Knockdown of Linc00052 alleviated spinal nerve ligation-triggered neuropathic pain through regulating miR-448 and JAK1

The dysfunction of the nervous system contributes to neuropathic pain. Long noncoding RNAs are reported to participate in neuropathic pain. Recently, Linc00052 is implicated to be closely associated with multiple diseases. Nevertheless, the mechanisms of Linc00052 remain barely explored in neuropathic pain development. Currently, spinal nerve ligation (SNL) triggered neuropathic pain was employed in our investigation. Here, we assessed the function of Linc00052 in SNL rat models. Interestingly, we reported Linc00052 was significantly elevated in SNL rats. Loss of Linc00052 could reduce neuropathic pain progression via regulating the behaviors of neuropathic pain. Additionally, knockdown of Linc00052 repressed the processes of neuroinflammation. Interleukin (IL)-6 and tumor necrosis factor α level were inhibited while IL-10 was induced by the silence of Linc00052. Moreover, we predicted miR-448 can serve as a target of Linc00052. miR-448 exerts a crucial power in several diseases. Currently, we exhibited miR-448 was remarkably downregulated in SNL rats. RNA immunoprecipitation experiments validated the association between miR-448 and Linc00052. Inhibition of Linc00052 could reverse the roles of miR-448 on neuropathic pain development. Furthermore, Janus kinase 1 (JAK1) was displayed as the putative target of miR-448 in the present investigation. It was showed that JAK1 was induced in SNL rats. Loss of miR-448 could dramatically induce the expression of JAK1, which was rescued by knockdown of Linc00052. Taken these together, our study implied that Linc00052 functioned as a novel target of neuropathic pain via sponging miR-448 and regulating JAK1.     

MiR-134-5p attenuates neuropathic pain progression through targeting Twist1

Neuropathic pain is a kind of chronic pain because of dysfunctions of somatosensory nerve system. Recently, many studies have demonstrated that microRNAs (miRs) play crucial roles in neuropathic pain development. This study was designed to investigate the effects of miR-134-5p on the process of neuropathic pain progression in a rat model established by chronic sciatic nerve injury (CCI). First, we observed that miR-134-5p was significantly decreased in CCI rat models. Overexpression of miR-134-5p strongly alleviated neuropathic pain behaviors including mechanical and thermal hyperalgesia. Meanwhile, inflammatory cytokine expression, such as IL-6, IL-1β and TNF-α in CCI rats were greatly repressed by upregulation of miR-134-5p. Twist1 has been widely regarded as a poor prognosis biomarker in diverse diseases. Here, by using bioinformatic analysis, 3′-untranslated region (UTR) of Twist1 was predicted to be a downstream target of miR-134-5p in our study. Here, we found that overexpression of miR-134-5p was able to suppress Twist1 dramatically. Furthermore, it was exhibited that Twist1 was increased in CCI rats time-dependently and Twist1 was inhibited in vivo. Subsequently, downregulation of Twist1 in CCI rats could depress neuropathic pain progression via inhibiting neuroinflammation. In conclusion, our current study indicated that miR-134-5p may inhibit neuropathic pain development through targeting Twist1. Our findings suggested that miR-134-5p might provide a novel therapeutic target for neuropathic pain.     

miR-124-3p attenuates neuropathic pain induced by chronic sciatic nerve injury in rats via targeting EZH2

Emerging evidence has suggested that microRNAs play a critical role in neuropathic pain development. However, the biological role of miRNAs in regulating neuropathic pain remains barely known. In our present study, we found that miR-124-3p was significantly downregulated in rats after chronic sciatic nerve injury (CCI). In addition, it was showed that overexpression of miR-124-3p obviously repressed mechanical allodynia and heat hyperalgesia. Meanwhile, it has been reported that neuroinflammation can contribute a lot to neuropathic pain progression. Here, we found that inflammatory cytokine (IL-6, IL-1β, and TNF-⍺) protein expression in rats after CCI greatly increased and miR-124-3p mimics depressed inflammation cytokine levels. Consistently, miR-124-3p alleviated inflammation production in lipopolysaccharide-incubated spinal microglial cells. Bioinformatics analysis revealed that EZH2 acted as a direct target of miR-124-3p, which participated in the miR-124-3p-modulated effects on neuropathic pain development and neuroinflammation. We observed that miR-124-3p was able to promote neuroinflammation and neuropathic pain through targeting EZH2. The direct correlation between them was validated in our current study using dual-luciferase reporter assays. Subsequently, it was manifested that EZH2 abrogated the inhibitory role of miR-124-3p on neuropathic pain progression in CCI rats. Taken these together, our findings highlighted a novel contribution of miR-124-3p to neuropathic pain and indicated the possibilities for developing novel therapeutic options for neuropathic pain.     

DGCR5 attenuates neuropathic pain through sponging miR-330-3p and regulating PDCD4 in CCI rat models

Neuropathic pain caused by somatosensory nervous system dysfunction is a serious public health problem. Some long noncoding RNAs (lncRNAs) can participate in physiological processes involved in neuropathic pain. However, the effects of lncRNA DGCR5 in neuropathic pain have not been explored. Therefore, in our current study, we concentrated on the biological roles of DGCR5 in neuropathic pain. Here, it was observed that DGCR5 was significantly decreased in chronic sciatic nerve injury (CCI) rat models. DGCR5 overexpression was able to alleviate neuropathic pain development including mechanical and thermal hyperalgesia. In addition, the current understanding of miR-330-3p function in neuropathic pain remains largely incomplete. Here, we found that miR-330-3p was greatly increased in CCI rats and DGCR5 can modulate miR-330-3p expression negatively. Upregulation of DGCR5 repressed inflammation-correlated biomarkers including interleukin 6 (IL-6), tumor necrosis factor α, and IL-1β in CCI rats by sponging miR-330-3p. The negative correlation between DGCR5 and miR-330-3p was confirmed in our current study. Inhibition of miR-330-3p suppressed neuropathic pain progression by restraining neuroinflammation in vivo. In addition, PDCD4 was predicted as a downstream target of miR-330-3p. Furthermore, PDCD4 was significantly increased in CCI rats and DGCR5 regulated PDCD4 expression through sponging miR-330-3p in CCI rat models. Taken these together, it was implied that DGCR5/miR-330-3p/PDCD4 axis participated in neuropathic pain treatment.     

miR-21-5p inhibits neuropathic pain development via directly targeting C-C motif ligand 1 and tissue inhibitor of metalloproteinase-3

MicroRNAs (miRNA) play important roles in neuroinflammation and neuropathic pain development; however, the underlying mechanism requires further investigation. The expression of miR-21-5p was remarkably upregulated in chronic constrictive injury (CCI) rat model. A significant alleviated neuropathic pain development and reduced the expression of cytokines was observed in CCI rat after exogenous injection of miR-21-5p mimic. The dual-luciferase analysis revealed that tissue inhibitor of metalloproteinase-3 (TIMP3) and chemokines C-C motif ligand 1 (CCL1) was direct downstream target of miR-21-5p. Moreover, silencing of TIMP3 and CCL1 could rescue mechanical allodynia, thermal hyperalgesia and cytokine release in CCI rat, suggesting that TIMP3 and CCL1 exert their function by mediating neuroinflammation in neuropathic pain development. Therefore, we have identified a novel miR-21-5p–CCL1/TIMP3-cytokine axis in regulation of neuropathic pain development in CCI rat model, which is valuable for enhancing our understanding of neuropathic pain and developing miRNAs as potential therapeutic options in the future.     

Retracted: MicroRNA-217 relieved neuropathic pain through targeting toll-like receptor 5 expression

Neuropathic pain is the most common chronic pain that is caused by nerve injury or disease that influences the nervous system. Increasing evidence suggested that microRNAs (miRNAs) play a crucial role in neuropathic pain and neuroinflammation development. However, the functional role of miR-217 in the development of neuropathic pain remains unknown. In this study, we used rats to establish a neuropathic pain model and showed that the miR-217 expression level was upregulated in the spinal dorsal horn of bilateral sciatic nerve chronic constriction injury (bCCI). However, the expression of miR-217 was not changed in the anterior cingulated cortex (ACC), hippocampus, and dorsal root ganglion (DRG) of bCCI rats. Ectopic expression of miR-217 attenuated neuropathic pain and suppressed neuroinflammation expression in vivo. We identified toll-like receptor 5 (TLR5) as a direct target gene of miR-217 in the PC12 cell. In addition, we demonstrated that the expression level of TLR5 was upregulated in bCCI rats. Moreover, restoration of TLR5 rescued the inhibitory roles induced by miR-217 overexpression on neuropathic pain and neuroinflammation development. These data suggested that miR-217 played a pivotal role in the development of neuropathic pain partly through regulating TLR5 expression.     

miR-194 relieve neuropathic pain and prevent neuroinflammation via targeting FOXA1

The emerging role of microRNAs (miRNAs) have been deeply explored in multiple diseases including neuropathic pain. miR-194 was widely reported to be a tumor suppressor and was related to the inflammatory response. The critical role of neuroinflammation on neuropathic pain leads to a thinking about the relationship between miR-194 and neuropathic pain. However, the function of miR-194 in neuropathic pain remains unknown. This study was aimed to explore the relationship between miR-194 and neuropathic pain progression by chronic sciatic nerve injury (CCI). miR-194 abnormally downregulated in the CCI model rat and its overexpression significantly alleviates neuroinflammation in vivo. We predict Forkhead box protein A1 (FOXA1) as a direct target of miR-194, whose restoration can markedly reverse the effects of miR-194 on neuropathic pain. Overall, our study demonstrated a novel mechanism of neuropathic pain progression that miR-194 alleviates neuropathic pain via targeting FOXA1 and preventing neuroinflammation by downregulating inflammatory cytokines containing cyclooxygenase 2, interleukin 6 (IL-6), and IL-10 in vivo, which can be reversed by the overexpression of FOXA1.     

Overexpression of miR-98 attenuates neuropathic pain development via targeting STAT3 in CCI rat models

MicroRNA (miRNA) are significant regulators of neuropathic pain development and neuroinflammation can contribute a lot to the progression of neuropathic pain. Recently, miR-98 has been reported to be involved in various diseases. However, little is known about the role of miR-98 in neuropathic pain development and neuroinflammation. Therefore, our study was aimed to investigate the function of miR-98 in neuropathic pain via establishing a rat model using chronic constriction injury (CCI) of the sciatic nerve. Here, we observed that miR-98 was downregulated in CCI rat models. Overexpression of miR-9 was able to inhibit neuropathic pain progression. Recently, STAT3 has been reported to serve a key role in various processes, including inflammation. Interestingly, our study indicated that STAT3 was dramatically upregulated and activated in CCI rats. By using informatics analysis, STAT3 was predicted as a direct target of miR-98 and the direct correlation was confirmed. Then, miR-98 was overexpressed in CCI rats and it was found that miR-98 was able to repress neuropathic pain development via inhibiting the neuroinflammation. As displayed, interleukin 6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) expression was obviously induced in CCI rats, while miR-98 reduced their protein levels. Finally, we found that overexpression of STAT3 reversed the inhibitory effect of miR-98 on neuropathic pain development. Taken these together, we reported that overexpression of miR-98 attenuated neuropathic pain development via targeting STAT3 in CCI rat models.     

Analgesic Activity of Catalpol in Rodent Models of Neuropathic Pain,and Its Spinal Mechanism

Neuropathic pain is a major health issue that represents considerable social and economic burden worldwidely. In this study, we investigated the potential of catalpol, an iridoid glucoside of Rehmannia glutinosa Steud, to alleviate neuropathic pain. The potential analgesic effects of catalpol were evaluated by chronic constriction injury (CCI) and lumbar 5 spinal nerve ligation (L5 SNL) model. In addition, we explored whether catalpol altered the degree of microglia activation and neuroinflammation in rat spinal cord after CCI induction. Repeated administration of catalpol (1, 5, 25, and 125 mg/kg) reversed mechanical allodynia induced by CCI and L5 SNL in a dose-dependent manner in rats. Levels of activated microglia, activated NF-κB, and proinflammatory cytokines (IL-1β, IL-6, TNF-α) in lumber spinal cord were elevated in rats following CCI induction, and catalpol significantly inhibited these effects. Our results demonstrated that catalpol produces significant antinociceptive action in rodent behavioral models of neuropathic pain and that this effect is associated with modulation of neuroinflammation in spinal cord.     

Dendritic cell-derived exosomal miR-3064-5p inhibits SIRT6/PCSK9 to protect the blood-brain barrier after subarachnoid hemorrhage

The protection of the blood-brain barrier (BBB) is the key direction to improving subarachnoid hemorrhage (SAH). Therefore, developing appropriate targeted drugs and therapies has become an urgent task for SAH patients. In this study, we investigated the role of dendritic cells (DCs) exosomal miR-3064-5p in repairing the BBB, providing a new basis for treating SAH. We detected the expression of miR-3064-5p in exosomes secreted by DCs (DCs-exo). An SAH rat model was constructed by intravascular perforation and characterized by HE and TUNEL-IF staining. We found that overexpression of miR-3064-5p in SAH rats suppressed iNOS expression and promoted the accumulation of tight junction proteins (Occludin, Claudin-3, ZO-1), whereas knockdown of miR-3064-5p exerted the opposite effect. Dual-LUC assay confirmed that miR-3064-5p could target and inhibit SIRT6. Knockdown of SIRT6 inhibited inflammatory cytokine (IL-6, IL-1β, IFN-γ, and TGF-β1) levels and apoptosis. The results of the co-IP assay showed that SIRT6 interacted with PCSK9, and knockdown of SIRT6 suppressed the expression of PCSK9. Moreover, DCs-exo reduced brain edema, upregulated miR-3064-5p and downregulated SIRT6 and PCSK9 in SAH rats. DCs-exo reduced inflammatory factors and increased tight junction proteins in SAH rats. Overexpression of miR-3064-5p enhanced the protective effect of DCs-exo, while overexpression of SIRT6 partially counteracted the effect. This study confirmed that DCs could secrete miR-3064-5p to ameliorate BBB damage after SAH. Mechanistically, miR-3064-5p alleviated BBB damage by targeting and inhibiting SIRT6/PCSk9 signaling pathway.     

Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury

Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation.     

CRNDE enhances neuropathic pain via modulating miR-136/IL6R axis in CCI rat models

Neuropathic pain has been reported as a type of chronic pain due to the primary dysfunction of the somatosensory nervous system. It is the most serious types of chronic pain, which can lead to a significant public health burden. But, the understanding of the cellular and molecular pathogenesis of neuropathic pain is barely complete. Long noncoding RNAs (lncRNAs) have recently been regarded as modulators of neuronal functions. Growing studies have indicated lncRNAs can exert crucial roles in the development of neuropathic pain. Therefore, our present study focused on the potential role of the lncRNA Colorectal Neoplasia Differentially Expressed (CRNDE) in neuropathic pain progression. Firstly, a chronic constrictive injury (CCI) rat model was built. CRNDE was obviously increased in CCI rats. Interestingly, overexpression of CRNDE enhanced neuropathic pain behaviors. Neuroinflammation was induced by CRNDE and as demonstrated, interleukin-10 (IL-10), IL-1, IL-6, and tumor necrosis factor-α (TNF-α) protein levels in CCI rats were activated by LV-CRNDE. For another, miR-136 was obviously reduced in CCI rats. Previously, it is indicated that miR-136 participates in the spinal cord injury via an inflammation in a rat model. Here, firstly, we verified miR-136 could serve as CRNDE target. Loss of miR-136 triggered neuropathic pain remarkably via the neuroinflammation activation. Additionally, IL6R was indicated as a target of miR-136 and miR-136 regulated its expression. Subsequently, we confirmed that CRNDE could induce interleukin 6 receptor (IL6R) expression positively. Overall, it was implied that CRNDE promoted neuropathic pain progression via modulating miR-136/IL6R axis in CCI rat models.     

MiR‐150 alleviates neuropathic pain via inhibiting toll‐like receptor 5

MicroRNAs (miRNAs) are reported as vital participators in the pathophysiological course of neuropathic pain. However, the underlying mechanisms of the functional roles of miRNAs in neuropathic pain are largely unknown. This study was designed to explore the potential role of miR‐150 in regulating the process of neuropathic pain in a rat model established by chronic sciatic nerve injury (CCI). Overexpression of miR‐150 greatly alleviated neuropathic pain development and reduced inflammatory cytokine expression, including COX‐2, interleukin IL‐6, and tumor necrosis factor (TNF)‐α in CCI rats. By bioinformatic analysis, 3′‐untranslated region (UTR) of Toll‐like receptor (TLR5) was predicted to be a target of miR‐150. TLR5 commonly serves as an important regulator of inflammation. Overexpression of miR‐150 significantly suppressed the expression of TLR5 in vitro and in vivo. Furthermore, upregulation of TLR5 decreased the miR‐150 expression and downregulation of TLR5 increased miR‐150, respectively. Overexpression of TLR5 significantly reversed the miR‐150‐induced suppressive effects on neuropathic pain. In conclusion, our current study indicates that miR‐150 may inhibit neuropathic pain development of CCI rats through inhibiting TLR5‐mediated neuroinflammation. Our findings suggest that miR‐150 may provide a novel therapeutic target for neuropathic pain treatment.     

Upregulation of miR-183 represses neuropathic pain through inhibiton of MAP3K4 in CCI rat models

Many studies have verified that microRNAs contribute a lot to neuropathic pain progression. Furthermore, nerve-related inflammatory cytokines play vital roles in neuropathic pain progression. miR-183 has been identified to have a common relationship with multiple pathological diseases. However, the potential effects of miR-183 in the process of neuropathic pain remain undetermined. Therefore, we performed the current study with the purpose of finding the functions of miR-183 in neuropathic pain progression using a chronic sciatic nerve injury (CCI) rat model. We demonstrated that miR-183 expression levels were evidently reduced in CCI rats in contrast with the control group. Overexpression of miR-183 produced significant relief of mechanical hyperalgesia, as well as thermal hyperalgesia in CCI rats. Furthermore, neuropathic pain-correlated inflammatory cytokine expression levels containing interleukin-6 (IL-6) and interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) were obviously inhibited by upregulation of miR-183. Meanwhile, dual-luciferase reporter assays showed MAP3K4 was a direct downstream gene of miR-183. The expression levels of MAP3K4 were modulated by the increased miR-183 negatively, which lead to the downregulation of IL-6, IL-1β, and COX-2, and then reduced neuropathic pain progression, respectively. Overall, our study pointed out that miR-183 was a part of the negative regulator which could relieve neuropathic pain by targeting MAP3K4. Thus it may provide a new clinical treatment for neuropathic pain patients clinical therapy.     

Intrathecal Injection of Human Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorates Neuropathic Pain in Rats

Neuropathic pain (NP) is a clinically incurable disease with miscellaneous causes, complicated mechanisms and available therapies show poor curative effect. Some recent studies have indicated that neuroinflammation plays a vital role in the occurrence and promotion of NP and anti-inflammatory therapy has the potential to relieve the pain. During the past decades, mesenchymal stem cells (MSCs) with properties of multipotentiality, low immunogenicity and anti-inflammatory activity have showed excellent therapeutic effects in cell therapy from animal models to clinical application, thus aroused great attention. However there are no reports about the effect of intrathecal human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on NP which is induced by peripheral nerve injury. Therefore, in this study, intrathecally transplanted HUC-MSCs were utilized to examine the effect on neuropathic pain induced by a rat model with spinal nerve ligation (SNL), so as to explore the possible mechanism of those effects. As shown in the results, the HUC-MSCs transplantation obviously ameliorated SNL-induced mechanical allodynia and thermal hyperalgesia, which was related to the inhibiting process of neuroinflammation, including the suppression of activated astrocytes and microglia, as well as the significant reduction of pro-inflammatory cytokines Interleukin-1β (IL-1β) and Interleukin ?17A (IL-17A) and the up-regulation of anti-inflammatory cytokine Interleukin ?10 (IL-10). Therefore, through the effect on glial cells, pro-inflammatory and anti-inflammatory cytokine, the targeting intrathecal HUC-MSCs may offer a novel treatment strategy for NP.     

Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain

Chronic pain states are characterized by long-term sensitization of spinal cord neurons that relay nociceptive information to the brain. Among the mechanisms involved, up-regulation of Cav1.2-comprising L-type calcium channel (Cav1.2-LTC) in spinal dorsal horn have a crucial role in chronic neuropathic pain. Here, we address a mechanism of translational regulation of this calcium channel. Translational regulation by microRNAs is a key factor in the expression and function of eukaryotic genomes. Because perfect matching to target sequence is not required for inhibition, theoretically, microRNAs could regulate simultaneously multiple mRNAs. We show here that a single microRNA, miR-103, simultaneously regulates the expression of the three subunits forming Cav1.2-LTC in a novel integrative regulation. This regulation is bidirectional since knocking-down or over-expressing miR-103, respectively, up- or down-regulate the level of Cav1.2-LTC translation. Functionally, we show that miR-103 knockdown in naive rats results in hypersensitivity to pain. Moreover, we demonstrate that miR-103 is down-regulated in neuropathic animals and that miR-103 intrathecal applications successfully relieve pain, identifying miR-103 as a novel possible therapeutic target in neuropathic chronic pain.     

MiR-183-5p Alleviates Chronic Constriction Injury-Induced Neuropathic Pain Through Inhibition of TREK-1

MicroRNAs have been implicated in nerve injury and neuropathic pain. In the previous study we had shown that miR-96 can attenuate neuropathic pain through inhibition of Nav1.3. In this study, we investigated the role of miR-183, a same cluster member of microRNA with miR-96, in neuropathic pain and its potential mechanisms. We found that the expression level of miR-183-5p in dorsal root ganglion was decreased with the development of neuropathic pain induced by chronic constriction sciatic nerve injury (CCI). By contrast, the TREK-1, a K⁺ channel, was increased. Further investigation identified that intrathecal injection of miR-183-5p mimic efficiently ameliorated neuropathic pain and inhibited the expression of TREK-1, a predicted target gene of miR-183-5p. Luciferase assays confirmed the binding of miR-183-5p and TREK-1. In addition, over-expression of TREK-1 blocked the roles of miR-183-5p in neuropathic pain. Our findings suggested that miR-183-5P participated in the regulation of CCI-induced neuropathic pain through inhibiting the expression of TREK-1.     

The rate and magnitude of atmospheric pressure change that aggravate pain-related behavior of nerve injured rats

Complaints of patients with chronic pain may increase when the weather changes. The exact mechanism for weather change-induced pain has not been clarified. We have previously demonstrated that artificially lowering barometric pressure (LP) intensifies pain-related behaviors in rats with neuropathic pain [chronic constriction injury (CCI) and spinal nerve ligation (SNL)]. In the present study, we examined the rate and magnitude of LP that aggravates neuropathic pain. We measured pain-related behaviors [number of paw lifts to von Frey hair (VFH) stimulation] in awake rats after SNL or CCI surgery, and found that rates of decompression ≥5 hPa/h and ≥10 hPa/h and magnitudes of decompression ≥5 hPa and ≥10 hPa augmented pain-related behaviors in SNL and CCI rats, respectively. These results indicate that LP within the range of natural weather patterns augments neuropathic pain in rats, and that SNL rats are more sensitive to LP than CCI rats.