Evidence-Based Complementary and Alternative Medicine

Review Article

Neural Acupuncture Unit: A New Concept for Interpreting Effects and Mechanisms of Acupuncture

Table 1

Major non-neuronal neuroactive mediators involved in the modulation of NAU afferent fiber excitability.


Mediators	Non-neuronal cells releasing neuroactive mediators	Receptors and actions on NAU afferent fiber terminals	Effects on NAU afferent fiber excitability	Reference

Serotonin (5-HT)	Platelets, mast cells	5-HT₃ receptor	+	[17]
		5-HT₁ receptor		[203]
Noradrenaline (NA)	Mainly released from sympathetic nerve varicosities. Epidermal cells may be NA-storing cells.	Receptors		[51]
Acetylcholine	Keratinocytes and injured efferent fiber terminals	Muscarinic M₂ receptor		[204]
Histamine	Mast cells	H₃ receptor		[17]
		H₁ receptor	+
Glutamate/aspartate	All skin epithelial cells and macrophage	Autoreceptors (?)	(?)	[35, 36, 205]
γ-aminobutyric acid (GABA)	Macrophages and lymphocytes	GABA_A receptors		[206, 207]
β-endorphin	Keratinocytes, melanocytes, dermal fibroblasts, and leukocytes	μ-opiate receptors		[47, 48, 208]
Substance P (SP)	Mast cells, fibroblasts, platelets, keratinocytes, and macrophages.	Autoreceptor (?)	(?)	[14, 37, 38, 46]
Calcitonin gene-related peptide (CGRP)	Epithelial cells, T cells, macrophages	Autoreceptor (?)	(?)	[39, 209, 210]
Somatostatin (SS)	Merkel cells, keratinocytes	SS receptors		[21, 211–213]
Nitric Oxide (NO)	Local tissues	Inhibits SP release from primary afferent terminals and enhances acetylcholine and β-endorphin.		[50, 214, 215]
ATP/cGMP	Epidermal cells	P2X and P2Y receptor		[31, 214, 216]
Adenosine	Degraded from ATP released in response to mechanical, electrical, or heat stimulation.	A₁ receptor		[31]
Bradykinin	Local tissues and cells	B_1/2 receptors	+	[217–219]
Cytokines (IL-1β, IL-6, IL-8, and TNF-α)	Local tissues and cells	Stimulate afferent fibers and augment their excitability	+	[217–221]
Cytokines (IL-4 and IL-10)	Local tissues and cells	Inhibits the production of inflammatory pain signals in afferent terminals		[220, 222]
Prostaglandins	Local tissues and cells	EP receptors	+	[221, 223]

^aQuestion marks (?) indicate to be determined.