Acupuncture, Inflammation, and the Endocannabinoid System

Recent research shows that the endocannabinoid system plays a key role in the analgesic and anti-inflammatory effects of acupuncture, especially in acute inflammatory pain and motor system–related diseases such as osteoarthritis.

1. Endocannabinoid System and Electroacupuncture at Ex-LE4 & ST35

The endocannabinoid system includes cannabinoid receptors (such as CB1R and CB2R), endogenous ligands, and related enzymes. It is involved in pain modulation, immune regulation, and inflammatory responses. Animal studies have shown that electroacupuncture (EA) can activate this system to relieve joint pain and protect cartilage.

In a rat model of knee osteoarthritis, EA at Neixiyan (Ex-LE4) and Dubi (ST35):

• Enhances CB2 receptor (CB2R) expression in the knee meniscus and fibroblasts
• Inhibits the release of IL-1β, reducing local inflammatory responses
• Improves mechanical and thermal pain thresholds, reducing pain sensitivity
• Prevents cartilage loss and alleviates joint dysfunction
• Improves weight-bearing percentage on the affected limb

These findings suggest that activation of the CB2R-mediated endocannabinoid pathway is an important component of acupuncture’s protective effect in osteoarthritis and joint inflammation.

2. How Acupuncture Reduces Inflammation and Pain in the Motor System

Across multiple models of motor system disorders, acupuncture has been shown to:

• Inhibit the expression of chemokines
• Suppress the TLR4/NF-κB signaling pathway
• Inhibit activation of monocytes/macrophages

Downstream, this leads to reduced expression of key inflammatory mediators:

• MMPs (matrix metalloproteinases)
• NLRP3 inflammasome
• IL-1β
• TNF-α

As a result, acupuncture can:

• Reduce inflammatory pain perception
• Inhibit synovial tissue proliferation
• Protect the morphology of articular cartilage

In addition, activation of the endocannabinoid system forms part of the anti-inflammatory action of acupuncture, particularly in joint and motor system disorders.

3. Commonly Used Acupoints in Motor System Disorders

Both single local points and matched acupoint combinations are used in studies of motor system dysfunction. Among them:

• ST36 (Zusanli) – the most frequently used point across models
• ST35 (Dubi) and Ex-LE4 (Neixiyan) – commonly used around the knee joint
• Local acupoints near the knee or ankle – often selected for joint-related symptoms
• BL57 (Chengshan) – often used in models of muscle and tendon injury

These selections reflect the principle of combining local points with distal, meridian-related points to regulate both local tissue conditions and systemic inflammatory responses.

4. Bidirectional Regulation: Different Effects in Different Models

Acupuncture exhibits bidirectional regulation, meaning it helps restore disordered functions toward normal rather than only suppressing or only activating one pathway.

For example, acupuncture at the same points, such as ST36 and GB34:

• In osteoarthritis models – down-regulates pro-inflammatory factors and alleviates joint damage
• In muscle atrophy models – with appropriate stimulation, up-regulates macrophage inflammatory factors in muscle tissue and supports muscle regeneration

This difference may be related to the type and stage of disease, and suggests that acupuncture dynamically modulates the immune–inflammatory network rather than acting as a simple “on/off” switch.

近年研究指出，內源性大麻素系統（endocannabinoid system） 在針灸的 鎮痛與抗發炎作用中扮演關鍵角色，尤其與 急性發炎性疼痛及運動系統相關疾病（如退化性關節炎）密切相關。

一、內源性大麻素系統與電針內膝眼（Ex-LE4）與犢鼻（ST35）

內源性大麻素系統包括 大麻素受體（如 CB1R、CB2R）、內源性配體及相關酵素， 參與疼痛調節、免疫反應與發炎過程。動物實驗顯示，電針可以啟動此系統，達到 緩解關節疼痛與保護軟骨的效果。

在膝關節退化（knee osteoarthritis）大鼠模型中，對 內膝眼（Neixiyan, Ex-LE4） 與 犢鼻（ST35） 施以電針，可：

• 增加膝半月板及纖維母細胞中 CB2 受體（CB2R） 的表達
• 抑制 IL-1β 的釋放，降低局部發炎反應
• 提升 機械性與熱刺激痛閾值，減少疼痛敏感度
• 預防 關節軟骨流失，改善關節功能
• 改善患肢的 負重比例，反映出疼痛與功能的綜合改善

這些結果說明，透過 CB2R 的內源性大麻素通路，是針灸在退化性膝關節炎與關節發炎 中發揮保護作用的重要機制之一。

二、針灸在運動系統疾病中的抗發炎作用總結

在多種運動系統疾病模型中，針灸顯示出明顯的 抑制發炎與減輕疼痛的作用，主要包括：

• 抑制 趨化因子（chemokines） 的表達
• 抑制 TLR4/NF-κB 訊號通路
• 阻止 單核球／巨噬細胞 的活化

下游則進一步減少以下發炎介質的表達：

• MMPs（基質金屬蛋白酶）
• NLRP3 發炎小體
• IL-1β
• TNF-α

因此，針灸可以：

• 減少發炎性疼痛的感受
• 抑制滑膜組織增生
• 保護關節軟骨形態與結構

此外，內源性大麻素系統的活化 也是針灸抗發炎作用的一部分，在關節與運動系統相關 疾病中尤其重要。

三、運動系統疾病中常見的針灸穴位運用

在運動系統功能障礙的研究與臨床應用中，會使用單一局部穴位，也會使用 局部配穴與遠端配穴的組合。常見的穴位包括：

• 足三里（ST36）：各種發炎、免疫與肌肉修復模型中最常使用的穴位之一
• 犢鼻（ST35）、內膝眼（Ex-LE4）：常用於膝關節周邊局部治療
• 膝與踝關節附近之局部穴：應用於關節腫痛、退化與運動傷害
• 承山（BL57）：常用於肌肉、肌腱損傷等相關模型

這樣的選穴方式，反映了「局部－經絡－整體」的思路：一方面紓緩局部病變，一方面 調節經絡氣血與全身發炎狀態。

四、雙向調節：為何同一組穴位在不同疾病模型中表現不同？

針灸具有明顯的雙向調節（bidirectional regulation）特性： 並非單純「抑制」或「活化」某條路徑，而是協助失衡的生理功能回復到較為正常的狀態。

例如，同樣是 足三里（ST36）、陽陵泉（GB34）：

• 在退化性關節炎（OA）模型中： 主要是下調發炎細胞激素，減輕關節破壞與疼痛。
• 在肌肉萎縮模型中： 在適當刺激下，反而上調肌肉組織中的巨噬細胞相關因子，促進肌肉修復與再生。

這顯示針灸的效應會隨疾病類型與病程階段而改變，更接近「動態調節」而非單向干預， 也是中醫所謂「扶正祛邪」、「調和陰陽」在現代研究中的一種體現。