Neurobiology of Pain最新文献

{"title":"Cell specific regulation of NaV1.7 activity and trafficking in rat nodose ganglia neurons","authors":"Santiago I. Loya-López ,&nbsp;Paz Duran ,&nbsp;Dongzhi Ran ,&nbsp;Aida Calderon-Rivera ,&nbsp;Kimberly Gomez ,&nbsp;Aubin Moutal ,&nbsp;Rajesh Khanna","doi":"10.1016/j.ynpai.2022.100109","DOIUrl":"10.1016/j.ynpai.2022.100109","url":null,"abstract":"<div><p>The voltage-gated sodium NaV1.7 channel sets the threshold for electrogenesis. Mutations in the gene encoding human NaV1.7 (<em>SCN9A</em>) cause painful neuropathies or pain insensitivity. In dorsal root ganglion (DRG) neurons, activity and trafficking of NaV1.7 are regulated by the auxiliary collapsin response mediator protein 2 (CRMP2). Specifically, preventing addition of a small ubiquitin-like modifier (SUMO), by the E2 SUMO-conjugating enzyme Ubc9, at lysine-374 (K374) of CRMP2 reduces NaV1.7 channel trafficking and activity. We previously identified a small molecule, designated <strong>194</strong>, that prevented CRMP2 SUMOylation by Ubc9 to reduce NaV1.7 surface expression and currents, leading to a reduction in spinal nociceptive transmission, and culminating in normalization of mechanical allodynia in models of neuropathic pain. In this study, we investigated whether NaV1.7 control via CRMP2-SUMOylation is conserved in nodose ganglion (NG) neurons. This study was motivated by our desire to develop <strong>194</strong> as a safe, non-opioid substitute for persistent pain, which led us to wonder how <strong>194</strong> would impact NaV1.7 in NG neurons, which are responsible for driving the cough reflex. We found functioning NaV1.7 channels in NG neurons; however, they were resistant to downregulation via either CRMP2 knockdown or pharmacological inhibition of CRMP2 SUMOylation by <strong>194.</strong> CRMP2 SUMOylation and interaction with NaV1.7 was consered in NG neurons but the endocytic machinery was deficient in the endocytic adaptor protein Numb. Overexpression of Numb rescued CRMP2-dependent regulation on NaV1.7, rendering NG neurons sensitive to <strong>194.</strong> Altogether, these data point at the existence of cell-specific mechanisms regulating NaV1.7 trafficking.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"12 ","pages":"Article 100109"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/09/f1/main.PMC9755031.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10404950","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":"Investigation on how dynamic effective connectivity patterns encode the fluctuating pain intensity in chronic migraine","authors":"Iege Bassez ,&nbsp;Frederik Van de Steen ,&nbsp;Sophie Hackl ,&nbsp;Pauline Jahn ,&nbsp;Astrid Mayr ,&nbsp;Daniele Marinazzo ,&nbsp;Enrico Schulz","doi":"10.1016/j.ynpai.2022.100100","DOIUrl":"10.1016/j.ynpai.2022.100100","url":null,"abstract":"<div><p>Chronic migraine is characterised by persistent headaches for &gt;15 days per month; the intensity of the pain is fluctuating over time. Here, we explored the dynamic interplay of connectivity patterns between regions known to be related to pain processing and their relation to the ongoing dynamic pain experience. We recorded EEG from 80 sessions (20 chronic migraine patients in 4 separate sessions of 25 min). The patients were asked to continuously rate the intensity of their endogenous headache. On different time-windows, a dynamic causal model (DCM) of cross spectral responses was inverted to estimate connectivity strengths. For each patient and session, the evolving dynamics of effective connectivity were related to pain intensities and to pain intensity changes by using a Bayesian linear model. Hierarchical Bayesian modelling was further used to examine which connectivity-pain relations are consistent across sessions and across patients.</p><p>The results reflect the multi-facetted clinical picture of the disease. Across all sessions, each patient with chronic migraine exhibited a distinct pattern of pain intensity-related cortical connectivity. The diversity of the individual findings are accompanied by inconsistent relations between the connectivity parameters and pain intensity or pain intensity changes at group level. This suggests a rejection of the idea of a common neuronal core problem for chronic migraine.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"12 ","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/d8/main.PMC9424568.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40343105","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":"Investigation on how dynamic effective connectivity patterns encode the fluctuating pain intensity in chronic migraine","authors":"I. Bassez, Frederik Van de Steen, Sophie Hackl, Pauline Jahn, A. Mayr, D. Marinazzo, E. Schulz","doi":"10.1101/2022.02.23.481583","DOIUrl":"https://doi.org/10.1101/2022.02.23.481583","url":null,"abstract":"Chronic migraine is characterised by persistent headaches for more than 15 days per month; the intensity of the pain is fluctuating over time. Here, we explored the dynamic interplay of connectivity patterns between regions known to be related to pain processing and their relation to the ongoing dynamic pain experience. We recorded EEG from 80 sessions (20 chronic migraine patients in 4 separate sessions of 25 minutes). The patients were asked to continuously rate the intensity of their endogenous headache. On different time-windows, a dynamic causal model (DCM) of cross spectral responses was inverted to estimate connectivity strengths. For each patient and session, the evolving dynamics of effective connectivity were related to pain intensities and to pain intensity changes by using a Bayesian linear model. Hierarchical Bayesian modelling was further used to examine which connectivity-pain relations are consistent across sessions and across patients. The results reflect the multi-facetted clinical picture of the disease. Across all sessions, each patient with chronic migraine exhibited a distinct pattern of pain intensity-related cortical connectivity. The diversity of the individual findings are accompanied by inconsistent relations between the connectivity parameters and pain intensity or pain intensity changes at group level. This suggests a rejection of the idea of a common neuronal core problem for chronic migraine.","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44198126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical spreading depression and meningeal nociception","authors":"Simone Carneiro-Nascimento,&nbsp;Dan Levy","doi":"10.1016/j.ynpai.2022.100091","DOIUrl":"10.1016/j.ynpai.2022.100091","url":null,"abstract":"<div><p>Migraine results in an enormous burden on individuals and societies due to its high prevalence, significant disability, and considerable economic costs. Current treatment options for migraine remain inadequate, and the development of novel therapies is severely hindered by the incomplete understanding of the mechanisms responsible for the pain. The sensory innervation of the cranial meninges is now considered a key player in migraine headache genesis. Recent studies have significantly advanced our understanding of some of the processes that drive meningeal nociceptive neurons, which may be targeted therapeutically to abort or prevent migraine pain. In this review we will summarize our current understanding of the mechanisms that contribute to the genesis of the headache in one migraine subtype – migraine with aura. We will focus on animal studies that address the notion that cortical spreading depression is a critical process that drives meningeal nociception in migraine with aura, and discuss recent insights into some of the proposed underlying mechanisms.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"11 ","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452073X22000083/pdfft?md5=40c3bcd08027c20c065bd225488cd5a8&pid=1-s2.0-S2452073X22000083-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41389722","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":"Evaluation of calcium-sensitive adenylyl cyclase AC1 and AC8 mRNA expression in the anterior cingulate cortex of mice with spared nerve injury neuropathy","authors":"Stephanie Shiers ,&nbsp;Hajira Elahi ,&nbsp;Stephanie Hennen ,&nbsp;Theodore J. Price","doi":"10.1016/j.ynpai.2021.100081","DOIUrl":"10.1016/j.ynpai.2021.100081","url":null,"abstract":"<div><p>The anterior cingulate cortex (ACC) is a critical region of the brain for the emotional and affective components of pain in rodents and humans. Hyperactivity in this region has been observed in neuropathic pain states in both patients and animal models and ablation of this region from cingulotomy, or inhibition with genetics or pharmacology can diminish pain and anxiety. Two adenylyl cyclases (AC), AC1 and AC8 play an important role in regulating nociception and anxiety-like behaviors through an action in the ACC, as genetic and pharmacological targeting of these enzymes reduces mechanical hypersensitivity and anxiety-like behavior, respectively. However, the distribution of these ACs in the ACC has not been studied in the context of neuropathic pain. To address this gap in knowledge, we conducted RNAscope <em>in situ</em> hybridization to assess AC1 and AC8 mRNA distribution in mice with spared nerve injury (SNI). Given the key role of AC1 in nociception in neuropathic, inflammatory and visceral pain animal models, we hypothesized that AC1 would be upregulated in the ACC of mice following nerve injury. This hypothesis was also founded on data showing increased AC1 expression in the ACC of mice with zymosan-induced visceral inflammation. We found that AC1 and AC8 are widely expressed in many regions of the mouse brain including the hippocampus, ACC, medial prefrontal cortex and midbrain regions, but AC1 is more highly expressed. Contrary to our hypothesis, SNI causes an increase in AC8 mRNA expression in NMDAR-2B (Nr2b) positive neurons in the contralateral ACC but does not affect AC1 mRNA expression. Our findings show that changes in <em>Adcy1</em> mRNA expression in the ACC are insufficient to explain the important role of this AC in mechanical hypersensitivity in mice following nerve injury and suggest a potential unappreciated role of AC8 in regulation of ACC synaptic changes after nerve injury.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"11 ","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39804126","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":"Adenosine receptors: Emerging non-opioids targets for pain medications","authors":"Soo-Min Jung ,&nbsp;Lee Peyton ,&nbsp;Hesham Essa ,&nbsp;Doo-Sup Choi","doi":"10.1016/j.ynpai.2022.100087","DOIUrl":"10.1016/j.ynpai.2022.100087","url":null,"abstract":"<div><p>Physical and emotional pain deteriorates the quality of well-being. Also, numerous non-invasive and invasive treatments for diagnosed diseases such as cancer medications and surgical procedures cause various types of pain. Despite the multidisciplinary approaches available to manage pain, the unmet needs for medication with minimal side effects are substantial. Especially with the surge of opioid crisis during the last decades, non-opioid analgesics may reduce life-threatening overdosing and addictive liability. Although many clinical trials supported the potential potency of cannabis and cannabidiol (CBD) in pain management or treatment, the long-term benefits of cannabis or CBD are still not evident. At the same time, growing evidence shows the risk of overusing cannabis and CBD. Therefore, it is urgent to develop novel analgesic medications that minimize side effects. All four well-identified adenosine receptors, A₁, A_2A, A_2B, and A₃, are implicated in pain. Recently, a report demonstrated that an adenosine A₁R-specific positive allosteric modulator (PAM) is a potent analgesic without noticeable side effects. Also, several A₃R agonists are being considered as promising analgesic agent. However, the importance of adenosine in pain is relatively underestimated. To help readers understand, first, we will summarize the historical perspective of the adenosine system in preclinical and clinical studies. Then, we will discuss possible interactions of adenosine and opioids or the cannabis system focusing on pain. Overall, this review will provide the potential role of adenosine and adenosine receptors in pain treatment.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"11 ","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452073X22000046/pdfft?md5=d8b24875d22a9486ca1abb163b22e994&pid=1-s2.0-S2452073X22000046-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47278713","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":"Differential DNA methylation in Black and White individuals with chronic low back pain enrich different genomic pathways","authors":"Edwin N. Aroke ,&nbsp;Pamela Jackson ,&nbsp;Lingsong Meng ,&nbsp;Zhiguang Huo ,&nbsp;Demario S. Overstreet ,&nbsp;Terence M. Penn ,&nbsp;Tammie L. Quinn ,&nbsp;Yenisel Cruz-Almeida ,&nbsp;Burel R. Goodin","doi":"10.1016/j.ynpai.2022.100086","DOIUrl":"10.1016/j.ynpai.2022.100086","url":null,"abstract":"<div><p>Compared to Non-Hispanic Whites (NHWs), individuals who self-identify as Non-Hispanic Blacks (NHBs) in the United States experience more severe and disabling chronic low back pain (cLBP). We hypothesized that differences in DNA methylation (DNAm) play a role in racial disparities in cLBP.</p></div><div><h3>Purpose</h3><p>To determine the relationship between DNAm levels and racial group differences in adults with cLBP. Our study’s secondary purpose was to perform a race-stratified comparison of adults with cLBP and pain-free controls and identify functional genomic pathways enriched by annotated differentially methylated genes.</p></div><div><h3>Patients and Methods</h3><p>We recruited 49 NHBs and 49 NHWs (49 cLBP and 49 pain-free controls, PFCs), analyzed DNAm from whole blood using reduced representation bisulfite sequencing, and identified enriched genomic pathways.</p></div><div><h3>Results</h3><p>Among participants with cLBP, we identified 2873 differentially methylated loci (DML; methylation differences of at least 10% and p &lt; 0.0001), many of which were annotated to genes of importance to pain pathology. These DMLs significantly enriched pathways to involved in nociception/pain processing (<em>Dopamine-DARPP32 Feedback in cAMP signaling</em>, <em>GABA Receptor Signaling</em>, <em>Opioid Signaling</em>) and neuronal differentiation (e.g., <em>Calcium Signaling, Axon Guidance Signaling</em>, and <em>Endocannabinoid Neuronal Synapse</em>). Our race stratified analyses of individuals with cLBP versus PFCs revealed 2356 DMLs in NHBs and 772 DMLs in NHWs with p &lt; 0.0001 and &gt; 10% methylation difference. Ingenuity Pathway Analysis revealed that many pathways of significance to pain such as <em>Corticotropin Releasing Hormone Signaling, White Adipose Tissue Browning,</em> and <em>GABA Receptor Signaling pathways</em>, were more significant in NHBs than NHWs.</p></div><div><h3>Conclusion</h3><p>Even though an individual’s self-identified race is a social construct, not a biological variable, racism associated with that classification affects virtually every aspect of life, including disease risk. DNAm induced alterations in stress signaling pathways may explain worse pain outcomes in NHBs.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"11 ","pages":"Article 100086"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/90/af/main.PMC8885563.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10641123","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":"Capsaicin suppresses interleukin-31-induced itching partially involved in inhibiting the expression of dorsal root ganglion interleukin-31 receptor A in male mice","authors":"Iwao Arai ,&nbsp;Minoru Tsuji ,&nbsp;Hiroshi Takeda ,&nbsp;Nobutake Akiyama ,&nbsp;Saburo Saito","doi":"10.1016/j.ynpai.2022.100088","DOIUrl":"10.1016/j.ynpai.2022.100088","url":null,"abstract":"<div><p>To elucidate the mechanisms underlying the antipruritic effect of capsaicin, we investigated how topical application of capsaicin (0.01, 0.1 and 1.0% w/v) affects spontaneous scratching in NC/Nga mice, inerleukin-31 (IL-31) induced in BALB/c mice, and IL-31 receptor A (IL-31RA) and transient receptor potential vanilloid member 1 (TRPV1) mRNA expression in dorsal root ganglia (DRG). Capsaicin concentration-dependently suppressed long-lasting scratching (over 1.0 s, itch-associated scratching) and short-lasting scratching (0.3–1.0 s, locomotor activity) immediately after the application. Total long-lasting scratching and short-lasting scratching counts for 24 h and IL-31RA mRNA expression in the DRG significantly decreased with increasing concentration of capsaicin. Furthermore, 1.0% capsaicin suppressed long-lasting scratching and short-lasting scratching for more than 72 h. At this point, DRG IL-31RAmRNA was significantly decreased, but there was no change in cutaneous IL-31RA and TRPV1 mRNA. Thus capsaicin suppresses long-lasting scratching by inhibiting IL-31RA mRNA expression in the DRG. Next, we examined the effect of capsaicin on IL-31-induced long-lasting scratching in BALB/c mice. Repeated administration of IL-31 (50 μg/kg, subcutaneous) every 12 h for 3 days apparently increased long-lasting scratching counts and IL-31RA mRNA in the DRG. These increases were significantly suppressed by pretreatment with 1.0% capsaicin. TRPV1 mRNA in the DRG was also decreased within 1–24 h after capsaicin application. These results suggest that the strong and prolonged antipruritic action for IL-31-induced itching of capsaicin was caused by desensitization of C-fibers, and, in addition, the long-lasting inhibition of IL-31RA mRNA expression in the DRG.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"11 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452073X22000058/pdfft?md5=703ae1ea1154abe54d4b8e637940bd0a&pid=1-s2.0-S2452073X22000058-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43665771","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":"Calcium imaging for analgesic drug discovery","authors":"Federico Iseppon ,&nbsp;John E. Linley ,&nbsp;John N. Wood","doi":"10.1016/j.ynpai.2021.100083","DOIUrl":"10.1016/j.ynpai.2021.100083","url":null,"abstract":"<div><p>Somatosensation and pain are complex phenomena involving a rangeofspecialised cell types forming different circuits within the peripheral and central nervous systems. In recent decades, advances in the investigation of these networks, as well as their function in sensation, resulted from the constant evolution of electrophysiology and imaging techniques to allow the observation of cellular activity at the population level both <em>in vitro</em> and <em>in vivo</em>. Genetically encoded indicators of neuronal activity, combined with recent advances in DNA engineering and modern microscopy, offer powerful tools to dissect and visualise the activity of specific neuronal subpopulations with high spatial and temporal resolution. In recent years various groups developed <em>in vivo</em> imaging techniques to image calcium transients in the dorsal root ganglia, the spinal cord and the brain of anesthetised and awake, behaving animals to address fundamental questions in both the physiology and pathophysiology of somatosensation and pain. This approach, besides giving unprecedented details on the circuitry of innocuous and painful sensation, can be a very powerful tool for pharmacological research, from the characterisation of new potential drugs to the discovery of new, druggable targets within specific neuronal subpopulations. Here we summarise recent developments in calcium imaging for pain research, discuss technical challenges and advances, and examine the potential positive impact of this technique in early preclinical phases of the analgesic drug discovery process.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"11 ","pages":"Article 100083"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39860110","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":"CCK2 receptors in chronic pain","authors":"Justin E. LaVigne,&nbsp;Sascha R.A. Alles","doi":"10.1016/j.ynpai.2022.100092","DOIUrl":"10.1016/j.ynpai.2022.100092","url":null,"abstract":"<div><p>The cholecystokinin receptor system, specifically cholecystokinin 2 receptor (CCK2R) is a historic target for pain management that has shown limited success. However, new approaches to target CCK2R have incited fresh enthusiasm for this target. In this mini-review, we discuss what is known about CCK2R in peripheral and central circuits under naïve physiological conditions and under conditions of chronic pain, the interactions of CCK2Rs with opioids and briefly, recent efforts to develop new treatments targeting CCK2R for chronic pain.</p></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"11 ","pages":"Article 100092"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452073X22000095/pdfft?md5=ce6f175ba9aabf5926bae742ea2b173c&pid=1-s2.0-S2452073X22000095-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42350046","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}