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Trigeminal neuralgia (TN) is debilitating and is usually accompanied by mood disorders. The lateral habenula (LHb) is considered to be involved in the modulation of pain and mood disorders, and the present study aimed to determine if and how the LHb participates in the development of pain and anxiety in TN. To address this issue, a mouse model of partial transection of the infraorbital nerve (pT-ION) was established. pT-ION induced stable and long-lasting primary and secondary orofacial allodynia and anxiety-like behaviors that correlated with the increased excitability of LHb neurons. Adeno-associated virus (AAV)-mediated expression of hM4D(Gi) in glutamatergic neurons of the unilateral LHb followed by clozapine-N-oxide application relieved pT-ION-induced anxiety-like behaviors but not allodynia. Immunofluorescence validated the successful infection of AAV in the LHb, and microarray analysis showed changes in gene expression in the LHb of mice showing allodynia and anxiety-like behaviors after pT-ION. Among these differentially expressed genes was Tacr3, the downregulation of which was validated by RT-qPCR. Rescuing the downregulation of Tacr3 by AAV-mediated Tacr3 overexpression in the unilateral LHb significantly reversed pT-ION-induced anxiety-like behaviors but not allodynia. Whole-cell patch clamp recording showed that Tacr3 overexpression suppressed nerve injury-induced hyperexcitation of LHb neurons, and western blotting showed that the pT-ION-induced upregulation of p-CaMKII was reversed by AAV-mediated Tacr3 overexpression or chemicogenetic inhibition of glutamatergic neurons in the LHb. Moreover, not only anxiety-like behaviors, but also allodynia after pT-ION were significantly alleviated by chemicogenetic inhibition of bilateral LHb neurons or by bilateral Tacr3 overexpression in the LHb. In conclusion, Tacr3 in the LHb plays a protective role in treating trigeminal nerve injury-induced allodynia and anxiety-like behaviors by suppressing the hyperexcitability of LHb neurons. These findings provide a rationale for suppressing unilateral or bilateral LHb activity by targeting Tacr3 in treating the anxiety and pain associated with TN.
Learn More >The effect of headache on cognitive performance is controversial, due to conflicting results obtained from studies in clinical or population settings. We aimed to understand if migraine and other headaches modify the rates of decline on different cognitive measures, during a 5-year interval.
Learn More >Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS-associated depression by using a mouse model of experimental autoimmune prostatitis (EAP).
Learn More >Background and aims A multimodal rehabilitation programme (MMRP) is an evidence-based treatment of chronic pain conditions. The complexity involved in chronic pain needs to be identified and evaluated in order to adapt the rehabilitation to patients' needs. The aim was to investigate the multivariate relationships between self-reported variables in patients with chronic pain before taking part in MMRP in primary care, with a special focus on gender and degree of sick leave. Methods Prior to MMRP, 397 patients (339 women and 58 men) filled in a questionnaire about pain, healthcare aspects, health-related quality of life, anxiety and depression, coping, physical function, and work-related variables e.g. sick leave. Data were analysed by principal component analysis (PCA) and partial least square analysis. Results The PCA identified four components that explained 47% of the variation in the investigated data set. The first component showed the largest variation and was primarily explained by anxiety and depression, quality of life, acceptance (activity engagement), and pain-related disability. Gender differences were only seen in one component with the pain variables having the highest loadings. Degree of sick leave was not well explained by the variables in the questionnaire. Conclusions The questionnaire filled out by the patients prior to participation in MMRP in primary care identified much of the complexity of chronic pain conditions but there is room for improvement, e.g. regarding explanation of work-related factors. In the multivariate analysis, gender did not fall out as an important factor for how most patients answered the questions. Implications There are not many studies that describe patients who undergo MMRP in primary care since previously such patients were treated mostly in specialist care. More knowledge is needed about these patients in order to improve rehabilitation plans and interventions. The results suggest that the questionnaire identifies the complexity among chronic pain patients in primary care. The identified components could improve assessment before MMRP and contribute to better tailored programmes.
Learn More >Background and aims In the spring of 2019, Professor Steven J. Linton, the founder of the Center for Health and Medical Psychology (CHAMP) at Örebro University, Sweden, formally retired. As a tribute to his scholarly work covering decades of influence and inspiration to the field of pain psychology, the research center organized a topical conference titled "Pain in the 21st century: Where do we come from and where are we going?", which resulted in this state-of the-art synthesis. The aim of this declaration is to highlight lessons learned but not in the least is meant to inspire and guide our continued journey forward, developing pain psychology into the 21st century. Methods Several collaborators of Professor Linton have summarized and reflected on the current state-of-the-art of pain psychology from the perspective of his input to the field, as well as on developments from the last years of advancements in pain psychology. Results The topics have been divided into six themed sections covering the fear avoidance model, transdiagnostics, secondary prevention, risk- and protective factors, communication and contextual factors. The sections cover a broad spectrum, from basic experimental studies, integrating emotion and motivational theories into current theoretical models, to applied research on the effect of early interventions as well as sophisticated emotion-focused treatment models for pain patients with concurrent emotional ill-health. Conclusions There have been major advancements within pain psychology research during the last decades, moving the field towards a more comprehensive picture, taking emotional and motivational aspects into account to understand pain sufferers. Although psychologically informed interventions in general mainly focus on the individual, it has been put forward that pain management is highly influenced by the surrounding environment, including communication with health care providers, and the occupational and social context. Implications Professor Steven J. Linton has been at the forefront of pain psychology research during the last decades, and inspired by his work this journey will continue into the 21st century, with the ultimate goal of enhancing the understanding and treatment for all people suffering from persistent and disabling pain.
Learn More >Transcutaneous electrical nerve stimulation (TENS), manual acupuncture (MA), and spinal cord stimulation (SCS) are used to treat a variety of pain conditions. These non-pharmacological treatments are often thought to work through similar mechanisms, and thus should have similar effects for different types of pain. However, it is unclear if each of these treatments work equally well on each type of pain condition. The purpose of this study was to compared the effects of TENS, MA, and SCS on neuropathic, inflammatory, and non-inflammatory pain models.
Learn More >Opioid analgesic misuse and abuse has given rise to an epidemic that has added to an increase in opioid-related overdoses and deaths. Adults with persistent noncancer pain (PNCP) are primarily treated with opioid analgesics. Many remain on these medications long term. Most of these patients are unaware of other effective measures for managing PNCP, such as nonpharmacologic modalities (NPMs). This lack of familiarity with NPMs presents a key contributor to the problem of NPM underuse among adult PNCP patients. This integrative review sought to identify key factors that contribute to NPMs underuse and the effect of education on patients' adoption or use for PNCP management.
Learn More >Chronic pain has a tremendous personal and socioeconomic impact and remains difficult to treat. Therefore, it seems important to provide an update on the current understanding regarding lifestyle factors in people with chronic pain across the lifespan, and explaining that clinicians should address various lifestyle factors concomitantly into an individually-tailored multimodal lifestyle intervention for people having chronic pain. Lifestyle factors such as physical (in)activity, sedentary behaviour, stress, poor sleep, unhealthy diet and smoking are associated with chronic pain severity and sustainment. This applies to all age categories, that is, chronic pain across the lifespan. Yet current treatment options often do not, or only partly address the many lifestyle factors associated with chronic pain, or attempt to address them in a standard format rather than providing an individually tailored multimodal lifestyle intervention. The evidence regarding lifestyle factors is available in adults, but limited in children and elderly having chronic pain, providing important avenues for future research. In conclusion, it is proposed that treatment approaches for people having chronic pain should address all relevant lifestyle factors concomitantly into an individually-tailored multimodal intervention. Ultimately, this should lead to a higher clinical impact with higher effect sizes and subsequently decreasing the psychological and socio-economic burden of chronic pain in the Western world. This article is protected by copyright. All rights reserved.
Learn More >Individual differences in emotional functioning, pain appraisal processing, and perceived social support may play a relevant role in the subjective experience of pain. Due to the paucity of data regarding individuals with Rheumatoid Arthritis (RA), the present study aimed to examine pain intensity, emotional functioning (psychological distress and alexithymia), pain appraisal (pain beliefs, pain catastrophizing, and pain-related coping strategies) and social support, and their relationships with the health-related quality of life (HRQoL) in patients with RA. Data were collected from 108 female patients diagnosed with RA. Clinically relevant levels of depressive and anxiety symptoms assessed by the HADS subscales were present in 34% and 41% of the patients, respectively, and about 24% of them exhibited the presence of alexithymia. The results of hierarchical multiple regression analyses showed that pain intensity, alexithymia, the maladaptive beliefs regarding the stability of pain and the coping strategy of guarding explained 54% of the variance in the physical component of HRQoL (p < 0.001). Depression subscale of the HADS, alexithymia, the coping strategy of resting, and the rumination factor of pain catastrophizing significantly explained 40% of the variance in the mental component of HRQoL (p < 0.001). The present findings provide evidence regarding the importance of emotional functioning and pain appraisal in the negative impact of RA on patients' quality of life. These findings provide additional evidence for the biopsychosocial model of chronic pain, further supporting the complex interaction between emotional, cognitive, and behavioral processes in patients with chronic pain.
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