Effects of Electroacupuncture in a Mouse Model of Fibromyalgia: Role of N-Methyl-D-Aspartate Receptors and Related Mechanisms

Abstract

ObjectiveN-methyl-D-aspartate receptor (NMDAR) activation and downstream transduction pathways are crucial for pain signalling. Fibromyalgia (FM) is a common pain syndrome of unclear aetiology that is often drug-refractory but may benefit from treatment with electroacupuncture (EA). We examined the contributions of NMDAR signalling to FM pain and EA responses in a mouse model.MethodsA model of FM was established by acid saline injection in 32 mice and subgroups (n=8 each) were treated with EA (2 Hz, 15 min daily for 4 days) or minimal acupuncture (MA). Expression of NMDAR subunits, calmodulin-dependent protein kinase II (CaMKII), cyclic AMP response element binding protein (pCREB) and their corresponding phospho-activated forms were measured by Western blotting and immunohistochemistry.ResultsAcid saline injection induced significant mechanical hyperalgesia (paw withdrawal threshold 2.18±0.27 g, p<0.05 vs controls), which was reversed by EA (4.23±0.33 g, p<0.05 vs FM group) but not by MA (2.37±0.14 g, p<0.05 vs EA group). Expression levels of phosphorylated N-methyl-D-aspartate receptor (pNR)1 and pNR2B were significantly increased in the dorsal root ganglion of FM model mice (132.21±14.4% and 116.69±3.22% of control values), whereas NR1 and NR2B levels were unchanged (97.31±3.79% and 97.07%±2.27%, respectively). Expression levels of pCaMKIIα and pCREB were also higher in the FM group, and these changes were reversed by EA but not by MA. Similar changes in expression were observed in spinal cord neurons.ConclusionsReduced NMDAR−CaMKIIα−pCREB signalling is implicated in the positive effects of EA in FM. NMDAR signalling components may represent promising therapeutic targets for FM treatment.

Electric Stimulation of Ear Reduces the Effect of Toll-Like Receptor 4 Signaling Pathway on Kainic Acid-Induced Epileptic Seizures in Rats

“…Acupuncture has been used in Asia for thousands of years to treat diseases. A number of studies have indicated that electroacupuncture (EA) can be used to treat stroke-induced dementia [ 16 ], epilepsy [ 3 ], body weight control [ 17 ], Parkinson's disease [ 18 ], depression [ 19 ], and pain [ 20 , 21 ]. Initially, scientists determined that acupuncture treatment worked through the release of endogenous opiates [ 22 ], serotonin [ 23 ], and adenosine [ 24 ].…”

Electroacupuncture Attenuates CFA-induced Inflammatory Pain by suppressing Nav1.8 through S100B, TRPV1, Opioid, and Adenosine Pathways in Mice

“…Over the past thirty years, studies have investigated the relationship between acupuncture and endogenous central opiates 14 . However, 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 .…”

The current treatment of fibromyalgia

“…The expression levels of regulatory mechanisms of NMDA receptor function signal were increased in spinal cord neurons in an FM model in mice, where hyperalgesia was induced by intramuscular injection of acid saline solution 59 . The analgesic effects in this animal model were associated with the reduction of NMDA receptor signaling, a result that may represent a new therapeutic target for FM 61 . The contribution of NMDA receptor activity to FM symptoms has also been related to the efficacy of gabapentinoid drugs.…”