炎调方对脓毒症急性肺损伤大鼠肺组织热休克蛋白70 mRNA和p38丝裂原活化蛋白激酶的影响

目的 探讨炎调方对脓毒症急性肺损伤（ALI）大鼠肺组织热休克蛋白70（HSP70）mRNA和p38丝裂原活化蛋白激酶（p38 MAPK）的调控作用。方法 将清洁级健康雄性SD大鼠随机分为假手术组、模型组、炎调方（生药量9.9 g/kg）组、谷氨酰胺组、槲皮素组,采用盲肠结扎穿孔术法（CLP）建立脓毒症ALI模型。观察大鼠一般状况,各组分别于术后4、6、8、10、12、18、24 h采集肺组织标本,HE染色观察肺组织病理学改变;实时荧光定量PCR法检测肺组织HSP70 mRNA的表达水平;Western Blotting法检测肺组织p38 MAPK的蛋白表达水平。结果 炎调方组、谷氨酰胺组大鼠与模型组比较,术后不同时间点的精神状态、活动量等明显好转,可见少量稀便;肺组织损伤程度明显减轻,腔内出血较少,肺实变较轻。炎调方组不同时间点的肺组织HSP70 mRNA表达水平显著高于假手术组、模型组（除24 h时间点外）、槲皮素组（P<0.01）,在8、12、18、24 h时间点显著低于谷氨酰胺组（P<0.01）;炎调方组不同时间点的肺组织p38 MAPK的蛋白表达量显著低于模型组、槲皮素组（P<0.01）,在4、6、10 h时间点明显低于谷氨酰胺组（P<0.05、0.01）。结论 炎调方可通过上调肺组织HSP70 mRNA的表达,下调肺组织p38 MAPK的蛋白表达,改善肺组织损伤,对脓毒症ALI发挥保护作用。     

炎调方对脓毒症急性肺损伤大鼠肺组织髓过氧化物酶和丙二醛水平的影响

目的 观察炎调方对脓毒症急性肺损伤(ALI)大鼠肺组织髓过氧化物酶(MPO)、丙二醛(MDA)水平的影响。方法 清洁级健康雄性SD大鼠随机分为对照组、假手术组、模型组、炎调方组、地塞米松组,炎调方组ig 9.9 g/kg炎调方,地塞米松组ig 0.45 mg/kg地塞米松,每天给药1次,连续给药3 d。末次ig 2 h后采用盲肠结扎穿孔术(CLP)制备脓毒症ALI模型,分别于造模后24 h处死动物,进行肺组织HE染色,测定各组大鼠湿/干重比(W/D),肺组织MPO、MDA水平。结果 模型组大鼠肺组织损伤程度、MPO及MDA水平较对照组及假手术组显著增高(P<0.01),炎调方组、地塞米松组肺组织损伤程度、MPO及MDA水平较模型组显著降低(P<0.05、0.01)。结论 炎调方可有效减轻脓毒症ALI大鼠的炎症及氧化应激反应。     

血必净注射液静脉和口服给药防治脓毒症药效特点研究

目的 比较血必净注射液（XBJ）iv和ig给药防治脓毒症的药效特点，为XBJ口服创新中药研发提供参考。方法 采用盲肠结扎穿孔（CLP）法制备大鼠脓毒症模型，ip脂多糖（LPS）法制备小鼠脓毒症模型，分别于造模后0、12、24、36、48、60 h利用iv和ig 2种方式给予XBJ（4 mL·kg^-1），比较2种给药方式对脓毒症模型动物死亡率的影响；通过肺湿质量/干质量、肺组织炎症因子——肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）水平测定，比较2种给药方式对LPS诱导脓毒症急性肺损伤（ALI）的影响；通过HE染色、FITC透过实验考察2种给药方式对LPS诱导脓毒症小鼠肠屏障功能的影响。结果 与模型组比较，XBJ iv和ig给药均可降低脓毒症实验动物死亡率，在CLP大鼠模型中，iv给药效果优于ig给药，而在LPS小鼠模型中，ig给药效果优于iv给药。与模型组比较，XBJ ig组和XBJ iv组小鼠的肺湿质量/干质量显著降低（P＜0.05）；XBJ iv组肺组织中TNF-α、IL-1β水平显著降低（P＜0.01、0.001），XBJ ig组肺组织中TNF-α水平显著降低（P＜0.001）；LPS造模后6、12 h，XBJ ig组小鼠血清FITC浓度显著降低（P＜0.05、0.01），XBJ iv组小鼠血清FITC浓度无明显变化；XBJ ig较XBJ iv具有更优改善脓毒症小鼠回肠病理改变的作用。结论 XBJ iv和ig给药均对脓毒症有明确的治疗作用，iv给药具有保护脓毒症ALI的药效特点，而ig给药具有改善脓毒症肠屏障功能障碍的药效特点。     

基于NF-κB信号通路研究前列闭尔通栓对大鼠慢性非细菌性前列腺炎的影响

目的 探讨前列闭尔通栓对自身免疫性前列腺炎（EAP）大鼠的影响及作用机制。方法 50只SD大鼠采用前列腺蛋白提纯液联合完全弗氏佐剂制备EAP大鼠模型，另取10只作为对照组，造模成功大鼠随机分为模型组、前列通栓（0.42 g·只^-1）组和前列闭尔通栓低、中、高剂量（0.33、0.66、0.99 g·只^-1）组，直肠给药28 d。压力换能器测定膀胱内压变化速率，显微镜计数测定前列腺液中卵磷脂小体、白细胞数量，ELISA法检测前列腺组织炎症因子，HE染色观察前列腺组织病理变化，Westernblotting检测前列腺组织核因子κB（NF-κB）p65、磷酸化κB抑制因子激酶（p-IKK-α）/IKK-α、肿瘤坏死因子-α（TNF-α）、磷酸化IκB激酶-α（p-IκB-α）/IκB-α、环氧化酶-2（COX-2）蛋白表达；实时荧光定量PCR（qRT-PCR）法检测重组人趋化因子配体5（CXCL5）、白细胞介素-6（IL-6）、TNF-α、COX-2基因表达。结果 与对照组比较，模型组大鼠膀胱内压变化速率显著降低（P<0.01）；白细胞数量显著增加、卵磷脂小体数量显著减少（P<0.01）；前列腺组织TNF-α、IL-8水平显著升高（P<0.01），IL-10水平显著降低（P<0.01）；前列腺组织炎症反应明显，病理评分显著升高（P<0.01）；前列腺组织NF-κB p65、p-IKK-α、p-IκB-α、TNF-α、COX-2蛋白表达显著升高（P<0.05、0.01）；前列腺组织CXCL5、COX-2、TNF-α基因表达升高（P<0.05）。与模型组比较，前列闭尔通栓中剂量组膀胱内压变化速率显著升高（P<0.01）；各剂量组白细胞数量显著减少、卵磷脂小体数量显著增加（P<0.01）；中、高剂量组TNF-α、IL-8水平显著降低（P<0.05、0.01）；各剂量组前列腺组织炎症反应明显减轻，病理评分显著降低（P<0.01）；各剂量组前列腺组织p-IκBα/IκBα、COX-2蛋白表达显著降低（P<0.01）；低剂量组前列腺组织p-IKK-α/IKK-α蛋白表达显著降低（P<0.05）；低、高剂量组前列腺组织NF-κB p65蛋白表达显著降低（P<0.05）；中剂量组前列腺组织TNF-α蛋白表达显著降低（P<0.05） ；各剂量组前列腺组织CXCL5、IL-6、COX-2基因表达显著降低（P<0.05）。结论 前列闭尔通栓可有效改善EAP大鼠前列腺组织病理形态，减轻炎症反应，其作用机制可能与抑制NF-κB信号通路相关蛋白NF-κB p65、p-IKK-α、TNF-α、p-IκB-α表达相关。     

金合欢素对糖尿病肾病大鼠肾损伤及TLR4/NF-κB信号通路的影响

目的 探讨金合欢素对糖尿病肾病（DN）大鼠肾损伤及Toll样受体4（TLR4）/核因子-κB（NF-κB）信号通路的影响。方法 通过高脂高糖饲料喂养及ip链脲佐菌素（STZ）建立DN大鼠模型,将造模成功的大鼠随机分为模型组,金合欢素低、高剂量（40、80 mg ·kg^-1）组,金合欢素（80 mg ·kg^-1）＋脂多糖（LPS,0.1 mg ·kg^-1）组,缬沙坦（20 mg ·kg^-1）组,每组10只,并以正常喂养且不ip STZ的10只大鼠作为对照组。干预结束后,尾静脉取血,检测大鼠空腹血糖含量;收集大鼠24 h尿液,分析尿蛋白含量;腹部主动脉取血,ELISA法检测血清中血肌酐、血尿素氮水平及肿瘤坏死因子-α （TNF-α）、白细胞介素-6（IL-6）水平;分离双肾组织,透射电镜及HE染色检测肾组织损伤情况;Western blotting检测Toll样受体4（TLR4）/核因子-κB（NF-κB）通路相关蛋白表达。结果 与对照组比较,模型组肾组织严重受损,血糖、尿蛋白、血肌酐、血尿素氮、血清TNF-α和IL-6水平、肾组织TLR4和p-NF-κB p65/NF-κB p65蛋白表达显著增加（P<0.05）;与模型组比较,缬沙坦和金合欢素低、高剂量组肾组织损伤得到缓解,血糖、尿蛋白、血肌酐、血尿素氮、血清TNF-α和IL-6水平、肾组织TLR4和p-NF-κB p65/NF-κB p65蛋白表达显著降低（P<0.05）;与金合欢素高剂量组相比,金合欢素＋LPS组肾组织损伤加剧,血糖、尿蛋白、血肌酐、血尿素氮、血清TNF-α和IL-6水平、肾组织TLR4和p-NF-κB p65/NF-κB p65蛋白表达显著增加（P<0.05）。结论 金合欢素通过抑制TLR4/NF-κB信号通路改善DN大鼠肾损伤。     

基于网络药理学和实验验证探讨升降散治疗急性肺损伤作用及机制

目的 基于网络药理学和动物实验探究升降散治疗急性肺损伤（ALI）的作用机制。方法 在中药系统药理学分析平台数据库（TCMSP）和Swiss Target Prediction数据库中检索升降散的成分及靶点,在基因数据库（Gene Cards）中检索ALI的疾病靶点。将药物与疾病交集靶点上传至STRING数据平台进行蛋白质-蛋白质相互作用（PPI）分析,运用DAVID网站进行基因本体（GO）富集分析和京都基因与基因组百科全书（KEGG）通路分析。体内实验,除对照组外,升降散各给药组分别ig给药20 mL·kg^-1药液（散剂、水煎液高、低剂量分别为175、350 mg·kg^-1）,每天早晚各1次,共连续给药14 d;地塞米松组第12天开始ip地塞米松（5 mg·kg^-1）,连续给药3 d;除对照组外,其余各组第15天分别向气管内滴注1 mg·mL^-1脂多糖（5 mg·kg^-1）进行造模,观察肺组织病理损伤情况,ELISA法检测白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）水平,实时荧光半定量聚合酶链式反应（qRT-PCR）法检测Toll样受体4 （TLR4）、磷酸化-丝裂原活化蛋白激酶p38 （p38-MAPK）、细胞外调节蛋白激酶（ERK）、c-Jun氨基末端激酶（JNK-1） mRNA表达量,Western blotting法检测核因子κB（NF-κB）和人核因子κB抑制蛋白α（IκBα）表达量。结果 网络药理学预测出升降散活性成分32个,关键靶点292个,ALI疾病靶点有1 454个,两者交集靶点95个;升降散治疗ALI的关键靶点主要参与NF-κB、MAPK等信号通路。通过ALI小鼠模型实验结果显示,升降散能够显著减轻ALI小鼠肺部组织炎症,改善肺泡间隔及肺泡壁增厚程度;降低血清中炎症因子IL-6、IL-1β、TNF-α的水平（P＜0.05、0.01）;下调TLR4、p38-MAPK、ERK、JNK-1 mRNA的表达量（P＜0.05、0.01）;Western blotting结果表明升降散可通过抑制NF-κB蛋白磷酸化水平（P＜0.01）,激活IκBα蛋白（P＜0.01）,缓解ALI。结论 升降散能够基于多成分、多靶点、多通路的特点相互协同治疗ALI,其机制可能与NF-κB、MAPK等信号通路有关,且散剂治疗ALI的作用优于水煎液。     

银杏叶提取物注射液对脂多糖致大鼠急性肺损伤肺组织的保护作用

目的 观察银杏叶提取物注射液（GBE）对脂多糖（LPS）致大鼠急性肺损伤（ALI）肺组织的保护作用及其可能机制。方法 24只健康雄性Wistar大鼠随机分为对照组、LPS组和GBE组,每组8只。尾静脉注射LPS建立ALI模型,光镜下观察大鼠肺组织形态学改变;检测肺组织中超氧化物歧化酶活性（SOD）和丙二醛（MDA）含量及血清中白细胞介素-6（IL-6）的表达变化。结果 与对照组相比,LPS组肺组织中SOD活性降低、MDA含量增加、血清中IL-6含量增加（P<0.05）;应用GBE后,肺组织SOD活性升高、MDA含量减少、血清中IL-6含量减少（P<0.05）。结论 GBE可有效减轻ALI肺组织的炎症反应,其机制可能与其提高大鼠抗氧化能力、升高血清中IL-6的含量有关。     

苦碟子注射液对大鼠脑缺血再灌注损伤炎症及TLR-4/NF-κB信号的影响

目的 考察苦碟子注射液对大鼠脑缺血再灌注损伤的保护作用,并从炎症角度探讨其保护机制。方法 改良线栓法建立大鼠大脑中动脉栓塞（MCAO）模型,激光多普勒血流仪（LDF）监测大鼠脑血流变化。雄性SD大鼠随机分为假手术、模型组及苦碟子注射液高、低剂量组。缺血2 h再灌注24 h后进行神经功能缺损评分;断头取闹,称脑湿质量,计算脑指数;TTC染色法检测脑梗死面积;HE染色观察脑组织病理形态;并取血、脑组织,Elisa试剂盒检测炎症因子表达,Western Blotting技术检测TLR-4、NF-κB蛋白表达。结果 与假手术组比较,模型组神经功能缺损较严重（P<0.01）,脑指数和脑梗死面积也显著升高;给予苦碟子注射液后能改善神经功能缺损症状（P<0.01）,显著降低模型组的脑指数和脑梗死面积,减少神经元坏死,同时苦碟子注射液还可显著降低脑匀浆和血清TNF-α水平（P<0.05）,增加局部脑组织IL-10水平（P<0.05）。Western Blotting结果显示,苦碟子注射液可降低TLR-4、NF-κB蛋白的表达（P<0.05）。结论 苦碟子注射液对大鼠脑缺血再灌注损伤有明确的保护作用,具有降低脑缺血再灌注后TNF-α,并升高IL-10水平的作用,其作用机制可能与其下调TLR-4/NF-κB信号通路有关。     

川芎嗪通过抑制NF-κB信号通路减轻膜性肾病大鼠的炎症反应和肾脏损伤

目的 探讨川芎嗪通过抑制NF-κB信号途径减轻膜性肾病大鼠的炎性反应和肾损伤的作用和机制。方法 Wistar大鼠分为对照组、模型组和川芎嗪低、高剂量（60、120 mg/kg）组,称量各组大鼠的体质量和肾脏质量,计算肾脏系数;双缩脲法测定各组大鼠24 h尿蛋白水平;全自动生化分析仪检测各组大鼠血清肌酐、尿素氮（BUN）、脂联素、总胆固醇（TC）、三酰甘油（TG）水平;HE染色观察各组大鼠肾组织病理变化;实时荧光定量PCR（qRT-PCR）法检测各组大鼠肾组织中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和巨噬细胞趋化蛋白-1（MCP-1）mRNA的表达;ELISA法检测各组大鼠血清中丙二醛（MDA）、超氧化物歧化酶（SOD）的表达;免疫组织化学法检测各组大鼠肾组织中p-NF-κB的表达;Western blotting检测各组大鼠肾组织中p-NF-κB蛋白的表达。结果 与模型组比较,川芎嗪低、高剂量组大鼠的肾质量及肾脏系数均显著降低（P<0.05、0.01）,尿蛋白和血清肌酐、BUN、脂联素、TC、TG水平显著下调（P<0.05、0.01）,肾组织病理损伤明显减轻,肾小球基底膜增厚和肾小球萎缩减轻,肾组织中TNF-α、IL-1β、MCP-1 mRNA的表达水平显著下降（P<0.05、0.01）,血清中MDA水平显著下调,SOD水平显著上调（P<0.05、0.01）,肾组织p-NF-κB的表达水平显著下调（P<0.05、0.01）。结论 川芎嗪对大鼠膜性肾病有较好的治疗效果,调节炎性因子的表达、改善肾脏组织形态,其机制与NF-κB通路有关。     

甲氨蝶呤对脂多糖诱导的大鼠脊髓神经胶质细胞pIκBα-NF-κBp65-炎性因子通路的影响

目的 观察甲氨蝶呤对脂多糖（lipopolysaccharide,LPS）诱导的大鼠脊髓神经胶质细胞pIκBα-NF-κBp65-炎性因子通路的影响。方法 脊髓组织块法培养神经胶质细胞。将分离的神经胶质细胞接种于多孔板培养48 h后,分为空白对照组、LPS组、LPS+pIκBα抑制剂组、LPS+甲氨喋呤组。随后应用免疫印迹法测定各组分的pIκBα与胞核及胞浆NF-κBp65水平变化,酶免疫法（ELISA）测定炎性因子TNF-α、IL^-1β、IL-6含量。结果 神经胶质细胞经LPS诱导后,pIκBα、胞核NF-κBp65和细胞上清液炎性因子TNF-α、IL^-1β、IL-6水平均显著增加（P<0.05或P<0.01）。甲氨喋呤可明显抑制经LPS诱导的神经胶质细胞pIκBα水平,显著降低胞核NF-κBp65水平和细胞上清液炎性因子TNF-α、IL^-1β、IL-6的含量（P<0.05）。结论 甲氨喋呤对LPS诱导的脊髓神经胶质细胞pIκBα-NF-κBp65-炎性因子通路有显著的抑制作用。     

Current understanding of the mixed pain concept: a brief narrative review

Despite having been referenced in the literature for over a decade, the term “mixed pain” has never been formally defined. The strict binary classification of pain as being either purely neuropathic or nociceptive once left a good proportion of patients unclassified; even the recent adoption of “nociplastic pain” in the IASP Terminology leaves out patients who present clinically with a substantial overlap of nociceptive and neuropathic symptoms. For these patients, the term “mixed pain” is increasingly recognized and accepted by clinicians. Thus, an independent group of international multidisciplinary clinicians convened a series of informal discussions to consolidate knowledge and articulate all that is known (or, more accurately, thought to be known) and all that is not known about mixed pain. To inform the group’s discussions, a Medline search for the Medical Subject Heading “mixed pain” was performed via PubMed. The search strategy encompassed clinical trial articles and reviews from January 1990 to the present. Clinically relevant articles were selected and reviewed. This paper summarizes the group’s consensus on several key aspects of the mixed pain concept, to serve as a foundation for future attempts at generating a mechanistic and/or clinical definition of mixed pain. A definition would have important implications for the development of recommendations or guidelines for diagnosis and treatment of mixed pain.     

Animal models of pain for drug discovery

One of the greatest challenges to discovering more efficacious medications for pain control has been the heterogeneity of the chronic pain condition in humans. It is now appreciated that distinct mechanisms contribute to normal physiological pain, pain arising from tissue damage and pain arising from injury to the nervous system. To study pain transmission, identify new pain targets and characterise the potential analgesic profile of novel compounds, an array of experimental animal pain models has been developed (mainly in rodents) attempting to replicate the many human pain conditions, including inflammatory, neuropathic, visceral and cancer pain states. The authors review commonly used rodent models of acute and chronic pain that have been used in an attempt to identify novel analgesic drugs. Although these animal models have helped to better understand pain physio–pharmacology mechanisms, one should remember that even for patients labelled under the same ‘pain condition’, the pain experience is unique, increasing the difficulty of modelling such painful states in animals. Looking back at decades of pain research, it is clear that the transition from preclinical findings to clinical applications in the treatment of pain has been difficult and that more predictive models need to be developed to facilitate the discovery and development of novel pain medications. For these reasons, particular attention has been given in this review to the more recently developed models of visceral, osteoarthritic and bone cancer pain.     

对晚期重度癌痛伴有爆发性疼痛患者的临床回顾性调查

目的:研究调查北京肿瘤医院宁养院15例晚期重度癌痛伴爆发性疼痛(简称:爆发痛)患者,回顾观察宁养院在控制慢性癌痛、减少爆发痛处理的合理性,为规范化疼痛治疗和爆发痛处理提供借鉴。方法:选取宁养院2007年9月至2007年12月开始治疗,并于2007年12月至2008年3月期间死亡的病例中的晚期癌痛伴爆发痛,且使用阿片类药物超过6周、病程记录完整的全部患者15例,对患者镇痛药物使用和爆发痛控制方法进行分析。对患者疼痛控制情况、爆发痛次数、爆发痛强度(用VAS评分)以及爆发痛控制药物使用方法进行评价。结果:经过宁养院镇痛治疗后患者VAS疼痛评分显著下降,爆发痛次数显著减少;多数患者(11/15)为复合性痛;疼痛处理中普遍使用了辅助药物及个体化使用了强阿片类药物,并以即释吗啡控制爆发痛。结论:对晚期癌痛伴爆发痛患者按照WHO三阶梯止痛原则实施综合性个体化的止痛方案,可以控制慢性癌痛,有效减少爆发痛次数。     

Prospects and challenges in opioid analgesia for pain management

Abstract

Pain is still one of the most prevalent and distressing symptom in patients with chronic pain. Opioids are the most potent existing analgesics available in clinical practice. However, they are not always effective, particularly in the non-cancer population. Alternately adverse effects may limit their analgesic activity. Several different drug-development strategies have attempted to reduce side effects by exploiting anatomic barriers to drug distribution and to provide different analgesic mechanisms, as in the case of the oxycodone–naloxone combination or tapentadol. New delivery systems have been developed for a more effective management of breakthrough pain. Pharmacogenetics could play a critical role in personalizing pain management in the future.     

Pharmacoeconomics of opioid therapy for chronic non-malignant pain

Chronic non-malignant pain (CNMP) is widely prevalent and associated with significant costs. Costs related to chronic pain include medical services and medications, treatment of medication-related toxicity and work absenteeism. The use of non-narcotic analgesics is associated with inadequate pain-relief for many patients, as well as significant and costly organ toxicity. When used appropriately and judiciously, opioid medications can be a useful addition to the treatment plan for patients with CNMP. Opioids can provide long-term, safe and cost-effective pain relief.     

Emerging concepts on the use of ketamine for chronic pain

ABSTRACT

Introduction: The use of ketamine infusions for chronic pain has surged, with utilization exceeding the proliferation of knowledge. A proposed mechanism for the long-term benefit in chronic pain is that ketamine may alter the affective-motivational component of pain.

Areas covered: In this review, we discuss the classification and various dimensions of pain, and explore the effects of ketamine on different pain categories and components. The relationship between ketamine’s action at the NMDA receptor, the development of chronic pain, and the its possible role in preventing the persistence of pain are examined. We also summarize animal models evaluating the antinociceptive effects of ketamine and risk mitigation strategies of ketamine-associated side effects.

Expert opinion: Although ketamine exerts most of its analgesic effects via the NMDA receptor, recent evidence suggests that other receptors such as AMPA, and active metabolites such as nor-ketamine, may also play a role in pain relief and alleviation of depression. Data from clinical studies performed in patients with chronic pain and depression, and the observation that ketamine’s analgesic benefits outlast its effects on quantitative sensory testing, suggest that the enduring effects on chronic pain may be predominantly due ketamine’s ability to modulate the affective-motivational dimension of pain.     

Activation of Kv7 channels with the anticonvulsant retigabine alleviates neuropathic pain behaviour in the streptozotocin rat model of diabetic neuropathy

Abstract

Diabetic peripheral neuropathy (DPN) is the most incapacitating complication of diabetes mellitus. Up to 50% of patients with DPN develop peripheral neuropathic pain (PNP). The underlying ionic and molecular mechanisms of diabetic PNP (DPNP) are poorly understood. However, voltage gated potassium (K_v7) channels which have been implicated in the pathogenesis of other types of PNP are likely to be involved. Here we examined, in the streptozotocin (STZ) rat model of DPNP, whether activating the Kv7 channels with a potent activator retigabine (ezogabine) would reverse/attenuate behavioural signs of DPNP. STZ rats exhibited behavioural indices of mechanical and heat hypersensitivity, but not cold hypersensitivity or spontaneous pain, 35?days after STZ injection. Retigabine given at a dose of 15?mg/kg (but not at 7.5?mg/kg, i.p.) significantly attenuated mechanical, but not heat hypersensitivity in DPNP rats, and was as effective as the positive control gabapentin. This analgesic effect of retigabine was completely reversed by the K_v7/M channel blocker XE991 (3?mg/kg, i.p.) indicating that the anti-allodynic effects of retigabine were mediated by K_v7 channels. In conclusion, the findings suggest that Kv7 channels are involved in DPNP pathogenesis, and that strategies that target their activation may prove to be effective in treating DPNP.