Molecular Pain最新文献

{"title":"Electroacupuncture improves allodynia and central sensitization via modulation of microglial activation associated P2X4R and inflammation in a rat model of migraine.","authors":"Min Zhou, Fang Pang, Dongmei Liao, Yunhao Yang, Ying Wang, Zhuxin Yang, Xinlu He, Chenglin Tang","doi":"10.1177/17448069241258113","DOIUrl":"10.1177/17448069241258113","url":null,"abstract":"<p><p><b>Background:</b> Recent studies have demonstrated that activated microglia were involved in the pathogenesis of central sensitization characterized by cutaneous allodynia in migraine. Activation of microglia is accompanied by increased expression of its receptors and release of inflammatory mediators. Acupuncture and its developed electroacupuncture (EA) have been recommended as an alternative therapy for migraine and are widely used for relieving migraine-associated pain. However, it remains rare studies that show whether EA exerts anti-migraine effects via inhibiting microglial activation related to a release of microglial receptors and the inflammatory pathway. Therefore, this study aimed to investigate EA' ability to ameliorate central sensitization via modulation of microglial activation, microglial receptor, and inflammatory response using a rat model of migraine induced by repeated epidural chemical stimulation. <b>Methods:</b> In the present study, a rat model of migraine was established by epidural repeated inflammatory soup (IS) stimulation and treated with EA at Fengchi (GB20) and Yanglingquan (GB34) and acupuncture at sham-acupoints. Pain hypersensitivity was further determined by measuring the mechanical withdrawal threshold using the von-Frey filament. The changes in c-Fos and ionized calcium binding adaptor molecule 1 (Ibal-1) labeled microglia in the trigeminal nucleus caudalis (TNC) were examined by immunflurescence to assess the central sensitization and whether accompanied with microglia activation. In addition, the expression of Ibal-1, microglial purinoceptor P2X4, and its associated inflammatory signaling pathway mediators, including interleukin (IL)-1β, NOD-like receptor protein 3 (NLRP3), and Caspase-1 in the TNC were investigated by western blot and real-time polymerase chain reaction analysis. <b>Results:</b> Allodynia increased of c-Fos, and activated microglia were observed after repeated IS stimulation. EA alleviated the decrease in mechanical withdrawal thresholds, reduced the activation of c-Fos and microglia labeled with Ibal-1, downregulated the level of microglial purinoceptor P2X4, and limited the inflammatory response (NLRP3/Caspase-1/IL-1β signaling pathway) in the TNC of migraine rat model. <b>Conclusions:</b> Our results indicate that the anti-hyperalgesia effects of EA ameliorate central sensitization in IS-induced migraine by regulating microglial activation related to P2X4R and NLRP3/IL-1β inflammatory pathway.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241258113"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922867","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":"Assessment of orofacial nociceptive behaviors of mice with the sheltering tube method: Oxaliplatin-induced mechanical and cold allodynia in orofacial regions.","authors":"Saurav Gupta, Jennifer Ling, Jianguo G Gu","doi":"10.1177/17448069241261687","DOIUrl":"10.1177/17448069241261687","url":null,"abstract":"<p><p>Preclinical studies on pathological pain rely on the von Frey test to examine changes in mechanical thresholds and the acetone spray test to determine alterations in cold sensitivity in rodents. These tests are typically conducted on rodent hindpaws, where animals with pathological pain show reliable nocifensive responses to von Frey filaments and acetone drops applied to the hindpaws. Pathological pain in orofacial regions is also an important clinical problem and has been investigated with rodents. However, performing the von Frey and acetone spray tests in the orofacial region has been challenging, largely due to the high mobility of the head of testing animals. To solve this problem, we implemented a sheltering tube method to assess orofacial nociception in mice. In experiments, mice were sheltered in elevated tubes, where they were well accommodated because the tubes provided safe shelters for mice. Examiners could reliably apply mechanical stimuli with von Frey filament, cold stimuli with acetone spray, and light stimuli with a laser beam to the orofacial regions. We validated this method in Nav1.8-ChR2 mice treated with oxaliplatin that induced peripheral neuropathy. Using the von Frey test, orofacial response frequencies and nociceptive response scores were significantly increased in Nav1.8-ChR2 mice treated with oxaliplatin. In the acetone spray test, the duration of orofacial responses was significantly prolonged in oxaliplatin-treated mice. The response frequencies to laser light stimulation were significantly increased in Nav1.8-ChR2 mice treated with oxaliplatin. Our sheltering tube method allows us to reliably perform the von Frey, acetone spray, and optogenetic tests in orofacial regions to investigate orofacial pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241261687"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179535","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":"Neurotropin^® ameliorates chronic pain associated with scar formation in a mouse model: A gene expression analysis of the inflammatory response.","authors":"Xuan Zhou, Hiroki Iida, Yuqiang Li, Akinobu Ota, Lisheng Zhuo, Reiko Nobuhara, Yuki Terajima, Mitsuru Naiki, A Hari Reddi, Koji Kimata, Takahiro Ushida","doi":"10.1177/17448069241245420","DOIUrl":"10.1177/17448069241245420","url":null,"abstract":"<p><p><i>Background</i>: Scar formation after trauma and surgery involves an inflammatory response and can lead to the development of chronic pain. Neurotropin^<b>®</b> (NTP) is a nonprotein extract of inflamed skin of rabbits inoculated with vaccinia virus. It has been widely used for the treatment of chronic pain. However, the in vivo effects of NTP on painful scar formation have not been determined. To investigate the molecular mechanisms underlying the effects of NTP on the inflammatory response, we evaluated gene expression in the scar tissues and dorsal root ganglions (DRGs) of mice administered NTP and control mice. <i>Methods and results</i>: Mice injected with saline or NTP were used as controls; other mice were subjected to surgery on the left hind paw to induce painful scar formation, and then injected with saline or NTP. Hind paw pain was evaluated by measuring the threshold for mechanical stimulation using the von Frey test. The paw withdrawal threshold gradually returned to pre-operative levels over 4 weeks post-operation; NTP-treated mice showed a significantly shortened recovery time of approximately 3 weeks, suggesting that NTP exerted an analgesic effect in this mouse model. Total RNA was extracted from the scarred hind paw tissues and DRGs were collected 1 week post-operation for a microarray analysis. Gene set enrichment analysis revealed that the expression of some gene sets related to inflammatory responses was activated or inhibited following surgery and NTP administration. Quantitative real-time reverse transcription-polymerase chain reaction analysis results for several genes were consistent with the microarray results. <i>Conclusion</i>: The administration of NTP to the hind paws of mice with painful scar formation following surgery diminished nociceptive pain and reduced the inflammatory response. NTP inhibited the expression of some genes involved in the response to surgery-induced inflammation. Therefore, NTP is a potential therapeutic option for painful scar associated with chronic pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241245420"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11080750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175604","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":"Corrigendum to “BDNF-TrkB signaling pathway-mediated microglial activation induces neuronal KCC2 downregulation contributing to dynamic allodynia following spared nerve injury”","authors":"","doi":"10.1177/17448069231222686","DOIUrl":"https://doi.org/10.1177/17448069231222686","url":null,"abstract":"","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"234 ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139195324","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 holistic approach to the <i>CHRNA7</i> gene, <i>hsa-miR-3158-5p</i>, and 15q13.3 hotspot CNVs in migraineurs.","authors":"Sedat Yasin, Şenay Görücü Yılmaz, Sırma Geyik, Sibel Oğuzkan Balcı","doi":"10.1177/17448069231152104","DOIUrl":"10.1177/17448069231152104","url":null,"abstract":"<p><p>Migraine is a neurological disease characterized by severe headache attacks. Combinations of different genetic variations such as copy number variation (CNV) in a gene and microRNA (miRNA) expression can provide a holistic approach to the disease as a pathophysiological, diagnostic, and therapeutic target. CNVs, the Cholinergic Receptor Nicotinic Alpha 7 Subunit (<i>CHRNA7</i>) gene, and expression of gene-targeting miRNAs (<i>hsa-miR-548e-5p</i> and <i>hsa-miR-3158-5p</i>) in migraineurs (<i>n</i> = 102; with aura, <i>n</i> = 43; without aura, <i>n</i> = 59) and non-migraines (<i>n</i> = 120) aged 15-60 years, comparative, case-control study was conducted. Genetic markers were compared with biochemical parameters (BMI, WBC, Urea, GFR, ESR, CRP, HBG). All analyzes were performed by quantitative Real-Time PCR (q-PCR) and fold change was calculated with the 2^-ΔΔCT method. The diagnostic power of the <i>CHRNA7</i> gene, CNV, and miRNAs were analyzed with the receiver operating curve (ROC). <i>CHRNA7</i> gene and <i>hsa-miR-3158-5p</i> are down-regulated in migraineurs and the gene is controlled by this miRNA via CNVs (<i>p</i> < .05). Both deletion and duplication were detected in patients with migraine for CVN numbers (<i>p</i> = .05). The number of CNV deletions was higher than duplications. When <i>CHRNA7</i>-CNV-<i>hsa-miR-3158-5p</i> was modeled together in the ROC analysis, the area under the curve (AUC) was 0.805, and the diagnostic power was \"good\". In migraineurs, the <i>CHRNA7</i> gene can be controlled by <i>hsa-miR-3158-5p</i> via CNVs to modulate the mechanism of pain. These three genetic markers have diagnostic potential and may be used in antimigraine treatments.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"19 ","pages":"17448069231152104"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e8/66/10.1177_17448069231152104.PMC9850133.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9193322","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":"Genetic evidence of the function of Phox2a-expressing anterolateral system neurons in the transmission of chronic pain.","authors":"Xinying Zhang,&nbsp;Magali Millecamps,&nbsp;Artur Kania","doi":"10.1177/17448069231170546","DOIUrl":"https://doi.org/10.1177/17448069231170546","url":null,"abstract":"<p><p>The development of the chronic neuropathic pain state often originates at the level of peripheral sensory neurons, whose abnormal function elicits central sensitization and maladaptive plasticity in the nociceptive circuits of the spinal dorsal horn. These changes eventually reach supraspinal areas bringing about cognitive and affective co-morbidities of chronic pain such as anxiety and depression. This transmission presumably relies on the function of spinal projection neurons at the origin of the anterolateral system (AS). However, the identity of these neurons and the extent of their functional contribution remain unknown. Here, we asked these questions in the context of the mouse AS neurons that require the transcription factor Phox2a for their normal target connectivity and function in transmitting acute nociceptive information to the brain. To this end, we examined the effects of a spinal cord-specific loss of Phox2a (Phox2a^cKO) on the development of central sensitization evoked by the spared nerve injury (SNI) model of chronic pain. We found that SNI-treated Phox2a^cKO mice developed normal reflexive spinal responses such as mechanical allodynia evidenced by a decreased withdrawal threshold to von Frey filament stimulation and dynamic brush. On the other hand, Phox2a^cKO attenuated the development of cold but not mechanical hyperalgesia, in behavioral paradigms that require the relay of nociceptive information to the brain. Furthermore, Phox2a^cKO attenuated anxio-depressive-like behaviors evoked by SNI, measured by performance in the open field test and tail suspension test. Thus, Phox2a AS neurons play a critical role in the generation and maintenance of chronic neuropathic pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"19 ","pages":"17448069231170546"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/71/a5/10.1177_17448069231170546.PMC10291149.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760090","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":"Duloxetine prevents bortezomib and paclitaxel large-fiber chemotherapy-induced peripheral neuropathy (LF-CIPN) in sprague dawley rats.","authors":"Niloufar Mansooralavi,&nbsp;Eugen V Khomula,&nbsp;Jon D Levine","doi":"10.1177/17448069231185694","DOIUrl":"https://doi.org/10.1177/17448069231185694","url":null,"abstract":"<p><p>Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating, treatment-limiting, side-effect of several classes of chemotherapy drugs. While negatively impacting oncology patients' quality of life, chemotherapy-induced large-fiber (LF) neuropathy is amongst the least well understood components of CIPN, and one for which there is currently no established therapy. Preliminary clinical observations have led to the suggestion that Duloxetine, which is used for the treatment of pain associated with small-fiber CIPN (SF-CIPN), may be effective against LF-CIPN. In the present experiments we developed a model of LF-CIPN and studied the effect of Duloxetine on LF-CIPN induced by two neurotoxic chemotherapy agents: the proteasome inhibitor, Bortezomib, a first-line treatment of multiple myeloma; and, the anti-microtubule taxane, Paclitaxel, used in the treatment of solid tumors. Since there are currently no models for selective the study of LF-CIPN, our first aim was to establish a pre-clinical model in the rat. LF-CIPN was evaluated with the Current Perception Threshold (CPT) assay, which uses a high frequency (1000 Hz) electrical stimulus protocol that selectively activates large-fiber myelinated afferents. Our second aim was to use this model to test the hypothesis that Duloxetine can prevent LF-CIPN. We report that Bortezomib and Paclitaxel induce elevation of CPT, compatible with loss of large-fiber function, which are prevented by Duloxetine. Our findings support the clinical observation that Duloxetine may be an effective treatment for the large-fiber CIPN. We also suggest that CPT could be used as a biomarker for LF-CIPN in patients receiving neurotoxic chemotherapy.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"19 ","pages":"17448069231185694"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10288414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760379","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 reactivity following acute exposure to experimental pain testing in people with HIV and chronic pain.","authors":"Shannon R Gilstrap, Joanna M Hobson, Michael A Owens, Dyan M White, Melissa J Sammy, Scott Ballinger, Robert E Sorge, Burel R Goodin","doi":"10.1177/17448069231195975","DOIUrl":"10.1177/17448069231195975","url":null,"abstract":"<p><p><b>Background:</b> Physical stressors can cause a physiological response that can contribute to an increase in mitochondrial dysfunction and Mitochondrial DNA damage (mtDNA damage). People living with HIV (PWH) are more likely to suffer from chronic pain and may be more susceptible to mitochondrial dysfunction following exposure to a stressor. We used Quantitative Sensory Testing (QST) as an acute painful stressor in order to investigate whether PWH with/without chronic pain show differential mitochondrial physiological responses. <b>Methods:</b> The current study included PWH with (<i>n</i> = 26), and without (<i>n</i> = 29), chronic pain. Participants completed a single session that lasted approximately 180 min, including QST. Blood was taken prior to and following the QST battery for assays measuring mtDNA damage, mtDNA copy number, and mtDNA damage-associated molecular pattern (DAMP) levels (i.e., ND1 and ND6). <b>Results:</b> We examined differences between those with and without pain on various indicators of mitochondrial reactivity following exposure to QST. However, only ND6 and mtDNA damage were shown to be statistically significant between pain groups. <b>Conclusion:</b> PWH with chronic pain showed greater mitochondrial reactivity to laboratory stressors. Consequently, PWH and chronic pain may be more susceptible to conditions in which mitochondrial damage/dysfunction play a central role, such as cognitive decline.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"19 ","pages":"17448069231195975"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/a1/10.1177_17448069231195975.PMC10467217.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10116721","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":"Acute sleep deprivation aggravates nitroglycerin-evoked hyperalgesia in mice.","authors":"Zhe Yu, Bozhi Li, Wenjing Tang, Zhao Dong, Ruozhuo Liu, Shengyuan Yu","doi":"10.1177/17448069221149645","DOIUrl":"10.1177/17448069221149645","url":null,"abstract":"<p><p>Sleep deprivation can trigger migraine, and migraineurs often choose to sleep to relieve headaches during acute migraine. This study aimed to explore the effect of acute sleep deprivation on hyperalgesia induced by nitroglycerin in mice. In part one, after either 6-h sleep deprivation or 6-h normal sleep, mice were intraperitoneally injected with nitroglycerin or saline. The mechanical pain threshold and withdrawal latency of the hindpaw were measured every 30 min for 6 h. Next, the same sleep deprivation and injection procedure was performed with new mice, and mice were sacrificed 4.5 h after injection. The trigeminal nucleus caudalis and upper cervical spinal segments were taken for immunofluorescence Fos staining. In part two, after injection of saline or nitroglycerin, the mice were either deprived of sleep for 6 h or allowed to sleep without interference. The mechanical and thermal pain threshold were measured after 6 h. In part three, we compared the sleep time of mice after intraperitoneal injection of saline or nitroglycerin without interference. Sleep deprivation for 6 h did not cause any changes in the baseline pain thresholds in mice. However, pretreatment with 6-h sleep deprivation significantly prolonged the duration of hyperalgesia induced by nitroglycerin. Additionally, the expression of Fos at 4.5 h was significantly higher in the 6-h sleep deprivation and nitroglycerin group than in the other three groups. When intraperitoneal injection was given first, the mechanical pain threshold of the hind paw was significantly lower in the group that received nitroglycerin with 6-h sleep deprivation than in the other groups. Compared to the saline injection, one-time nitroglycerin injection would result in a significant increase in sleep latency and decrease in sleep duration for the normal mice. Acute sleep deprivation significantly aggravated the hyperalgesia induced by nitroglycerin in mice, which highlights the importance of sleep disorders for migraine.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"19 ","pages":"17448069221149645"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fe/f7/10.1177_17448069221149645.PMC9830572.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10645666","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":"Co-Administration of nalbuphine to improve morphine tolerance in mice with bone cancer pain.","authors":"Bingxu Ren,&nbsp;Jiannan Zhang,&nbsp;Xiaohu Yang,&nbsp;Dapeng Sun,&nbsp;Duanyang Sheng,&nbsp;Qiang Fang,&nbsp;Zhonghua Ji","doi":"10.1177/17448069231178741","DOIUrl":"https://doi.org/10.1177/17448069231178741","url":null,"abstract":"<p><strong>Background: </strong>Kappa-opioid receptor (KOR) agonists are known for having opposite and/or different effects compared with Mu-opioid receptor (MOR) agonists. This study is aimed at clarifying the analgesic effect and tolerance of nalbuphine combined with morphine, and quantifying the mRNA and protein expression of spinal MOR and KOR in a mouse bone cancer pain (BCP) model treated with nalbuphine and morphine.</p><p><strong>Method: </strong>BCP model was prepared in C3H/HeNCrlVr Mice by implanting the sarcoma cells into the intramedullary space of the femur. The paw withdrawal thermal latency (PWL) measured by thermal radiometer was used to assess thermal hyperalgesia. PWL testing was performed after implantation and drug administration according to the protocol. Hematoxylin-eosin staining in the spinal cord and x-ray in the femoral intramedullary canal was detected. Real-time PCR and western blot analysis played a role in detecting spinal MOR and KOR expression changes.</p><p><strong>Results: </strong>In tumor-implanted mice, the spinal MOR and KOR protein and mRNA expression was down-regulated when compared to that in sham-implanted mice (<i>p</i> < 0.05). Morphine therapy can lead to a decrease in spinal μ receptor expression. Similarly, the nalbuphine therapy can lead to a decrease in the expression of κ receptor protein and mRNA at the spinal cord level (<i>p</i> < 0.05). Morphine, nalbuphine, or nalbuphine co-administration with morphine all can extend the paw withdrawal thermal latency (PWL) to radiant thermal stimulation in tumor-implanted mice (<i>p</i> < 0.05). Compared with the morphine treatment group, nalbuphine co-administration with morphine delayed the reduction of PWL value again (<i>p</i> < 0.05).</p><p><strong>Discussion: </strong>BCP itself may induce down-regulation of the spinal MOR and KOR expression. A low dose of nalbuphine co-administration with morphine led to the delayed emergence of morphine tolerance. The part of the mechanism may be due to the regulation of spinal opioid receptors expression.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"19 ","pages":"17448069231178741"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d6/96/10.1177_17448069231178741.PMC10226037.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9548941","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}