2025 神经病理性疼痛（Neuropathic Pain）综述：Nav1.7 / TRPV1 / P2X7 / NGF-TrkA 核心靶点与机制

神经病理性疼痛（Neuropathic Pain）发病机制概览

神经病理性疼痛（neuropathic pain），又称神经性疼痛或神经病变性疼痛，是由躯体感觉神经系统本身的损伤或疾病直接引起的一类慢性疼痛综合征，全球患病率大约在 7–10% 左右，在糖尿病患者、肿瘤化疗人群、脊髓损伤以及多发性硬化等人群中发生率更高。典型病因包括糖尿病周围神经病变、带状疱疹后神经痛、化疗诱导周围神经病变、脊髓损伤相关疼痛以及三叉神经痛等，患者常描述为烧灼样、电击样、刀割样或针刺样疼痛，可伴随自发痛、触诱发痛（轻触即可引发明显疼痛）和痛觉过敏等复杂感受。

 

与炎症性或伤害性感觉疼痛不同，神经病理性疼痛的本质是神经系统本身发生了“病理性重塑”：外周伤害感受器和背根神经节神经元在离子通道表达和放电模式上出现持久改变（例如 Nav1.7/Nav1.8/Nav1.9 等电压门控钠通道上调导致异位放电），脊髓背角及更高位中枢（丘脑、皮层）内兴奋性传入信号被持续放大，同时抑制性调节（GABA 能和甘氨酸能神经元）功能减弱，出现所谓“去抑制”（disinhibition），再加上小胶质细胞和星形胶质细胞被激活，通过 P2X4/P2X7 受体、炎症因子和神经营养因子（如 BDNF）与神经元形成恶性正反馈回路，使得疼痛由急性伤害性信号演变为一种独立存在的“神经网络疾病”。在外周层面，TRPV1、TRPA1 等瞬时受体电位通道对热、机械和化学刺激高度敏化；在中枢层面，N-甲基-D-天冬氨酸受体（NMDAR）介导的兴奋毒性、mTOR 及下游通路参与的可塑性改变进一步巩固了异常疼痛记忆。

 

由于其发生基础不再是简单的炎症或组织损伤，传统非甾体抗炎药（NSAIDs）和镇痛药在神经病理性疼痛中的疗效普遍有限，且长期应用常受制于耐受性、不良反应和成瘾风险，这也是为什么当前指南更强调钙通道调节剂（如加巴喷丁、普瑞巴林）、5-hydroxytryptamine-norepinephrine再摄取抑制剂以及局麻药贴剂等机制更贴近“神经调控”的方案。然而，即便在标准治疗下，仍有相当比例患者处于“部分缓解甚至难治”状态，提示我们仍迫切需要围绕 Nav 通道、TRPV1/P2X4/P2X7、NGF–TrkA 轴以及中枢抑制性回路等关键节点开发更精准的靶向药物和生物制剂，这也是近年来新一代小分子、单克隆抗体与基因调控疗法持续集中的研发方向。

 

神经病理性疼痛五大核心靶点

类别 / 靶点	基因	蛋白全称	UniProt ID	病理作用与代表药物
1. 电压门控钠通道 （外周兴奋性）	SCN9A	Sodium channel protein type 9 subunit alpha (Nav1.7)	Q15858	数十个选择性抑制剂在研，VX-150已Ⅲ期
	SCN10A	Sodium channel protein type 10 subunit alpha (Nav1.8)	Q9Y5Y9	VX-548（Vertex）2024 FDA提交上市
	SCN11A	Sodium channel protein type 11 subunit alpha (Nav1.9)	Q9UI33	冷痛觉异常关键
2. TRP & Ca2?通道 （多模态敏化）	TRPV1	Transient receptor potential cation channel subfamily V member 1	Q8NER1	热痛核心，辣椒素贴剂已上市
	TRPA1	Transient receptor potential cation channel subfamily A member 1	O75762	冷痛、化学刺激
	TRPM8	Transient receptor potential cation channel subfamily M member 8	Q7Z2W7	冷超敏
	CACNA2D1	Voltage-dependent calcium channel subunit alpha-2/delta-1 (α2δ-1)	P54289	普瑞巴林、加巴喷丁直接靶点
3. 神经-免疫接口 （小胶质激活）	P2RX4	P2X purinoceptor 4	Q99571	最早激活标志物
	P2RX7	P2X purinoceptor 7	Q99572	多个脑渗透抑制剂Ⅱ期
	CCR2	C-C chemokine receptor type 2	P41597	单核细胞浸润
	CX3CR1	CX3C chemokine receptor 1 (Fractalkine receptor)	P49238	小胶质-神经元串话
4. 神经营养因子轴	NGF	Beta-nerve growth factor	P01138	Tanezumab、Fasinumab抗体
	NTRK1	High affinity nerve growth factor receptor (TrkA)	P04629	高选择性小分子在研
	BDNF	Brain-derived neurotrophic factor	P23560	脊髓中枢敏化
	NTRK2	BDNF/NT-3 growth factors receptor (TrkB)	Q16620	选择性拮抗剂临床前
5. 中枢调制受体	OPRM1	Mu-type opioid receptor	P35372	经典强效镇痛
	OPRD1	Delta-type opioid receptor	P41143	无成瘾风险
	OPRK1	Kappa-type opioid receptor	P41145	外周限制性激动剂
	CNR1	Cannabinoid receptor 1 (CB1)	P21554	医用cannabis主要靶点

想要了解其他神经系统疾病的相关靶点（如阿尔茨海默病、肌萎缩侧索硬化（ALS）、帕金森病、亨廷顿病等），可参考 abinScience 神经科学专题。

 

神经病理性疼痛新研究进展

以下表格总结了神经病理性疼痛领域的关键临床与基础研究突破，数据来源于期刊、临床试验注册与权威机构。

进展主题	关键发现/试验结果	发表/更新时间	潜在影响	引用来源
VX-548（Vertex，Nav1.8）	两项Ⅲ期急性痛试验达标，2024年底向FDA提交NDA，神经病理性疼痛适应症扩展试验启动；Phase 2显示在糖尿病周围神经痛中显著降低痛感评分	2024 NEJM + Vertex公告	高选择性Nav抑制剂有望打破30年镇痛药空白	[1]
抗NGF抗体长期安全性	Tanezumab骨关节炎痛Ⅲ期联合NSAIDs安全性可控，某些抗NGF抗体在特定适应症与给药方案下，安全性信号逐步明确，相关临床限制有所调整	2024 Ann Rheum Dis	重启神经病理性疼痛适应症开发	[2]
P2X7脑渗透抑制剂	JNJ-55308942等多个候选药在糖尿病神经痛Ⅱ期显示剂量依赖镇痛；2025年系列论文证实P2X7在小胶质激活中的核心作用	2024-2025临床更新 + Pain期刊	神经炎症-疼痛轴潜在疾病修饰药	[3]
NGF-TrkA轴机制综述	NGF通过激活TrkA增强Nav1.7表达，促进外周敏化；抑制NGF可逆转TRPV1转导	2025 Curr Issues Mol Biol	支持抗NGF单抗在神经病变性疼痛的应用	[4]
小胶质激活综述	P2X4/P2X7介导ATP驱动的IL-1β释放，是神经炎症-神经病理痛典型靶点	2022 Int J Mol Sci	指导小胶质模型实验设计	[5]
Nav1.7/1.8交互作用	Nav1.8与Nav1.7协同驱动神经元过度兴奋；在神经病理性疼痛模型中双敲除显著缓解痛敏	2024 J Gen Physiol	支持联合Nav抑制策略	[6]
TRPV1双向作用	TRPV1敏化导致热痛觉过敏，脱敏（如高浓度辣椒素）则产生镇痛	2024 Front Mol Neurosci	解释辣椒素贴剂临床疗效	[7]
纳米材料慢性疼痛治疗	新型纳米递送系统可靶向DRG或脊髓，实现精准镇痛	2025 J Headache Pain	跨疾病慢性疼痛新策略	[8]

 

abinScience 神经病理性疼痛研究重组蛋白与抗体产品清单

以下为 abinScience 针对神经病理性疼痛核心靶点的全部102款产品，已按类别分组并默认折叠（点击“展开”即可查看完整清单）。

对合作伙伴与经销商意味着：一个覆盖 Nav1.7、TRPV1、P2X7、NGF-TrkA、α2δ-1、opiates、cannabinoid受体等全通路的完整产品矩阵，支持从体外筛选到在体模型的全流程实验。统一批次质控与详尽技术资料，方便快速向客户推荐。

 

货号	品名（英文全称）
HC047012	Recombinant Human Delta-type opioid receptor (OPRD1) Protein, N-His-KSI
HX943012	Recombinant Human Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1) Protein, N-His
HY107012	Recombinant Human High affinity nerve growth factor receptor (NTRK1) Protein, N-His
HW331012	Recombinant Human CX3C chemokine receptor 1 (CX3CR1) Protein, N-GST & C-His
HS929022	Recombinant Human Sodium channel protein type 9 subunit alpha (SCN9A) Protein, N-GST & C-His
HB935022	Recombinant Human Brain-derived neurotrophic factor (BDNF) Protein, N-His
MB935012	Recombinant Human Brain-derived neurotrophic factor (BDNF) Protein, N-His
HB822012	Recombinant Human Cannabinoid receptor 1 (CNR1) Protein, N-GST & C-His
HS929012	Recombinant Human Sodium channel protein type 9 subunit alpha (SCN9A) Protein, N-His
HP943012	Recombinant Human P2X purinoceptor 4 (P2RX4) Protein, N-GST & C-His
HP943022	Recombinant Human P2X purinoceptor 4 (P2RX4) Protein, N-His
HB935011	Recombinant Human Brain-derived neurotrophic factor (BDNF) Protein, C-His
HV713012	Recombinant Human P2X purinoceptor 7 (P2RX7) Protein, N-His
HV711012	Recombinant Human Transient receptor potential cation channel subfamily V member 1 (TRPV1) Protein, N-His
HS892012	Recombinant Human BDNF/NT-3 growth factors receptor (NTRK2) Protein, N-His
HB935012	Recombinant Human Brain-derived neurotrophic factor (BDNF) Protein, N-His
HF909012	Recombinant Human Beta-nerve growth factor (NGF) Protein, N-His
HF909011	Recombinant Human Beta-nerve growth factor (NGF) Protein, C-Fc
HF525012	Recombinant Human Transient receptor potential cation channel subfamily A member 1 (TRPA1) Protein, N-His

   

货号	品名（英文全称）
HW331033	Anti-Human CX3C chemokine receptor 1 (CX3CR1) Antibody (SAA2443)
HF909013	Anti-Human Beta-nerve growth factor (NGF) Antibody (PG110)
HF909116	Research Grade povovetug
HA561013	Anti-Human Mu-type opioid receptor (OPRM1) Antibody (BMS986122)
HC047014	Anti-Human Delta-type opioid receptor (OPRD1) Polyclonal Antibody
HX943014	Anti-Human Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1) Polyclonal Antibody
HY107014	Anti-Human High affinity nerve growth factor receptor (NTRK1) Polyclonal Antibody
HW331014	Anti-Human CX3C chemokine receptor 1 (CX3CR1) Polyclonal Antibody
HW331023	Anti-Human CX3C chemokine receptor 1 (CX3CR1) Nanobody (11H11)
HB822043	Anti-Cannabinoid receptor 1 (CNR1) Antibody (L112/22)
HB822023	Anti-Cannabinoid receptor 1 (CNR1) Antibody (L112/26)
HB822033	Anti-Cannabinoid receptor 1 (CNR1) Antibody (L112/49)
HB822010	InVivoMAb Anti-Human Cannabinoid receptor 1 (CNR1) Nanobody (5D12)
HB822020	InVivoMAb Anti-Human Cannabinoid receptor 1 (CNR1) Nanobody (5G11)
HB822030	InVivoMAb Anti-Human Cannabinoid receptor 1 (CNR1) Nanobody (6B7)
HS929013	Anti-Human Sodium channel protein type 9 subunit alpha (SCN9A) Antibody (SAA1834)
HA935013	Anti-Human Sodium channel protein type 11 subunit alpha (SCN11A) Antibody (SAA1857)
HW331013	Anti-Human CX3C chemokine receptor 1 (CX3CR1) Antibody (SAA1640)
HX943013	Anti-Human Voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1) Antibody (SAA1645)
HV711013	Anti-Human Transient receptor potential cation channel subfamily V member 1 (TRPV1) Antibody (SAA1705)
HW387013	Anti-Human Kappa-type opioid receptor (OPRK1) Nanobody (SAA1169)
HB822013	Anti-Human Cannabinoid receptor 1 (CNR1) Nanobody (SAA1274)
HB935010	InVivoMAb Anti-Human Brain-derived neurotrophic factor (BDNF) (Iv0093)
HF909010	InVivoMAb Anti-Human Beta-nerve growth factor (NGF) (Iv0066)
HB822014	Anti-Human Cannabinoid receptor 1 (CNR1) Polyclonal Antibody
HF525014	Anti-Human Transient receptor potential cation channel subfamily A member 1 (TRPA1) Polyclonal Antibody
HV711014	Anti-Human Transient receptor potential cation channel subfamily V member 1 (TRPV1) Polyclonal Antibody
HS929014	Anti-Human Sodium channel protein type 9 subunit alpha (SCN9A) Polyclonal Antibody
HP943014	Anti-Human P2X purinoceptor 4 (P2RX4) Polyclonal Antibody
HP943024	Anti-Human P2X purinoceptor 4 (P2RX4) Polyclonal Antibody
HV713014	Anti-Human P2X purinoceptor 7 (P2RX7) Polyclonal Antibody
HS892014	Anti-Human BDNF/NT-3 growth factors receptor (NTRK2) Polyclonal Antibody
HB935014	Anti-Human Brain-derived neurotrophic factor (BDNF) Polyclonal Antibody
HF909014	Anti-Human Beta-nerve growth factor (NGF) Polyclonal Antibody
DF909018	Tanezumab ELISA Kit
HF909016	Research Grade Tanezumab
HF909026	Research Grade Fasinumab
HF909036	Research Grade Fulranumab

 

参考文献

1. Khalil MW, et al. Selective inhibition of NaV1.8 with VX-548 for acute pain: results from randomized clinical trials. N Engl J Med. 2023.
2. Hochberg MC, et al. Long-term safety and efficacy of subcutaneous tanezumab versus nonsteroidal anti-inflammatory drugs for hip or knee osteoarthritis: a randomized trial. Arthritis Rheumatol. 2021;73(5):859–871.
3. Ursu D, et al. Gain and loss of function of P2X7 receptors: mechanisms, pharmacology and relevance to diabetic neuropathic pain. Mol Pain. 2014;10:37. doi:10.1186/1744-8069-10-37.
4. García-Domínguez M. NGF in neuropathic pain: understanding its role and therapeutic opportunities. Curr Issues Mol Biol. 2025;47(2):93. doi:10.3390/cimb47020093.
5. Chen T, et al. Silencing P2X7R alleviates diabetic neuropathic pain via inhibition of TRPV1 in dorsal root ganglia. Int J Mol Sci. 2022;23(14):7799. doi:10.3390/ijms23147799.
6. Vasylyev DV, et al. Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain. J Gen Physiol. 2024;156(11):e202413596. doi:10.1085/jgp.202413596.
7. Gao N, et al. The dual role of TRPV1 in peripheral neuropathic pain: pain switches caused by its sensitization or desensitization. Front Mol Neurosci. 2024;17:1400118. doi:10.3389/fnmol.2024.1400118.
8. Sun R, et al. Emerging treatments for chronic neuropathic pain from a cross-disease perspective: developments and applications of nanomaterials. J Headache Pain. 2025;26:143. doi:10.1186/s10194-025-02081-5.