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Scientific Mechanism of Acupuncture for pain  
 Acupuncture has been increasingly used as an integrative or
complementary therapy for pain. It is well-tolerated with little risk
of serious adverse effects.   Researches on acupuncture for pain
have quickly increased. Based on PubMed, number of research
papers on acupuncture for pain have reached to 634 at 2019 only.
Those available research works have provided enough scientific
data to support acupuncture benefits in the pain treatment, such
as low back pain, tension headache and chronic headache,
migraine headache, prophylaxis, and myofascial pain, et al.
    For example, Andrew Vickers et al reviewed 39 clinical trials which involved
in 20827 patients with wide range pains including non-specific
musculoskeletal pain, osteoarthritis, chronic headache, migraine,  shoulder
pain, neck pain and lower back pain et al,  This review conclude that
acupuncture is not only effective for the treatment of chronic pain, but also
treatment effects persisting over time. The specific effects of needling at
correct acupuncture point locations are important contributors to the
treatment effect. The pain reducing following acupuncture cannot be
explained solely in terms of placebo effects.  
     The inserted needles stimulate the local free-nerve endings (receptors), which sent signal to the central nervous system (CNS) through afferent
neural pathways. Every level of the CNS responds to the signals, leading to downstream effects—activating a healing process. The crosstalk of the
nervous system with the endocrine system and immune system amplify and enhance these effects.
  A 2019 literature systematically which reviews 46 studies found that visceral pain behaviors were significantly alleviated in response to
acupuncture treatment in groups compared to in sham acupuncture or no-treatment groups. Acupuncture reduced visceral pain behavior and
induced significant changes in neuronal activity as well as in the levels of pain/inflammation-related cytokines and neurotransmitters in the
brain-gut axis, including Acupuncture  beta-endorphin, epinephrine, cortisol, and prostaglandin E2 in plasma, the levels of c-Fos, substance P,
corticotropin-releasing hormone, P2X3, acetylcholinesterase (AchE), N-methyl-D-aspartate (NMDA) receptors, and serotonin in the gut/spinal
    Acupuncture also produces a series of
biochemical reactions. Although tissue
injury by acupuncture is minimal and self-
heal, the injury enough initiates a healing
process. Researches have shown that
acupuncture greatly increases the
concentration of many neural and
nonneuronal bioactive factors, such as
noradrenaline, beta-endorphin,
acetylcholine, and somatostatin.
Acupuncture also activates local cells
including mast cells, fibroblasts,
microphages, lymphocytes, and
keratinocytes. All of these cells participate
heal proess by releasing  bioactive factors
including  neurotransmitters;
neuromodulators; hormones; cytokines;
and inflammatory factors including  
substance P, calcium gene–related
peptide (CGRP), histamine, serotonin (5-
hydroxytryptamine), interleukin (IL)-1, IL-4,
IL-6, IL-8, tumor necrosis factor–a, and
  While acupuncture, inserting needle causes a small tissue damage. Injured cells release chemicals, such as substance P, to stimulate
Mass cells. Activated Mass cells release histamine to increases capillary blood flow and permeability. Phagocytes and growth factors leave
the capillaries and migrated into the location to repair injured tissue (Figure 1).
 Erythema is observed around needles area during acupuncture treatment (Figure 2), which indicates blood flow on the location is increased.
 To understand reaction of immune cells around acupuncture needles, we injected the beads, which are similar diameter to acupuncture
needle (125-250um), into damaged muscle on mouse.  Muscle cross sections showed that T cells, which were identified by antibodies to
CD45, migrated into the beads to form a ring around beads(Figure 3).   
  Erythema is considered an early sign of positive therapeutic outcome.
      Acupuncture needling is a mechanical
stimulation to local connective tissue in additional
to the stimulation of never receptors.   Helene
Langevin reported torque developing during
acupuncture needle grasp (Figure 1) .Rotating of
acupuncture needles windings connective tissue
around the acupuncture needle and pulls collagen
fibers and matrix deformation. Muscle cross
sections showed  histological changes while  
needle was rotated (Figure 2D), compared with
the chance while needle was not rotated (Figure
2C). The mechanical signals were transduced
into fibroblasts and/or other cells attached to
collagen fibers at focal adhesions. The cellular
response is to active local healing process by
autocrine and paracrine cellular effects.  
Spinal Cord
IL-1β, IL-6, PGE2
Opioids, TNF-α
5-HT1AR, 5-HT2AR
Akt, α2-adrenoceptors GluN2A
GluA1, p-GluN1, Glutamate, IL-1β, IL-6
Muscarinic cholinergic receptor
Norepinephrine, Opioids, Serotonin
Substance P, N/OFQ
p-38 MAPK, PI3K, TNF-α
IL-1 receptor
type I
Neuropathic pain
IL-1β, IL-6, TNF-α
5-HT1AR, 5-HT3R, α2-adrenoceptors
Aspartate, COX-2,  GABA, GABA receptor A,
GABA receptor B, GDNF, GFRα-1,
Glutamine, Glycine, IL-6, IL-1β
Inducible Nitric Oxide Synthases
Matrix Metallopeptidase-2/-9 ,
Opioids, p38 MAPK, PGE2, Serotonin
Somatostatin, Superoxide anion,Taurine,
Visceral pain
β-endorphins, NK1
Substance P, TNF-α,
p38 MAPK
5-HT, β-
CRF, GluN1
Substance P
Cancer pain
IL-1β, dynorphines, Substance P, TRPV1
Figure 1
Figure 2
Figure 3
Figure 1
Figure 2
4. References
1. Neuronal reaction
2. Biophysical reactions
3. Biochemical reactions
4. Increased blood flow