Peripheral Nerves, the Brain, and How Acupuncture Calms Inflammation

1. From SPARC to Electroacupuncture: Stimulating the Body to Heal Itself

In 2014, the US National Institutes of Health (NIH) launched the SPARC program (Stimulating Peripheral Activity to Relieve Condition). The idea is simple but powerful:

If we can precisely stimulate peripheral nerves, we may be able to relieve specific diseases.

Vagal nerve stimulation (VNS) is one example, but it usually requires an invasive surgical procedure. Because of this, researchers have become very interested in electroacupuncture (EA) as a less invasive way to activate somatosensory–autonomic pathways.

One classic finding comes from Torres-Rosas et al.:

• EA at ST36 (Zusanli) activates the sciatic nerve
• This activation can control systemic inflammation

In the same year, another study showed that:

• In animal models, electroacupuncture pretreatment at ST36 and SP6 induces significant protective effects against acute lung injury, and these effects are dependent on the integrity of the sciatic nerve trunk.
• EA improves lung ventilation function
• EA reduces IL-1β, IL-6, TNF-α, and MPO levels in lung injury models

A key point is this:

• When the sciatic nerve is cut, the protective effect of EA disappears
• But when the peroneal or tibial nerves are cut, the protection remains

These findings indicate that although the sciatic nerve does not anatomically pass through ST36 or SP6, animal experiments demonstrate that the anti-inflammatory effects induced by electroacupuncture stimulation at these acupoints depend on the integrity of sensory afferent signaling at the level of the sciatic nerve trunk. When the sciatic nerve is transected, the protective effects of electroacupuncture against acute lung injury are completely abolished; in contrast, transection of either the peroneal or tibial nerve alone allows partial preservation of this protective effect. This suggests that the observed anti-inflammatory response is not mediated by a single peripheral nerve branch, but rather requires the sciatic nerve trunk to function as an integrated afferent signaling conduit.

The authors also point out that the detailed pathway from dorsal root ganglia (DRG) to the spinal cord for acupuncture signaling is still not fully understood and needs further study.

2. Acupuncture and the Brain: Brainstem, Vagus Nerve, and Spleen

Acupuncture does not only act through local nerves. It also requires multi-level participation of the central nervous system (CNS).

Somatosensory signals from acupoints travel to key brain regions, including:

• Nucleus tractus solitarius (NTS)
• Dorsal motor nucleus of vagus (DMV)
• Hypothalamus
• Amygdala and other primary brain structures

When acupuncture is applied, researchers observe:

• Strong discharges from brainstem nuclei
• Increased c-Fos–positive cells (a marker of neuronal activity) in the NTS and DMV

Manual acupuncture (MA) at ST36 has been shown to:

• Reduce TNF-α production in the spleen and serum
• This effect is mediated through activation of the vagus nerve and splenic nerve, originating from the dorsal vagal complex (DVC)

This fits with the concept of the “inflammatory reflex”, where the vagus nerve helps turn down excessive inflammation via a brain–spleen circuit.

3. Different Acupoints, Different Brain Patterns

Not all acupoints activate the exact same brain circuits.

• Takahashi et al. found that acupuncture at ST36 increases c-Fos–positive cells in the NTS and DMV.
• In contrast, acupuncture at ST25 increases c-Fos–positive cells in the NTS and the rostral ventrolateral medulla (RVM).

This suggests that different acupoints project to different brainstem nuclei, which may explain why acupoints have specific indications in classical acupuncture theory.

At the level of the hypothalamus, electroacupuncture at:

• LI4, LI11, GV14, and GV20

has been shown (via MRI in both rats and humans) to:

• Increase functional connectivity between the anterior hypothalamus and the amygdala
• Enhance the production of anti-inflammatory cytokines

In other words, these acupoints don’t just “calm the body” – they reshape brain network activity involved in stress, emotion, and inflammation.

4. Neuroanatomical Tracing: Following the Path from Stomach and ST36 to the Brain

Using neuroanatomical tracers injected into the stomach and ST36, researchers have confirmed that multiple brain regions participate in acupuncture signaling:

• NTS (nucleus tractus solitarius)
• DMV (dorsal motor nucleus of vagus)
• Raphe nuclei
• Area postrema
• Lateral hypothalamic area (LHA)
• Paraventricular nucleus (PVN) of the hypothalamus

These structures are deeply involved in autonomic regulation, stress responses, and neuroendocrine–immune modulation.

5. Take-Home Message

Putting all this together, the review concludes:

• Somatic afferents (sensory signals) activated by acupuncture are transmitted through peripheral nerves (like the sciatic nerve)
• They are then relayed to brainstem nuclei (NTS, DMV, RVM, raphe, etc.)
• From there, they project to higher centers, including the hypothalamus and amygdala
• Through these circuits, acupuncture modulates the vagus nerve, splenic nerve, and multiple neuroimmune pathways to produce systemic anti-inflammatory effects

This offers a modern neuro-immune explanation of how “needling a point on the leg” can influence inflammation in organs like the lungs or spleen.

一、從 SPARC 到電針：刺激周邊神經，啟動自體調節

2014 年，美國國家衛生研究院（NIH）提出 SPARC 計畫（Stimulating Peripheral Activity to Relieve Condition）， 核心概念是：

透過精準刺激周邊神經，來緩解特定疾病狀態。

迷走神經刺激（VNS）就是其中一種作法，但傳統 VNS 通常需要侵入性手術植入電極， 因此研究者開始積極關注電針（EA, electroacupuncture）， 作為較低侵入性的「體感－自律神經調節」工具。

Torres-Rosas 等人的研究顯示：

• 對足三里（ST36）施以電針，可啟動坐骨神經（sciatic nerve）
• 此一啟動能調控全身性發炎反應

同一年，另一研究指出：

• 針對 ST36 與 SP6 進行電針預處理，其誘發的保護效應在動物模型中顯示依賴坐骨神經幹的完整性，並可對急性肺損傷產生明顯保護作用。
• 電針可改善肺部通氣功能
• 並降低 IL-1β、IL-6、TNF-α、MPO 等發炎指標

關鍵發現是：

• 切斷坐骨神經時，電針的保護作用就消失
• 但若只切斷腓神經（peroneal）或脛神經（tibial），保護效果仍存在

這說明：雖然坐骨神經在解剖學上並不直接經過 ST36 或 SP6，但動物實驗顯示，電針刺激這些穴位所誘發的抗發炎效應，依賴坐骨神經幹層級的感覺傳入完整性。當坐骨神經被切斷時，電針對急性肺損傷的保護作用即完全消失；相對地，僅切斷腓神經或脛神經時，該保護效應仍可部分保留，顯示此效應並非由單一周邊分支神經所介導，而是需要坐骨神經幹作為整體訊號匯流通路。

作者也提到，從脊神經節（DRG）到脊髓的針灸訊號傳遞路徑， 目前仍缺乏完整研究，值得進一步探索。

二、針灸與腦幹：迷走神經、脾臟與發炎反射

針灸的作用不只是停留在局部神經，而是需要 多層次中樞神經系統（CNS）的參與。

穴位接受刺激後，其體感訊號會投射到多個關鍵腦區，包括：

• 孤束核（NTS, nucleus tractus solitarius）
• 迷走神經背側運動核（DMV）
• 下視丘（hypothalamus）
• 杏仁核（amygdala）等

研究發現，針灸刺激後：

• 多個腦幹核團的放電活性顯著上升
• NTS 與 DMV 內 c-Fos 陽性細胞（神經元活化標記）明顯增加

對足三里（ST36）施以手針（MA）時，還可觀察到：

• 脾臟與血清中的 TNF-α 減少
• 這與迷走神經與脾神經的活性增加有關，而其上游起源於 背側迷走複合體（DVC）

這與所謂的「發炎反射（inflammatory reflex）」概念相呼應： 大腦透過迷走－脾臟路徑，主動下調過度的發炎反應。

三、不同穴位，啟動不同腦區組合

並非所有穴位都啟動完全相同的腦區。

• Takahashi 等人發現：刺激足三里（ST36）， 會增加孤束核（NTS）與迷走神經背側運動核（DMV）中 c-Fos 陽性細胞數。
• 而刺激天樞（ST25），則增加 NTS 與延髓腹外側吻端區（RVM）的 c-Fos 陽性細胞。

這顯示，不同穴位具有不同的腦幹投射模式， 也可能解釋為何傳統針灸理論中，各穴位有特定適應證與主治範圍。

在下視丘層級上，對LI4、LI11、GV14、GV20施以電針， 透過動物與人體的核磁共振（MRI）研究可見：

• 增加前下視丘（anterior hypothalamus）與杏仁核之間的功能連結
• 並且促進抗發炎細胞激素的產生

換句話說，這些穴位不只是「讓身體放鬆」，而是實際上在重塑與 壓力、情緒、發炎相關的腦網絡活動。

四、神經解剖追蹤：從胃與足三里到腦幹與下視丘

透過在胃與足三里（ST36）注射神經示蹤劑的神經解剖追蹤研究， 學者證實下列腦區參與針灸訊號的傳遞與整合：

• NTS（孤束核）
• DMV（迷走神經背側運動核）
• 縫線核（raphe nuclei）
• 最後區（area postrema）
• 外側下視丘區（LHA）
• 下視丘室旁核（PVN）

這些結構與以下功能密切相關： 自律神經調控、壓力與情緒反應、神經內分泌與免疫調節。

五、小結：從腿部穴位，到腦幹與下視丘的抗發炎迴路

綜合這些研究，作者提出：

• 針灸啟動的體感傳入訊號，先經由周邊神經（如坐骨神經）
• 再傳遞到腦幹核團（NTS、DMV、RVM、縫線核等）
• 進一步投射至下視丘、杏仁核等高階中樞
• 透過這些中樞－自律－免疫的整合路徑，調節迷走神經、脾神經與多條 神經免疫通路，最終產生全身性抗發炎效果

這提供了一個現代神經免疫的框架，來理解： 為什麼「扎在腿上的一針」，可以影響到肺臟、脾臟、免疫系統與發炎狀態。