How Acupoints “Turn On” the Body’s Anti-Inflammatory System

1. Acupoints Are 3D Micro-Environments, Not Just “Points on the Skin”

Modern research suggests that most acupoints are not flat dots, but three-dimensional micro-environments beneath a thin layer of skin. They typically contain:

• A dense distribution of nerves
• Regularly arranged blood vessels
• Rich connective tissue and fibroblasts
• Immune cells such as macrophages and mast cells

This unique structure makes acupoints ideal “hubs” to receive, amplify, and transmit acupuncture signals— especially in inflammatory diseases.

In chronic inflammatory pain models (such as CFA – Complete Freund’s Adjuvant), acupuncture has been shown to:

• Strengthen the communication network among local cells in the acupoint
• Regulate multiple cytokines and chemokines, amplifying and transmitting the acupuncture signal from the local site to the rest of the body

At ST36 (Zusanli), manual acupuncture (MA) particularly activates fibroblasts and macrophages, which then initiate a cascade of signaling changes.

2. Key Pathways Triggered at ST36: ERK, NF-κB, and Adenosine

Gene expression analyses show that MA at ST36 can:

• Modulate 236 genes
• Affect at least seven signaling pathways, including:
  • ERK, p38, JNK
  • P53
  • BCR, TCR
  • TLR-related pathways

Among these, the ERK pathway is especially prominent.

At the same time, ST36 stimulation is associated with up-regulation of NF-κB signaling and related inflammatory genes, such as:

• p-p65, p-p50, Nfkbia
• IL-1β, IL-6
• CXCL1, CCL2
• Rela, NF-κB1

Interestingly, if you block NF-κB, the analgesic effect of acupuncture is weakened— acupuncture works partly by engaging, then “re-regulating,” inflammatory pathways rather than shutting them off completely.

Another important mediator in acupoints is adenosine:

• Acupuncture increases adenosine at the acupoint
• Adenosine binds to A1 receptors
• This mediates both anti-inflammatory and analgesic effects in CFA models

3. Cannabinoid System, Mast Cells, and Local Mediators

Electroacupuncture (EA) at ST36 for 7 days has been shown to:

• Up-regulate CB2 receptors (CB2R) in the acupoint (without significantly affecting CB1R)
• Inhibit calcium influx and suppress the TLR4/NF-κB pathway in the spleen
• Down-regulate serum levels of TNF-α, IL-1β, IL-6

This suggests that the local cannabinoid system in the acupoint is closely involved in acupuncture’s anti-inflammatory action.

Acupuncture also promotes mast cell degranulation and fibroblast remodeling, which leads to the release of:

• ATP
• Substance P (SP)
• Tryptase
• Histamine (HA)
• Interleukins
• 5-HT (serotonin)
• Other neuroimmune mediators

These substances help “translate” mechanical needle stimulation into biochemical signals.

4. DAMPs: Controlled Micro-Injury That Activates Immunity

Acupuncture is considered a form of “minimally invasive” stimulation. Needle insertion and manipulation cause a small, controlled amount of cell damage at the acupoint, leading to the release of DAMPs (damage-associated molecular patterns) such as:

• HMGB1
• Adenosine
• Heat shock proteins (HSPs)

The authors’ work suggests that HMGB1 increases at the acupoint after acupuncture and contributes to pain relief.

DAMPs then:

• Activate local immune cells (e.g., macrophages, mast cells)
• Promote the release of interleukins and other inflammatory mediators
• At the same time, local glucocorticoid levels at the acupoint rise after MA, which may help limit excessive inflammation

In other words, acupuncture creates a controlled inflammatory micro-network at the acupoint, which then drives a beneficial systemic anti-inflammatory response.

5. Exosomes: Tiny Carriers of the Acupuncture Signal

Exosomes are small vesicles that carry lipids, proteins, mRNA, miRNA, and DNA between cells, acting like molecular “messages in a bottle.”

• Exercise is known to stimulate skeletal muscle to release exosomes, which then affect distant organs and metabolic systems.
• Preliminary data from acupuncture research show that when local exosome release and mast cell activity at the acupoint are blocked, the analgesic and anti-inflammatory effects of acupuncture are weakened.

Mast cell–derived exosomes (MC-Exos) can:

• Activate B cells and T cells
• Stimulate TRPV receptors on sensory nerves
• Release multiple neuroimmune signaling molecules

These exosomes are believed to be important carriers of the acupuncture effect from the needle site to other areas of the body.

6. Summary: How a “Point” Becomes a Dynamic Anti-Inflammatory Network

In short, when an acupoint is stimulated:

1. Local fibrous tissue is stretched and partially disrupted → mild controlled cell damage
2. Damage-related factors (DAMPs) are released → HMGB1, adenosine, HSPs
3. Immune cells (macrophages, mast cells, fibroblasts) are activated
4. ERK and NF-κB pathways and multiple neuroimmune mediators (e.g., adenosine, CB2R, SP, interleukins) are engaged
5. Exosomes are released from local cells, helping to propagate the signal
6. A dynamic network inside and around the acupoint is formed, which amplifies acupuncture information and translates it into a systemic anti-inflammatory response

This perspective helps explain why a tiny needle at one small point can influence inflammation throughout the body.

一、穴位是「立體微環境」，不是皮膚上的一個點

現代解剖與組織學研究發現，多數穴位其實是具有立體結構的微環境， 在薄薄的皮膚下，常見：

• 密集分布的神經末梢
• 規則排列的微血管網絡
• 大量結締組織與纖維母細胞
• 巨噬細胞、肥大細胞等免疫細胞

這些條件讓穴位成為非常理想的「訊號樞紐」，能接收、放大、再傳遞針灸刺激， 尤其在發炎相關疾病中格外重要。

在 CFA（完全佛氏佐劑，Complete Freund’s Adjuvant）等慢性發炎疼痛模式中，研究發現：

• 針灸會增強穴位內細胞之間的網絡連結強度
• 透過多種細胞激素與趨化因子的變化，將「針灸訊息」由局部擴散到全身

在足三里（ST36），手針（MA）尤其會活化纖維母細胞與巨噬細胞， 再進一步啟動一連串訊號通路。

二、足三里啟動的關鍵訊號：ERK、NF-κB 與腺苷

基因晶片分析顯示，刺激 ST36 可：

• 調控約 236 個基因表現
• 影響至少七條訊號路徑，包含：
  • ERK、p38、JNK
  • P53
  • BCR、TCR
  • TLR 受體相關訊號

其中以ERK 路徑最為顯著。

同時，ST36 刺激也與NF-κB 訊號上調有關，相關基因包括：

• p-p65、p-p50、Nfkbia
• IL-1β、IL-6
• CXCL1、CCL2
• Rela、NF-κB1 等

有趣的是，當使用NF-κB 抑制劑時，針灸的鎮痛效果反而減弱， 顯示針灸並不是「完全關掉發炎」，而是透過啟動 → 調節 → 重新平衡來產生治療效果。

在穴位中，腺苷（adenosine）也是關鍵因子之一：

• 針刺會增加穴位局部的腺苷
• 腺苷與A1 受體結合
• 進而產生鎮痛與抗發炎作用（CFA 模型）

三、大麻素系統、肥大細胞與局部釋放物質

研究也發現，對 ST36 連續 7 天施以電針，可：

• 上調穴位局部CB2 受體（CB2R）表達，對 CB1R 影響較小
• 抑制鈣離子內流，進而抑制脾臟中的TLR4/NF-κB 訊號
• 降低血清TNF-α、IL-1β、IL-6濃度

這顯示穴位局部的大麻素系統，參與了針灸的抗發炎效應。

此外，針灸會促進肥大細胞脫顆粒與纖維母細胞結構重塑， 並誘導一系列物質的釋放，例如：

• ATP
• P 物質（Substance P, SP）
• Tryptase
• 組織胺（Histamine, HA）
• 各種介白素（Interleukins）
• 5-羥色胺（5-HT, serotonin）等

這些物質有助於將「機械式針刺激」轉譯為「生化訊號」。

四、DAMPs：可控的「微小損傷」，點燃免疫啟動

針灸被視為一種「微侵入性」刺激。 針刺與提插捻轉會造成穴位局部輕微可控的組織損傷，進而釋放：

• HMGB1
• 腺苷
• 熱休克蛋白（HSP）

作者的研究也發現，穴位 HMGB1 增加與針灸鎮痛效果相關。

這些 DAMPs 會：

• 活化局部免疫細胞（如巨噬細胞、肥大細胞）
• 促進介白素等發炎介質釋放
• 同時，手針後穴位局部類固醇樣物質（glucocorticoids）含量上升， 可能在穴位微環境中「適度限制」過度發炎

因此，可以把穴位看成一個被精準啟動、可控的發炎微網絡， 再藉此推動全身性的抗發炎與免疫調節效果。

五、外泌體（Exosomes）：從穴位傳遞訊息的小囊泡

外泌體（Exosomes）是帶有脂質、蛋白質、mRNA、miRNA、DNA 的小囊泡， 負責細胞與細胞之間的訊息傳遞。

• 運動可促使骨骼肌收縮並釋放外泌體入血，進而影響遠端器官與代謝系統。
• 初步研究顯示：當阻斷穴位局部的外泌體與肥大細胞活性時， 針灸的鎮痛與抗發炎效果會明顯下降。

由肥大細胞衍生的外泌體（MC-Exos）已知可以：

• 活化B 細胞與 T 細胞
• 刺激感覺神經末梢上的TRPV 受體
• 釋放多種神經免疫訊號分子

推測這些外泌體可能是穴位訊號由局部傳遞到全身的重要「載體」。

六、小結：從「一針一點」，到「動態抗發炎網絡」

綜合來看，當穴位受到針刺刺激時，會發生一連串事件：

1. 局部纖維組織被牽拉、部分斷裂 → 輕微可控的細胞損傷
2. 釋放DAMPs（如 HMGB1、腺苷、HSP 等）
3. 活化巨噬細胞、肥大細胞、纖維母細胞等免疫與支持細胞
4. 啟動ERK、NF-κB等發炎訊號，並調節腺苷、CB2R、SP、介白素等神經免疫分子
5. 刺激局部細胞釋放外泌體，將訊號傳向周邊與遠端
6. 在穴位內形成一個動態網絡，將針灸訊息「放大」並轉換為全身性的抗發炎反應

這樣的機制，幫助我們從現代生物醫學角度理解： 為什麼「在一個小點上扎一針」，可以對全身發炎與免疫狀態產生影響。