Abstract
Pain is associated with several conditions, such as inflammation, that result from altered peripheral nerve properties. Electroacupuncture (EA) is a common Chinese clinical medical technology used for pain management. Using an inflammatory pain mouse model, we investigated the effects of EA on the regulation of neurons, microglia, and related molecules. Complete Freund’s adjuvant (CFA) injections produced a significant mechanical and thermal hyperalgesia that was reversed by EA or a transient receptor potential V1 (TRPV1) gene deletion. The expression of the astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, receptor for advanced glycation end-products (RAGE), TRPV1, and other related molecules was dramatically increased in the dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) of CFA-treated mice. This effect was reversed by EA and TRPV1 gene deletion. In addition, endomorphin (EM) and N6-cyclopentyladenosine (CPA) administration reliably reduced mechanical and thermal hyperalgesia, thereby suggesting the involvement of opioid and adenosine receptors. Furthermore, blocking of opioid and adenosine A1 receptors reversed the analgesic effects of EA. Our study illustrates the substantial therapeutic effects of EA against inflammatory pain and provides a novel and detailed mechanism underlying EA-mediated analgesia via neuronal and non-neuronal pathways.
Highlights
Several channels, receptors, and signaling molecules within neurons and microglia are responsible for pain transmission
Mechanical hyperalgesia was observed in the Complete Freund’s adjuvant (CFA) group on days 1 and 2 after CFA injection (CFA: 1.65 ± 0.16 g and 1.85 ± 0.15 g, respectively) when compared with the other groups (Control: 3.68 ± 0.29 g and 3.67 ± 0.12 g; EA: 3.53 ± 0.09 g and 3.61 ± 0.14 g; and transient receptor potential vanilloid 1 (TRPV1)−/−: 3.69 ± 0.19 g and 3.52 ± 0.09 g, respectively)
The withdraw latencies were similar among groups prior to CFA injection (Control: 11.58 ± 0.8 s, CFA: 11.35 ± 0.94 s, EA: 10.55 ± 0.74 s, and TRPV1−/−: 10.14 ± 0.83 s)
Summary
Receptors, and signaling molecules within neurons and microglia are responsible for pain transmission. Expressed TRPV1 is involved in the detection of thermal and mechanical pain[12]. Relatively recent studies showed that the antinociceptive effect of acupuncture may be related to changes in the expression of various ionotropic receptor channels and voltage-gated channels, including N-methyl-D-aspartate receptors (NMDARs), acid-sensing ion channel 3 (ASIC3), TRPV1, local adenosine, and Nav channels[12,15,16,17,18]. Our previous studies demonstrated that EA results in antinociceptive effects and reduces mechanical and thermal hyperalgesia in an inflammatory mouse model via inhibition of TRPV1 and its related pathways[12]. We assessed the expression of non-neuronal markers, including GFAP, Iba-1, S100B, and RAGE, and neuronal TRPV1-related molecules during inflammatory pain. This study provides new information on the relationships between EA, inflammatory pain, neurons, and microglia
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