Pathways that elicit long-term changes in gene expression in nociceptive neurons following nerve injury: contributions to neuropathic pain

2004 ◽  
Vol 26 (2) ◽  
pp. 195-203 ◽  
Author(s):  
Ying-Ju Sung ◽  
Richard T. Ambron
Keyword(s):  
Gene Expression ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Nociceptive Neurons ◽  
Long Term Changes

scholarly journals Microglia–Astrocyte Communication via C1q Contributes to Orofacial Neuropathic Pain Associated with Infraorbital Nerve Injury

2020 ◽  
Vol 21 (18) ◽  
pp. 6834
Author(s):  
Sayaka Asano ◽  
Yoshinori Hayashi ◽  
Koichi Iwata ◽  
Akiko Okada-Ogawa ◽  
Suzuro Hitomi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Glial Fibrillary Acidic Protein ◽  
Nerve Injury ◽  
Fluorescence Intensity ◽  
Time Window ◽  
Infraorbital Nerve ◽  
Nociceptive Neurons ◽  
Mechanical Hypersensitivity ◽  
Injury Causes ◽  
Immunohistochemical Analyses

Trigeminal nerve injury causes a distinct time window of glial activation in the trigeminal spinal subnucleus caudalis (Vc), which are involved in the initiation and maintenance phases of orofacial neuropathic pain. Microglia-derived factors enable the activation of astrocytes. The complement component C1q, which promotes the activation of astrocytes, is known to be synthesized in microglia. However, it is unclear whether microglia–astrocyte communication via C1q is involved in orofacial neuropathic pain. Here, we analyzed microglia-astrocyte communication in a rat model with infraorbital nerve injury (IONI). The orofacial mechanical hypersensitivity induced by IONI was significantly attenuated by preemptive treatment with minocycline. Immunohistochemical analyses revealed that minocycline inhibited the increase in c-Fos immune-reactive (IR) cells and the fluorescence intensity of both Iba1 and glial fibrillary acidic protein (GFAP) in the Vc following IONI. Intracisternal administration of C1q caused orofacial mechanical hypersensitivity and an increase in the number of c-Fos-IR cells and fluorescence intensity of GFAP. C1q-induced orofacial mechanical hypersensitivity was completely abrogated by intracisternal administration of fluorocitrate. The present findings suggest that the enhancement in the excitability of Vc nociceptive neurons is produced by astrocytic activation via the signaling of C1q released from activated microglia in the Vc following IONI, resulting in persistent orofacial neuropathic pain.

scholarly journals Short- and long-term changes in gene expression mediated by the activation of TLR9

2010 ◽  
Vol 47 (6) ◽  
pp. 1317-1324 ◽  
Author(s):  
Sven Klaschik ◽  
Debra Tross ◽  
Hidekazu Shirota ◽  
Dennis M. Klinman
Keyword(s):  
Gene Expression ◽  
Long Term Changes ◽  
Short And Long Term

scholarly journals Spinal NGF Restores Opioid Sensitivity in Neuropathic Rats: Possible Role of NGF as a Regulator of CCK-Induced Anti-Opioid Effects

2000 ◽  
Vol 5 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Catherine M Cahill ◽  
Terence J Coderre
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Postnatal Period ◽  
Spontaneous Pain ◽  
Pain Mechanisms ◽  
Nociceptive Neurons ◽  
Nociceptive Transmission ◽  
Chronic Pain Conditions ◽  
Injury Models

The breadth of peripheral effects produced by nerve growth factor (NGF) in nociceptive processing has been well documented. However, less is known about the functional significance of central NGF in nociceptive transmission. The effect of NGF on the nervous system is dependent on the developmental stage. During the prenatal developmental period, NGF is critical for survival of nociceptors; in the postnatal period it regulates the expression of nociceptor phenotype, and in the adult it contributes to pain following an inflammatory insult. The implications for central NGF in the expression and regulation of spinal neuropeptides that are involved in pain mechanisms are reviewed. Knowledge has been gained by studies using peripheral nerve injury models that cause a deprivation of central NGF. These models also give rise to the development of pain syndromes, which encompass spontaneous pain, hyperalgesia and allodynia, routinely referred to as neuropathic pain. These models provide an approach for examining the contribution of central NGF to nociceptive transmission. Chronic pain emanating from a nerve injury is typically refractory to traditional analgesics such as opioids. Recent evidence suggests that supplementation of spinal NGF restores morphine-induced antinociception in an animal model of neuropathic pain. This effect appears to be mediated by alterations in spinal levels of cholecystokinin. The authors hypothesize that NGF is critical in maintaining neurochemical homeostasis in the spinal cord of nociceptive neurons, and that supplementation may be beneficial in restoring and/or maintaining opioid analgesia in chronic pain conditions resulting from traumatic nerve injury.

scholarly journals Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Songxue Su ◽  
Mengqi Li ◽  
Di Wu ◽  
Jing Cao ◽  
Xiuhua Ren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Anterior Cingulate Cortex ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Anterior Cingulate ◽  
Anxiety And Depression ◽  
Gene Transcript

Chronic neuropathic pain caused by nerve damage is a most common clinical symptom, often accompanied by anxiety- and depression-like symptoms. Current treatments are very limited at least in part due to incompletely understanding mechanisms underlying this disorder. Changes in gene expression in the dorsal root ganglion (DRG) have been acknowledged to implicate in neuropathic pain genesis, but how peripheral nerve injury alters the gene expression in other pain-associated regions remains elusive. The present study carried out strand-specific next-generation RNA sequencing with a higher sequencing depth and observed the changes in whole transcriptomes in the spinal cord (SC), anterior cingulate cortex (ACC), and amygdala (AMY) following unilateral fourth lumbar spinal nerve ligation (SNL). In addition to providing novel transcriptome profiles of long non-coding RNAs (lncRNAs) and mRNAs, we identified pain- and emotion-related differentially expressed genes (DEGs) and revealed that numbers of these DEGs displayed a high correlation to neuroinflammation and apoptosis. Consistently, functional analyses showed that the most significant enriched biological processes of the upregulated mRNAs were involved in the immune system process, apoptotic process, defense response, inflammation response, and sensory perception of pain across three regions. Moreover, the comparisons of pain-, anxiety-, and depression-related DEGs among three regions present a particular molecular map among the spinal cord and supraspinal structures and indicate the region-dependent and region-independent alterations of gene expression after nerve injury. Our study provides a resource for gene transcript expression patterns in three distinct pain-related regions after peripheral nerve injury. Our findings suggest that neuroinflammation and apoptosis are important pathogenic mechanisms underlying neuropathic pain and that some DEGs might be promising therapeutic targets.

scholarly journals ARA290, a Peptide Derived from the Tertiary Structure of Erythropoietin, Produces Long-term Relief of Neuropathic Pain

2011 ◽  
Vol 115 (5) ◽  
pp. 1084-1092 ◽  
Author(s):  
Maarten Swartjes ◽  
Aurora Morariu ◽  
Marieke Niesters ◽  
Michael Brines ◽  
Anthony Cerami ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Tertiary Structure ◽  
Cold Allodynia ◽  
Cardiovascular Side Effects ◽  
Common Receptor ◽  
Rats And Mice

Background Exogenous erythropoietin inhibits development of allodynia in experimental painful neuropathy because of its antiinflammatory and neuroprotective properties at spinal, supraspinal, and possibly peripheral sites. The authors assess the effect of a nonhematopoietic erythropoietin analog, ARA290, on tactile and cold allodynia in a model of neuropathic pain (spared nerve injury) in rats and mice lacking the β-common receptor (βcR mice), a component of the receptor complex mediating tissue protection. Methods Twenty-four hours after peripheral nerve injury, rats and mice were injected with ARA290 or vehicle (five 30-μg/kg intraperitoneal injections at 2-day intervals, followed by once/week, n = 8/group). In a separate group of eight rats, ARA290 treatment was restricted to five doses during the initial 2 weeks after surgery. Results In rats, irrespective of treatment paradigm, ARA290 produced effective, long-term (as long as 15 weeks) relief of tactile and cold allodynia (P < 0.001 vs. vehicle-treated animals). ARA290 was effective in wild-type mice, producing significant relief of allodynia. In contrast, in βcR mice no effect of ARA290 was observed. Conclusions ARA290 produces long-term relief of allodynia because of activation of the β-common receptor. It is argued that relief of neuropathic pain attributable to ARA290 treatment is related to its antiinflammatory properties, possibly within the central nervous system. Because ARA290, in contrast to erythropoietin, is devoid of hematopoietic and cardiovascular side effects, ARA290 is a promising new drug in the prevention of peripheral nerve injury-induced neuropathic pain in humans.

scholarly journals Adolescent Social Isolation Reprograms the Medial Amygdala: Transcriptome and Sex Differences in Reward

2020 ◽  
Author(s):  
Deena M. Walker ◽  
Xianxiao Zhou ◽  
Aarthi Ramakrishnan ◽  
Hannah M. Cates ◽  
Ashley M. Cunningham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Social Isolation ◽  
Medial Amygdala ◽  
Isolation Stress ◽  
Transcriptional Profiles ◽  
Network Analyses ◽  
Long Term Changes ◽  
Differential Gene ◽  
Key Driver

ABSTRACTAdolescence is a sensitive window for reward- and stress-associated behavior. Although stress during this period causes long-term changes in behavior in males, how females respond is relatively unknown. Here we show that social isolation stress in adolescence, but not adulthood, induces persistent but opposite effects on anxiety- and cocaine-related behaviors in male vs. female mice, and that these effects are reflected in transcriptional profiles within the adult medial amygdala (meA). By integrating differential gene expression with co-expression network analyses, we identified crystallin mu (Crym), a thyroid-binding protein, as a key driver of these transcriptional profiles. Manipulation of Crym specifically within adult meA neurons recapitulates the behavioral and transcriptional effects of social isolation and re-opens a window of plasticity that is otherwise closed. Our results establish that meA is essential for sex-specific responses to stressful and rewarding stimuli through transcriptional programming that occurs during adolescence.

scholarly journals Long-term culture expanded alveolar macrophages restore full epigenetic identity in vivo

2021 ◽  
Author(s):  
Michael Sieweke ◽  
Sethuraman Subramanian ◽  
Clara Busch ◽  
Kaaweh Molawi ◽  
Laufey Geirsdottir ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alveolar Macrophages ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Open Chromatin ◽  
Mechanistic Analysis ◽  
Long Term Changes ◽  
Cellular Identity

Abstract Alveolar macrophages (AM) are tissue resident macrophages of the lung that can be expanded in culture, but it is unknown to what extent culture affects their in vivo identity. Here we show that long-term ex vivo expanded mouse AM (exAM) maintain core AM gene expression but show culture adaptations related to adhesion, metabolism and proliferation. Strikingly, even after several months in culture exAM reacquired full transcriptional and epigenetic identity upon transplantation into the lung and could self-maintain in the natural niche long-term. Changes in open chromatin regions (OCR) observed in culture were fully reversible in transplanted exAM (texAM) and resulted in a gene expression profile indistinguishable from resident AM. Our results demonstrate that long-term proliferation of AM in culture does not compromise cellular identity in vivo. The demonstrated robustness of exAM identity provides new opportunities for mechanistic analysis and highlights the therapeutic potential of ex vivo expanded macrophages.

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