Review Article

The Role of Neuroglial Crosstalk and Synaptic Plasticity-Mediated Central Sensitization in Acupuncture Analgesia

Table 1

Central sensitization regulatory mechanism of acupuncture analgesia.

Refs.Pain modelIntervention methodsAcupointsAcupuncture parameterPain-related behaviorTest siteBiochemical measurements

4.1 Acupuncture inhibits the ascending excitatory pathway

Zhao et al. [42]CCIEAST36, SP62 Hz, 2 mA for 30 minsMechanical allodyniaSpinal cordNR2B↓
Lee et al. [43]CFAEAST36, SP62 Hz, 1 mA for 30 minsThermal hyperalgesiaSpinal cordPhospho-GluR2↓
Han et al. [44]CFAEAST36, SP62-15 Hz, 1 mA for 30 minsMechanical allodynia, thermal hyperalgesiaSpinal cordGluR2 phosphorylation↓
Kim et al. [45]CFAEAST36, SP62 Hz, 1 mA for 30 minsThermal hyperalgesiaSpinal cordGFAP↓, GLAST↑, GLT-1↑
Zeng et al. [46]SNIEAST36, SP62 Hz, 3 mA for 30 minsMechanical allodyniaSpinal cordGLAST↑, GLT-1↑
Zhou et al. [47]CFAEAST36, BL60Alternative 2 Hz/120 Hz, 1-2 mA for 30 minsSpinal cordCalcium voltage-gated channel subunit ↓, calcium voltage-gated channel auxiliary subunit gamma↓

4.2 Acupuncture regulates the descending pain modulatory system

Hu et al. [48]CFAEAST36, BL602 Hz/100 Hz, 1-2 mA for 30 minsMechanical allodyniaRVMp38MAPK↓
Yuan et al. [49]KOAEAEx-LE4, ST352 Hz, 15 Hz or 100 Hz, 1 mA/0.1 mA for 30 minsMechanical allodynia, thermal hyperalgesiavlPAGEndocannabinoid-CB1R-GABA-5-HT↑
Li et al. [50]Hyperalgesia during ethanol withdrawalEAST362 Hz, 0.2-03 mA for 20 minsThermal hyperalgesiaHabenulaMORs↑
Meng et al. [51]Paclitaxel-induced neuropathic painEAGB3010 Hz, 2 mA for 30 minsMechanical allodyniaSpinal cordμ and δ opioid receptor↑
Huang et al. [52]CCIEAGV20, GV1415 Hz, 1 mA for 20 minsMechanical allodynia and thermal hyperalgesiaPAGGABAA↑, GABA↑, GLU↓
Jiang et al. [53]CCIEAEX-B22/15 Hz, 2 mA for 30 minsMechanical allodynia, thermal hyperalgesiaSpinal cordGABAA
Li et al. [54]CCIEAST36, GB34Alternative 2 Hz/100 Hz, 1.5 mA for 30 minsMechanical allodynia, thermal hyperalgesiaSpinal cordKCC2↑, GABAA receptor γ2↑
Choi et al. [55]PTX-induced neuropathic painEAST362 Hz, 2 mA for 30 minsMechanical allodynia and thermal hyperalgesiaSpinal cordalpha2- and beta-adrenoceptors↑
Choi et al. [56]PTX-induced neuropathic painBVALI11, ST36Mechanical allodyniaSpinal cordα2-adrenoceptor↑
Kim et al. [57]Ankle sprain painEASI610 Hz, 2 mA for 30 minsWeight-bearing force on the affected footSpinal cordα2-adrenoceptor↑
Zhang et al. [58]CFAEAGB3010 Hz, 3 mA for 40 minsThermal hyperalgesiaSpinal cordα2-ARs↑, 5-HTRs↑
da Silva et al. [59]Uninjured ratsEAST36, SP62, 100, or 2/100 Hz, 1.4-1.5 mA for 20 minsThermal hyperalgesiaSpinal cordNorepinephrine, acetylcholine, endogenous opioids, or GABA
Wu et al. [60]Pain-depression dyadEAST36, SP6100 Hz, 1.0, 1.5, and 2.0 mA, each for 15 minMechanical allodyniaDorsal raphe nucleus5-HT↑
Zhang et al. [61]CFAEAGB3010 Hz, 3 mA, twice for 20 min eachThermal hyperalgesiaSpinal cord5-HT↑, 5-HT1AR↑
Zhang et al. [62]CIPEAGB3010 Hz, 2 mA for 30 minsMechanical allodynia and thermal hyperalgesiaSpinal cord5-HT1AR↑, p-CaMKII↓
Li et al. [63]Osteoarthritis-induced painEAST36, GB3010 Hz, 2 mA for 30 minsWeight-bearing force on the affected footSpinal cord5-HT2A/2C↑

4.3 Role of the tripartite synapse in acupuncture analgesia

Liang et al. [64]SNLEAST36, BL602, 100, or 2/100 Hz, 1-2 mA for 30 minsMechanical allodyniaSpinal cordGFAP↓, OX-42↓
Choi et al. [65]SCIMAGV26, GB34Turned at a rate of 2 spins per second for 30 s, and retained for 30 minsMechanical allodynia, thermal hyperalgesiaSpinal cordp38MAPK↓, ERK↓, PGE2↓
Lee et al. [66]SCIMAGV26, GB34Turned at a rate of two spins per second for 30 s, retained for 30 minsMechanical allodynia, thermal hyperalgesiaSpinal cordJNK↓, CCL2↓, CCL4↓, and CCL20↓
Wang et al. [67]CCIEAST36, GB34Alternative 2 Hz/100 Hz, 1 mA for 30 minsSpinal cordIL-1𝛽↓, TNF-α↓, BDNF↓, NT3/4↓, NGF↓
Yu et al. [68]CFAEAST36, SP6Alternative 2 Hz/100 Hz, 2 mA for 20 minsMechanical allodynia, thermal hyperalgesiaSpinal cordIL-10↑, IL-1β↓, NLRP3↓, TNF-α
Dai et al. [69]Paw incision painEASP6, GB34Alternative 2 Hz/100 Hz, 1-2-3 mA for 30 minsMechanical allodyniaSpinal cordIL-10↑, LTP↓
Ali et al. [70]SNLEAST36, SP62 Hz, 2-3 mA for 20 minsMechanical allodyniaSpinal cordIL-10↑, β-endorphin↑
Zhao et al. [71]PTX-induced neuropathic painEAST3610 Hz, 1 mA for 30 minsMechanical allodyniaSpinal cordTMEM119↓, GFAP↓, TLR-4/NF-κb↓, TNF-α, and IL-1β
Hsu et al. [72]CFAEAST362 Hz, 1 mA for 15 minsMechanical allodynia, thermal hyperalgesiaSpinal cord/thalamusTLR2↓, pPI3K↓, pAkt↓, pmTOR↓, pERK↓, pp38↓, pJNK↓, pCREB↓, pNFκB↓, Nav1.7↓, Nav1.8↓

4.4 Role of chemokines and their receptors in acupuncture analgesia

Gao et al. [73]Neck-incision painEALI18, LI4, PC6, or ST36, GB34Alternative 2 Hz/100 Hz, 1 mA, 30 minsThermal painSpinal cordATP↓, P2X7R↓, CX3CL1↓, CX3CR1↓, p38 MAPK proteins↓
Li et al. [74]CFAEAST362 Hz for 30 minsMechanical allodynia, thermal hyperalgesiaSpinal cordCX3CL1↓, p38 MAPK phosphorylation↓, IL-1↓, IL-6↓, and TNF-α
Li et al. [75]Paw incision painACAGB34, SP6Alternative 2 Hz/100 Hz, 1, 2, 3 mA per 10 minsMechanical allodynia, thermal painSpinal cordCX3CR signaling
Hu et al. [76]CPIPEAST36, BL60Alternative 2 Hz/100 Hz, 0.5-1.5 mA, 30 minsMechanical hyperalgesiaSpinal cordCXCL12/CXCR4↓, ERK↓

ACA: acupuncture-combined anesthesia; BVA: bee venom acupuncture; CCI: chronic constriction injury; CFA: complete Freund’s adjuvant; CIP: chemotherapy-induced pain; CPIP: chronic postischemic pain; EA: electroacupuncture; MA: manual acupuncture; SNL: spinal nerve ligation; SCI: spinal cord injury; TENS: transcutaneous electric nerve stimulation; RVM: rostral ventromedial medulla; PAG: periaqueductal gray; vlPAG: ventral lateral periaqueductal gray.