Acupuncture, a therapeutic practice rooted in traditional Chinese medicine and integrated with modern neuroscience, achieves its effects by stimulating sensory nerves at specific anatomical points known as acupoints. This review systematically explores the therapeutic components of acupuncture, emphasizing the interplay between sensory nerve characteristics and neural signaling pathways. Key factors such as acupoint location, needling depth, stimulation intensity, retention time, and the induction of sensations (e.g., Deqi) are analyzed for their roles in neural activation and clinical outcomes. The review highlights how variations in spinal segment targeting, tissue-specific receptor activation, and stimulation modalities (e.g., manual acupuncture, electroacupuncture, moxibustion) influence therapeutic effects. Emerging evidence underscores the significance of ion channels, dermatomes, myotomes, and gene-specific pathways in mediating systemic effects. Additionally, the differential roles of mechanical, thermal and nociceptive stimuli and the temporal dynamics of sensory and immune responses are addressed. While insights from animal models have advanced our understanding, their translation to clinical practice requires further investigation. This comprehensive review identifies critical parameters for optimizing acupuncture therapy, advocating for individualized treatment strategies informed by neuroanatomical and neurophysiological principles, ultimately enhancing its precision and efficacy in modern medicine. Please cite this article as: Wie HS, Kim SN. Therapeutic components of acupuncture stimulation based on characteristics of sensory nerve and nervous signaling pathway. J Integr Med. 2025; 23(2): 106-112.
Humans ; Acupuncture Therapy/methods* ; Signal Transduction ; Animals ; Sensory Receptor Cells/physiology* ; Acupuncture Points

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
Mice ; Animals ; Diabetes Mellitus, Experimental/metabolism* ; Axons/physiology* ; Diabetic Neuropathies ; Sensory Receptor Cells/metabolism* ; Neuralgia/metabolism*

The voltage-gated Na channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.
Animals ; Antibodies, Monoclonal ; therapeutic use ; Biotin ; metabolism ; Cells, Cultured ; Disease Models, Animal ; Female ; Ganglia, Spinal ; cytology ; HEK293 Cells ; Humans ; Hybridomas ; chemistry ; Hyperalgesia ; drug therapy ; Male ; Mice ; Mice, Inbred C57BL ; NAV1.5 Voltage-Gated Sodium Channel ; metabolism ; NAV1.7 Voltage-Gated Sodium Channel ; chemistry ; immunology ; metabolism ; Neuralgia ; drug therapy ; metabolism ; Protein Binding ; drug effects ; Recombinant Proteins ; biosynthesis ; therapeutic use ; Sensory Receptor Cells ; drug effects ; physiology

Chronic pain and itch are a pathological operation of the somatosensory system at the levels of primary sensory neurons, spinal cord and brain. Pain and itch are clearly distinct sensations, and recent studies have revealed the separate neuronal pathways that are involved in each sensation. However, the mechanisms by which these sensations turn into a pathological chronic state are poorly understood. A proposed mechanism underlying chronic pain and itch involves abnormal excitability in dorsal horn neurons in the spinal cord. Furthermore, an increasing body of evidence from models of chronic pain and itch has indicated that synaptic hyperexcitability in the spinal dorsal horn might not be a consequence simply of changes in neurons, but rather of multiple alterations in glial cells. Thus, understanding the key roles of glial cells may provide us with exciting insights into the mechanisms of chronicity of pain and itch, and lead to new targets for treating chronic pain and itch.
Animals ; Chronic Pain ; pathology ; Humans ; Neuralgia ; metabolism ; Pruritus ; pathology ; Sensory Receptor Cells ; physiology ; Spinal Cord ; pathology

Peripheral itch stimuli are transmitted by sensory neurons to the spinal cord dorsal horn, which then transmits the information to the brain. The molecular and cellular mechanisms within the dorsal horn for itch transmission have only been investigated and identified during the past ten years. This review covers the progress that has been made in identifying the peptide families in sensory neurons and the receptor families in dorsal horn neurons as putative itch transmitters, with a focus on gastrin-releasing peptide (GRP)-GRP receptor signaling. Also discussed are the signaling mechanisms, including opioids, by which various types of itch are transmitted and modulated, as well as the many conflicting results arising from recent studies.
Action Potentials ; drug effects ; Analgesics, Opioid ; pharmacology ; Animals ; Humans ; Pruritus ; metabolism ; pathology ; Sensory Receptor Cells ; metabolism ; Spinal Cord ; pathology ; Synaptic Transmission ; physiology

Voltage-gated sodium channels (VGSCs) in primary sensory neurons play a key role in transmitting pain signals to the central nervous system. BmK I, a site-3 sodium channel-specific toxin from scorpion Buthus martensi Karsch, induces pain behaviors in rats. However, the subtypes of VGSCs targeted by BmK I were not entirely clear. We therefore investigated the effects of BmK I on the current amplitude, gating and kinetic properties of Nav1.8, which is associated with neuronal hyperexcitability in DRG neurons. It was found that BmK I dose-dependently increased Nav1.8 current in small-sized (<25 μm) acutely dissociated DRG neurons, which correlated with its inhibition on both fast and slow inactivation. Moreover, voltage-dependent activation and steady-state inactivation curves of Nav1.8 were shifted in a hyperpolarized direction. Thus, BmK I reduced the threshold of neuronal excitability and increased action potential firing in DRG neurons. In conclusion, our data clearly demonstrated that BmK I modulated Nav1.8 remarkably, suggesting BmK I as a valuable probe for studying Nav1.8. And Nav1.8 is an important target related to BmK I-evoked pain.
Aniline Compounds ; pharmacology ; Animals ; Cell Size ; Cells, Cultured ; Electrophysiological Phenomena ; drug effects ; Furans ; pharmacology ; Ganglia, Spinal ; cytology ; Kinetics ; Male ; NAV1.8 Voltage-Gated Sodium Channel ; metabolism ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; antagonists & inhibitors ; pharmacology ; Scorpions ; Sensory Receptor Cells ; drug effects ; metabolism ; physiology ; Sodium Channel Blockers ; pharmacology ; Voltage-Gated Sodium Channel Agonists ; pharmacology

Successful assessing intestinal lumen content with ultrasound signals might lay a strong basis for the development of the artificial anal sphincter. In the present study, we utilized a modified MLU02-212 ultrasonic gas bubble detector to test the distal part of proximal colon in each rabbit, for the group of twenty healthy New Zealand rabbits. Voltage signals of solid, liquid, gas and empty content of the lumen were collected and compared. The results indicated that there were significant differences among the voltage signals in the 4 conditions (P = 0.000), respectively. Multiple comparison showed significant differences existed in any pair of the four conditions (P = 0.000). Three signal non-overlapping regions existed in these 4 conditions. Thus it seemed that ultrasound could be utilized to distinguish various contents inside the intestinal lumen and could act as "artificial sensory nerve".
Anal Canal ; innervation ; physiology ; Animals ; Artificial Organs ; Colon ; diagnostic imaging ; Enteric Nervous System ; physiology ; Fecal Incontinence ; surgery ; Female ; Gastrointestinal Contents ; Gastrointestinal Motility ; physiology ; Male ; Rabbits ; Sensory Receptor Cells ; physiology ; Ultrasonography

Lung cancer is a major medical problem. Despite advances in molecular biology and pharmacology, the outcome of lung cancer treatment is unsatisfactory. Clinically, inflammation and cancer are closely associated, and, genetically, these two processes are regulated by the same gene loci. Inflammation promotes cancer formation. Increasing evidence shows that neuroimmune interaction involving inflammatory disease and the vagus nerves are crucial in the interaction. Airway sensory receptors are biosensors that detect the lung inflammatory process through various mediators and cytokines. This information is transmitted through vagal afferents to the brain and produces a host of responses that regulate the extent and intensity of inflammation. Tumor cells express receptors for neurotransmitters and provide a substrate for direct interaction with neurons. Thus, neural regulation of the immune response is targeted towards inflammation as well as tumors. The airway sensors can detect cancer-related cytokines, which provides a direct pathway to inform the brain of tumor growth. The knowledge of how these sensors may monitor tumor progression and provide neuroimmune interaction in the control of tumor development and metastasis will improve our treatment of lung cancer.
Carcinogenesis ; Cytokines ; physiology ; Humans ; Inflammation ; pathology ; Lung ; innervation ; pathology ; Lung Neoplasms ; pathology ; Sensory Receptor Cells ; physiology ; Vagus Nerve ; physiology

The cytoplasmic polyadenylation element (CPE)-binding protein (CPEB) binds to CPE containing mRNAs on their 3' untranslated regions (3'UTRs). This RNA binding protein comes out many important tasks, especially in learning and memory, by modifying the translational efficiency of target mRNAs via poly (A) tailing. Overexpressed CPEB has been reported to induce the formation of stress granules (SGs), a sort of RNA granule in mammalian cell lines. RNA granule is considered to be a potentially important factor in learning and memory. However, there is no study about RNA granule in Aplysia. To examine whether an Aplysia CPEB, ApCPEB1, forms RNA granules, we overexpressed ApCPEB1-EGFP in Aplysia sensory neurons. Consistent with the localization of mammalian CPEB, overexpressed ApCPEB1 formed granular structures, and was colocalized with RNAs and another RNA binding protein, ApCPEB, showing that ApCPEB1 positive granules are RNA-protein complexes. In addition, ApCPEB1 has a high turnover rate in RNA granules which were mobile structures. Thus, our results indicate that overexpressed ApCPEB1 is incorporated into RNA granule which is a dynamic structure in Aplysia sensory neuron. We propose that ApCPEB1 granule might modulate translation, as other RNA granules do, and furthermore, influence memory.
Animals ; Aplysia/genetics/*metabolism ; Fluorescence Recovery After Photobleaching ; RNA/genetics/metabolism ; Sensory Receptor Cells/*metabolism ; mRNA Cleavage and Polyadenylation Factors/genetics/metabolism/*physiology

We previously reported that nidogen is an extracellular matrix protein regulating Schwann cell proliferation and migration. Since Schwann cells play a critical role in peripheral nerve regeneration, nidogen may play a role in it via regulation of Schwann cells. Here, we demonstrate direct evidence that nidogen induces elongation of regenerative axon growth of adult sensory neurons, and that the effect is Schwann cell dependent. Continuous infusion of recombinant ectodomain of tumor endothelial marker 7, which specifically blocks nidogen function in Schwann cells, suppressed regenerative neurite growth in a sciatic nerve axotomy model. Taken together, it is likely that nidogen is required for proper regeneration of peripheral nerves after injury.
Animals ; Axotomy ; Cell Movement ; Cell Proliferation ; Male ; Membrane Glycoproteins/*physiology ; Membrane Proteins/pharmacology ; *Nerve Regeneration ; Nerve Tissue Proteins/pharmacology ; Neurites/drug effects/*physiology/ultrastructure ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/pharmacology ; Schwann Cells/cytology/*physiology ; Sensory Receptor Cells/*physiology