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.

Copaiba oil minimizes inflammation and promotes parenchyma re-epithelization in acute allergic asthma model induced by ovalbumin in BALB/c mice.

Introduction: Asthma is a condition of airflow limitation, common throughout the world, with high mortality rates, especially as it still faces some obstacles in its management. As it constitutes a public health challenge, this study aimed to investigate the effect of copaiba oil (e.g., Copaifera langsdorffii), as a treatment resource, at doses of 50 and 100 mg/kg on certain mediators of acute lung inflammation (IL-33, GATA3, FOXP3, STAT3, and TBET) and early mechanisms of lung remodeling (degradation of elastic fiber tissues, collagen deposition, and goblet cell hyperplasia). Methods: Using an ovalbumin-induced acute allergic asthma model in BALB/c mice, we analyzed the inflammatory mediators through immunohistochemistry and the mechanisms of lung remodeling through histopathology, employing orcein, Masson's trichrome, and periodic acid-Schiff staining. Results: Copaiba oil treatment (CO) reduced IL-33 and increased FOXP3 by stimulating the FOXP3/GATA3 and FOXP3/STAT3 pathways. Additionally, it upregulated TBET, suggesting an additional role in controlling GATA3 activity. In the respiratory epithelium, CO decreased the fragmentation of elastic fibers while increasing the deposition of collagen fibers, favoring epithelial restructuring. Simultaneously, CO reduced goblet cell hyperplasia. Discussion: Although additional research is warranted, the demonstrated anti-inflammatory and re-epithelializing action makes CO a viable option in exploring new treatments for acute allergic asthma.

Comparative neurotoxicity of dietary methylmercury and waterborne inorganic mercury in fish: Evidence of optic tectum vulnerability through morphometric and histopathological assessments.

This work investigated the effects of inorganic mercury (iHg) and methylmercury (MeHg) on the fish optic tectum morphology, viz. in relation to: (i) vulnerability of specific optic tectum layers; (ii) preferential targeting of Hg forms to neurons or glial cells; (iii) comparative toxicity of iHg and MeHg in this brain area that is in the maintenance of several fish behaviors. Two experiments exposing juvenile white seabream (Diplodus sargus) to waterborne iHg [HgCl2 (2 µg L-1)] and dietary MeHg (8.7 µg g-1) were performed, comprising both exposure (7 and 14 days; E7 and E14, respectively) and post-exposure (28 days; PE28) periods. Morphometric assessments were performed using stereological methods where the layers of the optic tectum were outlined, while its area and the number of neurons and glial cells were estimated. A histopathological assessment was also performed per section and per layer of optic tectum. iHg exposure did not trigger the loss of neurons during the exposure periods, while a decrease of glial cells was detected in a single layer of the optic tectum at E14. Differently, upon MeHg exposure, a decrease on the number of neurons and glial cells was found in several layers of optic tectum. In the post-exposure, both Hg forms triggered the loss of neurons, while only MeHg exposure led to a decrease on the number of glia cells. The histopathological assessment pointed out a higher toxicity of MeHg in the optic tectum layers, particularly in the post-exposure period, while no significant alterations were found in fish exposed to iHg. Hg forms targeted preferentially neurons. iHg and MeHg are relevant neurotoxicants to fish, with MeHg exposure leading to a higher toxicity than iHg in the optic tectum. After 28 days of post-exposure, iHg and MeHg neurotoxicity remained prominent, suggesting long-term effects of these toxicants.

Sucrose preference test: A systematic review of protocols for the assessment of anhedonia in rodents.

Anhedonia is described as a decreased ability to experience rewarding and enjoyable activities, a core symptom of major depressive disorder. The sucrose preference test (SPT) is a widely used and reliable behavioural test to assess anhedonia in rodents, based on a two-bottle choice paradigm. To date, different protocols are in use, inducing variability between researchers and hampering comparisons between studies. We performed a systematic review of the SPT protocols used in 2021 to identify the parameters in which they differ and their potential impact. We searched a total of four databases (PubMed, Scopus, Web of Science and Science Direct), from 1st January 2021 to 31st December 2021, and screened a total of 1066 articles. After screening by title and abstract, a total of 415 articles were included in this review. We extracted and analysed the different procedures used, the type of sweet solution and the habituation, deprivation, and testing protocols. The overall quality of the studies was considered very good, however, SPT protocols were extremely variable between studies with a total of 65 different habituation protocols and 104 combinations of food/water deprivation and preference testing duration. As the SPT is one of the most used tests to assess anhedonia in rodents, this work raises awareness of the great variability in SPT protocols being currently used. Furthermore, we call for standardization in the protocol used, and overall improvement of data reporting of methodologies and results, to increase the consistency between studies and allow a better comparison of results between different labs.

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 New Gal in Town: A Systematic Review of the Role of Galanin and Its Receptors in Experimental Pain.

Galanin is a neuropeptide expressed in a small percentage of sensory neurons of the dorsal root ganglia and the superficial lamina of the dorsal horn of the spinal cord. In this work, we systematically reviewed the literature regarding the role of galanin and its receptors in nociception at the spinal and supraspinal levels, as well as in chronic pain conditions. The literature search was performed in PubMed, Web of Science, Scopus, ScienceDirect, OVID, TRIP, and EMBASE using "Galanin" AND "pain" as keywords. Of the 1379 papers that were retrieved in the initial search, we included a total of 141 papers in this review. Using the ARRIVE guidelines, we verified that 89.1% of the works were of good or moderate quality. Galanin shows a differential role in pain, depending on the pain state, site of action, and concentration. Under normal settings, galanin can modulate nociceptive processing through both a pro- and anti-nociceptive action, in a dose-dependent manner. This peptide also plays a key role in chronic pain conditions and its antinociceptive action at both a spinal and supraspinal level is enhanced, reducing animals' hypersensitivity to both mechanical and thermal stimulation. Our results highlight galanin and its receptors as potential therapeutic targets in pain conditions.

Sucrose intake and preference by Wistar Han rats are not influenced by sex or food/water deprivation.

Anhedonia is the decreased ability to experience pleasure from rewarding or enjoyable activities, a core symptom of depression. The sucrose preference test (SPT), based on a two-bottle choice paradigm, is a widely used behavioural paradigm for the evaluation of anhedonia in rodents. Up to now, different protocols have been reported regarding water/food deprivation and duration of exposure to the water/sucrose solutions. In this work, by comparing six of the most used SPT protocols regarding sucrose preference and total intake, in both male and female Wistar Han rats, we showed (i) food/water deprivation does not significantly impact sucrose intake and preference; (ii) increasing the duration of the test is associated with an increased sucrose preference and (iii) no sex-specific differences in the basal sucrose preference of Wistar Han rats. Our results call for standardization of protocols and suggest a protocol without food/water deprivation and a 12-hour duration (lights out) as more efficacious in the measurement of anhedonia in rodents. This protocol not only reduces the confounding factors of drinking patterns and the stress-inducing food/water deprivation but also is not sensitive to sex-specific differences in the total intake of liquid in Wistar Han rats.

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.

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.