Mechanisms of acupuncture-electroacupuncture on inflammatory pain

Abstract

Acupuncture, as a traditional treatment, has been extensively used in China for thousands of years. According to the World Health Organization (WHO), acupuncture is recommended for the treatment of 77 diseases. And 16 of these diseases are related to inflammatory pain. As a combination of traditional acupuncture and modern electrotherapy, electroacupuncture (EA) has satisfactory analgesic effects on various acute and chronic pain. Because of its good analgesic effects and no side effects, acupuncture has been widely accepted all over the world. Despite the increase in the number of studies, the mechanisms via which acupuncture exerts its analgesic effects have not been conclusively established. A literature review of related research is of great significance to elaborate on its mechanisms and to inform on further research directions. We elucidated on its mechanisms of action on inflammatory pain from two levels: peripheral and central. It includes the mechanisms of acupuncture in the periphery (immune cells and neurons, purinergic pathway, nociceptive ion channel, cannabinoid receptor and endogenous opioid peptide system) and central nervous system (TPRV1, glutamate and its receptors, glial cells, GABAergic interneurons and signaling molecules). In this review, we collected relevant recent studies to systematically explain the mechanisms of acupuncture in treating inflammatory pain, with a view to providing direction for future applications of acupuncture in inflammatory pain and promoting clinical development.

Keywords: Acupuncture; analgesia; central nerve system; inflammatory pain; peripheral nerve system.

Figure 1.

The peripheral mechanisms of acupuncture in treating inflammatory inflammatory pain. DRG: dorsal root ganglia; TRPV1: transient receptor potential vanilloid 1; PKC: protein kinase C; PI3K: phosphatidylinositide 3-kinase; SP: substance P; CB₂R: cannabinoid type 2 receptors; CREB: cyclic response-element binding protein; cAMP: Cyclic adenosine monophosphate; NF-κB: nuclear factor kappa-B; mTOR: mammalian target of rapamycin; PKA: protein kinase A; ERK: extracellular regulated protein kinases; JNK: c-Jun N-terminal kinase; AKT: protein kinase B; Nav1.7: Voltage gated sodium ion channel 1.7; Nav1.8:Voltage gated sodium ion channel 1.8; NK-1R: Neurokinin-1 receptor; CD68: Macrophage sialoprotein; TNF-α: Tumor necrosis factor-α; IL-1β:Interleukin-1β; IL-6: Interleukin-6; IL-10: Interleukin-10; S100B:S100 calcium binding protein B; RAGE:Advanced glycosylation end product receptor; COX-2: Cyclooxygenase; Iba-1: Ionized calcium binding adapter molecule 1; NLRP3: pyrin domain containing 3; FOXP3:Forkhead box protein P3; ANXA1:annexin1; FPR2/ALX receptor:Formyl peptide receptor 2; eATP: extracellular adenosine-triphosphate; NTPDase-2: nucleotidases; NTPDase-3: nucleotidases; MrgprC: Mas-related G protein-coupled receptor C; BAM22: bovine adrenal medulla 22 peptide; P70S6K: phosphoprotein 70 ribosomal protein S6 kinase.

Figure 2.

The central mechanisms of acupuncture in treating inflammatory inflammatory pain. SC: spinal cord; PFC: prefrontal cortex; PAG: periaqueductal gray; RVM: rostral ventromedial medulla; ACC: anterior cingulate cortex; TRPV1: transient receptor potential vanilloid 1; PKC: protein kinase C; PI3K: phosphatidylinositide 3-kinase; CREB: cyclic response-element binding protein; cAMP: Cyclic adenosine monophosphate; NF-κB: nuclear factor kappa-B; mTOR: mammalian target of rapamycin; PKA: protein kinase A; ERK: extracellular regulated protein kinases; JNK: c-Jun N-terminal kinase; AKT: protein kinase B; Nav1.7: Voltage gated sodium ion channel 1.7; Nav1.8: Voltage gated sodium ion channel 1.8; ASIC3: acid sensing ion channel subunit 3; GluA1:glutamate receptor 1; GluA2: glutamate receptor 2; ICA69: Islet cells Antigen 69; PICK1: protein interacting with Cα kinase 1; NRG1: Neuromodulin 1; ErbB4: Receptor protein tyrosine kinase ErbB4; TLR2:Toll like receptor 2; GRK2: G protein coupled receptor kinase 2; p38MAPK: p38 mitogen-activated protein kinases; AIC3:acid-sensing ion channel 3; NR1: N-methyl-D-aspartate receptors NR1; NR2: N-methyl-D-aspartate receptors NR2; IFN-γ: Interferon γ; IL-4: Interleukin-4; IL-6: Interleukin-6.