What is the mechanism of stimulating the ST36 (Zusanli) point in patients with nausea and vomiting, regardless of the underlying cause?

Mechanisms of ST36 (Zusanli) Stimulation for Nausea and Vomiting

Stimulating ST36 works through multiple neurobiological pathways including modulation of gastrointestinal motility via substance P and motilin regulation, anti-inflammatory effects through TLR4 and cytokine suppression, and central nervous system modulation involving the brain-gut axis and nucleus raphe magnus. 1

Primary Mechanisms of Action

Gastrointestinal Motility Regulation

ST36 stimulation exerts bidirectional control over gastric motility through neurotransmitter modulation:

• Manual acupuncture at ST36 regulates substance P (SP) and motilin (MTL) levels in both the gastric antrum and nucleus raphe magnus (NRM) of the brainstem. 2 In gastric hyperactivity states, ST36 stimulation decreases intragastric pressure, gastric SP and MTL content, and MTL immunoactivity in the NRM while increasing SP immunoactivity. 2

• In gastric hypoactivity conditions, ST36 stimulation reverses these effects, increasing intragastric pressure, gastric systolic frequency, and normalizing SP and MTL expression. 2 This bidirectional adjustment is critical for treating both hypermotility and hypomotility disorders that cause nausea and vomiting.

Anti-Inflammatory and Immune Modulation

Electroacupuncture at ST36 reduces pro-inflammatory mediators that contribute to visceral hypersensitivity and gastrointestinal symptoms:

• ST36 stimulation inhibits TLR4 expression in colonic mast cells and reduces serum levels of IL-1β and IL-8, which are key inflammatory cytokines involved in gastrointestinal dysfunction. 1

• The treatment decreases mucosal mast cell numbers and down-regulates corticotropin-releasing hormone (CRH) in the hypothalamus, addressing the stress-related component of nausea and vomiting. 1

• In chronic psychological stress models, electroacupuncture at ST36 repairs damage to interstitial cells of Cajal (ICC) in the small intestine, which are critical pacemaker cells for gastrointestinal motility. 3 The restoration of ICC morphology and number directly improves gastrointestinal motility dysfunction.

Brain-Gut Axis Modulation

ST36 stimulation affects central nervous system processing and the bidirectional communication between the brain and gut:

• Electroacupuncture at ST36 decreases levels of 5-HT, CGRP, and increases NPY in the gut-brain axis, restoring balance in neuronal pathways that regulate nausea and vomiting. 1

• fMRI studies demonstrate that ST36 acupuncture activates the opercular part of the right inferior frontal gyrus, left superior temporal gyrus, and right median cingulate/paracingulate gyri. 4 These regions map to the auditory network and salience network, which are involved in pain processing, secondary somatosensory function, and mood regulation—all relevant to nausea perception and control.

• The left olfactory cortex shows positive needle retention time-dependent activation, suggesting dose-dependent central nervous system effects. 4

Spinal Cord Central Sensitization

ST36 stimulation modulates spinal cord mechanisms involved in visceral sensation:

• Electroacupuncture at ST36 and ST37 significantly inhibits hyperphosphorylation of spinal cord NMDA receptors (pNR1) in models of chronic visceral hypersensitivity. 1 This mechanism is particularly relevant for nausea associated with visceral pain or hypersensitivity.

Clinical Evidence for Nausea and Vomiting

Direct clinical trials support ST36's antiemetic effects:

• In a multicenter randomized controlled trial of 246 patients with chemotherapy-induced nausea and vomiting, electroacupuncture at ST36 combined with granisetron achieved a 90.5% total effective rate compared to 84.0% with granisetron alone (P < 0.01). 5 Both groups showed decreased nausea and vomiting scores, but the electroacupuncture group demonstrated superior symptom reduction (P < 0.001). 5

Important Caveats

The evidence base has significant limitations for non-cancer populations:

• Most mechanistic studies are conducted in animal models (primarily rats), and translation to human physiology requires caution. 1, 3, 2

• The American Gastroenterological Association notes that while acupuncture improved quality of life in IBS patients compared to Western medicine, it did not show superiority compared to sham acupuncture, suggesting potential placebo effects in some contexts. 6

• The optimal stimulation parameters (manual vs. electroacupuncture, frequency, duration) vary across studies, with electroacupuncture typically using 2-5 Hz at 0.5-1.3 mA for 15-30 minutes. 1, 2