Suppression of P2X3 receptor‐mediated currents by the activation of α2A‐adrenergic receptors in rat dorsal root ganglion neurons

AimsThe α₂‐adrenergic receptor (α₂‐AR) agonists have been shown to be effective in the treatment of various pain. For example, dexmedetomidine (DEX), a selective α_2A‐AR agonist, can be used for peripheral analgesia. However, it is not yet fully elucidated for the precise molecular mechanisms. P2X3 receptor is a major receptor processing nociceptive information in primary sensory neurons. Herein, we show that a functional interaction of α_2A‐ARs and P2X3 receptors in dorsal root ganglia (DRG) neurons could contribute to peripheral analgesia of DEX.MethodsElectrophysiological recordings were carried out on rat DRG neurons, and nociceptive behavior was quantified in rats.ResultsThe activation of α_2A‐ARs by DEX suppressed P2X3 receptor‐mediated and α,β‐methylene‐ATP (α,β‐meATP)‐evoked inward currents in a concentration‐dependent and voltage‐independent manner. Pre‐application of DEX shifted the α,β‐meATP concentration‐response curve downwards, with a decrease of 50.43 ± 4.75% in the maximal current response of P2X3 receptors to α,β‐meATP in the presence of DEX. Suppression of α,β‐meATP‐evoked currents by DEX was blocked by the α_2A‐AR antagonist BRL44408 and prevented by intracellular application of the G_i/o protein inhibitor pertussis toxin, the adenylate cyclase activator forskolin, and the cAMP analog 8‐Br‐cAMP. DEX also suppressed α,β‐meATP‐evoked action potentials through α_2A‐ARs in rat DRG neurons. Finally, the activation of peripheral α_2A‐ARs by DEX had an analgesic effect on the α,β‐meATP‐induced nociception.ConclusionsThese results suggested that activation of α_2A‐ARs by DEX suppressed P2X3 receptor‐mediated electrophysiological and behavioral activity via a G_i/o proteins and cAMP signaling pathway, which was a novel potential mechanism underlying analgesia of peripheral α_2A‐AR agonists.     

Role of hesperidin in P2X3 receptor-mediated neuropathic pain in the dorsal root ganglia

Aim: This study investigated whether the neuronal P2X3 receptor in rat dorsal root ganglia (DRG) mediated the effects of hesperidin on neuropathic pain.

Materials and methods: The chronic constriction injury (CCI) model was used as a model of neuropathic pain. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured. The mRNA and protein expression levels were assayed by real-time RT-PCR and Western blotting.

Results: The results showed that mechanical and thermal hyperalgesia in the CCI rats were increased as compared to those in the sham group. The expression levels of P2X3 mRNA and protein in CCI rats were higher than those in the sham group. Dual-labelling immunofluorescence showed that the elevated P2X3 receptor was co-expressed with the neuronal marker NeuN in the DRG of CCI rats. Hesperidin treatment decreased both the mechanical and thermal hyperalgesia, and upregulated P2X3 expression in the CCI rats. Hesperidin treatment also reduced the ERK1/2 phosphorylation in the DRG of CCI rats. Moreover, hesperidin inhibited the P2X3 agonist ATP-induced currents in HEK293 cells transfected with the P2X3 plasmid. Therefore, hesperidin treatment could reverse the elevated expression of neuronal P2X3 receptor and reduce the activation of ERK1/2 in the DRG of CCI rats.

Conclusions: Our findings suggested that hesperidin inhibited the nociceptive transmission mediated by the P2X3 receptor in neurons of DRG, and thus, relieved the mechanical and thermal hyperalgesia in CCI rats.     

Mechanism of interleukin-1 beta-induced calcitonin gene-related peptide production from dorsal root ganglion neurons of neonatal rats

Calcitonin gene-related peptide (CGRP) is synthesized in dorsal root ganglion (DRG) neurons and released from primary afferent neurons to mediate hemodynamic effects and neurogenic inflammation. The effect of the proinflammatory cytokine interleukin-1 (IL-1)-beta on CGRP release from these sensory neurons was investigated. The results showed that IL-1beta (1 ng/ml) could directly induce CGRP release following prolonged incubation (24 hr) with these neurons. Treatment with IL-1beta (0.1-1.0 ng/ml) significantly increased CGRP release in a concentration-dependent manner. In addition, pretreatment of DRG cells with actinomycin D at 1 microM or cyclohexamide at 10 microM for 30 min inhibited 1 ng/ml IL-1beta-induced CGRP release in DRG neurons of neonatal rats. The inhibitors of PKC, JNK MAPK and NF-kappaB, but not p38 or ERK1/2 MAPK, blocked IL-1beta-induced CGRP release. RNase protection assay showed that IL-1beta could cause alpha-CGRP mRNA increase in a time- and concentration-dependent manner, although the level of beta-CGRP mRNA was not affected. These results indicate that IL-1beta may activate PKC, which in turn initiates JNK MAPK and activates NF-kappaB and finally induces alpha-CGRP gene expression and release from these sensory neurons.     

去甲肾上腺素对背根神经节神经元P物质释放的调节作用(英文)

目的观察激活或抑制α-肾上腺素受体是否影响体外培养的背根神经节(dorsal root ganglion,DRG)神经元P物质(substance P,SP)的释放。方法胎龄15天的Wistar大鼠DRG神经元培养2天后,分别用去甲肾上腺素(nora-drenaline,NA)(1×10-4mol/L)、α1-受体拮抗剂哌唑嗪(1×10-6mol/L)+NA(1×10-4mol/L)、α2-受体拮抗剂育亨宾(1×10-5mol/L)+NA(1×10-4mol/L)孵育4天。用RT-PCR法检测DRG神经元编码SP蛋白的PPTmRNA表达水平,用Western blot法检测DRG神经元SP蛋白的表达水平,用酶联免疫吸附测定法检测SP的基础释放量和辣椒素刺激后的释放量。结果 NA单独孵育显著增加了DRG神经元辣椒素刺激后的SP释放量,α1-受体拮抗剂哌唑嗪预处理可阻断NA的效应,而α2-受体拮抗剂育亨宾不产生此作用。在各种实验条件下,PPT mRNA水平、SP蛋白表达水平和SP的基础释放量没有显著性差异。结论 NA通过激活α1-受体增加了DRG神经元辣椒素刺激后的SP释放量,这一作用可能与去甲肾上腺素能的疼痛调...     

Potentiation of the P2X3 ATP receptor by PAR-2 in rat dorsal root ganglia neurons, through protein kinase-dependent mechanisms, contributes to inflammatory pain

Proinflammatory agents trypsin and mast cell tryptase cleave and activate protease-activated receptor-2 (PAR-2), which is expressed on sensory nerves and causes neurogenic inflammation. P2X3 is a subtype of the ionotropic receptors for adenosine 5'-triphosphate (ATP), and is mainly localized on nociceptors. Here, we show that a functional interaction of the PAR-2 and P2X3 in primary sensory neurons could contribute to inflammatory pain. PAR-2 activation increased the P2X3 currents evoked by α, β, methylene ATP in dorsal root ganglia (DRG) neurons. Application of inhibitors of either protein kinase C (PKC) or protein kinase A (PKA) suppressed this potentiation. Consistent with this, a PKC or PKA activator mimicked the PAR-2-mediated potentiation of P2X3 currents. In the in vitro phosphorylation experiments, application of a PAR-2 agonist failed to establish phosphorylation of the P2X3 either on the serine or the threonine site. In contrast, application of a PAR-2 agonist induced trafficking of the P2X3 from the cytoplasm to the plasma membrane. These findings indicate that PAR-2 agonists may potentiate the P2X3, and the mechanism of this potentiation is likely to be a result of translocation, but not phosphorylation. The functional interaction between P2X3 and PAR-2 was also confirmed by detection of the α, β, methylene-ATP-evoked extracellular signal-regulated kinases (ERK) activation, a marker of neuronal signal transduction in DRG neurons, and pain behavior. These results demonstrate a functional interaction of the protease signal with the ATP signal, and a novel mechanism through which protease released in response to tissue inflammation might trigger the sensation to pain through P2X3 activation.     

Regulation of chick dorsal root ganglion growth cone filopodia by protein kinase C

Growth cone filopodia function both as structural and sensory devices during neuronal pathfinding and their presence is important for correct growth cone navigation. It is assumed that a growth cone can adjust the area of the environment it can explore by regulating the length and number of its filopodial sensors, and in several cell types, these parameters are controlled by the intracellular calcium concentration ([Ca(2+)](i)). In the present report, we address the question whether [Ca(2+)](i) is a general regulator of growth cone filopodia, or whether different cell types utilize different second-messenger systems for this purpose. We show that increasing [Ca(2+)](i) in growth cones of chick dorsal root ganglion (DRG) neurons does not affect average filopodial length in this cell type, suggesting that this parameter is not controlled by [Ca(2+)](i) in chick DRG neurons. Further, we demonstrate that the second-messenger protein kinase C (PKC) is involved in the regulation of filopodial length in chick DRG neurons. Activation of PKC with the phorbol ester, phorbol myristate-13-acetate (PMA), caused filopodial shortening, whereas inhibition of PKC with either bisindolylmaleimide I or calphostin C caused a significant elongation of filopodia. Although the pathway through which PKC mediates its effect on growth cone filopodia in chick DRG neurons remains to be identified, our results indicate that filopodial regulation by [Ca(2+)](i), though clearly important in several other neuronal cell types in vitro, appears to be less important in chick DRG neurons. Rather, we find that in chick DRG neurons, filopodial parameters are controlled by PKC.     

Role of puerarin in the signalling of neuropathic pain mediated by P2X3 receptor of dorsal root ganglion neurons

Tissue injury or inflammation of the nervous system may result in chronic neuropathic pain characterized by sensitivity to painful stimuli. P2X₃ receptors play a crucial role in facilitating pain transmission. Puerarin is an active compound of a traditional Chinese medicine Ge-gen, and Ge-gen soup has anti-inflammatory effects. The present research investigated the role of puerarin in the signalling of chronic neuropathic pain mediated by P2X₃ receptors of rat dorsal root ganglion neurons. Chronic constriction injury (CCI) rat model was adopted. Sprague-Dawley rats were randomly divided into blank control group (Ctrl), sham group (Sham), puerarin-treated control group (Ctrl + PUE), chronic constriction injury (CCI) group and puerarin-treated CCI group (CCI + PUE). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by the von-Frey test and the Hargreaves’ test respectively. The stain values of P2X₃ protein and mRNA in L4/L5 dorsal root ganglion (DRG) were detected by immunohistochemistry, western blot and in situ hybridization. At day 4-7 after the operation of CCI rats, MWT and TWL in group CCI and CCI + PUE were lower than those in group Ctrl, Sham and Ctrl + PUE, while there was no difference among group Ctrl, Sham and Ctrl + PUE. At day 7-10 after operation, MWT and TWL in group CCI + PUE was higher than those in group CCI, but there was no significant difference between group CCI + PUE and group Ctrl (p > 0.05). At day 14 after operation, the stain values of P2X₃ proteins and mRNAs in L4/L5 DRG of group CCI were higher than those in group Ctrl, Sham, Ctrl + PUE and CCI + PUE, while the stain values of P2X₃ proteins and mRNAs in group CCI + PUE were significantly decreased compared with those in group CCI. Therefore, puerarin may alleviate neuropathic pain mediated by P2X₃ receptors in dorsal root ganglion neurons.     

Plasticity of developing and adult dorsal root ganglion neurons as revealed in vitro

We review recent data on the plasticity of dorsal root ganglion (DRG) neurons as revealed during cultivation in vitro. Some experiments on cultured developing DRG neurons and on adult DRG neurons in vivo are also mentioned. Cultured developing and adult DRG neurons can be switched from an apolar to a multipolar phenotype by fetal calf serum or fibronectin. The effect is concentration dependent and occurs through an early modification of cell-substratum interaction. Adult DRG neurons synthesize and release within hours after injury TGFβ-1, which is a mitogen and a differentiation factor for Schwann cells. Finally, adult DRG neurons express in vitro neurotransmitters that are not expressed in vivo. This neurotransmitter plasticity can be modulated in vitro by some growth factors and in vivo by distal or proximal axotomy.     

Exogenous brain-derived neurotrophic factor relieves pain symptoms of diabetic rats by reducing excitability of dorsal root ganglion neurons

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes lacking of effective treatments. Enhanced excitability of dorsal root ganglion (DRG) neuron plays a crucial role in the progression of diabetic neuropathic hyperalgesia. Brain-derived neurotrophic factor (BDNF) is known as a neuromodulator of nociception, but whether and how BDNF modulates the excitability of DRG neurons in the development of DPN remain to be clarified. This study investigated the role of exogenous BDNF and its high-affinity tropomyosin receptor kinase B (TrkB) in rats with streptozotocin-induced diabetic neuropathic pain. The results showed that continued intrathecal administration of BDNF to diabetic rats dramatically alleviated mechanical and thermal hyperalgesia, as well as inhibited hyperexcitability of DRG neurons. These effects were blocked by pretreatment with TrkB Fc (a synthetic fusion protein consisting of the extracellular ligand-binding domain of the TrkB receptor). The expression of BDNF and TrkB was upregulated in the DRG of diabetic rats. Intrathecal administration of BDNF did not affect this upregulation. These data provide novel information that exogenous BDNF relieved pain symptoms of diabetic rats by reducing hyperexcitability of DRG neurons and might be the potential treatment of painful diabetic neuropathy.     

神经生长因子对培养的大鼠背根神经节神经元P物质释放的调节作用

目的观察神经生长因子（nerve growth factor, NGF）对原代培养的背根神经节（dorsal root ganglion, DRG）神经元中P物质（substance P, SP）的基础释放量和辣椒素诱发释放量的调节效应。方法将15 天胚龄的Wistar大鼠DRG神经元培养于含有不同浓度NGF的DMEM/F12培养液中,不含NGF的培养液培养的神经元作为对照。72小时后,用RT-PCR检测神经元中SP mRNA和辣椒素受体（vanilloid receptor 1, VR1）mRNA的表达,用放射免疫分析（radioimmunoassay,RIA）法检测SP的基础释放量和辣椒素（100 nmol/L）刺激10 min后的诱发释放量。结果SPmRNA和VR1 mRNA在NGF孵育的标本中表达增加,并与孵育液中NGF的浓度呈剂量依赖关系。SP的基础释放量和辣椒素诱发释放量在NGF孵育的标本中均增加,而且诱发释放量与NGF的浓度呈剂量依赖关系。结论NGF使DRG神经元SP的基础释放量和诱发释放量增加,表明NGF能增加初级传入神经元感受伤害刺激的敏感性,该效应可能与SP和VR1的mRNA表达增加有关。     

神经生长因子对培养的大鼠背根神经节神经元P物质释放的调节作用(英文)

目的观察神经生长因子(nerve growth factor, NGF)对原代培养的背根神经节(dorsal root ganglion, DRG)神经元中P物质(substance P, SP)的基础释放量和辣椒素诱发释放量的调节效应。方法将15 天胚龄的Wistar大鼠DRG神经元培养于含有不同浓度NGF的DMEM/F12培养液中,不含NGF的培养液培养的神经元作为对照。72小时后,用RT-PCR检测神经元中SP mRNA和辣椒素受体(vanilloid receptor 1, VR1)mRNA的表达,用放射免疫分析(radioimmunoassay,RIA)法检测SP的基础释放量和辣椒素(100 nmol/L)刺激10 min后的诱发释放量。结果SPmRNA和VR1 mRNA在NGF孵育的标本中表达增加,并与孵育液中NGF的浓度呈剂量依赖关系。SP的基础释放量和辣椒素诱发释放量在NGF孵育的标本中均增加,而且诱发释放量与NGF的浓度呈剂量依赖关系。结论NGF使DRG神经元SP的基础释放量和诱发释放量增加,表明NGF能增加初级传入神经元感受伤害刺激的敏感性,该效应可能与SP和VR1的mRNA表达增加有关。     

Neurokinin 2 receptor-mediated activation of protein kinase C modulates capsaicin responses in DRG neurons from adult rats

Patch-clamp techniques and Ca2+ imaging were used to examine the interaction between neurokinins (NK) and the capsaicin(CAPS)-evoked transient receptor potential vanilloid receptor 1 (TRPV1) responses in rat dorsal root ganglia neurons. Substance P (SP; 0.2-0.5 microM) prevented the reduction of Ca2+ transients (tachyphylaxis) evoked by repeated brief applications of CAPS (0.5 microM). Currents elicited by CAPS were increased in amplitude and desensitized more slowly after administration of SP or a selective NK2 agonist, [Ala8]-neurokinin A (4-10) (NKA). Neither an NK1-selective agonist, [Sar9, Met11]-SP, nor an NK3-selective agonist, [MePhe7]-NKB, altered the CAPS currents. The effects of SP on CAPS currents were inhibited by a selective NK2 antagonist, MEN10,376, but were unaffected by the NK3 antagonist, SB 235,375. Phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C(PKC), also increased the amplitude and slowed the desensitization of CAPS responses. Phosphatase inhibitors, decamethrin and alpha-naphthyl acid phosphate (NAcPh), also enhanced the currents and slowed desensitization of CAPS currents. Facilitatory effects of SP, NKA and PDBu were reversed by bisindolylmaleimide, a PKC inhibitor, and gradually decreased in magnitude when the agents were administered at increasing intervals after CAPS application. The decrease was partially prevented by prior application of NAcPh. These data suggest that activation of NK2 receptors in afferent neurons leads to PKC-induced phosphorylation of TRPV1, resulting in sensitization of CAPS-evoked currents and slower desensitization. Thus, activation of NK2 autoreceptors by NKs released from the peripheral afferent terminals or by mast cells during inflammatory responses may be a mechanism that sensitizes TRPV1 channels and enhances afferent excitability.     

Downregulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain

There is large variability in the various pain responses including those to tissue injury among inbred mouse strains. However, the determinant factors for the strain-specific differences remain unknown. The P2X3 sensory-specific ATP-gated channel has been implicated as a damage-sensing molecule that evokes a pain sensation by receiving endogenous ATP from injured tissue. In this study, to clarify the contribution of the sensory P2X3 signalling to strain-specific differences in tissue injury pain, we examined whether the P2X3-mediated in vivo and in vitro responses in dorsal root ganglion (DRG) neurons are changed in the A/J inbred mouse strain, which is known to be resistant to tissue injury pain caused by formalin. Here we found that A/J mice exhibited a low magnitude of nocifensive behaviour induced by the P2X agonist alpha,beta-methylene ATP (alpha beta meATP) into the hindpaw compared with C57BL/6 J mice. This behaviour was blocked by P2X3 antisense oligodeoxynucleotides. The low magnitude of the in vivo pain sensation could be observed similarly in the in vitro response; the increase in the intracellular Ca(2+) increase by alpha beta meATP in capsaicin-sensitive DRG neurons from A/J mice was significantly lower than that from C57BL/6 J mice. In A/J DRG neurons the P2X3 protein level was significantly lower compared with C57BL/6 J DRG neurons. The change in P2X3 protein was selective because P2X2 protein was expressed equally in both strains. The present study suggests that the downregulation of sensory P2X3 could be one of the molecular predispositions to low sensitivity to tissue injury pain in the A/J inbred mouse strain.     

育亨宾对慢性压迫背根节神经元自发放电的兴奋作用

采用离体灌流背根节 (dorsalrootganglion ,DRG)和单纤维记录神经元自发放电的方法 ,观察到育亨宾对受损DRG神经元的自发放电呈现兴奋作用 ,并初步研究了其发生机制。用外源性育亨宾 (10 μmol/L)灌流损伤的DRG时 ,在 2 2个有自发放电的DRG神经元中 ,有 18个神经元产生明显反应。育亨宾对损伤神经元自发放电的兴奋作用 ,可被α1 肾上腺素能受体拮抗剂哌唑嗪 (5 μmol/L)明显阻断。用 6 羟多巴胺化学性交感神经切断和胍乙啶耗竭交感末梢后 ,育亨宾的兴奋作用均明显减小。结果表明 :育亨宾阻断交感节后神经末梢上的α2 肾上腺素能受体 ,引起去甲肾上腺素 (norepinephrine,NE)的释放 ;释放的NE作用于损伤DRG神经元上的α1 肾上腺素能受体 ,而对受损神经元自发放电呈现兴奋作用。提示交感节后神经末梢可能存在一种持续性抑制NE释放的新机制 ,这种抑制作用不依赖交感节后神经节和动作电位的存在     

Myocardial ischemic nociceptive signaling mediated by P2X3 receptor in rat stellate ganglion neurons

Adenosine 5'-triphosphate (ATP) is implicated in peripheral pain signaling through activation of P2X receptors. P2X(3) receptors have a high level of expression in, and selective location on sensory afferents. P2X receptors, particularly the P2X(3) subtype, are identified as targets for novel analgesics. The stellate ganglion (SG) is peripheral sympathetic ganglia involved in heart function. Surgical interventions of sympathetic afferent pathways abolish or relieve angina pectoris, so it is showed that cardiac pain is mediated by the activation of afferents in sympathetic nerves. The cervicothoracic sympathetic ganglia, including the stellate ganglion, are implicated in sensations associated with myocardial ischemia or cardiac pain. In the present study we have examined P2X(3) involvement in cardiac nociceptive transmission. P2X receptor agonists activated currents (I(ATP)) in SG neurons. The I(ATP) amplitude and P2X(3) mRNA expression in myocardial ischemic injury group were much larger than those obtained in control group. Prostaglandin E(2) (PGE(2)) and substance P (SP) increased ATP-activated currents. P2X(3) receptor antagonist A-317491 reduced P2X agonist activated currents and P2X(3) mRNA expression. The results revealed that the myocardial ischemia induced the upregulation of P2X(3) receptor in function and morphous and P2X(3) receptor antagonist A-317491 inhibited P2X agonist activated currents and P2X(3) mRNA expression. The facts indicated that P2X(3) receptor in SG neurons was involved in cardiac nociceptive transmission.     

Inhibition of acid‐sensing ion channels by levo‐tetrahydropalmatine in rat dorsal root ganglion neurons

Levo‐tetrahydropalmatine (l‐THP), a main bioactive Chinese herbal constituent from the genera Stephania and Corydalis, has been in use in clinical practice for years in China as a traditional analgesic agent. However, the mechanism underlying the analgesic action of l‐THP is poorly understood. This study shows that l‐THP can exert an inhibitory effect on the functional activity of native acid‐sensing ion channels (ASICs), which are believed to mediate pain caused by extracellular acidification. l‐THP dose dependently decreased the amplitude of proton‐gated currents mediated by ASICs in rat dorsal root ganglion (DRG) neurons. l‐THP shifted the proton concentration–response curve downward, with a decrease of 40.93% ± 8.45% in the maximum current response to protons, with no significant change in the pH_0.5 value. Moreover, l‐THP can alter the membrane excitability of rat DRG neurons to acid stimuli. It significantly decreased the number of action potentials and the amplitude of the depolarization induced by an extracellular pH drop. Finally, peripherally administered l‐THP inhibited the nociceptive response to intraplantar injection of acetic acid in rats. These results indicate that l‐THP can inhibit the functional activity of ASICs in dissociated primary sensory neurons and relieve acidosis‐evoked pain in vivo, which for the first time provides a novel peripheral mechanism underlying the analgesic action of l‐THP. © 2014 Wiley Periodicals, Inc.     

PKC在角叉菜胶致炎引起的脊髓背角神经元敏感化中的作用

组织损伤或炎症引起的脊髓背角神经元兴奋性的变化同痛觉过敏、痛觉超敏、自发痛等病理过程密切相关。本实验大鼠足底注射角叉菜胶后 ,脊髓背角神经元发生敏感化 ,自发放电及对伤害性刺激的诱发反应明显增强。背角局部经微透析给予蛋白激酶 C(PKC)非特异性抑制剂氯丙嗪 (CPZ)或特异性抑制剂 H- 7后 ,自发及诱发反应均明显回降 ,提示 PKC激活参与中枢敏感化的形成与维持     

Electroacupuncture diminishes P2X2 and P2X3 purinergic receptor expression in dorsal root ganglia of rats with visceral hypersensitivity

Electroacupuncture at Shangjuxu (ST37) and Tianshu (ST25) can improve visceral hypersensitivity in rats. Colorectal distension was used to establish a rat model of chronic visceral hypersensitivity. Immunohistochemistry was used to detect P2X2 and P2X3 receptor expression in dorsal root ganglia from rats with chronic visceral hypersensitivity. Results demonstrated that abdominal withdrawal reflex scores obviously increased following establishment of the model, indicating visceral hypersensitivity. Simultaneously, P2X2 and P2X3 receptor expression increased in dorsal root ganglia. After bilateral electroacupuncture at Shangjuxu and Tianshu, abdominal withdrawal reflex scores and P2X2 and P2X3 receptor expression decreased in rats with visceral hypersensitivity. These results indicated that electroacupuncture treatment improved visceral hypersensitivity in rats with irritable bowel syndrome by reducing P2X2 and P2X3 receptor expression in dorsal root ganglia.