PAIN®Pub Date : 2025-01-01Epub Date: 2024-07-23DOI: 10.1097/j.pain.0000000000003337
Marcela Camargo Tozzo, Felipe J J Reis, Rafael Krasic Alaiti, Gisele Harumi Hotta, Anamaria Siriani de Oliveira
{"title":"Association between perception of harm and valence of shoulder movement images with disability levels related to chronic shoulder pain.","authors":"Marcela Camargo Tozzo, Felipe J J Reis, Rafael Krasic Alaiti, Gisele Harumi Hotta, Anamaria Siriani de Oliveira","doi":"10.1097/j.pain.0000000000003337","DOIUrl":"10.1097/j.pain.0000000000003337","url":null,"abstract":"<p><strong>Abstract: </strong>Recent studies highlight an interplay between pain perception and emotional responses. This necessitates a thorough investigation into how beliefs and motivational influences respond to visual stimuli of movements. Such an analysis is crucial for understanding the extent to which these factors contribute to disability levels associated with shoulder pain. We aimed to investigate the relationship between the perception of harm and the valence in images depicting shoulder movements and determine how these perceptions are linked to disability levels associated with shoulder pain. This cross-sectional study recruited 42 individuals with chronic shoulder pain. Participants were presented with 58 shoulder movements images. Each participant evaluated these images for emotional valence and arousal using the self-assessment manikin. For every image, they provided their level of avoidance, fear, and perception of harm in a numerical scale. We measured disability levels and pain catastrophizing using the Shoulder Pain and Disability Index and the Pain Catastrophizing Scale. A direct acyclic graph was used. Multiple linear regression analysis was conducted with shoulder disability as the dependent variable and perception of harm and valence as independent variables, adjusted for the confounders catastrophizing and arousal. This analysis resulted in a significant model ( F4,37 = 11.44; adjusted R2 = 0.547; P < 0.01). The perception of harm to shoulder movement (β = 0.11; P < 0.001; 95% confidence interval = 5.6-11.8) was significantly associated with the level of shoulder disability, whereas valence did not show a significant association (β = 0.26; P = 0.15; 95% confidence interval = 1.7-10.8). The perception of harm associated with shoulder movements images during daily activities was associated with disability. Individuals who believe that shoulder movements are harmful have greater disability.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"e10-e17"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PAIN®Pub Date : 2025-01-01Epub Date: 2024-10-15DOI: 10.1097/j.pain.0000000000003423
Niklas Noe-Steinmüller, Dmitry Scherbakov, Alexandra Zhuravlyova, Tor D Wager, Pavel Goldstein, Jonas Tesarz
{"title":"Reply to Duffee.","authors":"Niklas Noe-Steinmüller, Dmitry Scherbakov, Alexandra Zhuravlyova, Tor D Wager, Pavel Goldstein, Jonas Tesarz","doi":"10.1097/j.pain.0000000000003423","DOIUrl":"10.1097/j.pain.0000000000003423","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"166 1","pages":"222"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PAIN®Pub Date : 2025-01-01Epub Date: 2024-04-19DOI: 10.1097/j.pain.0000000000003250
Mark D Sullivan, Amanda C de C Williams
{"title":"The social nature of human pain.","authors":"Mark D Sullivan, Amanda C de C Williams","doi":"10.1097/j.pain.0000000000003250","DOIUrl":"10.1097/j.pain.0000000000003250","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"20-23"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PAIN®Pub Date : 2025-01-01Epub Date: 2024-07-26DOI: 10.1097/j.pain.0000000000003360
Bekir Nihat Dogrul, Caroline Machado Kopruszinski, Mahdi Dolatyari Eslami, Moe Watanabe, Shizhen Luo, Luiz Henrique Moreira de Souza, Robson Lilo Vizin, Xu Yue, Richard D Palmiter, Edita Navratilova, Frank Porreca
{"title":"Descending facilitation from rostral ventromedial medulla mu opioid receptor-expressing neurons is necessary for maintenance of sensory and affective dimensions of chronic neuropathic pain.","authors":"Bekir Nihat Dogrul, Caroline Machado Kopruszinski, Mahdi Dolatyari Eslami, Moe Watanabe, Shizhen Luo, Luiz Henrique Moreira de Souza, Robson Lilo Vizin, Xu Yue, Richard D Palmiter, Edita Navratilova, Frank Porreca","doi":"10.1097/j.pain.0000000000003360","DOIUrl":"10.1097/j.pain.0000000000003360","url":null,"abstract":"<p><strong>Abstract: </strong>Pharmacological ablation of rostral ventromedial medulla (RVM) mu opioid receptor-expressing cells before peripheral nerve injury prevents the development of neuropathic pain. However, whether these neurons are required for the expression of established neuropathic pain is not known. Male Oprm1Cre heterozygous (MOR Cre ) or wild-type (MOR WT ) mice received AAV8-hSyn-DIO-hM4D(Gi)-mCherry in the RVM. After partial sciatic nerve ligation (PSNL), we evaluated pain behaviors and descending control of nociception in response to acute or sustained chemogenetic inhibition of RVM-MOR cells expressing hM4D(Gi). A single systemic administration of hM4D(Gi) agonist clozapine-N-oxide (CNO) reversibly inhibited hind paw tactile allodynia and produced conditioned place preference only in MOR Cre mice with PSNL. Intrathecal CNO also reversibly inhibited PSNL-induced hind paw allodynia, suggesting that the spinal projections from these RVM-MOR cells are critical for manifestation of pain behaviors. Consistent with enhanced descending facilitation from RVM-MOR cells, MOR Cre -hM4D(Gi) mice with PSNL showed diminished descending control of nociception that was restored by systemic CNO. Sustained CNO in drinking water before PSNL prevented expression of chronic pain without affecting acute surgical pain; however, relief of chronic pain required sustained CNO treatment. Thus, in male mice, activity of spinally projecting RVM-MOR cells is required (1) for expression and manifestation of both sensory and affective dimensions of established neuropathic pain and (2) to promote descending facilitation that overcomes apparently intact descending inhibition to maintain chronic pain. Enhanced descending facilitation likely regulates the output signal from the spinal cord to the brain to shape the pain experience and may provide a mechanism for nonopioid management of pain.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"153-159"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PAIN®Pub Date : 2025-01-01Epub Date: 2024-08-23DOI: 10.1097/j.pain.0000000000003325
Paraskevi Sgourdou, Melanie Schaffler, Kyuhyun Choi, Nora M McCall, Justin Burdge, Joelle Williams, Gregory Corder, Marc V Fuccillo, Ishmail Abdus-Saboor, Douglas J Epstein
{"title":"Impaired pain in mice lacking first-order posterior medial thalamic neurons.","authors":"Paraskevi Sgourdou, Melanie Schaffler, Kyuhyun Choi, Nora M McCall, Justin Burdge, Joelle Williams, Gregory Corder, Marc V Fuccillo, Ishmail Abdus-Saboor, Douglas J Epstein","doi":"10.1097/j.pain.0000000000003325","DOIUrl":"10.1097/j.pain.0000000000003325","url":null,"abstract":"<p><strong>Abstract: </strong>The thalamus plays an important role in sensory and motor information processing by mediating communication between the periphery and the cerebral cortex. Alterations in thalamic development have profound consequences on sensory and motor function. In this study, we investigated a mouse model in which thalamic nuclei formation is disrupted because of the absence of Sonic hedgehog ( Shh ) expression from 2 key signaling centers that are required for embryonic forebrain development. The resulting defects observed in distinct thalamic sensory nuclei in Shh mutant embryos persisted into adulthood prompting us to examine their effect on behavioral responses to somatosensory stimulation. Our findings reveal a role for first-order posterior medial thalamic neurons and their projections to layer 4 of the secondary somatosensory cortex in the transmission of nociceptive information. Together, these results establish a connection between a neurodevelopmental lesion in the thalamus and a modality-specific disruption in pain perception.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"130-143"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PAIN®Pub Date : 2025-01-01Epub Date: 2024-07-09DOI: 10.1097/j.pain.0000000000003336
Eva Ryan, Hanna Grol-Prokopczyk, Christopher R Dennison, Anna Zajacova, Zachary Zimmer
{"title":"Is the relationship between chronic pain and mortality causal? A propensity score analysis.","authors":"Eva Ryan, Hanna Grol-Prokopczyk, Christopher R Dennison, Anna Zajacova, Zachary Zimmer","doi":"10.1097/j.pain.0000000000003336","DOIUrl":"10.1097/j.pain.0000000000003336","url":null,"abstract":"<p><strong>Abstract: </strong>Chronic pain is a serious and prevalent condition that can affect many facets of life. However, uncertainty remains regarding the strength of the association between chronic pain and death and whether the association is causal. We investigate the pain-mortality relationship using data from 19,971 participants aged 51+ years in the 1998 wave of the U.S. Health and Retirement Study. Propensity score matching and inverse probability weighting are combined with Cox proportional hazards models to investigate whether exposure to chronic pain (moderate or severe) has a causal effect on mortality over a 20-year follow-up period. Hazard ratios (HRs) with 95% confidence intervals (CIs) are reported. Before adjusting for confounding, we find a strong association between chronic pain and mortality (HR: 1.32, 95% CI: 1.26-1.38). After adjusting for confounding by sociodemographic and health variables using a range of propensity score methods, the estimated increase in mortality hazard caused by pain is more modest (5%-9%) and the results are often also compatible with no causal effect (95% CIs for HRs narrowly contain 1.0). This attenuation highlights the role of confounders of the pain-mortality relationship as potentially modifiable upstream risk factors for mortality. Posing the depressive symptoms variable as a mediator rather than a confounder of the pain-mortality relationship resulted in stronger evidence of a modest causal effect of pain on mortality (eg, HR: 1.08, 95% CI: 1.01-1.15). Future work is required to model exposure-confounder feedback loops and investigate the potentially cumulative causal effect of chronic pain at multiple time points on mortality.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"183-195"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PAIN®Pub Date : 2025-01-01Epub Date: 2024-07-26DOI: 10.1097/j.pain.0000000000003357
Sara Hestehave, Heather N Allen, Kimberly Gomez, Paz Duran, Aida Calderon-Rivera, Santiago Loya-López, Erick J Rodríguez-Palma, Rajesh Khanna
{"title":"Small molecule targeting Na V 1.7 via inhibition of CRMP2-Ubc9 interaction reduces pain-related outcomes in a rodent osteoarthritic model.","authors":"Sara Hestehave, Heather N Allen, Kimberly Gomez, Paz Duran, Aida Calderon-Rivera, Santiago Loya-López, Erick J Rodríguez-Palma, Rajesh Khanna","doi":"10.1097/j.pain.0000000000003357","DOIUrl":"10.1097/j.pain.0000000000003357","url":null,"abstract":"<p><strong>Abstract: </strong>Osteoarthritis (OA) is a highly prevalent and disabling joint disease, characterized by pathological progressive joint deformation and clinical symptoms of pain. Disease-modifying treatments remain unavailable, and pain-mitigation is often suboptimal, but recent studies suggest beneficial effects by inhibition of the voltage-gated sodium channel Na V 1.7. We previously identified compound 194 as an indirect inhibitor of Na V 1.7 by preventing SUMOylation of the Na V 1.7-trafficking protein, collapsin response mediator protein 2. Compound 194 reduces the functional activity of Na V 1.7 channels and produces effective analgesia in a variety of acute and neuropathic pain models. However, its effectiveness has not yet been evaluated in models of OA. Here, we explore the effects of 194 on pain-related outcomes in the OA-like monoiodoacetate model using behavioral assessment, biochemistry, novel in vivo fiber photometry, and patch clamp electrophysiology. We found that the monoiodoacetate model induced (1) increased pain-like behaviors and calcium responses of glutamatergic neurons in the parabrachial nucleus after evoked cold and mechanical stimuli, (2) conditioned place aversion to mechanical stimulation, (3) functional weight bearing asymmetry, (4) increased sodium currents in dorsal root ganglia neurons, and (5) increased calcitonin gene-related peptide-release in the spinal cord. Crucially, administration of 194 improved all these pain-related outcomes. Collectively, these findings support indirect inhibition of Na V 1.7 as an effective treatment of OA-related pain through the inhibition of collapsin response mediator protein 2-SUMOylation via compound 194.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"99-111"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PAIN®Pub Date : 2025-01-01Epub Date: 2024-09-18DOI: 10.1097/j.pain.0000000000003375
Mariela Rosa-Casillas, Allan I Basbaum
{"title":"Rostral ventral medulla circuits regulate both the sensory and affective dimensions of neuropathic pain: a commentary on Dogrul et al.","authors":"Mariela Rosa-Casillas, Allan I Basbaum","doi":"10.1097/j.pain.0000000000003375","DOIUrl":"10.1097/j.pain.0000000000003375","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"7-8"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PAIN®Pub Date : 2025-01-01Epub Date: 2024-07-10DOI: 10.1097/j.pain.0000000000003332
Seokha Jin, Hyung Joon Cho
{"title":"Cerebral hemodynamics as biomarkers for neuropathic pain in rats: a longitudinal study using a spinal nerve ligation model.","authors":"Seokha Jin, Hyung Joon Cho","doi":"10.1097/j.pain.0000000000003332","DOIUrl":"10.1097/j.pain.0000000000003332","url":null,"abstract":"<p><strong>Abstract: </strong>Neuropathic pain is one of the most challenging types of pain to diagnose and treat, a problem exacerbated by the lack of a quantitative biomarker. Recently, several clinical and preclinical studies have shown that neuropathic pain induces cerebral hemodynamic changes as a result of neuroplasticity in the brain. Our hypothesis in this study is that neuropathic pain leads to cerebral hemodynamic changes over postoperative time in a spinal nerve ligation (SNL) rat model, which has not been longitudinally explored previously. Furthermore, by identifying multiple regional hemodynamic features that are the most distinct between SNL and sham groups, where the sham group underwent only an incision without SNL, it may be possible to classify the SNL group regardless of when the onset of pain occurs. We investigate cerebral hemodynamic changes using dynamic susceptibility contrast magnetic resonance imaging in a rat model up to 28 days after ligating L5/L6 spinal nerves. We trained a linear support vector machine with relative cerebral blood volume data from different brain regions and found that the prediction model trained on the nucleus accumbens, motor cortex, pretectal area, and thalamus classified the SNL group and sham group at a 79.27% balanced accuracy, regardless of when the onset of pain occurred (SNL/sham: 60/45 data points). From the use of the SNL model without prior knowledge of the onset time of pain, the current findings highlight the potential of relative cerebral blood volume in the 4 highlighted brain regions as a biomarker for neuropathic pain.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"171-182"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}