Modulation of Nerve Injury–induced HDAC4 Cytoplasmic Retention Contributes to Neuropathic Pain in Rats

2015 ◽  
Vol 123 (1) ◽  
pp. 199-212 ◽  
Author(s):  
Tzer-Bin Lin ◽  
Ming-Chun Hsieh ◽  
Cheng-Yuan Lai ◽  
Jen-Kun Cheng ◽  
Yat-Pang Chau ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Histone Deacetylases ◽  
Spinal Nerve ◽  
Sprague Dawley ◽  
Withdrawal Threshold ◽  
Dorsal Horn Neurons ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Interfering Rna

Abstract Background: The histone deacetylases (HDACs) have been implicated in pain hypersensitivity. This study investigated the potential involvement of an HDAC4-related mechanism in the spinal nerve ligation (SNL)-induced nociceptive hypersensitivity. Methods: The left L5 to L6 spinal nerves of 627 adult male Sprague–Dawley rats were surgically ligated. The withdrawal threshold of hind paws and the abundances, cellular location, and interactions of proteins in the dorsal horn were assayed before and after surgery. The 14-3-3β-targeting small-interfering RNA, a serum- and glucocorticoid-inducible kinase 1 (SGK1) antagonist, or an HDAC inhibitor was spinally injected to elucidate the role of 14-3-3β, SGK1, and HDAC4. Results: Without affecting the HDAC4 level, SNL provoked SGK1 phosphorylation (mean ± SEM from 0.24 ± 0.02 to 0.78 ± 0.06 at day 7, n = 6), HDAC4 phosphorylation (from 0.38 ± 0.03 to 0.72 ± 0.06 at day 7, n = 6), 14-3-3β expression (from 0.53 ± 0.09 to 0.88 ± 0.09 at day 7, n = 6), cytoplasmic HDAC4 retention (from 1.18 ± 0.16 to 1.92 ± 0.11 at day 7, n = 6), and HDAC4-14-3-3β coupling (approximately 2.4-fold) in the ipsilateral dorsal horn in association with behavioral allodynia. Knockdown of spinal 14-3-3β expression prevented the SNL-provoked HDAC4 retention (from 1.89 ± 0.15 to 1.32 ± 0.08 at day 7, n = 6), HDAC4-14-3-3β coupling (approximately 0.6-fold above SNL 7D), and behavioral allodynia (from 0.16 ± 0.3 to 6 ± 1.78 at day 7, n = 7), but not SGK1 (from 0.78 ± 0.06 to 0.71 ± 0.04 at day 7, n = 6) or HDAC4 (from 0.75 ± 0.15 to 0.68 ± 0.11 at day 7, n = 6) phosphorylation. Conclusion: Neuropathic pain maintenance involves the spinal SGK1 activation–dependent HDAC4 phosphorylation and its subsequent association with 14-3-3β that promotes cytoplasmic HDAC4 retention in dorsal horn neurons.

Neuropathic Allodynia Involves Spinal Neurexin-1β-dependent Neuroligin-1/Postsynaptic Density-95/NR2B Cascade in Rats

2015 ◽  
Vol 123 (4) ◽  
pp. 909-926 ◽  
Author(s):  
Tzer-Bin Lin ◽  
Cheng-Yuan Lai ◽  
Ming-Chun Hsieh ◽  
Jian-Lin Jiang ◽  
Jen-Kun Cheng ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Small Interfering Rna ◽  
Postsynaptic Density ◽  
Spinal Nerve ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Withdrawal Threshold ◽  
Sprague Dawley Rats ◽  
Rna Targeting ◽  
Interfering Rna

Abstract Background: Neuroligin-1 (NL1) forms a complex with the presynaptic neurexin-1β (Nrx1b), regulating clustering of N-methyl-d-aspartate receptors with postsynaptic density-95 (PSD-95) to underlie learning-/memory-associated plasticity. Pain-related spinal neuroplasticity shares several common features with learning-/memory-associated plasticity. The authors thereby investigated the potential involvement of NL1-related mechanism in spinal nerve ligation (SNL)–associated allodynia. Methods: In 626 adult male Sprague–Dawley rats, the withdrawal threshold and NL1, PSD-95, phosphorylated NR2B (pNR2B) expressions, interactions, and locations in dorsal horn (L4 to L5) were compared between the sham operation and SNL groups. A recombinant Nrx1b Fc chimera (Nrx1b Fc, 10 μg, 10 μl, i.t., bolus), antisense small-interfering RNA targeting to NL1 (10 μg, 10 μl, i.t., daily for 4 days), or NR2B antagonist (Ro 25-6981; 1 μM, 10 μl, i.t., bolus) were administered to SNL animals to elucidate possible cascades involved. Results: SNL-induced allodynia failed to affect NL1 or PSD-95 expression. However, pNR2B expression (mean ± SD from 13.1 ± 2.87 to 23.1 ± 2.52, n = 6) and coexpression of NL1–PSD-95, pNR2B–PSD-95, and NL1-total NR2B were enhanced by SNL (from 10.7 ± 2.27 to 22.2 ± 3.94, 11.5 ± 2.15 to 23.8 ± 3.32, and 8.9 ± 1.83 to 14.9 ± 2.27 at day 7, n = 6). Furthermore, neuron-localized pNR2B PSD-95–pNR2B double-labeled and NL1/PSD-95/pNR2B triple-labeled immunofluorescence in the ipsilateral dorsal horn was all prevented by Nrx1b Fc and NL1-targeted small-interfering RNA designed to block and prevent NL1 expression. Without affecting NL1–PSD-95 coupling, Ro 25-6981 decreased the SNL-induced PSD-95–pNR2B coprecipitation (from 18.7 ± 1.80 to 14.7 ± 2.36 at day 7, n = 6). Conclusion: SNL-induced allodynia, which is mediated by the spinal NL1/PSD-95/pNR2B cascade, can be prevented by blockade of transsynaptic Nrx1b–NL1 interactions.

Peripheral Nerve Injury Sensitizes the Response to Visceral Distension but Not Its Inhibition by the Antidepressant Milnacipran

2004 ◽  
Vol 100 (3) ◽  
pp. 671-675 ◽  
Author(s):  
Sang-Wook Shin ◽  
James C. Eisenach
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Visceral Pain ◽  
Spinal Nerve ◽  
Reflex Response ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Withdrawal Threshold ◽  
Sprague Dawley Rats ◽  
Lumbar Spinal

Background Manipulations that cause hypersensitivity to visceral stimuli have been shown to also result in hypersensitivity to somatic stimuli coming from convergent dermatomes, but the converse has not been examined. The authors tested whether lumbar spinal nerve ligation in rats, a common model of neuropathic pain that results in hypersensitivity to somatic stimuli, also leads to hypersensitivity to visceral stimuli coming from convergent dermatomes and whether pharmacology of inhibition differed between these two sensory modalities. Methods Female Sprague-Dawley rats were anesthetized, and the left L5 and L6 spinal nerves were ligated. Animals received either intrathecal saline or milnacipran (0.1-3 microg), and withdrawal thresholds to mechanical testing in the left hind paw, using von Frey filaments, and visceral testing, using balloon colorectal distension, were determined. Results Nerve ligation resulted in decreases in threshold to withdrawal to somatic mechanical stimulation (from 13 +/- 1.8 g to 2.7 +/- 0.7 g) and also in decreases in threshold to reflex response to visceral stimulation (from 60 mmHg to 40 mmHg). Intrathecal milnacipran increased withdrawal threshold to somatic stimulation in a dose-dependent manner but failed to alter the response to noxious visceral stimulation. Conclusions Injury of nerves innervating somatic structures enhances nociception from stimulation of viscera with convergent input from nearby dermatomes, suggesting that somatic neuropathic pain could be accompanied by an increased likelihood of visceral pain. Lack of efficacy of the antidepressant milnacipran against visceral stimuli suggests that visceral hypersensitivity may not share the same pharmacology of inhibition as somatic hypersensitivity after nerve injury.

Inhibition of Spinal Prostaglandin Synthesis Early after L5/L6 Nerve Ligation Prevents the Development of Prostaglandin-dependent and Prostaglandin-independent Allodynia in the Rat

2003 ◽  
Vol 99 (5) ◽  
pp. 1180-1188 ◽  
Author(s):  
Michael P. Hefferan ◽  
Darren D. O'Rielly ◽  
Christopher W. Loomis
Keyword(s):  
Glutamate Release ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Sprague Dawley ◽  
Nociceptive Transmission ◽  
Withdrawal Threshold ◽  
Sham Surgery ◽  
Cyclooxygenase 1 ◽  
Sprague Dawley Rats ◽  
Spinal Segments

Background Prostaglandins, synthesized in the spinal cord in response to noxious stimuli, are known to facilitate nociceptive transmission, raising questions about their role in neuropathic pain. The current study tested the hypothesis that spinal nerve ligation-induced allodynia is composed of an early prostaglandin-dependent phase, the disruption of which prevents allodynia. Methods Male Sprague-Dawley rats, fitted with intrathecal drug delivery or microdialysis catheters, underwent left L5-L6 spinal nerve ligation or sham surgery. Paw withdrawal threshold, brush-evoked behavior, and the concentration of prostaglandin E2 (PGE2) in spinal cerebrospinal fluid ([PGE2]dialysate) were determined for up to 24 days. PGE2-evoked glutamate release from spinal slices was also determined. Results Paw withdrawal threshold decreased from at least 15 g (control) to less than 4 g, beginning 1 day after ligation. Brushing the affected hind paw evoked nociceptive-like behavior and increased [PGE2]dialysate (up to 257 +/- 62% of baseline). There was no detectable change in basal [PGE2]dialysate from preligation values. The EC50 of PGE2-evoked glutamate release (2.4 x 10-11 M, control) was significantly decreased in affected spinal segments of allodynic rats (8.9 x 10-15 M). Treatment with intrathecal S(+)-ibuprofen or SC-560, beginning 2 h after ligation, prevented the decrease in paw withdrawal threshold, the brush-evoked increase in [PGE2]dialysate, and the change in EC50 of PGE2-evoked glutamate release. R(-)-ibuprofen or SC-236 had no effect. Conclusions The results of this study provide solid evidence that spinal prostaglandins, synthesized by cyclooxygenase-1 in the first 4-8 h after ligation, are critical in the pathogenesis of prostaglandin-dependent and prostaglandin-independent allodynia and that their early pharmacologic disruption affords protection against this neuropathic state in the rat.

Intrathecal Lidocaine Reverses Tactile Allodynia Caused by Nerve Injuries and Potentiates the Antiallodynic Effect of the COX Inhibitor Ketorolac

2003 ◽  
Vol 98 (1) ◽  
pp. 203-208 ◽  
Author(s):  
Weiya Ma ◽  
Wei Du ◽  
James C. Eisenach
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Spinal Nerve ◽  
Tactile Allodynia ◽  
Withdrawal Threshold ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Cox Inhibitor ◽  
Antiallodynic Effect ◽  
Von Frey Filaments

Background Systemic lidocaine and other local anesthetics reduce hypersensitivity states induced by both acute inflammation and peripheral nerve injury in animals and produce analgesia in some patients with chronic pain. The mechanisms underlying the antiallodynic effect of systemic lidocaine are unclear, although most focus is on peripheral mechanisms. Central mechanisms, particularly at the spinal dorsal horn level, are less known. In this study, the authors aimed to determine whether intrathecal lidocaine has an antiallodynic effect on established mechanical allodynia in two well-characterized neuropathic pain rat models: partial sciatic nerve ligation (PSNL) and spinal nerve ligation (SNL). Methods Lidocaine (100-300 micro g) was intrathecally injected in PSNL and SNL rats. The withdrawal threshold of both hind paws in response to mechanical stimulation was measured using a series of calibrated von Frey filaments. Results This single injection reduced ongoing tactile allodynia in PSNL and SNL rats. The antiallodynic effect of intrathecal lidocaine lasted longer in PSNL (> 3 days) than in SNL rats (< 3 days). Intraperitoneal lidocaine (300 micro g) had no effect on tactile allodynia in PSNL rats. In SNL rats, prior intrathecal lidocaine (200 and 300 micro g) potentiated the antiallodynic effect of intrathecal ketorolac, a nonselective cyclooxygenase inhibitor. Intrathecal ketorolac alone had no antiallodynic effect on SNL rats. However, prior intrathecal lidocaine (100 micro g) failed to potentiate the antiallodynic effect of intrathecal ketorolac. Conclusion The authors' data suggest that intrathecal lidocaine possibly suppressed the hyperexcitability of the dorsal horn neurons and likely interacted with eicosanoid systems in the spinal dorsal horn.

scholarly journals Sodium Hydrosulfide Relieves Neuropathic Pain in Chronic Constriction Injured Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jian-qing Lin ◽  
Hui-qin Luo ◽  
Cai-zhu Lin ◽  
Jin-zhuan Chen ◽  
Xian-zhong Lin
Keyword(s):  
Neuropathic Pain ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sodium Hydrosulfide ◽  
Withdrawal Threshold ◽  
Molecular Events ◽  
Relieve Pain ◽  
Sprague Dawley Rats ◽  
Clinical Potential ◽  
Dose Dependent

Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain (NPP). Channel protein pCREB of that activity has been shown to mitigate the onset of associated molecular events in the nervous system, and sodium hydrosulfide (NaHS) could inhibit the expression of pCREB. However, whether NaHS could relieve the pain, it needs further experimental research. Furthermore, the clinical potential that NaHS was used to relieve pain was limited so it would be required. To address these issues, the rats of sciatic nerve chronic constriction injury (CCI) were given intraperitoneal injection of NaHS containing hydrogen sulfide (H2S). The experimental results showed that NaHS inhibited the reduction of paw withdrawal thermal latency (PWTL), mechanical withdrawal threshold (MWT), and the level of pCREB in CCI rats in a dose-dependent manner and they were greatly decreased in NaHSMgroup (P< 0.05). NaHS alleviates chronic neuropathic pain by inhibiting expression of pCREB in the spinal cord of Sprague-Dawley rats.

scholarly journals N-Acetylcysteine Attenuates Hyperalgesia in Rats with Diabetic Neuropathic Pain: Role of Oxidative Stress and Inflammatory Mediators and CXCR4

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Sisi Li ◽  
Xuying Li ◽  
Xiangbin Xie ◽  
Xiao Wei ◽  
Cong Yu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Prefrontal Cortex ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Diabetic Neuropathic Pain ◽  
Withdrawal Threshold ◽  
Sprague Dawley Rats ◽  
Therapeutic Value ◽  
Tnf Α

Objectives. CXCR4 plays critical roles in the development of diabetic neuropathic pain (DNP) in rats, and its mechanism is unknown. This study was aimed at evaluating the potential therapeutic value of the antioxidant N-acetylcysteine (NAC) against DNP in rats and how CXCR4 participates in the formation of DNP. Methods. Control or streptozotocin- (STZ-) induced diabetic Sprague-Dawley rats received vehicle or NAC for four weeks starting one week after STZ injection. Von Frey and Hargreaves Apparatus were used to analyze the behavioral changes of mechanical allodynia and heat hyperalgesia. CXCR4, p-CXCR4, interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) α in the spinal cord and the prefrontal cortex were detected by western blotting. Plasma IL-6, TNF-α, superoxide dismutase- (SOD-) 1, SOD-2, and lipid peroxidation products malondialdehyde (MDA) and 15-F2t-Isoprostane were detected by ELISA. Results. The values of paw withdrawal threshold (PWT) and paw withdrawal latencies (PWL) were reduced in diabetic rats compared to control rats that were concomitant with significant increases of CXCR4, p-CXCR4, IL-6, and TNF-α protein expressions in the spinal cord and prefrontal cortex. The treatment with NAC decreased the IL-6 and TNF-α protein expression and further increased CXCR4 and p-CXCR4 in the spinal cord and the cortex of diabetic rats that were accompanied with enhancement of PWT and PWL. NAC also significantly attenuated or reverted the increases of plasma IL-6, TNF-α, SOD-1, SOD-2, MDA, and 15-F2t-Isoprostane in diabetic rats. Conclusion. It is concluded that NAC treatment could effectively alleviate DNP and that induction of CXCR4 and p-CXCR4 may represent a mechanism whereby NAC attenuates DNP.

Antiallodynic Effects of Intrathecal Areca Nut for Spinal Nerve-Ligated and Chemotherapy-Induced Neuropathic Pain in Rats

Pharmacology ◽  
2018 ◽  
Vol 102 (5-6) ◽  
pp. 332-338 ◽  
Author(s):  
Hyung Gon Lee ◽  
Ji A Song ◽  
Dong Soo Han ◽  
Kyeong Wan Woo ◽  
Myung Ha Yoon
Keyword(s):  
Neuropathic Pain ◽  
Adrenergic Receptors ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Areca Nut ◽  
Sprague Dawley ◽  
Once Daily ◽  
Spinal Nerves ◽  
Sprague Dawley Rats ◽  
Von Frey Filaments

This study examined the effects of intrathecal areca nut on spinal nerve-ligated and chemotherapy-induced neuropathic pain (NP), and investigated the relevance of spinal 5-hydroxytryptamine (5-HT) and α2-adrenergic receptors to those effects. For drug administration, intrathecal catheters were inserted into the subarachnoid space of male Sprague-Dawley rats. NP was induced either by spinal nerve ligation (left spinal nerves L5 and L6) or by chemotherapeutic injection (intraperitoneal cisplatin, 2 mg/kg/day, once daily for 4 days). Paw withdrawal thresholds (PWT) were mechanically assessed using von Frey filaments. The involvement of 5-HT and α2-adrenergic receptors in antiallodynia was determined using antagonists with the following receptor specificities: nonselective 5-HT (dihydroergocristine), 5-HT7 (SB269970), nonselective α2-adrenoceptor (yohimbine), α-2A (BRL 44408), α-2B (ARC 239), and α-2C (JP 1302). Intrathecal areca nut significantly increased the PWT in both spinal nerve-ligated and chemotherapy-induced NP (‡ p < 0.001). Intrathecal dihydroergocristine, SB269970, yohimbine, BRL 44408, ARC 239, and JP 1302 significantly reversed the antiallodynic effects of areca nut in both NP states (‡ p < 0.001). Collectively, intrathecal areca nut suppressed mechanical allodynia induced by spinal nerve ligation and cisplatin injection. Furthermore, spinal 5-HT7 receptor and α2A, α2B, and α2C-adrenoceptors contributed to the antiallodynic effects of areca nut.

Morphine-induced Spinal Release of Adenosine Is Reduced in Neuropathic Rats

2001 ◽  
Vol 95 (6) ◽  
pp. 1455-1459 ◽  
Author(s):  
Andreas Sandner-Kiesling ◽  
Xinhui Li ◽  
James C. Eisenach
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Lumbar Spinal Cord ◽  
Sprague Dawley ◽  
Dorsal Spinal Cord ◽  
Adenosine Release ◽  
Sprague Dawley Rats ◽  
Lumbar Spinal

Background Spinally administered opioids show decreased potency and efficacy in the treatment of neuropathic pain. As reported previously, morphine stimulates spinal opioid receptors to effect adenosine release, which acts at adenosine receptors to produce analgesia. The authors hypothesized that morphine induces less adenosine release in neuropathic compared with normal rats, explaining its reduced potency and efficacy. Methods Sprague-Dawley rats (200-250 g) were divided into three groups: no surgery (n = 52), sham surgery (n = 20), or left L5 and L6 spinal nerve ligation (n = 64). Two weeks after surgery, mechanical hypersensitivity of the left hind paw was verified. For each experiment, a crude synaptosomal P2 suspension was prepared by homogenizing cervical and lumbar dorsal spinal cord halves from four rats, followed by differential centrifugation, and aliquots incubated with morphine sulfate from 10(-8) to 10(-4) m alone or in presence of 10(-5) m dipyridamole. Extrasynaptosomal concentrations of adenosine were analyzed by high-pressure liquid chromatography. Results Synaptosomal release of adenosine in the absence of morphine was similar between groups. Morphine produced a concentration-dependent adenosine release, which was less in synaptosomes from dorsal lumbar spinal cord in spinal nerve ligation compared with normal or sham animals. This reduction was removed by adding dipyridamole. Conclusion Morphine normally stimulates spinal release of adenosine, a potent antihypersensitivity compound. Because this effect of morphine is diminished in spinal nerve ligation animals, one explanation for decreased efficacy and potency of opioids in the treatment of neuropathic pain may be a dipyridamole-sensitive disruption in the opioid-adenosine link in the spinal cord.

scholarly journals CircAnks1a in the spinal cord regulates hypersensitivity in a rodent model of neuropathic pain

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Su-Bo Zhang ◽  
Su-Yan Lin ◽  
Meng Liu ◽  
Cui-Cui Liu ◽  
Huan-Huan Ding ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Posttranscriptional Regulation ◽  
Spinal Nerve ◽  
Circular Rnas ◽  
Mirna Sponge ◽  
Dorsal Horn Neurons ◽  
Non Coding Rnas

Abstract Circular RNAs are non-coding RNAs, and are enriched in the CNS. Dorsal horn neurons of the spinal cord contribute to pain-like hypersensitivity after nerve injury in rodents. Here we show that spinal nerve ligation is associated with an increase in expression of circAnks1a in dorsal horn neurons, in both the cytoplasm and the nucleus. Downregulation of circAnks1a by siRNA attenuates pain-like behaviour induced by nerve injury. In the cytoplasm, we show that circAnks1a promotes the interaction between transcription factor YBX1 and transportin-1, thus facilitating the nucleus translocation of YBX1. In the nucleus, circAnks1a binds directly to the Vegfb promoter, increases YBX1 recruitment to the Vegfb promoter, thereby facilitating transcription. Furthermore, cytoplasmic circAnks1a acts as a miRNA sponge in miR-324-3p-mediated posttranscriptional regulation of VEGFB expression. The upregulation of VEGFB contributes to increased excitability of dorsal horn neurons and pain behaviour induced by nerve injury. We propose that circAnks1a and VEGFB are regulators of neuropathic pain.

scholarly journals IKBKB siRNA-Encapsulated Poly (Lactic-co-Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation

2021 ◽  
Vol 22 (11) ◽  
pp. 5657
Author(s):  
Seounghun Lee ◽  
Hyo-Jung Shin ◽  
Chan Noh ◽  
Song-I Kim ◽  
Young-Kwon Ko ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Microglial Activation ◽  
Glycolic Acid ◽  
Nuclear Factor Kappa B ◽  
Decisive Role ◽  
Plga Nanoparticles ◽  
Spinal Nerve ◽  
Nuclear Factor ◽  
Interfering Rna

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.

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