Memory surfacing among veterans with PTSD receiving hyperbaric oxygen therapy.

Introduction: Growing evidence demonstrates that hyperbaric oxygen therapy (HBO2) induces neuroplasticity and can benefit individuals with post-traumatic stress disorder (PTSD). The aim of the current study was to evaluate the rate and pattern of memory surfacing during the course of HBO2 among veterans with combat-related PTSD. Methods: In a post-hoc analysis of a prospective study of the effect of HBO2 on PTSD symptoms in veterans, we evaluated the rate and character of memory surfacing during the course of HBO2 treatment. The treatment consisted of 60 daily 90-minute sessions, at 2 atmospheres absolute (ATA) pressure and 100% oxygen. Results: For 10 (35.7%) of the 28 participants, surfacing of new memories was reported during the HBO2 treatment course. Memories surfaced mainly during the second month of the treatment, at the mean session of 30.5±13.2. For 9 of these 10 participants, prodromal symptoms such as distress, anxiety, or worsening depression were documented; and in four, somatic pain was reported prior to memory surfacing. The pain and distress of memory surfacing resolved over the course of one to 10 days. Discussion: Among individuals with PTSD, the surfacing of new memories, accompanied by emotional distress and somatic pain, is common during HBO2. The surfacing of memories sheds light on the biological effect of HBO2 on the brain sequela of PTSD. It is highly important that in treating patients for any indication, HBO2 medical teams be aware and capable of addressing memory surfacing, particularly in those with a history of trauma.

Imaging features inferring symptom onset due to spinal metastasis progression: a preliminary study.

BACKGROUND: Spinal metastases can cause intractable pain and neurological deficits, which can markedly worsen both patients' activities of daily living (ADL) and their health-related quality of life (QOL). Early intervention is essential to prevent irreversible neurological deficits and pain associated with spinal metastases. We investigated the imaging features of spinal metastases that led to neurological deficits. METHODS: We analyzed axial cross-sectional computed tomography (CT) images of cervical and thoracic spinal metastases in patients with and without lower limb motor paralysis, neuropathic pain, and local nociceptive pain. We distinguished regions of the spine associated with these respective symptoms, and explored their inferable performance using images obtained before symptom onset. In addition, we analyzed the imaging features and type of bone metastasis (osteolytic and osteoblastic). RESULTS: Spinal lesions occupied the area in and around the spinal canal and around the pedicle in patients with motor paralysis. Lesions around the pedicle and in the most posterior vertebral body part before symptom onset were inferable. In patients with neuropathic pain, spinal metastases spread along the pedicle before symptom onset, and had surrounded the spinal canal circumferentially at symptom onset. Local nociceptive pain was more common near the center of the vertebral body either at or before symptom onset. There was no difference in the imaging features according to the type of bone metastasis. CONCLUSIONS: Lesions in certain regions in the asymptomatic metastatic spine can indicate the onset of spinal metastasis-related symptoms in the next few months. Early therapeutic intervention might be applied to prevent neurological disorder.

Non-crisis related pain occurs in adult patients with sickle cell disease despite chronic red blood cell exchange transfusion therapy.

BACKGROUND: Chronic red blood cell transfusions reduce acute care utilization for sickle cell disease (SCD) pain. However, little is known about whether chronic transfusions treat or prevent the development of non-crisis pain. We investigated patient-report of pain in adults with SCD receiving chronic exchange transfusions (CET) compared to adults not on CET with similar disease characteristics. STUDY METHOD AND DESIGN: Eleven participants receiving chronic exchange transfusion (CET) for at least one year were compared to 33 participants not receiving CET. Participants completed validated patient-reported outcomes regarding pain impact and quality of life at regularly scheduled visits or before CET. One year of health care utilization and opioid prescriptions were examined. RESULTS: After 1:1 propensity matching was performed for age, genotype, WBC and neutrophil counts, patients on CET had lower Pain Impact scores (-5.1, p = 0.03) and higher Neuropathic (7.4, p < 0.001) and Nociceptive Pain Quality (3.7, p < 0.001) scores, all indicating worse pain. However, CET was associated with a reduction in annual all cause admissions (-3.1, p < 0.001), length of stay (-2.1 days, p < 0.001) and ED visits (-2.7, p < 0.001). CET was not associated with differences in opioids dispensed. CONCLUSIONS: After adjusting for disease characteristics, CET was associated with worse pain impact and neuropathic and nociceptive pain quality, lower health care utilization and with similar levels of opioids dispensed. This data suggest that CET may reduce hospitalizations for acute pain but may not adequately treat nociceptive or neuropathic pain in SCD.

Heightened affective response to perturbation of respiratory but not pain signals in eating, mood, and anxiety disorders.

Several studies have recently suggested that an abnormal processing of respiratory interoceptive and nociceptive (painful) stimuli may contribute to eating disorder (ED) pathophysiology. Mood and anxiety disorders (MA) are also characterized by abnormal respiratory symptoms, and show substantial comorbidity with ED. However, no studies have examined both respiratory and pain processing simultaneously within ED and MA. The present study systematically evaluated responses to perturbations of respiratory and nociceptive signals across the levels of physiology, behavior, and symptom report in a transdiagnostic ED sample (n = 51) that was individually matched to MA individuals (n = 51) and healthy comparisons (HC; n = 51). Participants underwent an inspiratory breath-holding challenge as a probe of respiratory interoception and a cold pressor challenge as a probe of pain processing. We expected both clinical groups to report greater stress and fear in response to respiratory and nociceptive perturbation than HCs, in the absence of differential physiological and behavioral responses. During breath-holding, both the ED and MA groups reported significantly more stress, feelings of suffocation, and suffocation fear than HC, with the ED group reporting the most severe symptoms. Moreover, anxiety sensitivity was related to suffocation fear only in the ED group. The heightened affective responses in the current study occurred in the absence of group differences in behavioral (breath hold duration, cold pressor duration) and physiological (end-tidal carbon dioxide, end-tidal oxygen, heart rate, skin conductance) responses. Against our expectations, there were no group differences in the response to cold pain stimulation. A matched-subgroup analysis focusing on individuals with anorexia nervosa (n = 30) produced similar results. These findings underscore the presence of abnormal respiratory interoception in MA and suggest that hyperreactivity to respiratory signals may be a potentially overlooked clinical feature of ED.

Microglia dependent BDNF and proBDNF can impair spatial memory performance during persistent inflammatory pain.

Inflammatory pain is commonly associated with cognitive impairment. However, its molecular mechanisms are poorly understood. Thus, this study was conducted to investigate the molecular mechanisms of behavioral changes associated with inflammatory pain. Briefly, 36 Wistar rats were randomly divided into two main groups: CFA group treated with 100 µL of Complete Freunds' Adjuvant (CFA) and CFA + Minocycline group treated with 100 µL of CFA+40 mg/kg/day of minocycline). After that, each group was divided into three subgroups based on different time points of the study. The pain was induced using CFA and subsequent behavioral changes (i.e., hyperalgesia and learning and spatial memory) were analyzed by the Morris Water Maze (MWM) task and Radiant Heat. Then, the cellular and molecular changes were assessed using Western Blotting, Immunohistochemistry, and Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) techniques. Results of the study indicated that CFA-induced pain impaired spatial learning and memory functions. Studying the cellular changes showed that persistent inflammatory pain increased the microglial activity in CA1 and Dentate Gyrus (DG) regions. Furthermore, an increase was observed in the percentage of TUNEL-positive cells. Also, pro-Brain-Derived Neurotrophic Factor (BDNF)/BDNF ratio, Caspase3, and Receptor-Interacting Protein kinase 3 (RIP3) levels increased in the rats' hippocampus following induction of persistent inflammatory pain. These changes were reversed following the cessation of pain as well as the injection of minocycline. Taking together, the results of the current study for the first time revealed that an increase in the microglia dependent proBDNF/BDNF ratio following persistent inflammatory pain leads to cell death of the CA1 and DG neurons that subsequently causes a cognitive deficit in the learning and spatial memory functions.

Pain is Associated With Increased Physical and Psychosocial Impairment in Youth With a History of Burn Injuries.

Burn injuries are significantly painful and associated with physical and psychological impairment. However, little research to-date has examined the potential role of the subjective experience of pain in either physical or psychological impairment in this population. This may be particularly important to examine, given that the pain experience can often be a significant barrier to recovery in other pediatric populations. The current study examined the cross-sectional and predictive relationships between patient-reported experience of pain (operationalized as PROMIS pain interference and self-reported pain intensity) and physical and psychosocial outcomes. Data were gathered as part of the Burn Model System National Database (1994-2018) with the data request inclusive of pediatric self-report PROMIS measures, child PTSD, and post-traumatic growth symptoms assessed at 6- and 12-month postdischarge following initial injury. A total of 65 youth between the ages of 6 and 16 years at the time of their injury were included in the dataset. Correlational and regression analyses indicated that pain interference was cross-sectionally and longitudinally associated with decreased physical functioning, depressive symptoms, and peer relationships. Pain intensity was significantly associated with and predictive of physical functioning and pain interference. Results of the current study are an important first step in understanding the pain experience and associated outcomes in youth with a history of burn injuries. Future research is needed to further examine these relationships. PERSPECTIVE: This study presents preliminary findings from a national database on pain-related outcomes both cross-sectionally and longitudinally in youth with a history of burn injury. To-date, pain-related outcomes are poorly understood in this population and the results of this study serve to inform future research and treatment-related efforts.

Influence of behavioral traits in the inter-individual variability of nociceptive, emotional and cognitive manifestations of neuropathic pain.

Neuropathic pain is a complex disorder associated with emotional and cognitive deficits that may impair nociceptive manifestations. There is high inter-individual variability in the manifestations of human neuropathic pain, which largely depends on personality traits. We aim to identify the influence of different behavioral traits in the inter-individual vulnerability to neuropathic pain manifestations using behavioral, electrophysiological and genetic approaches. We first selected mice with extreme social and emotional traits and look for correlation with the spontaneous neuronal activity in the central amygdala. Neuropathic pain was induced to these mice to evaluate the influence of behavioral traits on nociceptive manifestations and gene expression profiles in the amygdala. Our results show an association of the spontaneous central amygdala neuronal activity with the sociability behavior. We demonstrate that low sociable, high anxious and low depressive phenotypes develop enhanced nociceptive hypersensitivity after nerve injury. However, greater emotional alterations and cognitive impairment are observed in high sociable, anxious-like and depressive-like mice, indicating that nociceptive, emotional and cognitive manifestations of neuropathic pain do not correlate with each other. Gene analyses identify high Pdyn and Il6 levels in the amygdala as indicative of enhanced nociceptive hypersensitivity and reveal an association between high Gadd45 expression and attenuated emotional and cognitive manifestations of neuropathic pain.

Heart Rate Variability as an Indicator of Nociceptive Pain in Disorders of Consciousness?

CONTEXT: Heart rate variability is thought to reflect the affective and physiological aspects of pain and is emerging as a possible descriptor of the functional brain organization contributing to homeostasis. OBJECTIVES: To investigate whether the short-term Complexity Index (CIs), a measure of heart rate variability complexity is useful to discriminate responses to potentially noxious and nonnoxious stimulation in patients with different levels of consciousness. METHODS: Twenty-two patients (11 minimally conscious state [MCS], 11 vegetative state/unresponsive wakefulness syndrome [VS/UWS]) and 14 healthy controls (HC) were enrolled. We recorded the electrocardiographic response and calculated the CIs before (baseline), during, and after nonnoxious and noxious stimulation. Mann-Whitney and Wilcoxon's tests were used to investigate differences in CIs according to the level of consciousness (i.e., HC vs. patients and VS/UWS vs. MCS) and the three conditions (i.e., baseline, nonnoxious, noxious). The correlation between the three conditions and the Coma Recovery Scale-Revised was investigated by Spearman's correlations. RESULTS: We observed higher CIs values in HC as compared with patients during the baseline (P < 0.034) and after the noxious stimulation (P < 0.0001). We also found higher values in MCS versus VS/UWS patients after the noxious condition (P < 0.001) and lower values in the noxious versus nonnoxious condition solely for the VS/UWS group (P < 0.007). A correlation was found between CIs in noxious condition and Coma Recovery Scale-Revised scores. CONCLUSION: Our results suggest a less complex autonomic response to noxious stimuli in VS/UWS patients. Such method may help to better understand sympathovagal response to potentially painful stimulation in brain-injured patients.

Comparison of pain burden and psychological factors in Brazilian women living with HIV and chronic neuropathic or nociceptive pain: An exploratory study.

Psychological factors including pain catastrophizing and resilience associate with adjustment and quality of life in people living with chronic pain. Nevertheless, their presentation among females living with HIV and chronic pain has been poorly studied. Given that chronic pain in those living with HIV might occur due to different mechanisms (nociceptive or neuropathic), we hypothesize that the associated psychological states could also differ between these groups. We aimed to compare pain frequency and interference, psychological factors and sleep quality between females living with chronic nociceptive or neuropathic pain. Also, we explored correlations between psychological factors, pain severity and interference in females living with HIV and chronic pain. We performed a cross sectional study assessing females living with HIV and chronic pain, and compared it with a female HIV-positive, pain-free control sample in Brazil. To discriminate the most likely underlying mechanism for the chronic pain, we applied the Leeds Assessment for Neuropathic Signs and Symptoms (LANSS). Forty-nine females living with HIV and chronic pain were assessed, and divided in control (n = 12), nociceptive (n = 10) and neuropathic pain (n = 27) groups. Using validated scales, their pain catastrophizing, resilience, depression, anxiety and sleep disorders were assessed between May 2014 and August 2015. Compared to controls, females living with HIV and neuropathic chronic pain had higher pain frequency (p<0.001), interference on activities (p = 0.002), interference with emotions (p<0.001), catastrophizing (p<0.001), depression (p = 0.015), and lower resilience (p = 0.011). Catastrophizing was also significantly correlated to the burden of chronic pain. The type of chronic pain in females living with HIV should raise concerns regarding significant burden in psychological states in this population (particularly neuropathic pain). Using scales such as the LANSS to identify the type of choric pain, could be of use to address relevant issues for the patients, and to propose tailored therapies.

Differences in pain intensity in anti- and pro-nociceptive pain profile subgroups in patients with knee osteoarthritis.

AIM: Facilitated temporal summation is one component of central sensitization. The aim of this exploratory study was to classify pro-, eu- and antinociceptive subgroups based on wind-up ratio cut-off scores in patients with knee osteoarthritis (OA). PATIENTS & METHODS:  A total of 56 patients with knee OA met the inclusion criteria. Temporal summation was measured and wind-up ratio was calculated. Reference values of 180 healthy subjects were used to define wind-up ratio cut-off scores. RESULTS: Twenty-seven percent of patients showed a pro-nociceptive pain profile. Sixteen percent of patients showed an anti-nociceptive pain profile. A eu-nociceptive pain profile was present in 57% of patients. CONCLUSION: Central pain sensitization was present in approximately a third of knee OA patients. The results should be confirmed in larger studies.

Ischemic Ulcer Pain Is Both Nociceptive and Neuropathic Pain Based on a Discriminant Function Analysis Using the McGill Pain Questionnaire.

The McGill Pain Questionnaire (MPQ) is composed of 78 words reflecting the mechanisms underlying chronic pain conditions. Ischemic ulcer pain is generally regarded as a nociceptive and inflammatory pain condition. However, it is sometimes refractory to nonsteroidal anti-inflammatory drug (NSAID) and opioid treatment. We categorized ischemic pain into nociceptive/inflammatory pain (NocP) or neuropathic pain (NeP), on the basis of patients' descriptions of their pain using the MPQ. We investigated pain characteristics of 365 patients with NeP and 124 with NocP using the 78 words of the MPQ. We thereby developed a discriminant function, which efficiently discriminates descriptions of NocP from those of NeP. We applied this function to 18 ischemic pain patients (before and after peripheral revascularization) and categorized their pain as either NocP or NeP. The discriminant probability of the function was 72.8% (P <.05), suggesting relatively accurate discrimination of NocP from NeP. Among the 78 words, only "annoying" was not utilized for the function. On the basis of this function, 9 of the 18 ischemic pain patients' complaints were classified as NeP. Ten patients received revascularization and after revascularization, 7 of 10 patients' complaints were still NeP. Our results suggest that ischemic ulcer pain should be regarded as a mixed pain condition composed of both NocP and NeP and that it might be treated with medications for NeP (e.g., pregabalin, duloxetine) in combination with NSAIDs and opioids.

Neuropathic pain.

Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aß, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain.

Effects of disturbed sleep on gastrointestinal and somatic pain symptoms in irritable bowel syndrome.

BACKGROUND: Sleep disturbances are common, and perhaps are even more prevalent in irritable bowel syndrome (IBS). AIMS: To determine the effect of measured sleep on IBS symptoms the following day, IBS-specific quality of life (IBS-QOL) and non-GI pain symptoms. METHODS: IBS patients' sleep patterns were compared to healthy individuals via wrist-mounted actigraphy over 7 days. Daily bowel pain logs (severity, distress; 10-point Likert) stool pattern (Bristol scale) and supporting symptoms (e.g. bloating, urgency; 5-point Likert) were kept. Validated measures, including the GI Symptom Rating Scale-IBS, Visceral Sensitivity Index, Pittsburgh Sleep Quality Index and the IBS-Quality of Life were collected. Mediation analysis explored the relationship between sleep, mood and bowel symptoms. RESULTS: Fifty subjects (38.6 ± 1.0 years old, 44 female; 24 IBS and 26 healthy controls) completed sleep monitoring. IBS patients slept more hours per day (7.7 ± 0.2 vs. 7.1 ± 0.1, P = 0.008), but felt less well-rested. IBS patients demonstrated more waking episodes during sleep (waking episodes; 12.1 vs. 9.3, P < 0.001). Waking episodes predicted worse abdominal pain (P ≤ 0.01) and GI distress (P < 0.001), but not bowel pattern or accessory IBS symptoms (P > 0.3 for each). Waking episodes negatively correlated with general- and IBS-specific QOL in IBS (r = -0.58 and -0.52, P < 0.001 for each). Disturbed sleep effects on abdominal pain were partially explained by mood as an intermediate. CONCLUSIONS: Sleep disturbances are more common in irritable bowel syndrome, and correlate with IBS-related pain, distress and poorer irritable bowel syndrome-related quality of life. Disturbed sleep effects extend beyond the bowel, leading to worse mood and greater somatic pain in patients with the irritable bowel syndrome.

Changes Over Time of Prescription and Nonprescription Analgesics for Headache With or Without Other Somatic Pain: Effects of Prescription Regulatory Changes.

UNLABELLED: The aim of this study was to examine the association and changes over time between headaches with or without somatic pain and the self-reported use of pain medication. The study further examined whether the law amendment in 2003 in Norway releasing the sale of nonprescription drugs to shops has changed these relationships. The study is on the basis of repeated self-report cross-sectional studies from 1998 to 2012 in Norway. A total of 27,247 adults were included. As expected, there was a strong association between headache, especially headache with comorbid somatic pain and consumption of prescription versus nonprescription analgesics, although the overall consumption decreased slightly after 2003. We conclude that the strong association between especially headache, whether complicated by somatic pain or not, and the consumption of prescription-free analgesics did not seem to be negatively affected by the prescription regulatory changes. The very high use of nonprescription medication among headache patients suggests the need for continued observation and information regarding the risk of medication-overuse headache. PERSPECTIVE: In Norway, headache was strongly associated with use of over-the-counter analgesics, for other somatic pain prescription analgesics were equally common. Between 1998 and 2012 headache and related analgesic consumption was reduced and other somatic pain increased. Making over-the-counter analgesics available outside pharmacies in 2003 did not increase the self-reported intake.

Persistent, comorbid pain and anxiety can be uncoupled in a mouse model.

Clinically, pain and anxiety frequently coexist; however, these two conditions' interaction is limited and contradictory in animal studies. In this study, we combined social defeat (SD) stress with Freund's adjuvant (CFA)-induced persistent inflammatory pain to investigate the reciprocal relationship between anxiety-like and nociceptive behaviors in two mouse strains. C57BL/6J mice subjected to the 10-day period of SD stress by repeated CD-1 mice aggression exhibited significant social interaction avoidance behaviors in the social interaction (SI) test, which is believed to represent the symptoms of anxiety. These mice also displayed anxiety-like behaviors in elevated plus maze (EPM) and open field (OF) tests. Compared to C57BL/6J mice, FVB/NJNju mice showed less basal social contact, but their behavioral responses to 10-day SD stress were more resilient. CFA-inflammatory mice showed robust mechanical allodynia and thermal hyperalgesia in both strains, but did not develop obvious social avoidance and anxiety-like behaviors 10 days after CFA-inflammation. Interestingly, CFA-inflammatory mice exposed to SD stress were not accompanied by a worsening of pain and anxiety-like behaviors in most tests. In contrast, the SD stress-induced social avoidance was significantly antagonized by combining with CFA-inflammatory pain. These findings suggest that persistent inflammatory pain and SD stress-induced anxiety may not necessarily exacerbate one another in animal models of comorbidity.

[Somatic pain sensitivity under indometacin induced gastric and small intestinal injury in rats].

The aim was to study the effect of indometacin (IM) induced gastrointestinal injury on somatic pain sensitivity in awake rats. IM was administered at the ulcerogenic dose (35 mg/kg, s. c.) to fasted (24 h) and fed rats. Somatic pain sensitivity was evaluated using a tail flick test. Latency time was measured under conditions of the formation of gastric erosion (1 - 4 h after IM injection) as well as small intestinal injury (24, 48 and 72 h after IM injection). IM administration caused the gastric erosion formation only in fasted rats (4 h after the administration) and the small intestinal injury in both fasted and fed rats (24, 48, 72 h after the administration). Indomethacin-caused gastric and small intestinal injury resulted in an increase in tail flick latency. We did not observe any changes in tail flick latency in IM-treated rats without significant gastrointestinal injury. The gastrointestinal injury was accompanied by signs of chronic stress: long-lasting increase in corticosterone blood level, adrenal hypertrophy, thymus involution, and loss of body weight. Thus, the IM-induced gastrointestinal injury formation resulted in somatic pain inhibition in awake rats.

Dolor neuropático en pacientes afectados por la lepra / No disponible

Algunos pacientes con lepra pueden sufrir dolor crónico o dolor neuropático, tras el éxito del tratamiento. La prevalencia oscila entre un 17% y un 70% de los antiguos pacientes leprosos. El dolor neuropático se asocia con un deterioro de la calidad de vida de los pacientes y conlleva un elevado agravamiento de la morbilidad psicológica propia de los pacientes con lepra. El manejo de los pacientes con dolor neuropático puede requerir los servicios de salud durante muchos años y un elevado consumo de analgésicos

Some leprosy patients may suffer chronic pain or neuropathic pain after successful treatment. The prevalence ranges between 17% and 70 % of former leprosy patients. Neuropathic pain is associated with deterioration in the quality of life of patients and involves high worsening own psychological morbidity of patients with leprosy. The management of patients with neuropathic pain may require health services for many years and a high consumption of analgesic drugs

Early, middle, or late administration of zoledronate alleviates spontaneous nociceptive behavior and restores functional outcomes in a mouse model of CFA-induced arthritis.

This study was performed to evaluate whether early, middle, or late treatment of zoledronate, an approved bisphosphonate that blocks bone resorption, can reduce nociceptive behaviors in a mouse arthritis model. Arthritis was produced by repeated intra-articular knee injections of complete Freund's adjuvant (CFA). A dose-response curve with zoledronate (3, 30, 100, and 300 µg/kg, i.p., day 4 to day 25, twice weekly for 3 weeks) was performed, and the most effective dose of zoledronate (100 µg/kg, i.p.) was initially administered at different times of disease progression: day 4 (early), day 15 (middle), or day 21 (late) and continued until day 25 after the first CFA injection. Flinching of the injected extremity (spontaneous nociceptive behavior), vertical rearings and horizontal activity (functional outcomes), and knee edema were assessed. Zoledronate improved both functional outcomes and reduced flinching behavior. At day 25, the effect of zoledronate on flinching behavior and vertical rearings was greater in magnitude when it was given early or middle rather than late in the treatment regimen. Chronic zoledronate did not reduce knee edema in CFA-injected mice nor functional outcomes in naïve mice by itself. These results suggest that zoledronate may have a positive effect on arthritis-induced nociception and functional disabilities.

Time-dependent analysis of nociception and anxiety-like behavior in rats submitted to persistent inflammation of the temporomandibular joint.

Temporomandibular disorder (TMD) is prevalent in dental clinics and can involve problems with the masticatory muscles or the temporomandibular joints (TMJ). The pain of TMD is frequently associated with inflammation in the TMJs, but it's etiology is considered to be multifactorial and includes biologic, behavioral, environmental, social, emotional and cognitive factors. The purpose of this investigation was to evaluate the anxiety-like behavior in rats exposed to temporomandibular inflammation via injection of Freund's Adjuvant (CFA) with the elevated plus maze (EPM) and light/dark box (LDB) tests and to evaluate nociceptive behavior with the von Frey test at different periods. Moreover, this study measured TMJ inflammation using plasma extravasation (Evans blue test) and the intraarticular infiltration of polymorphonuclear neutrophils (myeloperoxidase quantification). The results showed that rats that were submitted to TMJ inflammation exhibited a decreased number of entries into the open arms of the EPM and a decrease in the time spent in the light compartment and in the number of transitions in the LDB. Additionally, the number of entries in closed arms in the EPM, used as indicator of locomotor activity, did not alter between treatments. Furthermore, increases in mechanical sensitivity and increases in plasma extravasation in the joint tissue occurred throughout the inflammation process, along with an increase in myeloperoxidase in the synovial fluid of TMJ. Our results suggest that the temporomandibular inflammation induced by CFA produced anxiety-like behaviors in rats and induced nociceptive behavior across different periods of inflammation.

Does Behcet's disease associate with neuropathic pain syndrome and impaired well-being?

Previously peripheral neuropathy signs have been reported in inflammatory chronic diseases but the presence of neuropathic pain syndrome (NPS) in Behcet's disease (BD) is unclear. The aim of this study was to investigate the association of BD with NPS and impaired quality of life and sleep quality. A total of 111 patients diagnosed as BD and 52 healthy controls were included. Pain severity was assessed by visual analogue scale (VAS) in rest and during activity. The NPS was diagnosed according to the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) index. The well-being and sleep disturbances of the groups were evaluated with Psychological General Well-Being (PGWB) Scale and Pittsburg Sleep Quality Index (PSQI). Although there were no one with NPS in healthy controls, the proportion of NPS in patients with BD was 19.8 % (p = 0.001). The VAS scores both in activity and at rest were higher in BD (p < 0.001). There was statistically significant decrease in total PGWB score in BD patients compared to healthy controls (p < 0.001). And significant increase in LANSS score was observed in patients with BD compared to healthy controls (p = 0.000). The total LANSS scores showed significant positive correlation with PSQI scores (r = 0.322) and negative correlation with total PGWB scores (r = -0.672) in patients with BD. We observed a positive correlation between LANSS and VAS (rest and activity) scores (r = 0.44, r = 0.42 respectively). The NPS seems to be associated with BD which should be taken into consideration in patients with neuropathic signs. The quality of life (QoL) and quality of sleep of the patients with BD were found to be impaired and this may be due to the presence of NPS.