Brain regions

Functional neuroimaging response to acupuncture

Acupuncture-associated effects

Primary somatosensory cortex

Activation

Pain and mechanoreceptor-activated signals

Prefrontal cortex

Activation

Cognition and emotion

Insula

Activation/deactivation

Pain

Anterior cingulate cortex (ACC)

Deactivation

Pain, attention, memory, and emotion

Hypothalamus

Activation

Autonomic, neuroendocrine, visceral function, and stress-processed center

Amygdala/hippocampus

Activation

Encoding emotional signals and short-term memory

Thalamus

Activation

Pivotal relay station processing sensory inputs

Cerebellum

Activation

Locomotor coordination, higher-order cognitive and emotional function

Periaqueductal grey (PAG) and raphe nuclei

Activation

Modulating opioidergic and serotonergic activity, involved in pain, sleep, and consciousness

Mediators

Non-neuronal cells releasing neuroactive mediators

Receptors and actions on NAU afferent fiber terminals

Effects on NAU afferent fiber excitability

Serotonin (5-HT)

Platelets, mast cells

5-HT₃ receptor

5-HT₁ receptor

+

-

Noradrenaline (NA)

Mainly released from sympathetic nerve varicosities. Epidermal cells may be NA-storing cells.

Alpha-2 receptor

-

Acetylcholine

Keratinocytes and injured efferent fiber terminals

Muscarinic M₂ receptor

-

Histamine

Mast cells

H₃ receptor

H₁ receptor

-

+

Glutamate/aspartate

All skin epithelial cells and macrophage

Autoreceptors

-(?)

γ- aminobutyric acid

 (GABA)

Macrophages and lymphocytes

GABA_A receptors

-

_beta-endorphin

Kertinocytes, melanocytes, dermal fibroblasts, and leulocytes

μ-opioid receptor

-

Substance P (SP)

Mast cells, fibroblasts, platelets, keratinocytes, and macrophages.

Autoreceptors

-(?)

Calcitonin gene-related peptide (CGRP)

Epithelial cells, T cells, macrophages

Autoreceptors

-(?)

Somatostatin (SS)

Merkel cells, keratinocytes

SS receptors

-

Nitric Oxide (NO)

Local tissues

Inhibits SP release from primary afferent terminals and enhances acetylcholine and _Beta-endorphin.

-

ATP/GMP

Epidermal cells

P2X and P2Y receptor

-

Adenosine

Degraded from ATP released in response to mechanical, electrical, or heat stimulation

A₁ receptor

-

Bradykinin

Local tissues and cells

B_1/2 receptors

+

Cytokines (IL-1beta, IL-6, IL-8 & TNF-alpha)

Local tissues and cells

Stimulate afferent fibers and augment their excitability

+

Cytokines (Il-4 & IL-10)

Local tissues and cells

Inhibits the production of inflammatory pain signals in afferent terminals

-

Prostaglandins

Local tissues and cells

EP receptors

+