{"title":"Effects of pain in lumbosacral stenosis and lifestyle-related factors on brain-derived neurotrophic factor expression profiles.","authors":"Dawid Sobański, Rafał Staszkiewicz, Małgorzata Sobańska, Damian Strojny, Beniamin Oskar Grabarek","doi":"10.1177/17448069241309001","DOIUrl":"https://doi.org/10.1177/17448069241309001","url":null,"abstract":"<p><p>This study investigated the role of brain-derived neurotrophic factor (BDNF) in patients with degenerative lumbar stenosis, focusing on its expression and correlation with pain intensity. The study examined 96 patients with lumbar stenosis and 85 control participants. BDNF levels in the yellow ligamentum flavum were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and western blot analysis. The results showed significantly higher BDNF expression at both messenger ribonucleic acid (mRNA; fold change = +1.35 ± 0.23; <i>p</i> < 0.05) and protein levels in patients (28.98 ± 6.40 pg/mg) compared to controls (4.56 ± 1.98 pg/mg; <i>p</i> < 0.05). Furthermore, BDNF levels correlated positively with pain intensity reported by patients, with higher expression observed in those experiencing more severe pain. The study also explored the influence of lifestyle factors, such as smoking and alcohol consumption, and related diseases, such as diabetes, on BDNF expression. Smoking, alcohol use, and diabetes were associated with significantly elevated BDNF levels (<i>p</i> < 0.05). These findings suggest that BDNF could serve as a biomarker for pain severity in degenerative lumbar stenosis at the protein level, although this was not consistently observed at the mRNA level; this highlights the potential for BDNF-targeted therapies in managing pain. Future research should involve larger longitudinal studies to validate these findings and explore therapeutic interventions. This study underscores the importance of considering molecular and lifestyle factors in the treatment of degenerative lumbar stenosis, aiming to improve patient outcomes through comprehensive, targeted approaches.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"21 ","pages":"17448069241309001"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondrial dysfunction in trigeminal ganglion contributes to nociceptive behavior in a nitroglycerin-induced migraine mouse model.","authors":"Xin-Ying Guan, Xin Dong, Yi-Xuan Wang, Bing-Chao Xu, Xiao-Bo Wu","doi":"10.1177/17448069251332100","DOIUrl":"10.1177/17448069251332100","url":null,"abstract":"<p><p>Migraine is a chronic episodic neurological disorder. However, its diagnosis and management remain unclear. The pathogenesis of migraine is intricately linked to the dysfunction of mitochondria and aberrant trigeminal neuronal activity. Here, we established a murine migraine model via intraperitoneal administration of nitroglycerin (NTG) to examine alterations in mitochondria-associated proteins and calcium signaling patterns within trigeminal neurons, while also investigating the underlying mechanisms. NTG-treated mice exhibited marked periorbital allodynia, decreased crossing of the central area, and decreased time spent in the central area in the open field test compared to Veh treated animals. Furthermore, increased calcium signaling in response to adenosine triphosphate (ATP) stimulation was observed in the trigeminal ganglion (TG) of mice with migraine. Meanwhile, mRNA levels of genes including nuclear respiratory factor-1 (<i>Nrf1)</i>, nuclear respiratory factor-2 (<i>Nrf2)</i> and peroxisome proliferator-activated receptor gamma coactivator 1-alpha <i>(Pgc-1)</i> were decreased in the TG. Pharmacological regulation of the mitochondrial function affected NTG-induced migraine chronic pain symptoms. TG mitochondria dysfunctions is implicated in the regulation of mechanical hyperalgesia through the modulation of calcium signaling in an NTG-induced migraine animal model.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251332100"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular PainPub Date : 2025-01-01Epub Date: 2025-05-10DOI: 10.1177/17448069251341882
Hailing Yang, Mei Yang, Tonghui Xu
{"title":"Whole-brain input architecture of primary and secondary somatosensory cortices in mice.","authors":"Hailing Yang, Mei Yang, Tonghui Xu","doi":"10.1177/17448069251341882","DOIUrl":"10.1177/17448069251341882","url":null,"abstract":"<p><p>The primary and secondary somatosensory cortices (S1 and S2) play crucial roles in processing sensory inputs from various body regions, encompassing tactile, pressure, thermal, and nociceptive stimuli. These cortices are anatomically distinct, with S1 primarily involved in mechanical and cold stimulus discrimination and S2 in the interpretation of mechanical and thermal inputs, particularly in pain perception. However, the upstream innervation patterns of the somatosensory system remain less explored. In this study, we employed a modified rabies virus (RV)-mediated transsynaptic retrograde tracing system to map and compare the whole-brain input patterns of S1 and S2 in mice. Our results revealed that both S1 and S2 receive inputs from diverse brain regions, including the cortical plate, thalamus, cortical subplate, striatum, and pallidum. Notably, the cortical plate emerged as the primary source of input neurons for both S1 and S2, while the thalamus demonstrated preferential projections to S1. Through quantitative analysis, we identified distinct input distribution patterns across 64 brain subregions, revealing that S1 and S2 exhibit complex internal circuitry, including abundant local projections. Furthermore, we observed notable variations in the proportional contributions of inputs from diverse subregions to S1 and S2. This comprehensive anatomical framework provides new insights into the neural circuits underlying somatosensory perception and modulation, with potential implications for the development of targeted therapeutic strategies for pain and other somatosensory disorders.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251341882"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular PainPub Date : 2025-01-01Epub Date: 2025-06-06DOI: 10.1177/17448069251351045
Jiaqi Dong, Jingyi Wei, Hongwei Tong, Xiaohua Shi, Menghui Yuan, Yiwei Cao, Mohammed A El-Magd, Qiang Chen, Hongxin Zhang, Peng Yuan, Jiao Mu
{"title":"Circadian gene NPAS2 modulates pain sensitization in CFA-induced inflammatory pain model.","authors":"Jiaqi Dong, Jingyi Wei, Hongwei Tong, Xiaohua Shi, Menghui Yuan, Yiwei Cao, Mohammed A El-Magd, Qiang Chen, Hongxin Zhang, Peng Yuan, Jiao Mu","doi":"10.1177/17448069251351045","DOIUrl":"10.1177/17448069251351045","url":null,"abstract":"<p><p>Pain, particularly chronic pain, is a major reason patients seek physical therapy. Inflammation plays a crucial role in both the development and persistence of chronic pain. Neuronal PAS domain protein 2 (NPAS2), a core circadian transcriptional regulator, has been implicated in modulating pain-related stress responses. In this study, we first examined NPAS2 expression in nociceptive-sensitized mice following complete Freund's adjuvant (CFA) administration. We then systematically investigated the effects of CFA on astrocyte activation and inflammatory factor release in NPAS2 knockout (KO) mice. Our results demonstrated that NPAS2 deletion did not alter baseline pain thresholds under normal physiological conditions. However, in CFA-injected mice, NPAS2 KO significantly lowered mechanical and thermal pain thresholds in 50% of subjects, leading to enhanced nociceptive sensitization. This effect may be attributed to the promotion of astrocyte activation and the upregulation of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α, and NF-κB. These findings highlight NPAS2 as a potential prognostic biomarker for pain chronification and a promising therapeutic target for biologically tailored pain interventions.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251351045"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neural Adaptation of the Reward System in Primary Dysmenorrhea.","authors":"Pei-Shan Hsu,Ching-Hsiung Liu,Ching-Ju Yang,Lin-Chien Lee,Wei-Chi Li,Hsiang-Tai Chao,Li-Fen Chen,Jen-Chuen Hsieh","doi":"10.1177/17448069241286466","DOIUrl":"https://doi.org/10.1177/17448069241286466","url":null,"abstract":"Introduction The brain's reward system (RS) reacts differently to pain and its alleviation. This study examined the correlation between RS activity and behavior during both painful and pain-free periods in individuals with primary dysmenorrhea (PDM) to elucidate their adaptive and maladaptive responses throughout the menstrual cycle. Methods Ninety-two individuals with PDM and 90 control participants underwent resting-state functional magnetic resonance imaging (rsfMRI) scans during their menstrual and peri-ovulatory phases. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analyses were used to evaluate RS responses. Psychological evaluations were conducted using the McGill Pain Questionnaire and the Pain Catastrophizing Scale. Results ReHo analysis showed higher values in the left putamen and right amygdala of the PDM group during the peri-ovulatory phase compared to the menstrual phase. ALFF analysis revealed lower values in the putamen of the PDM group compared to controls, regardless of phase. ReHo and ALFF values in the putamen, amygdala, and nucleus accumbens were positively correlated with pain scales during menstruation, while ALFF values in the ventral tegmental area inversely correlated with pain intensity. Those with severe PDM (pain intensity ≥ 7) displayed distinct amygdala ALFF patterns between pain and pain-free phases. PDM participants also had lower ReHo values in the left insula during menstruation, with no direct correlation to pain compared to controls. Discussion Our study highlights the pivotal role of the RS in dysmenorrhea management, exhibiting varied responses between menstrual discomfort and non-painful periods among individuals with PDM. During menstruation, the RS triggers mechanisms for pain avoidance and cognitive coping strategies, while it transitions to processing rewards during the peri-ovulatory phase. This demonstrates the flexibility of the RS in adapting to the recurring pain experienced by those with PDM.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"59 1","pages":"17448069241286466"},"PeriodicalIF":3.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular PainPub Date : 2024-07-31DOI: 10.1177/17448069241273692
Fahmi Agnesha, Eti Nurwening Solikhah, Djayanti Sari, Rianza Ainunnisa
{"title":"Analyzing Substance Levels and Pain Perception in Painless Labor: The Impact of Spinal Epidural Analgesia.","authors":"Fahmi Agnesha, Eti Nurwening Solikhah, Djayanti Sari, Rianza Ainunnisa","doi":"10.1177/17448069241273692","DOIUrl":"https://doi.org/10.1177/17448069241273692","url":null,"abstract":"<p><strong>Background: </strong>Inflammation affects labor by influencing contractions and dilation. Pain, often linked to tissue ischemia, involves mediators like nitric oxide (NO), TNF-α, and substance P (SP). Neuraxial analgesia, including combined spinal epidural analgesia (SEA) with levobupivacaine, is preferred for its effectiveness and minimal side effects in painless labor. Understanding the impact of painless labor techniques on biomolecular processes such as NO, TNF-α, and substance P levels is crucial for improving pain management strategies. This study investigates these effects in parturients undergoing SEA with levobupivacaine, contributing to the development of novel pain medications and enhancing obstetric care.</p><p><strong>Methods: </strong>This experimental study, conducted at a General Hospital in Indonesia, involved 60 expectant mothers in labor or in the third trimester, expected to give birth vaginally at Permata Hati Metro Hospital. Blood serum was used for analysis, and serum NO, TNF-α, and SP levels were assessed using ELISA kit.</p><p><strong>Results: </strong>There's a significant decrease in NO levels before and post-treatment in the SEA group compared to the control group (p < 0.05). However, no significant difference in TNF-α levels was observed between groups before and after treatment (p > 0.05). Additionally, there was no significant difference in SP levels between groups before treatment, but a significant difference was seen after treatment (p < 0.05). SEA significantly reduced labor pain compared to the control group (P < 0.05), with notable improvements in vital signs and APGAR scores, while also shortening labor duration (P < 0.001).</p><p><strong>Conclusion: </strong>In conclusion, SEA with levobupivacaine during painless labor reduces NO levels significantly and shows a trend of decreasing TNF-α and substance P levels, although not statistically significant, with clinical benefits for both patients and babies.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241273692"},"PeriodicalIF":2.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice.","authors":"Zi-Long Yi, Jin-Nan Lu, Jin-Jin Zhu, Tian-Tian He, Yi-Ran Xu, Zi-Wei Huang, Yong-Chang Li, Guang-Yin Xu","doi":"10.1177/17448069241260349","DOIUrl":"10.1177/17448069241260349","url":null,"abstract":"<p><p>Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by chronic visceral pain with a complex etiology and challenging treatment. Although accumulating evidence supports the involvement of central nervous system sensitization in the development of visceral pain, the precise molecular mechanisms remain incompletely understood. In this study, we highlight the critical regulatory role of lysine-specific demethylase 6B (KDM6B) in the anterior cingulate cortex (ACC) in chronic visceral pain. To simulate clinical IBS conditions, we utilized the neonatal maternal deprivation (NMD) mouse model. Our results demonstrated that NMD induced chronic visceral pain and anxiety-like behaviors in mice. Notably, the protein expression level of KDM6B significantly increased in the ACC of NMD mice, leading to a reduction in the expression level of H32K7me3. Immunofluorescence staining revealed that KDM6B primarily co-localizes with neurons in the ACC, with minimal presence in microglia and astrocytes. Injecting GSK-J4 (a KDM6B-specific inhibitor) into ACC of NMD mice, resulted in a significant alleviation in chronic visceral pain and anxiety-like behaviors, as well as a remarkable reduction in NR2B expression level. ChIP assay further indicated that KDM6B regulates NR2B expression by influencing the demethylation of H3K27me3. In summary, our findings underscore the critical role of KDM6B in regulating chronic visceral pain and anxiety-like behaviors in NMD mice. These insights provide a basis for further understanding the molecular pathways involved in IBS and may pave the way for targeted therapeutic interventions.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241260349"},"PeriodicalIF":3.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141096888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Low-frequency electroacupuncture exerts antinociceptive effects through activation of POMC neural circuit induced endorphinergic input to the periaqueductal gray from the arcuate nucleus","authors":"zhigang lu, Qian Wang, Zhonghao Li, Dengyun Nie, Xinru Mu, Yuxuan Wang, Yongwei Jiang, Yongchen Zhang","doi":"10.1177/17448069241254201","DOIUrl":"https://doi.org/10.1177/17448069241254201","url":null,"abstract":"It has been widely recognized that electroacupuncture (EA) inducing the release of β-endorphin represents a crucial mechanism of EA analgesia. The ARC is a vital component of the endogenous opioid peptide system. However, the specific mechanisms how EA facilitates the release of β-endorphin within the ARC, eliciting analgesic effects are yet to be elucidated. In this study, we conducted in vivo and in vitro experiments by transcriptomics, microdialysis, photogenetics, chemical genetics, and calcium imaging, combined with transgenic animals. Firstly, we detected 2Hz EA at the Zusanli (ST36) increased the level of β-endorphin and transcriptional level of POMC. Our transcriptomics profiling demonstrated that 2Hz EA at the ST36 modulates the expression of c-Fos and Jun B in ARC brain nuclear cluster, and the transcriptional regulation of 2Hz EA mainly occur in POMC neurons by immunofluorescence staining verification. Meaning while, 2Hz EA specifically activated the cAMP-PKA-CREB signaling pathway in ARC which mediating the c-Fos and Jun B transcription, and 2Hz EA analgesia is dependent on the activation of cAMP-PKA-CREB signaling pathway in ARC. In order to investigate how the β-endorphin produced in ARC transfer to integration center PAG, transneuronal tracing technology was used to observe the 2Hz EA promoted the neural projection from ARC to PAG compared to 100Hz EA and sham mice. Inhibited PAGGABA neurons, the transfer of β-endorphin from the ARC nucleus to the PAG nucleus through the ARCPOMC-PAGGABA neural circuit. Furthermore, by manipulating the excitability of POMC neurons from ARCPOMC to PAGGABA using inhibitory chemogenetics and optogenetics, we found that this inhibition significantly reduced transfer of β-endorphin from the ARC nucleus to the PAG nucleus and the effectiveness of 2Hz EA analgesia in neurological POMC Cre mice and C57BL/6J mice, which indicates that the transfer of β-endorphin depends on the activation of POMC neurons prefect from ARCPOMC to PAGGABA.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"131 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140811199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Regulation of the PD-1/PD-L1 Pathway in Imiquimod-Induced Chronic Psoriasis Itch and Itch Sensitization in Mouse","authors":"Zhehao Xu, Yue Wang, Changcheng Jiang, Zhengwei Wang, Yongfeng Chen, Manli Fan","doi":"10.1177/17448069241252384","DOIUrl":"https://doi.org/10.1177/17448069241252384","url":null,"abstract":"PD-1/PD-L1 inhibitors have been demonstrated to induce itch in both humans and experimental animals. However, whether the PD-1/PD-L1 pathway is involved in the regulation of chronic psoriatic itch remains unclear. This study aimed to investigate the role of the PD-1/PD-L1 pathway in imiquimod-induced chronic psoriatic itch. The intradermal injection of PD-L1 in the nape of neck significantly alleviated chronic psoriatic itch in imiquimod-treated skin. Additionally, we observed that spontaneous scratching behavior induced by imiquimod disappeared on day 21. Still, intradermal injection of PD-1/PD-L1 inhibitors could induce more spontaneous scratching for over a month, indicating that imiquimod-treated skin remained in an itch sensitization state after the spontaneous scratching behavior disappeared. During this period, there was a significant increase in PD-1 receptor expression in both the imiquimod-treated skin and the spinal dorsal horn in mice, accompanied by significant activation of microglia in the spinal dorsal horn. These findings suggest the potential involvement of the peripheral and central PD-1/PD-L1 pathways in regulating chronic itch and itch sensitization induced by imiquimod.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"1 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140631151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular PainPub Date : 2024-04-18DOI: 10.1177/17448069241252385
Saima Mumtaz, Najma Baseer, Syed Hamid Habib
{"title":"Concomitant use of Pre-emptive analgesia with Local and General Anesthesia in Rat Uterine Surgical Pain Model","authors":"Saima Mumtaz, Najma Baseer, Syed Hamid Habib","doi":"10.1177/17448069241252385","DOIUrl":"https://doi.org/10.1177/17448069241252385","url":null,"abstract":"Preemptive analgesia is used for postoperative pain management, providing pain relief with few adverse effects. In this study, the effect of a preemptive regime on rat behavior and c-fos expression in the spinal cord of the uterine surgical pain model was evaluated.
 Method: It was a lab-based experimental study in which sixty female Sprague-Dawley rats; eight to ten weeks old, weighing 150–300 gm were used. The rats were divided into three main groups: i) Control group (CG), ii) superficial pain group (SG) (with skin incision only), iii) deep pain group (with skin and uterine incisions). Each group was further divided into three subgroups based on the type of preemptive analgesia administered i.e., “tramadol, buprenorphine, and saline subgroups.” Pain behavior was evaluated using the “Rat Grimace Scale” (RGS) at 2, 4, 6, 9 and 24 hours post-surgery. Additionally, c-fos immunohistochemistry was performed on sections from the spinal dorsal horn (T12-L2), and its expression was evaluated using optical density and mean cell count two hours postoperatively. 
 Results: Significant reduction in the RGS was noted in both the superficial and deep pain groups within the tramadol and buprenorphine subgroups when compared to the saline subgroup (p≤0.05). There was a significant decrease in c-fos expression both in terms of number of c-fos positive cells and the optical density across the superficial laminae and lamina X of the spinal dorsal horn in both SD and DG (p≤0.05). In contrast, the saline group exhibited c-fos expression primarily in laminae I-II and III-IV for both superficial and deep pain groups and lamina X in the deep pain group only (p≤0.05).
 Conclusion: A preemptive regimen results in significant suppression of both superficial and deep components of pain transmission. These findings provide compelling evidence of the analgesic efficacy of preemptive treatment in alleviating pain response associated with uterine surgery.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"52 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}