHC, 89 used a progestin-only method, and 192 participants did not use any form of hormonal contraception. Allodynia was identified in 411 (84.6%) participants. Allodynia was linked to the presence of aura (OR = 2.76; CI 95% 1.55-4.91; p = 0.001), menstrually related migraine (OR = 2.14; CI 95% 1.28-3.57; p = 0.004), greater disability (MIDAS score 23 vs. 8; p < 0.001), depression (BDI score 14 vs. 10; p < 0.001), and anxiety (GAD-7 score 11 vs. 8; p < 0.001). In adjusted analysis, CHC was associated to protection against allodynia when jointly evaluated all CHC regimens (OR = 0.49 CI 95% 0.26-0.92; p = 0.028), as well as oral CHC individually (OR = 0.48 CI 95% 0.25-0.92; p = 0.027). CONCLUSION: CHC reduced the chances of women with migraine getting allodynia.

An Adapted Chronic Constriction Injury of the Sciatic Nerve Produces Sensory, Affective, and Cognitive Impairments: A Peripheral Mononeuropathy Model for the Study of Comorbid Neuropsychiatric Disorders Associated with Neuropathic Pain in Rats.

BACKGROUND: Chronic constriction injury (CCI) is a model of neuropathic pain induced by four loose ligatures around the sciatic nerve. This work aimed to investigate the sensory, affective, cognitive, and motor changes induced by an adaptation of the CCI model by applying a single ligature around the sciatic nerve. METHODS: Mechanical allodynia was measured from day 1 to day 28 postsurgery by the von Frey test. The beam walking test (BWT) was conducted weekly until 28 days after surgery. Anxiety- and depression-like behaviors, and cognitive performance were assessed through the open field (OF), forced swimming (FS), and novel object recognition (NOR) tests, respectively, 21 days after surgery. RESULTS: The two CCI models, both Bennett and Xie's model (four ligatures of the sciatic nerve) and a modification of it (one ligature), induced mechanical allodynia, increased immobility in the FS, and reduced recognition index in the NOR. The exploratory behavior and time spent in the central part of the arena decreased, while the defensive behavior increased in the OF. The animals subjected to the two CCI models showed motor alterations in the BWT; however, autotomy was observed only in the group with four ligatures and not in the group with a single ligature. CONCLUSIONS: Overall these results demonstrate that our adapted CCI model, using a single ligature around the sciatic nerve, induces sensory, affective, cognitive, and motor alterations comparable to the CCI model with four ligatures without generating autotomy. This adaptation to the CCI model may therefore represent an appropriate and more easily performed model for inducing neuropathic pain and study underlying mechanisms and effective treatments.

Co-occurrence of pain syndromes.

Many pain conditions in patients tend to co-occur, influencing the clinical expressions of each other in various ways. This paper summarizes the main concurrent pain conditions by analyzing the major interactions observed. In particular, co-occurrence will be examined in: visceral pain (especially ischemic heart disease, irritable bowel syndrome, dysmenorrhea/endometriosis and urinary pain), fibromyalgia, musculoskeletal pain and headache. Two concurrent visceral pains from internal organs sharing at least part of their central sensory projection can give rise to viscero-visceral hyperalgesia, i.e., enhancement of typical pain symptoms from both districts. Visceral pain, headache and musculoskeletal pains (myofascial pain from trigger points, joint pain) can enhance pain and hyperalgesia from fibromyalgia. Myofascial pain from trigger points can perpetuate pain symptoms from visceral pain conditions and trigger migraine attacks when located in the referred pain area from an internal organ or in cervico-facial areas, respectively. The pathophysiology of these pain associations is complex and probably multifactorial; among the possible processes underlying the mutual influence of symptoms recorded in the associations is modulation of central sensitization phenomena by nociceptive inputs from one or the other condition. A strong message in these pain syndrome co-occurrence is that effective treatment of one of the conditions can also improve symptoms from the other, thus suggesting a systematic and thorough evaluation of the pain patient for a global effective management of his/her suffering.

Myofascial pain, widespread pressure hypersensitivity, and hyperalgesia in the face, neck, and shoulder regions, in survivors of head and neck cancer.

PURPOSE: Medical treatment for head and neck cancer may induce the presence of inflammation, pain, and dysfunction. The purpose of the current study was to assess the presence of myofascial trigger points (TrPs) and their relationship with widespread pressure hypersensitivity and hyperalgesia in survivors of head and neck cancer (sHNC). METHODS: TrPs and pressure-pain thresholds (PPTs) were quantified in different muscles/joints in the head and neck of 30 sHNC (59.45 ± 13.13 years) and 28 age- and sex-matched controls (58.11 ± 12.67 years). RESULTS: The sHNC had more TrPs in all muscles on the affected side (p < 0.05) than did the healthy controls, and in the temporalis, masseter, and suboccipitalis muscles on the unaffected side (p < 0.05). They also had lower PPTs in all places (p < 0.05) except for the temporalis muscle (p = 0.114) and C5-C6 joint (p = 0.977). The intensity of cervical pain correlated positively with the presence of upper trapezius TrPs. CONCLUSIONS: sHNC suffering cervical and/or temporomandibular joint pain have multiple active TrPs and experience widespread pressure hypersensitivity and hyperalgesia, suggestive of peripheral and central sensitization.

Opioid-Based Anesthesia and Analgesia for Adult Cardiac Surgery: History and Narrative Review of the Literature.

Opioids have played in a key role in cardiac anesthesia and analgesia since the early years of cardiac surgery. Today, opioids continue to be the primary mode for analgesia in cardiac surgery, yet there is considerable variability in the choice, dose and route of used. A history of the use of opioids in cardiothoracic anesthesia is presented, followed by an examination of the differences among current opioids in use and of outcome variables important in cardiac anesthesia, such as postoperative analgesia, extubation times, fast-track cardiac anesthesia, chronic neuropathic pain, and cardioprotection. Topical issues such as the role of perioperative opioid use in the global opioid crisis, opioid-sparing techniques and novel opioids in development are also discussed.

Perioperative intravenous ketamine for acute postoperative pain in adults.

BACKGROUND: Inadequate pain management after surgery increases the risk of postoperative complications and may predispose for chronic postsurgical pain. Perioperative ketamine may enhance conventional analgesics in the acute postoperative setting. OBJECTIVES: To evaluate the efficacy and safety of perioperative intravenous ketamine in adult patients when used for the treatment or prevention of acute pain following general anaesthesia. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to July 2018 and three trials registers (metaRegister of controlled trials, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP)) together with reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA: We sought randomised, double-blind, controlled trials of adults undergoing surgery under general anaesthesia and being treated with perioperative intravenous ketamine. Studies compared ketamine with placebo, or compared ketamine plus a basic analgesic, such as morphine or non-steroidal anti-inflammatory drug (NSAID), with a basic analgesic alone. DATA COLLECTION AND ANALYSIS: Two review authors searched for studies, extracted efficacy and adverse event data, examined issues of study quality and potential bias, and performed analyses. Primary outcomes were opioid consumption and pain intensity at rest and during movement at 24 and 48 hours postoperatively. Secondary outcomes were time to first analgesic request, assessment of postoperative hyperalgesia, central nervous system (CNS) adverse effects, and postoperative nausea and vomiting. We assessed the evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included 130 studies with 8341 participants. Ketamine was given to 4588 participants and 3753 participants served as controls. Types of surgery included ear, nose or throat surgery, wisdom tooth extraction, thoracotomy, lumbar fusion surgery, microdiscectomy, hip joint replacement surgery, knee joint replacement surgery, anterior cruciate ligament repair, knee arthroscopy, mastectomy, haemorrhoidectomy, abdominal surgery, radical prostatectomy, thyroid surgery, elective caesarean section, and laparoscopic surgery. Racemic ketamine bolus doses were predominantly 0.25 mg to 1 mg, and infusions 2 to 5 µg/kg/minute; 10 studies used only S-ketamine and one only R-ketamine. Risk of bias was generally low or uncertain, except for study size; most had fewer than 50 participants per treatment arm, resulting in high heterogeneity, as expected, for most analyses. We did not stratify the main analysis by type of surgery or any other factor, such as dose or timing of ketamine administration, and used a non-stratified analysis.Perioperative intravenous ketamine reduced postoperative opioid consumption over 24 hours by 8 mg morphine equivalents (95% CI 6 to 9; 19% from 42 mg consumed by participants given placebo, moderate-quality evidence; 65 studies, 4004 participants). Over 48 hours, opioid consumption was 13 mg lower (95% CI 10 to 15; 19% from 67 mg with placebo, moderate-quality evidence; 37 studies, 2449 participants).Perioperative intravenous ketamine reduced pain at rest at 24 hours by 5/100 mm on a visual analogue scale (95% CI 4 to 7; 19% lower from 26/100 mm with placebo, high-quality evidence; 82 studies, 5004 participants), and at 48 hours by 5/100 mm (95% CI 3 to 7; 22% lower from 23/100 mm, high-quality evidence; 49 studies, 2962 participants). Pain during movement was reduced at 24 hours (6/100 mm, 14% lower from 42/100 mm, moderate-quality evidence; 29 studies, 1806 participants), and 48 hours (6/100 mm, 16% lower from 37 mm, low-quality evidence; 23 studies, 1353 participants).Results for primary outcomes were consistent when analysed by pain at rest or on movement, operation type, and timing of administration, or sensitivity to study size and pain intensity. No analysis by dose was possible. There was no difference when nitrous oxide was used. We downgraded the quality of the evidence once if numbers of participants were large but small-study effects were present, or twice if numbers were small and small-study effects likely but testing not possible.Ketamine increased the time for the first postoperative analgesic request by 54 minutes (95% CI 37 to 71 minutes), from a mean of 39 minutes with placebo (moderate-quality evidence; 31 studies, 1678 participants). Ketamine reduced the area of postoperative hyperalgesia by 7 cm² (95% CI -11.9 to -2.2), compared with placebo (very low-quality evidence; 7 studies 333 participants). We downgraded the quality of evidence because of small-study effects or because the number of participants was below 400.CNS adverse events occurred in 52 studies, while 53 studies reported of absence of CNS adverse events. Overall, 187/3614 (5%) participants receiving ketamine and 122/2924 (4%) receiving control treatment experienced an adverse event (RR 1.2, 95% CI 0.95 to 1.4; high-quality evidence; 105 studies, 6538 participants). Ketamine reduced postoperative nausea and vomiting from 27% with placebo to 23% with ketamine (RR 0.88, 95% CI 0.81 to 0.96; the number needed to treat to prevent one episode of postoperative nausea and vomiting with perioperative intravenous ketamine administration was 24 (95% CI 16 to 54; high-quality evidence; 95 studies, 5965 participants). AUTHORS' CONCLUSIONS: Perioperative intravenous ketamine probably reduces postoperative analgesic consumption and pain intensity. Results were consistent in different operation types or timing of ketamine administration, with larger and smaller studies, and by higher and lower pain intensity. CNS adverse events were little different with ketamine or control. Perioperative intravenous ketamine probably reduces postoperative nausea and vomiting by a small extent, of arguable clinical relevance.

Unraveling Self-Reported Signs of Central Sensitization in Breast Cancer Survivors with Upper Limb Pain: Prevalence Rate and Contributing Factors.

BACKGROUND: Hypersensitivity of the central nervous system to environmental and chemical stimuli is a clinical feature of central sensitization mechanisms that can be assessed with the central sensitization inventory (CSI). OBJECTIVE: The aim was to determine prevalence rate of this feature and explore the treatment-, patient-, pain-, and psychosocial-related variables associated with the degree of self-reported signs of central sensitization, assessed with the CSI (0-100), in breast cancer survivors at long-term. STUDY DESIGN: Cross-sectional study. SETTING: University Hospitals, Leuven, Belgium. METHODS: One hundred and forty-six women with persistent pain, more than one year after breast cancer surgery, were included. The following factors were analyzed by bivariable and multivariable analysis: 1) treatment-related variables (type of surgery, levels of lymph node dissected, radiotherapy, chemotherapy, hormone therapy, and trastuzumab); 2) patient's related variables (age and body mass index); 3) pain-related variables (pain intensity, pain quality, primary hyperalgesia, and index of widespread pain); and 4) psychosocial variables (the degree of pain catastrophizing and vigilance and awareness to pain). The dependent variable was degree of central sensitization measured with the CSI. Additionally, a stepwise regression was performed. RESULTS: Fifty-five (38%) patients reported signs of central sensitization measured with the CSI (i.e., > 40/100). From multivariable analysis, it appears that more severe pain quality and higher levels of pain catastrophizing contribute to a higher degree of central sensitization. The stepwise regression revealed that up to 24% of variance of the CSI can be explained by these factors. LIMITATIONS: A selection bias may be present since patients were all recruited from a larger cohort participating in clinical trials on the effectiveness of physical therapy after breast cancer treatment. CONCLUSION: Signs of central sensitization cannot be neglected in breast cancer survivors at long term. More severe pain quality and pain catastrophizing contribute to higher levels of central sensitization in this population. KEY WORDS: Breast neoplasm, pain, central sensitization mechanisms, central sensitization inventory.

Characterization of migraineurs presenting interictal widespread pressure hyperalgesia identified using a tender point count: a cross-sectional study.

BACKGROUND: Migraineurs exhibit pain hypersensitivity throughout the body during and between migraine headaches. Migraine is classified as a central sensitivity syndrome, typified by fibromyalgia showing widespread pressure hyperalgesia determined by a tender point. This study was performed to examine whether: 1) there is a subgroup of episodic migraineurs with widespread pressure hyperalgesia during and between attacks; 2) if such a subgroup exists, what is the prevalence and what is the difference between groups with interictal widespread hyperalgesia and acute allodynia regarding the demographic and clinical characteristics of migraine. METHODS: This was a cross-sectional study. A total of 176 consecutive episodic migraineurs and 132 age- and sex-matched controls were recruited. The presence of widespread pressure hyperalgesia was investigated using manual tender point survey. To classify a subject's response as widespread pressure hyperalgesia, the cutoff value for responders was defined as the positive tender point count below which 95% of controls responded. RESULTS: Based on the number of positive tender points in controls, the cutoff value of tender point count for pressure hyperalgesia responders was 7. Of the 176 subjects, interictal widespread pressure hyperalgesia and acute allodynia were observed in 74 (42%) and 115 (65.3%) patients, respectively. Univariate analysis indicated that risk factors associated with interictal widespread pressure hyperalgesia were female gender, younger age at migraine onset, higher frequency of migraine attacks, severe headache impact, cutaneous allodynia and depression. Multivariate logistic regression analysis confirmed that independent risk factors associated with interictal widespread pressure hyperalgesia were female gender, higher frequency of migraine attack and younger age at onset. CONCLUSION: Interictal widespread pressure hyperalgesia was common (42%) in the episodic migraineurs and was associated with younger age at onset, female gender, and higher frequency of headache, but not duration of migraine illness. Presence of interictal widespread pressure hyperalgesia is assumed to be an indicator of genetic susceptibility to migraine attacks. We expect that a tender point count, as an alternative to quantitative sensory testing, will become useful as a diagnostic indicator of interictal hyperalgesia in migraineurs to predict susceptibility to migraine attacks and to permit tailored treatment.

Local and Widespread Hyperalgesia After Isolated Tibial Shaft Fractures Treated with Intramedullary Nailing.

OBJECTIVES: Knee pain is accepted as a common complication to intramedullary nailing of tibial fractures. However, no studies have systematically studied the pain sequel following tibial fractures. The objective of this study was to assess pain and hyperalgesia from 6 weeks to 12 months postoperatively after intramedullary nailing of tibial shaft fracture. METHODS: A total of 39 patients were included in this 12-month follow-up study. After 6 weeks, 3, 6, and 12 months postoperatively the pain intensity was measured on a visual analog scale (VAS) and the pressure pain sensitivity was assessed bilaterally by pain pressure thresholds (PPTs). RESULTS: The mean age at the time of fracture was 42.9 years. Twelve months after surgery, the pain intensity for worst pain during the last 24 hours was 1.8 ± 2.7 cm. The PPTs progressively increased from 6 weeks after surgery to 12 months postoperatively for all PPT sites except for the forearm (P < 0.012). Moreover, the PPTs on the leg were generally reduced on the injured side compared with the non-injured side (P < 0.04). CONCLUSIONS: This study suggests that localized, distal, and bilateral hyperalgesia are common following an isolated tibial shaft fracture treated with intramedullary nailing, although no widespread (extrasegmental) hyperalgesia was detected. Such observations may be important for developing the most adequate rehabilitation procedure following a tibial fracture.

Recognizing and Reducing the Risk of Opioid Misuse in Orthopaedic Practice.

Orthopaedic surgeons often treat patients with chronic musculoskeletal pain. This musculoskeletal pain is increasingly being treated with opioid medications, contributing to the growing opioid epidemic in the United States. Opioid use and abuse before orthopaedic surgery are associated with worse clinical outcomes. This article reviews the risk factors for opioid use, misuse, and other behaviors in chronic pain patients, discusses the screening tools for opioid misuse in chronic pain patients, and provides recommendations for the orthopaedic surgeon's role in managing these complicated patients.

Characterization of Pain in Familial Amyloid Polyneuropathy.

UNLABELLED: Familial amyloid polyneuropathy (FAP) caused by transthyretin (TTR) mutation is a small-fiber predominant polyneuropathy, exposing patients with TTR-FAP to development of neuropathic pain. However, the painful nature of TTR-FAP has never been specifically addressed. In this study, we compared 2 groups of 16 patients with either painless or painful TTR-FAP with regard to various clinical and neurophysiologic variables, including laser evoked potential (LEP) recording and quantitative sensory testing. The 2 groups of patients did not differ on any clinical or neurophysiologic variable. Patients with painful TTR-FAP complained of ongoing burning pain sensations, pain aggravation at rest, paroxysmal pain (electric shock and stabbing sensations), or provoked pain (mostly dynamic mechanical allodynia). However, the symptomatic presentation of painful TTR-FAP evolved with the course of the disease. The duration of the disease and the severity of small-fiber lesions (increase in thermal thresholds and reduction in LEP amplitude) correlated negatively with the intensity of ongoing burning sensations and positively with the intensity of paroxysmal pain. In addition, small-fiber preservation correlated positively with cold allodynia and pain aggravation at rest and negatively with dynamic mechanical allodynia. Peripheral sensitization of small-diameter nociceptive axons might occur in early TTR-FAP and be responsible for the burning sensation and cold allodynia. As polyneuropathy and small-fiber loss progress, paroxysmal pain and dynamic mechanical allodynia may develop as a result of central sensitization generated by abnormal activities affecting relatively spared large-diameter sensory fibers. PERSPECTIVE: Pain in TTR-FAP includes several mechanisms varying with the course of the disease and the involvement of the different types of nerve fibers.

Heightened cold pain and pressure pain sensitivity in young female adults with moderate-to-severe menstrual pain.

This study investigated the association between menstrual pain severity and psychophysical measures of cold and pressure pain sensitivity. A cross-sectional design was used with young women (n = 432) from the Western Australian Pregnancy Cohort (Raine) Study. Menstrual pain severity and oral contraception use was obtained from questionnaires at 20 and 22-year follow-ups. A visual analog scale (VAS; range from 0 [none] to 10 [unbearable]) was used to measure menstrual pain severity at both 20 and 22 years over the 3-year period, with 3 groups created: (1) no pain or mild pain (VAS 0-3), (2) at least moderate pain at a minimum of 1 of the 2 time points (hereafter named "mixed)", and (3) severe pain (VAS 8-10). Cold pain sensitivity (dorsal wrist) and pressure pain sensitivity (lumbar spine, upper trapezius, dorsal wrist, and tibialis anterior) were assessed using standardised quantitative sensory testing protocols. Confounding variables included number of musculoskeletal pain sites, oral contraceptive use, smoking, physical activity, body mass index, psychological distress, and sleep. Severe menstrual pain and mixed menstrual pain were positively associated with heightened cold pain sensitivity (distant from menstrual pain referral site) and pressure pain sensitivity (local to menstrual pain referral site). These associations remained significant after adjusting for potential confounding variables including multisite musculoskeletal pain. Our findings suggest peripheral and central neurophysiological mechanisms contributing to heightened pain sensitivity in young women with moderate and severe menstrual pain. These data highlight the need for innovative management approaches to attenuate the negative impact of severe menstrual pain in young women.

The lesson of chronic migraine.

The hypothesis that central sensitization/allodynia is the common final mechanism responsible for the progression of migraine pain is supported by the possibility of tracing back to allodynic mechanisms the action of the main risk factors for chronic migraine validated by the recent literature. The comorbidity between migraine and idiopathic intracranial hypertension without papilledema is emerging as a new, commonly overlooked risk factor for migraine progression whose putative mechanism might also converge on the sensitization of central pain pathways. If headache progression always occurs at the end of a pathogenetic sequence typical of an individual susceptibility to allodynia, then the primary character of chronic migraine might be debated. Allodynia is not specific to migraine but is implied in the progressive amplification of pain after repeated stimuli, a universal adaptive phenomenon. Being largely conditioned by the individual comorbidity profile, allodynia may only in part be defined as primary in itself. Many migraine comorbid conditions, including a hidden idiopathic intracranial hypertension without papilledema, may emphasize susceptibility to allodynia and promote chronic migraine. These factors and comorbid conditions require to be individually assessed and adequately treated to optimize the therapeutic response.

Nerve pressure pain hypersensitivity and upper limb mechanosensitivity in breast cancer survivors: a case-control study.

OBJECTIVE: This study aims to investigate the presence of bilateral pressure pain hypersensitivity in arm trunk nerves and upper limb mechanosensitivity in breast cancer patients with neck-shoulder pain after medical treatments. METHODS: Twenty-two breast cancer survivors (mean age 49.05 ± 7.8 years) and matched healthy controls (mean age 50.76 ± 7.6 years) participated in the study. Neck and shoulder pain was evaluated using an 11-point numerical point rating scale. Pressure pain thresholds (PPTs) were bilaterally assessed over the median, radial, and ulnar nerve trunks and tibialis muscle, and the neurodynamics of the upper limb by neural tolerance to movement was evaluated in the median, radial, and ulnar nerves. RESULTS: Thirteen (59.1%) patients reported spontaneous neck pain, and 16 (72.7%) patients showed spontaneous shoulder/axillary pain. Analysis of variance revealed that breast cancer survivors showed significant between-group but not between-side differences over the median nerve trunk (group: P = < 0.001; side: P = 0.146), radial nerve trunk (group: P = < 0.001; side: P = 0.300), ulnar nerve trunk (group: P = < 0.001; side: P = 0.744), and tibialis anterior muscle (group: P = < 0.001; side: P = 0.118). The patients also showed statistically significant differences in range of motion (ROM) between groups and between sides in ULNT1(MEDIAN)(group: P = < 0.001; side: P = < 0.001) and ULNT(ULNAR) (group: P = 0.009; side: P = 0.002). The analysis did not show statistically significant differences in ROM between groups, but there was a statistical significance between sides for ULNT(RADIAL) (group: P = 0.081; side: P = 0.046). CONCLUSIONS: Breast cancer survivors present bilateral and widespread neural hypersensitivity, as they did in muscular tissue in previous studies. Breast cancer survivors demonstrate a reduction in ROM during ULNTs in the affected side.

Sleep features and central sensitization symptoms in primary headache patients.

BACKGROUND: Association between sleep disorders and headache is largely known. The aim of the present study was to evaluate sleep quality and quantity in a large cohort of primary headache patients, in order to correlate these scores with symptoms of central sensitization as allodynia, pericranial tenderness and comorbidity with diffuse muscle-skeletal pain. METHODS: One thousand six hundreds and seventy primary headache out patients were submitted to the Medical Outcomes Study (MOS) within a clinical assessment, consisting of evaluation of frequency of headache, pericranial tenderness, allodynia and coexistence of fibromyalgia syndrome (FM). RESULTS: Ten groups of primary headache patients were individuated, including patients with episodic and chronic migraine and tension type headache, mixed forms, cluster headache and other trigeminal autonomic cephalalgias. Duration but not sleep disturbances score was correlated with symptoms of central sensitization as allodynia and pericranial tenderness in primary headache patients. The association among allodynia, pericranial tenderness and short sleep characterized chronic migraine more than any other primary headache form. Patients presenting with FM comorbidity suffered from sleep disturbances in addition to reduction of sleep duration. CONCLUSION: Self reported duration of sleep seems a useful index to be correlated with allodynia, pericranial tenderness and chronic headache as a therapeutic target to be assessed in forthcoming studies aiming to prevent central sensitization symptoms development.

Vitamin D and central hypersensitivity in patients with chronic pain.

BACKGROUND: Low vitamin D is implicated in various chronic pain conditions with, however, inconclusive findings. Vitamin D might play an important role in mechanisms being involved in central processing of evoked pain stimuli but less so for spontaneous clinical pain. OBJECTIVE: This study aims to examine the relation between low serum levels of 25-hydroxyvitamin D3 (25-OH D) and mechanical pain sensitivity. DESIGN: We studied 174 patients (mean age 48 years, 53% women) with chronic pain. A standardized pain provocation test was applied, and pain intensity was rated on a numerical analogue scale (0-10). The widespread pain index and symptom severity score (including fatigue, waking unrefreshed, and cognitive symptoms) following the 2010 American College of Rheumatology preliminary diagnostic criteria for fibromyalgia were also assessed. Serum 25-OH D levels were measured with a chemiluminescent immunoassay. RESULTS: Vitamin deficiency (25-OH D < 50 nmol/L) was present in 71% of chronic pain patients; another 21% had insufficient vitamin D (25-OH D < 75 nmol/L). After adjustment for demographic and clinical variables, there was a mean ± standard error of the mean increase in pain intensity of 0.61 ± 0.25 for each 25 nmol/L decrease in 25-OH D (P = 0.011). Lower 25-OH D levels were also related to greater symptom severity (r = -0.21, P = 0.008) but not to the widespread pain index (P = 0.83) and fibromyalgia (P = 0.51). CONCLUSIONS: The findings suggest a role of low vitamin D levels for heightened central sensitivity, particularly augmented pain processing upon mechanical stimulation in chronic pain patients. Vitamin D seems comparably less important for self-reports of spontaneous chronic pain.

Widespread pressure pain hypersensitivity and ultrasound imaging evaluation of abdominal area after colon cancer treatment.

OBJECTIVE: To investigate the presence of widespread pressure pain sensitivity in cancer patients following partial colorectal resection in the abdominal and lower back area and to describe the presence of abnormalities in abdominal and lower back muscle morphology. METHODS: Twenty colon cancer survivors (eight females, mean age 56.60 ± 7.76 years) and 20 matched healthy controls (10 females, mean age 54.22 ± 8.12 years) participated. Abdominal and lower back pain was assessed after undergoing surgery using a Visual Analogue Scale (VAS) and Brief Pain Inventory (BPI). Pressure pain thresholds (PPTs) were bilaterally assessed over the supraumbilical, infraumbilical, and lower back areas and the second metacarpal. Ultrasound imaging was used to measure the depth of the abdominal muscles, the width of the midline abdominal fascia and the width of the lumbar multifidus. RESULTS: Ten months after finishing oncological treatments, patients who underwent partial colorectal resection reported significantly higher pain levels in the low-back area (P = 0.003) but not in the abdominal area (P = 0.426) compared with the matched controls. After surgery, the colon patients reported significantly higher BPI-intensity (P < 0.001) and BPI-interference scores (P = 0.009) compared with the matched controls. An analysis of variance (ANOVA) revealed significant between-groups difference in dominant-side lumbar, supraumbilical and infraumbilical (P ≥ 0.01), and second-metacarpal (P < 0.05) PPT levels. A significant between-groups difference was found by the ANOVA in ultrasound imaging of the depth of the internal oblique muscle (F = 4.887, P = 0.035) but not in the other ultrasound imaging measurements. CONCLUSIONS: Ten months after oncology treatment, colon cancer survivors show widespread pressure pain muscle hyperalgesia and reduced depths of dominant-side internal oblique muscles compared with matched controls.

Stereotactic neurosurgical technique and electrophysiological study in ablating the ventromedial shell of the nucleus accumbens.

OBJECTIVE: To describe in as much detail as possible the method for ablating the ventromedial shell of the nucleus accumbens (NAc) and investigate the efficacy and safety of the ablation treatment. METHODS: Sixty-five patients with drug addictions received operations within the time frame from 2004 to 2009. The ablation targets were located in the bilateral medial posterior inferior shell of the NAc. Intraoperative electrophysiological monitoring was performed. RESULTS: Tissue impedance in the shell of the NAc varied from 185 to 355 Ω. When stimulated with a low frequency (2 Hz) and a voltage above 3 V, 57 out of 65 (87.7%) patients experienced slight throbbing sensations. During the lesion procedure, fever was detected on the head and face of 59 patients (90.8%), the heart rate decreased in 19 cases (29.2%), and restlessness, irritability and hyperalgia were noted for all patients. Among the 65 patients, 52 (80%) no longer experienced a psychological craving for the drug. CONCLUSIONS: The shell of the NAc may be a promising surgical target for psychosurgery. Electrophysiological recordings revealed that the shell is indeed an appropriate structure.

[Chronic migraine: pathophysiology]. / Migraña crónica: fisiopatología.

Chronic migraine is considered a complication of episodic migraine. Several risk factors, which may be modifiable or non-modifiable, make varying contributions to the progression towards chronification. Every year 2.5% of patients with episodic migraine go on to suffer chronic migraine. Experimental studies point to a dysfunction in the descending pain modulatory system that would facilitate nociceptive afferents, in the absence of damage to tissues, and so chronic migraine would share a pathogenesis that is similar to that of fibromyalgia, irritable bowel syndrome or chronic tension-type headache (conditions that frequently coexist). This paper reviews the risk factors and the scientific evidence of the possible pathogenic mechanisms involved in the progression towards chronification.