Neurobiology of Pain最新文献

{"title":"The role of androgens in migraine pathophysiology","authors":"Adam J. Dourson ,&nbsp;Rachel S. Darken ,&nbsp;Thomas J. Baranski ,&nbsp;Robert W. Gereau 4th ,&nbsp;Whitney Trotter Ross ,&nbsp;Hadas Nahman-Averbuch","doi":"10.1016/j.ynpai.2024.100171","DOIUrl":"10.1016/j.ynpai.2024.100171","url":null,"abstract":"<div><div>Migraine affects ∼12 % of the worldwide population and is more prevalent in females, which suggests a role of sex hormones in migraine pathophysiology. Most studies have focused on estrogen and progesterone, and the involvement of androgens has been less studied. However, due to the recent advances in androgen interventions, which could advance new androgen-based migraine treatments, it is critical to better understand the role of androgens in migraine. Testosterone, the most studied androgen, was found to have an antinociceptive effect in various animal and human pain studies. Thus, it could also have a protective effect related to lower migraine severity and prevalence. In this review, we discuss studies examining the role of androgens on migraine-related symptoms in migraine animal models. Additionally, we summarize the results of human studies comparing androgen levels between patients with migraine and healthy controls, studies assessing the relationships between androgen levels and migraine severity, and intervention studies examining the impact of testosterone treatment on migraine severity. Many of the studies have limitations, however, the results suggest that androgens may have a minor effect on migraine. Still, it is possible that androgens are involved in migraine pathophysiology in a sub-group of patients such as in adolescents or postmenopausal women. We discuss potential mechanisms in which testosterone, as the main androgen tested, can impact migraine. These mechanisms range from the cellular level to systems and behavior and include the effect of testosterone on sensory neurons, the immune and vascular systems, the stress response, brain function, and mood. Lastly, we suggest future directions to advance this line of research.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"16 ","pages":"Article 100171"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142533683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic pain and complex regional pain syndrome are associated with alterations to the intestinal microbiota in both humans and mice. An observational cross-sectional study","authors":"Lara W. Crock ,&nbsp;Rachel Rodgers ,&nbsp;Nolan A. Huck ,&nbsp;Lawrence A. Schriefer ,&nbsp;Dylan Lawrence ,&nbsp;Leran Wang ,&nbsp;Gabriella P.B. Muwanga ,&nbsp;Vivianne L. Tawfik ,&nbsp;Megan T. Baldridge","doi":"10.1016/j.ynpai.2024.100173","DOIUrl":"10.1016/j.ynpai.2024.100173","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to evaluate pain metrics and gut microbiota differences from human subjects with complex regional pain syndrome (CRPS) compared to cohabitants (HHC) and non-cohabitating (biobank) controls. In addition, we aimed evaluate longitudinal changes of gut microbiota using a mouse model of acute and chronic CRPS.</div></div><div><h3>Methods</h3><div>In an observational, cross-sectional study, 25 patients with CRPS and 24 household controls (HHC) were recruited, completed pain questionnaires, and submitted stool samples. 23 biobank stool samples were matched to the CRPS group. Additionally, longitudinal stool samples were collected from a mouse model of acute and chronic CRPS. 16S rRNA gene sequencing analysis was performed on all samples.</div></div><div><h3>Results</h3><div>A diagnosis of CRPS is associated with higher pain, increased pain interference, and decreased physical and social function when compared to HHC. Interestingly, 46% of HHC reported significant daily pain. In the households where HHC were also suffering from pain, there was decreased bacterial richness and diversity when compared to households wherein only the participant with CRPS suffered from pain. Furthermore, when comparing households where the HHC had significant pain, CRPS was clinically more severe. In the mouse model of CRPS, we observed decreased bacterial richness and diversity when compared to non-cohabitating littermate controls.</div></div><div><h3>Conclusions</h3><div>Both humans living in chronic pain households and mice shared distinct taxa over the time course of disease and pain chronicity. These findings suggest that microbiota changes seen in CRPS as well as in a mouse model of CRPS may reflect pain chronicity and may indicate that pain alone can contribute to microbiota dysbiosis. The trial was registered at <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT03612193).</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"16 ","pages":"Article 100173"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurokinin1 − cholinergic receptor mechanisms in the medial Septum-Dorsal hippocampus axis mediates experimental neuropathic pain","authors":"Mohammed Zacky Ariffin ,&nbsp;Si Yun Ng ,&nbsp;Hamzah Nadia ,&nbsp;Darrel Koh ,&nbsp;Natasha Loh ,&nbsp;Naomi Michiko ,&nbsp;Sanjay Khanna","doi":"10.1016/j.ynpai.2024.100162","DOIUrl":"10.1016/j.ynpai.2024.100162","url":null,"abstract":"<div><p>The neurokinin-1 receptors (NK1Rs) in the forebrain medial septum (MS) region are localized exclusively on cholinergic neurons that partly project to the hippocampus and the cingulate cortex (Cg), regions implicated in nociception. In the present study, we explored the hypothesis that neurotransmission at septal NK1R and hippocampal cholinergic mechanisms mediate experimental neuropathic pain in the rodent chronic constriction injury model (CCI). Our investigations showed that intraseptal microinjection of substance P (SP) in rat evoked a peripheral hypersensitivity (PH)-like response in uninjured animals that was attenuated by systemic atropine sulphate, a muscarinic-cholinergic receptor antagonist. Conversely, pre-emptive destruction of septal cholinergic neurons attenuated the development of PH in the CCI model that also prevented the expression of cellular markers of nociception in the spinal cord and the forebrain. Likewise, anti-nociception was evoked on intraseptal microinjection of L-733,060, an antagonist at NK1Rs, and on bilateral or unilateral microinjection of the cholinergic receptor antagonists, atropine or mecamylamine, into the different regions of the dorsal hippocampus (dH) or on bilateral microinjection into the Cg. Interestingly, the effect of L-733,060 was accompanied with a widespread decreased in levels of CCI-induced nociceptive cellular markers in forebrain that was not secondary to behaviour, suggesting an active modulation of nociceptive processing by transmission at NK1R in the medial septum. The preceding suggest that the development and maintenance of neuropathic nociception is facilitated by septal NK1R-dH cholinergic mechanisms which co-ordinately affect nociceptive processing in the dH and the Cg. Additionally, the data points to a potential strategy for pain modulation that combines anticholinergics and anti-NKRs.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"16 ","pages":"Article 100162"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452073X24000138/pdfft?md5=4e1189eff9a9e0852ab70166f995d0bc&pid=1-s2.0-S2452073X24000138-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141963572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative orbital tightening for pain assessment using machine learning with DeepLabCut","authors":"Saurav Gupta,&nbsp;Akihiro Yamada,&nbsp;Jennifer Ling,&nbsp;Jianguo G. Gu","doi":"10.1016/j.ynpai.2024.100164","DOIUrl":"10.1016/j.ynpai.2024.100164","url":null,"abstract":"<div><p>Pain assessment in animal models is essential for understanding mechanisms underlying pathological pain and developing effective pain medicine. The grimace scale (GS), facial expression features in pain such as orbital tightening (OT), is a valuable measure for assessing pain in animal models. However, the classical grimace scale for pain assessment is labor-intensive, subject to subjectivity and inconsistency, and is not a quantitative measure. In the present study, we utilized machine learning with DeepLabCut to annotate the superior and inferior eyelid margins and the medial and lateral canthus of the eyes in animals’ video images. Based on the annotation, we quantified the eyelid distance and palpebral fissure width of the animals’ eyes so that the degree of OT in animals with pain could be measured and described quantitatively. We established criteria for the inclusion and exclusion of the annotated images for quantifying OT, and validated our quantitative grimace scale (qGS) in the mice with pain caused by capsaicin injections in the orofacial or hindpaw regions, the Nav1.8-ChR2 mice following orofacial noxious stimulation with laser light, and the oxaliplatin-treated mice following tactile stimulation with a von Frey filament. We showed that both the eyelid distance and the palpebral fissure width were shortened significantly in the animals in pain compared to the control animals without nociceptive stimulation. Collectively, the present study has established a quantitative orbital tightening for pain assessment in mice using DeepLabCut, providing a new tool for pain assessment in preclinical studies with mice.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"16 ","pages":"Article 100164"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452073X24000151/pdfft?md5=e0027044a63d893559b2dd5656b285ca&pid=1-s2.0-S2452073X24000151-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An investigation on the role of oxytocin in chronic neuropathic pain in a Wistar rat model","authors":"Michaela de Kock ,&nbsp;Sean Chetty ,&nbsp;Ahmed Sherif Isa ,&nbsp;Lihle Qulu-Appiah","doi":"10.1016/j.ynpai.2024.100152","DOIUrl":"10.1016/j.ynpai.2024.100152","url":null,"abstract":"<div><p><strong><em>Introduction</em></strong> Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect with ineffective preventative and curative treatment. Currently, only Duloxetine has been recommended as effective treatment for CIPN, which has shown individual-dependent, short-term analgesic effects, with limiting adverse effects and poor bioavailability. The neuropeptide, oxytocin, may offer significant analgesic and anxiolytic potential, as it exerts central and peripheral attenuating effects on nociception. However, it is unknown whether the intervention administered in a model of CIPN is an effective therapeutic alternative or adjuvant. <strong><em>Materials and Methods</em></strong> The intervention was divided into two phases. Phase 1 aimed to induce CIPN in adult Wistar rats using the chemotherapeutic agent Paclitaxel. Mechanical (electronic von Frey filament) and thermal (acetone evaporation test and Hargreaves test) hypersensitivity testing were used to evaluate changes due to the neuropathic induction. Phase 2 consisted of a 14-day intervention period with saline (o.g.), duloextine (o.g.), or oxytocin (i.n.) administered as treatment. Following the intervention, anxiety-like behaviour was assessed using the elevated plus maze (EPM) and light–dark box protocols. Analysis of peripheral plasma corticosterone, peripheral plasma oxytocin, and hypothalamic oxytocin concentrations were assessed using ELISA assays. <strong><em>Results</em></strong> The findings showed that we were able to successfully establish a model of chemotherapy-induced peripheral neuropathy during Phase 1, determined by the increase in mechanical and thermal nociceptive responses following Paclitaxel administration. Furthermore, the animals treated with oxytocin displayed a significant improvement in mechanical sensitivity over the intervention phase, indicative of an improvement in nociceptive sensitivity in the presence of neuropathic pain. Animals that received Paclitaxel and treated with oxytocin also displayed significantly greater explorative behaviour during the EPM, indicative of a reduced presence of anxiety-like behaviour. <strong><em>Conclusion</em></strong> Our results support the hypothesis that intranasally administered oxytocin may augment the analgesic and anxiolytic effects of duloxetine in a chemotherapy induced peripheral neuropathy model in a Wistar rat. Future studies should consider administering the treatments in combination to observe the potential synergistic effects.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"16 ","pages":"Article 100152"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452073X24000035/pdfft?md5=442035faf3faa47ca01167ceecffeeb0&pid=1-s2.0-S2452073X24000035-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-6 induces nascent protein synthesis in human dorsal root ganglion nociceptors primarily via MNK-eIF4E signaling","authors":"Molly E. Mitchell ,&nbsp;Gema Torrijos ,&nbsp;Lauren F. Cook,&nbsp;Juliet M. Mwirigi,&nbsp;Lucy He,&nbsp;Stephanie Shiers,&nbsp;Theodore J. Price","doi":"10.1016/j.ynpai.2024.100159","DOIUrl":"10.1016/j.ynpai.2024.100159","url":null,"abstract":"<div><p>Plasticity of dorsal root ganglion (DRG) nociceptors in the peripheral nervous system requires new protein synthesis. This plasticity is believed to be responsible for the physiological changes seen in DRG nociceptors in animal models of chronic pain. Experiments in human DRG (hDRG) neurons also support this hypothesis, but a direct observation of nascent protein synthesis in response to a pain promoting substance, like interleukin-6 (IL-6), has not been measured in these neurons. To fill this gap in knowledge, we used acutely prepared human DRG explants from organ donors. These explants provide a physiologically relevant microenvironment, closer to <em>in vivo</em> conditions, allowing for the examination of functional alterations in DRG neurons reflective of human neuropathophysiology. Using this newly developed assay, we demonstrate upregulation of the target of the MNK1/2 kinases, phosphorylated eIF4E (p-eIF4E), and nascently synthesized proteins in a substantial subset of hDRG neurons following exposure to IL-6. To pinpoint the specific molecular mechanisms driving this IL-6-driven increase in nascent proteins, we used the specific MNK1/2 inhibitor eFT508. Treatment with eFT508 resulted in the inhibition of IL-6-induced increases in p-eIF4E and nascent proteins. Additionally, using TRPV1 as a marker for nociceptors, we found that these effects occurred in a large number of human nociceptors. Our findings provide clear evidence that IL-6 drives nascent protein synthesis in human TRPV1+ nociceptors primarily via MNK1/2-eIF4E signaling. The work links animal findings to human nociception, creates a framework for additional hDRG signaling experiments, and substantiates the continued development of MNK inhibitors for pain.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"16 ","pages":"Article 100159"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452073X24000102/pdfft?md5=3ce74a80e5d2dccbe8fcbb7806e68708&pid=1-s2.0-S2452073X24000102-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141851198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotensin-expressing lateral hypothalamic neurons alleviate neuropathic and inflammatory pain via neurotensin receptor signaling","authors":"Rabail Khan ,&nbsp;Beenhwa Lee ,&nbsp;Kufreobong Inyang ,&nbsp;Hope Bemis ,&nbsp;Raluca Bugescu ,&nbsp;Geoffroy Laumet ,&nbsp;Gina Leinninger","doi":"10.1016/j.ynpai.2024.100172","DOIUrl":"10.1016/j.ynpai.2024.100172","url":null,"abstract":"<div><div>Persistent, severe pain negatively impacts health and wellbeing, but half of patients do not receive adequate relief from current treatments. Understanding signals that modulate central pain processing could point to new strategies to manage severe pain. Administering Neurotensin (Nts) or Nts receptor (NtsR) agonists into the brain provides analgesia comparable to pharmacologic opioids. However, the endogenous sources of Nts that modify pain processing and might be leveraged for pain relief remained unknown. We previously characterized a large population of Nts-expressing neurons in the lateral hypothalamic area (LHA^Nts neurons) that project to brain regions that participate in descending control of pain processing. We hypothesized that LHA^Nts neurons are an endogenous source of Nts and activating them would alleviate pain dependent on Nts signaling via NtsRs. To test this, we injected <em>Nts^Cre</em> mice in the LHA with AAVs to cre-dependently express either mCherry (Control) or the excitatory hM3Dq in LHA^Nts neurons, permitting their stimulation after treatment with the hM3Dq ligand clozapine N-oxide (CNO). Activating LHA^Nts neurons had no effect on thermal pain and mechanical responses in naïve mice. By contrast, both spared nerve injury- (SNI) and complete Freund’s adjuvant (CFA)-induced mechanical hypersensitivity was completely reversed by CNO-stimulation of LHA^Nts neurons. Pretreatment with the Nts receptor antagonist SR142948 reduced CNO-mediated analgesia, indicating that LHA^Nts neurons alleviate chronic pain in an Nts receptor-dependent manner. Taken together these data identify LHA^Nts neurons as an endogenous source of Nts that modulates central pain processing and may inform future development of Nts-based targets to treat severe pain.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"16 ","pages":"Article 100172"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142537641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of long-term hyperexcitability by memory-related cAMP signaling in isolated nociceptor cell bodies","authors":"Alexis Bavencoffe ,&nbsp;Michael Y. Zhu ,&nbsp;Sanjay V. Neerukonda ,&nbsp;Kayla N. Johnson ,&nbsp;Carmen W. Dessauer ,&nbsp;Edgar T. Walters","doi":"10.1016/j.ynpai.2024.100166","DOIUrl":"10.1016/j.ynpai.2024.100166","url":null,"abstract":"<div><div>Persistent hyperactivity of nociceptors is known to contribute significantly to long-lasting sensitization and ongoing pain in many clinical conditions. It is often assumed that nociceptor hyperactivity is mainly driven by continuing stimulation from inflammatory mediators. We have tested an additional possibility: that persistent increases in excitability promoting hyperactivity can be induced by a prototypical cellular signaling pathway long known to induce late-phase long-term potentiation (LTP) of synapses in brain regions involved in memory formation. This cAMP-PKA-CREB-gene transcription-protein synthesis pathway was tested using whole-cell current clamp methods on small dissociated sensory neurons (primarily nociceptors) from dorsal root ganglia (DRGs) excised from previously uninjured (“naïve”) male rats. Six-hour treatment with the specific Gαs-coupled 5-HT4 receptor agonist, prucalopride, or with the adenylyl cyclase activator forskolin induced long-term hyperexcitability (LTH) in DRG neurons that manifested 12–24 h later as action potential (AP) discharge (ongoing activity, OA) during artificial depolarization to −45 mV, a membrane potential that is normally subthreshold for AP generation. Prucalopride treatment also induced significant long-lasting depolarization of resting membrane potential (from −69 to −66 mV), enhanced depolarizing spontaneous fluctuations (DSFs) of membrane potential, and produced trends for reduced AP threshold and rheobase. LTH was prevented by co-treatment of prucalopride with inhibitors of PKA, CREB, gene transcription, or protein synthesis. As in the induction of synaptic memory, many other cellular signals are likely to be involved. However, the discovery that this prototypical memory induction pathway can induce nociceptor LTH, along with reports that cAMP signaling and CREB activity in DRGs can induce hyperalgesic priming, suggest that early, temporary, cAMP-induced transcriptional and translational mechanisms can induce nociceptor LTH that might last for long periods. The present results also raise the question of whether reactivation of primed signaling mechanisms by re-exposure to inflammatory mediators linked to cAMP synthesis during subsequent challenges to bodily integrity can “reconsolidate” nociceptor memory, extending the duration of persistent hyperexcitability.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"16 ","pages":"Article 100166"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The timing of the mouse hind paw incision does not influence postsurgical pain","authors":"Eleri L.F. McEachern ,&nbsp;Maria Zilic ,&nbsp;Susana G. Sotocinal ,&nbsp;Nader Ghasemlou ,&nbsp;Jeffrey S. Mogil","doi":"10.1016/j.ynpai.2024.100161","DOIUrl":"10.1016/j.ynpai.2024.100161","url":null,"abstract":"<div><p>Chronobiological approaches have emerged as tools to study pain and inflammation. Although time–of-day effects on the expression of pain after injury have been studied, it remains unaddressed whether the timing of the injury itself can alter subsequent pain behaviors. The aim of this study was to assess postsurgical pain behaviors in a mouse hind paw incision assay in a circadian-dependent manner. Incisions were made at one of four equally spaced time points over a 24-hour period, with evoked and spontaneous pain behaviors measured using the von Frey mechanical sensitivity test, Hargreaves’ radiant heat paw-withdrawal test, and the Mouse Grimace Scale. Algesiometric testing was performed in C57BL/6 mice prior to and at multiple time points after incision injury, at the same time of day, until pain resolution. No statistically significant differences were observed between groups. This study adds to the literature on circadian rhythms and their influence on pain in the pursuit of more biologically informed pre- and postoperative care.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"16 ","pages":"Article 100161"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452073X24000126/pdfft?md5=45cbc5cc70c3527e23264fe25bc82b00&pid=1-s2.0-S2452073X24000126-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141940518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pace of biological aging significantly mediates the relationship between internalized stigma of chronic pain and chronic low back pain severity among non-hispanic black but not non-hispanic white adults","authors":"Khalid W. Freij ,&nbsp;Fiona B.A.T. Agbor ,&nbsp;Kiari R. Kinnie ,&nbsp;Vinodh Srinivasasainagendra ,&nbsp;Tammie L. Quinn ,&nbsp;Hemant K. Tiwari ,&nbsp;Robert E. Sorge ,&nbsp;Burel R. Goodin ,&nbsp;Edwin N. Aroke","doi":"10.1016/j.ynpai.2024.100170","DOIUrl":"10.1016/j.ynpai.2024.100170","url":null,"abstract":"<div><div>This study aimed to determine the nature of the relationship between the internalized stigma of chronic pain (ISCP), the pace of biological aging, and racial disparities in nonspecific chronic low back pain (CLBP). We used Dunedin Pace of Aging from the Epigenome (DunedinPACE), Horvath’s, Hannum’s, and PhenoAge clocks to determine the pace of biological aging in adults, ages 18 to 82 years: 74 no pain, 56 low-impact pain, and 76 high-impact pain. Individuals with high-impact pain reported higher levels of ISCP and DunedinPACE compared to those with low-impact or no pain (p &lt; 0.001). There was no significant relationship between ISCP and epigenetic age acceleration from Horvath, Hannum, and PhenoAge clocks (<em>p</em> &gt; 0.05). Mediation analysis showed that an association between ISCP and pain severity and interference was mediated by the pace of biological aging (<em>p</em> ≤ 0.001). We further found that race moderated the indirect effect of ISCP on pain severity and interference, with ISCP being a stronger positive predictor of the pace of biological aging for non-Hispanic Blacks (NHBs) than for non-Hispanic Whites (NHWs). Future bio-behavioral interventions targeting internalized stigma surrounding chronic pain at various levels are necessary. A deeper understanding of the biological aging process could lead to improvements in managing nonspecific chronic low back pain (CLBP), particularly within underserved minority populations.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"16 ","pages":"Article 100170"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142533682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}