"A Double Twist" Presentation - A Case Report of Purulent Cardiac Tamponade following a Rare Complication of Small-Cell Lung Cancer Radiotherapy.

Background: Small cell lung cancer is an aggressive tumor with a poor prognosis that requires prompt treatment. While radiotherapy may enhance survival when superior vena cava syndrome is present, radiation therapy-induced pericardial disease can be a potential complication. Case Report: A 55-year-old man, who recently underwent radiotherapy for stage IV small-cell lung cancer complicated by superior vena cava syndrome, presented with chest pain and dyspnea. In the emergency room, he was dyspneic, hypotensive, and tachycardic. Pulmonary auscultation revealed the absence of lung sounds on the right. The initial electrocardiogram showed ST-segment elevation in lateral leads and in lead DII, with reciprocal changes in lead DIII. A bedside transthoracic echocardiogram revealed cardiac tamponade and emergent pericardiocentesis was performed, removing 500 ml of purulent fluid, resulting in an immediate clinical improvement. Thoracentesis was also performed, showing no empyema. Large spectrum empirical antibiotic therapy was started. Cultures from the pericardial fluid and peripheral blood grew multi-sensitive Streptococcus pneumoniae. Cytological analysis of the pericardial fluid was consistent with infection. The patient improved after 2 weeks of targeted antibiotic therapy and underwent the first cycle of chemotherapy. He was discharged with an early scheduled pulmonology appointment. Conclusions: Although the most common causes of pericardial effusion in lung cancer are malignant, non-malignant etiologies should also be considered. This patient had an infectious pericardial effusion most probably due to a pericardial-mediastinal mass fistula caused by radiotherapy. This was a diagnostic challenge, both in the emergency room as well in the inpatient setting. LEARNING POINTS: Small cell lung cancer is a fast-growing cancer that exhibits aggressive behavior.In patients with lung cancer, malignant pericardial effusions are more common than non-malignant ones.Purulent pericardial effusions, especially those due to lung cancer, are rare in developed countries with very few reports in the literature.

Obstructive Sleep Apnea Syndrome in Heavy Truck Drivers: A Portuguese Prospective Cohort Study.

INTRODUCTION: Heavy truck drivers with untreated obstructive sleep apnea (OSA) are at higher risk of driving accidents. This study aims to estimate the prevalence of OSA and to identify the most frequent symptoms and comorbidities in heavy truck drivers. METHODS: This cohort study included the employees of a Portuguese transport company between 2019 and 2022. A home sleep apnea test (HSAT) was performed on all patients. SPSS® was used for statistical analysis, and a p-value lower than 0.05 was considered statistically significant. RESULTS: A total of 86 truck drivers were included, with a mean age of 48.02 years (min. 24, max 66) and a mean body mass index (BMI) of 30.14±4.4 kg/m². After performing an HSAT, it was found that 77.9% of drivers (n=67) had OSA, with a mean apnea-hypopnea index (AHI) of 16.72±14.69 events/hour. Concerning diagnosed patients, 44.78% (n=30) had mild, 31.32% (n=23) moderate, and 20.89% (n=14) severe OSA. Obesity, hypertension, and dyslipidemia had a statistically significant association. There were no statistically significant differences between patients with and without type II diabetes mellitus. The presence of nighttime and daytime symptoms had a statistically significant correlation with OSA diagnosis. Despite only eight patients reporting a high score on the Epworth Sleepiness Scale (ESS), 14 patients reported previous episodes of falling asleep while driving, which might be associated with the non-valorization of daytime sleepiness in these patients. The patients who reported previous episodes of falling asleep while driving were older and had higher BMI, higher ESS, and higher AHI. CONCLUSIONS: In the evaluated truck drivers, the prevalence of OSA was very high (77.9%), which reinforces the importance of screening for this pathology since, when left untreated, it is a major risk factor for exercising their profession safely.

Baccharis dracunculifolia DC Consumption Improves Nociceptive and Depressive-like Behavior in Rats with Experimental Osteoarthritis.

Osteoarthritis (OA) persistently activates nociceptors, leading to chronic pain, which is often accompanied by the comorbid development of emotional impairments (anxiety and depression), an effect associated with microgliosis. Baccharis dracunculifolia DC (Asteraceae), a Brazilian edible plant, is an important source of active compounds with anti-inflammatory abilities. Thus, we evaluated its ability to reverse OA-induced nociceptive and emotional-like impairments in osteoarthritic ovariectomized female rats using the kaolin/carrageenan (K/C) model. Four weeks after OA induction, mechanical hyperalgesia was confirmed, and the treatment started. Control animals (SHAMs) were treated with phosphate-buffered saline (PBS), while arthritic animals (ARTHs) either received PBS or B. dracunculifolia 50 mg/kg (Bd50) and 100 mg/kg (Bd100), via gavage, daily for five weeks. At the end of the treatment, anxiety-like behavior was assessed using the Open Field Test (OFT), anhedonia was assessed using the Sucrose Preference Test (SPT), and learned helplessness was assessed using the Forced Swimming Test (FST). After occision, microglia were stained with IBA-1 and quantified in brain sections of target areas (prefrontal cortex, amygdala, and periaqueductal grey matter). Treatment with B. dracunculifolia extract reversed OA-induced mechanical hyperalgesia and partly improved depressive-like behavior in OA animals' concomitant to a decrease in the number of M1 microglia. Our findings suggest that B. dracunculifolia extracts can potentially be used in the food industry and for the development of nutraceuticals and functional foods.

Injection of kaolin/carrageenan in the rat knee joint induces progressive experimental knee osteoarthritis.

ABSTRACT: Osteoarthritis (OA), the most common joint disorder worldwide, is characterized by progressive degeneration of articular and periarticular structures, leading to physical and emotional impairments that greatly affect the quality of life of patients. Unfortunately, no therapy has been able to halt the progression of the disease. Owing to the complexity of OA, most animal models are only able to mimic a specific stage or feature of the human disorder. In this work, we demonstrate the intraarticular injection of kaolin or carrageenan leads to the progressive degeneration of the rat's knee joint, accompanied by mechanical hyperalgesia and allodynia, gait impairments (reduced contact area of the affected limb), and radiological and histopathological findings concomitant with the development of human grade 4 OA. In addition, animals also display emotional impairments 4 weeks after induction, namely, anxious and depressive-like behaviour, important and common comorbidities of human OA patients. Overall, prolonging kaolin or carrageenan-induced monoarthritis mimics several important physical and psychological features of human OA in both male and female rodents and could be further applied in long-term studies of OA-associated chronic pain.

A biocompatible and injectable hydrogel to boost the efficacy of stem cells in neurodegenerative diseases treatment.

AIMS: Stem cell therapies emerged as treatment modalities with potential to cure neurodegenerative diseases (NDs). However, despite high expectations, their clinical use is still limited. Critical issues in treatment outcomes may be related to stem cells formulation and administration route. We develop a hydrogel as a cell carrier, consisting of compounds (phospholipids and hyaluronic acid-HA) naturally present in the central nervous system (CNS). The HA-based hydrogel physically crosslinked with liposomes is designed for direct injection into the CNS to significantly increase the bone marrow mesenchymal stem cells (BMSCs) bioavailability. MATERIALS AND METHODS: Hydrogel compatibility is confirmed in vitro with BMSCs and in vivo through its intracerebroventricular injection in rats. To assess its efficacy, the main cause of chronic neurologic disability in young adults is selected, namely multiple sclerosis (MS). The efficacy of the developed formulation containing a lower number of cells than previously reported is demonstrated using an experimental autoimmune encephalomyelitis (EAE) rat model. KEY FINDINGS: The distribution of the engineered hydrogel into corpus callosum can be ideal for NDs treatment, since damage of this white matter structure is responsible for important neuronal deficits. Moreover, the BMSCs-laden hydrogel significantly decreases disease severity and maximum clinical score and eliminated the relapse. SIGNIFICANCE: The engineering of advanced therapies using this natural carrier can result in efficacious treatments for MS and related debilitating conditions.

Correlation between pain severity and levels of anxiety and depression in osteoarthritis patients: a systematic review and meta-analysis.

OBJECTIVES: Osteoarthritis (OA) is a chronic degenerative musculoskeletal disease that causes articular damage and chronic pain, with a prevalence of up to 50% in individuals >60 years of age. Patients suffering from chronic painful conditions, including OA, also frequently report anxiety or depression. A systematic review and meta-analysis were performed to assess the correlation between pain severity and depressive and anxious symptomatology in OA patients. METHODS: A systematic search was conducted using four databases (PubMed, Medline, Scopus, and Web of Science) from inception up to 14 January 2020. We included original articles evaluating pain severity and anxiety and/or depression severity in OA-diagnosed patients. Detailed data were extracted from each study, including patients' characteristics and pain, anxiety, and depression severity. When available, the Pearson correlation coefficient between pain and depression severity and pain and anxiety severity was collected, and a meta-analysis of random effects was applied. RESULTS: This systematic review included 121 studies, with a total of 38 085 participants. The mean age was 64.3 years old, and the subjects were predominantly female (63%). The most-used scale to evaluate pain severity was the Western Ontario and the McMaster Universities Osteoarthritis Index, while for anxiety and depression, the Hospital Anxiety and Depression Scale was the most used. The meta-analysis showed a moderate positive correlation between pain severity and both anxious (r = 0.31, P <0.001) and depressive symptomatology (r = 0.36, P <0.001). CONCLUSION: Our results demonstrate a significant correlation between pain and depression/anxiety severity in OA patients, highlighting the need for its routine evaluation by clinicians.

Modulating inflammation through the neutralization of Interleukin-6 and tumor necrosis factor-α by biofunctionalized nanoparticles.

Biological agents that neutralize the activity of pro-inflammatory cytokines are revolutionizing the treatment of inflammatory conditions. However, the antibodies (Abs) short half-life and off-target distribution critically limit their efficacy and safety. Therefore, this work proposes the immobilization of anti-TNF-α and anti-IL-6 Abs at the surface of polymeric nanoparticles (NPs) in order to extend and increase the Abs therapeutic efficacy, owing to the protection from degradation that the NPs provide, and to avoid off-target side effects through local administration. In an in vitro model of inflammation, biofunctionalized NPs were able to reduce the harmful effects on human chondrocytes provided by inflammatory macrophages, being demonstrated the additive effects of the dual neutralization. Significantly, biofunctionalized NPs ameliorated inflammation more efficiently than soluble Abs in an in vivo experimental model of inflammation, exhibiting a safe profile, a prolonged action, and a stronger efficacy. Hence, as this strategy is able to increase the therapeutic efficacy of the currently available treatments, it is a promising potential therapeutic option for inflammatory conditions.

Nociceptive, emotional, electrophysiological, and histological characterization of the chronic constriction injury model in female Wistar Han rats.

Chronic neuropathic pain affects 7-10 % of the population and is often accompanied by comorbid emotional disorders, which greatly reduce the quality of life of the patients, impairing physical, cognitive, emotional, and social functioning. Despite the higher prevalence and severity of chronic pain in women, the number of publications using female animals remains scarce. While in the chronic constriction injury (CCI) model the development of mechanical/thermal hyperalgesia, allodynia and spontaneous pain has been shown in both sexes, little is known on CCI-induced emotional impairments and sciatic nerve histopathology in female rats, as well as on the contributions of ovarian hormones to peripheral nerve injury. In this work, young adult rats (Wistar Han) were assigned to one of five groups: gonadally intact females (SHAM/SHAM), ovariectomized females (SHAM/OVX), gonadally intact females with CCI (CCI/SHAM); ovariectomized females with CCI (CCI/OVX) and males with CCI (CCIM). In the postoperative period, CCI animals, both females and males, displayed visible gait abnormalities, limping and guarding the affected hind paw although locomotion was not affected. Neuropathic females developed sustained mechanical allodynia, with CCI/OVX animals displaying symptoms two weeks before CCI/SHAM females. Interestingly, regarding mechanical and cold allodynia, CCI males slowly recovered from week 3 onwards. While CCI induced neither anxiety- nor depressive-like behaviour in females, ovariectomy per se induced anhedonic-like behaviour, regardless of CCI surgery. Histopathological analysis of the sciatic nerve showed CCI induced nerve damage, fibrosis, myelin sheath degradation and inflammation. Single-cell electrophysiological data from the rostral ventromedial medulla (RVM) suggests this area is partly involved in descending facilitation associated with experimental neuropathic pain. Altogether, our findings demonstrate CCI females display distinct sensory, emotional, electrophysiological, and histopathological impairments from males, and that ovariectomy aggravates females' responses to peripheral nerve injury.

Emotional and cognitive impairments in the peripheral nerve chronic constriction injury model (CCI) of neuropathic pain: A systematic review.

BACKGROUND AND OBJECTIVE: Emotional and cognitive impairments are common comorbidities of chronic neuropathic pain that significantly impact the quality of life of patients. While the nociceptive components of the peripheral nerve chronic constriction injury (CCI) animal model have been extensively analyzed, data related to the development of mood and cognitive disorders, and especially its impact on female rats remains fragmented. We systematically reviewed the literature analyzing the methods used to induce and evaluate the development of emotional- and cognitive-like impairments and sex-specific differences in the CCI model. DATABASES AND DATA TREATMENT: We searched PubMed, Google Scholar and Web of Science from inception to September 30th, 2019, and a total of 44 papers were considered eligible for inclusion. We included animal studies assessing nociception, locomotion, anxious-like, depressive-like and cognitive behaviours after the CCI induction. RESULTS: The overall quality of the studies was considered moderate to high. Overall, the induction of CCI leads to the development of emotional impairments, namely anxiety- and depressive-like behaviours, as well as cognitive impairments. With the majority of the studies using male subjects, the lack of evidence on female animals prevents the evaluation of sex-specific differences. CONCLUSIONS: This review supports the development of an anxiodepressive-like phenotype, associated with cognitive impairments, in CCI-induced animals. These results support the use of this animal model for the study of the mechanisms underlying these comorbidities, as well as a screening tool for the development/repurposing of drugs that tackle both the neuropathy-induced nociceptive and emotional impairments, such as tricyclic antidepressants. Importantly, our review also highlights the need for studies performed in female rodents as these are almost non-existent.

[Chronic Pain After Outpatient Inguinal Hernioplasty: Retrospective Cohort Study]. / Dor Crónica Pós-Hernioplastia Inguinal em Regime de Ambulatório: Estudo de Coorte Retrospetivo.

INTRODUCTION: Chronic postoperative pain is the most frequent late complication of inguinal hernia repair surgery. The aim of this study is to evaluate the incidence of chronic post-hernioplasty pain in outpatient care at Centro Hospitalar do Porto, describe it, analyse its relation with other variables defined in the literature and study its functional interference. MATERIAL AND METHODS: We performed a retrospective cohort study between February and May 2016, using a structured telephone interview composed of questions from the authors and sections of published questionnaires, two of which are validated for the Portuguese language and culture. We included men who underwent ambulatory inguinal hernioplasty, by laparotomy or laparoscopy, at Centro Hospitalar do Porto, between January 2011 and October 2015. RESULTS: In a final sample of 829 surgeries, the incidence of chronic post-hernioplasty pain was 24.0% [confidence interval: 21.2 - 27.1]. The development of chronic post-hernioplasty pain was higher in patients with pre-surgical pain and younger age and was related with the presence of pain during the first month after surgery. No relationship was found between surgical technique and the development of chronic post-hernioplasty pain. Of the individuals with chronic pain, 65.0% mentioned moderate-severe 'pain on the average' and 37.7% presented descriptors suggestive of neuropathic pain. The only parameter evaluated with which chronic post-hernioplasty pain 'did not interfere completely' was sleep. DISCUSSION: The prevalence found for chronic posthernioplasty pain with significant functional interference is in line with data retrieved from literature. The predictive potential of pre-surgical pain and young age for the development of chronic posthernioplasty pain is also in agreement with previous studies. Limitations were found to this study given its retrospective nature. CONCLUSION: The high prevalence of chronic post-hernioplasty pain raises the urgent need for raising awareness regarding this issue among health care professionals. The main areas for improvement are diagnosis, follow-up and treatment of pain.

Introdução: A dor crónica pós-cirúrgica é a complicação tardia mais frequente da cirurgia de reparação de hérnia inguinal. Este trabalho visa determinar a incidência de dor crónica pós-hernioplastia inguinal em ambulatório no Centro Hospitalar do Porto, estudar a sua relação com determinadas variáveis descritas na literatura, avaliar as suas características e interferência funcional.Material e Métodos: Realizámos um estudo de coorte retrospetivo, entre fevereiro e maio de 2016, por entrevista telefónica estruturada composta por perguntas dos autores e secções de três questionários publicados, dois dos quais validados para a língua e cultura portuguesas. Incluímos os homens submetidos a hernioplastia inguinal, por laparotomia ou laparoscopia, em ambulatório, no Centro Hospitalar do Porto, entre janeiro de 2011 e outubro de 2015.Resultados: Na amostra final de 829 hernioplastias, a incidência de dor crónica pós-hernioplastia foi de 24,0% [intervalo de confiança: 21,2 - 27,1]. O desenvolvimento de dor crónica foi superior nos doentes com dor pré-cirúrgica, nos doentes mais jovens e relacionou-se com o momento de início da dor pós-cirúrgica. Não encontrámos relação com a via de abordagem, clássica ou laparoscópica. Dos indivíduos com dor crónica, 65,0% apresentaram dor 'em média' moderada ou forte e 37,7% apresentavam descritores sugestivos de dor de origem neuropática. A dor crónica pós-hernioplastia do ponto de vista funcional apenas 'não interferiu completamente' com o sono.Discussão: A prevalência encontrada de dor crónica pós-hernioplastia, com interferência funcional importante, é congruente com os dados disponíveis na literatura. O potencial preditor da presença de dor pré-cirúrgica e idade jovem do doente para o desenvolvimento de dor crónica pós-hernioplastia é também corroborado pela literatura. Tratando-se de um estudo de coorte retrospetivo, o estudo apresenta as limitações inerentes.Conclusão: A elevada prevalência de dor crónica pós-hernioplastia encontrada apontam para a urgência na sensibilização dos profissionais de saúde para esta problemática e otimização do follow-up, diagnóstico e tratamento da dor.

Minocycline reduces mechanical allodynia and depressive-like behaviour in type-1 diabetes mellitus in the rat.

A common and devastating complication of diabetes mellitus is painful diabetic neuropathy (PDN) that can be accompanied by emotional disorders such as depression. A few studies have suggested that minocycline that inhibits microglia may attenuate pain hypersensitivity in PDN. Moreover, a recent study reported that minocycline has an acute antidepressive-like effect in diabetic animals. Here we studied whether (i) prolonged minocycline treatment suppresses pain behaviour in PDN, (ii) the minocycline effect varies with submodality of pain, and (iii) the suppression of pain behaviour by prolonged minocycline treatment is associated with antidepressive-like effect. The experiments were performed in streptozotocin-induced rat model of type-1 diabetes. Pain behaviour was evoked by innocuous (monofilaments) and noxious (paw pressure) mechanical stimulation, innocuous cold (acetone drops) and noxious heat (radiant heat). Depression-like behaviour was assessed using forced swimming test. Minocycline treatment (daily 80mg/kg per os) of three-week duration started four weeks after induction of diabetes. Diabetes induced mechanical allodynia and hyperalgesia, cold allodynia, heat hypoalgesia, and depression-like behaviour. Minocycline treatment significantly attenuated mechanical allodynia and depression-like behaviour, while it failed to produce significant changes in mechanical hyperalgesia, cold allodynia or heat hypoalgesia. The results indicate that prolonged per oral treatment with minocycline has a sustained mechanical antiallodynic and antidepressive-like effect in PDN. These results support the proposal that minocycline might provide a treatment option for attenuating sensory and comorbid emotional symptoms in chronic PDN.

Galanin-Mediated Behavioural Hyperalgesia from the Dorsomedial Nucleus of the Hypothalamus Involves Two Independent Descending Pronociceptive Pathways.

Activation of the dorsomedial nucleus of the hypothalamus (DMH) by galanin (GAL) induces behavioural hyperalgesia. Since DMH neurones do not project directly to the spinal cord, we hypothesized that the medullary dorsal reticular nucleus (DRt), a pronociceptive region projecting to the spinal dorsal horn (SDH) and/or the serotoninergic raphe-spinal pathway acting on the spinal 5-HT3 receptor (5HT3R) could relay descending nociceptive facilitation induced by GAL in the DMH. Heat-evoked paw-withdrawal latency (PWL) and activity of SDH neurones were assessed in monoarthritic (ARTH) and control (SHAM) animals after pharmacological manipulations of the DMH, DRt and spinal cord. The results showed that GAL in the DMH and glutamate in the DRt lead to behavioural hyperalgesia in both SHAM and ARTH animals, which is accompanied particularly by an increase in heat-evoked responses of wide-dynamic range neurons, a group of nociceptive SDH neurones. Facilitation of pain behaviour induced by GAL in the DMH was reversed by lidocaine in the DRt and by ondansetron, a 5HT3R antagonist, in the spinal cord. However, the hyperalgesia induced by glutamate in the DRt was not blocked by spinal ondansetron. In addition, in ARTH but not SHAM animals PWL was increased after lidocaine in the DRt and ondansetron in the spinal cord. Our data demonstrate that GAL in the DMH activates two independent descending facilitatory pathways: (i) one relays in the DRt and (ii) the other one involves 5-HT neurones acting on spinal 5HT3Rs. In experimental ARTH, the tonic pain-facilitatory action is increased in both of these descending pathways.

A role of supraspinal galanin in behavioural hyperalgesia in the rat.

INTRODUCTION: In chronic pain disorders, galanin (GAL) is able to either facilitate or inhibit nociception in the spinal cord but the contribution of supraspinal galanin to pain signalling is mostly unknown. The dorsomedial nucleus of the hypothalamus (DMH) is rich in galanin receptors (GALR) and is involved in behavioural hyperalgesia. In this study, we evaluated the contribution of supraspinal GAL to behavioural hyperalgesia in experimental monoarthritis. METHODS: In Wistar-Han males with a four week kaolin/carrageenan-induced monoarthritis (ARTH), paw-withdrawal latency (PWL) was assessed before and after DMH administration of exogenous GAL, a non-specific GALR antagonist (M40), a specific GALR1 agonist (M617) and a specific GALR2 antagonist (M871). Additionally, the analysis of c-Fos expression after GAL injection in the DMH was used to investigate the potential involvement of brainstem pain control centres. Finally, electrophysiological recordings were performed to evaluate whether pronociceptive On- or antinociceptive Off-like cells in the rostral ventromedial medulla (RVM) relay the effect of GAL. RESULTS: Exogenous GAL in the DMH decreased PWL in ARTH and SHAM animals, an effect that was mimicked by a GALR1 agonist (M617). In SHAM animals, an unselective GALR antagonist (M40) increased PWL, while a GALR2 antagonist (M871) decreased PWL. M40 or M871 failed to influence PWL in ARTH animals. Exogenous GAL increased c-Fos expression in the RVM and dorsal raphe nucleus (DRN), with effects being more prominent in SHAM than ARTH animals. Exogenous GAL failed to influence activity of RVM On- or Off-like cells of SHAM and ARTH animals. CONCLUSIONS: Overall, exogenous GAL in the DMH had a pronociceptive effect that is mediated by GALR1 in healthy and arthritic animals and is associated with alterations of c-Fos expression in RVM and DRN that are serotonergic brainstem nuclei known to be involved in the regulation of pain.

Pronociception from the dorsomedial nucleus of the hypothalamus is mediated by the rostral ventromedial medulla in healthy controls but is absent in arthritic animals.

The dorsomedial nucleus of the hypothalamus (DMH) has been proposed to participate in stress-induced hyperalgesia through facilitation of pronociceptive cells in the rostroventromedial medulla (RVM). We hypothesized that the DMH participates in hyperalgesia induced by arthritis. The DMH was pharmacologically manipulated while assessing heat-evoked nociceptive behavior or the discharge rates of pronociceptive RVM ON- and antinociceptive RVM OFF-like cells in NAIVE, SHAM and monoarthritic (ARTH) animals. In NAIVE and SHAM animals, the changes in nociceptive behavior induced by activation of the DMH by glutamate and inhibition by lidocaine were in line with earlier evidence indicating that the DMH has a nociceptive facilitating role. However, in ARTH animals, neither activation nor inhibition of the DMH influenced pain-like behavior evoked by stimulation of an uninflamed skin region (paw and tail). In accordance with these behavioral results, activation or inhibition of the DMH induced pronociceptive changes in the discharge rates of RVM cells in NAIVE and SHAM animals, which suggests that the DMH has a pronociceptive role mediated by the RVM in normal animals. However, in ARTH animals, both glutamate and lidocaine in the DMH failed to influence either pain-like behavior or noxious stimulation-evoked responses of RVM cells, while blocking the DMH increased spontaneous activity in the pronociceptive RVM ON cells. Our data indicate that the DMH participates in descending facilitation of cutaneous nociception in healthy controls, but it is not engaged in the regulation of cutaneous nociception in monoarthritic animals, while a minor role in tonic suppression of nociception in arthritis cannot be discarded.

Dissociated modulation of conditioned place-preference and mechanical hypersensitivity by a TRPA1 channel antagonist in peripheral neuropathy.

Transient receptor potential ankyrin 1 (TRPA1) channel antagonists have suppressed mechanical hypersensitivity in peripheral neuropathy, while their effect on ongoing neuropathic pain is not yet known. Here, we assessed whether blocking the TRPA1 channel induces place-preference, an index for the relief of ongoing pain, in two experimental rat models of peripheral neuropathy. Diabetic neuropathy was induced by streptozotocin and spared nerve injury (SNI) model of neuropathy by ligation of two sciatic nerve branches. Conditioned place-preference (CPP) paradigm involved pairing of the drug treatment with one of the chambers of a CPP device once or four times, and the time spent in each chamber was recorded after conditioning sessions to reveal place-preference. The mechanical antihypersensitivity effect was assessed by the monofilament test immediately after the conditioning sessions. Intraperitoneally (30mg/kg; diabetic and SNI model) or intrathecally (10µg; diabetic model) administered Chembridge-5861528 (CHEM) was used as a selective TRPA1 channel antagonist. In diabetic and SNI models of neuropathy, CHEM failed to induce CPP at a dose that significantly attenuated mechanical hypersensitivity, independent of the route of drug administration or number of successive conditioning sessions. Intrathecal clonidine (an α2-adrenoceptor agonist; 10µg), in contrast, induced CPP in SNI but not control animals. The results indicate that ongoing pain, as revealed by CPP, is less sensitive to treatment by the TRPA1 channel antagonist than mechanical hypersensitivity in peripheral neuropathy.