Effects of electroacupuncture on the pain threshold and the NMDA R1 mRNA in DRG on neuropathic pain rats

Abstract

To observe the effect of multiple electroacupuncture (EA) on the pain threshold and the regulation of N-methyl-D-aspartate (NMDA) receptor in dorsal root ganglia (DRG) of neuropathic pain rats. Rats were prepared with a unilateral chronic constriction injury (CCI) to the sciatic nerve. EA was done in acupoints "Huan Tiao" and "Yang Ling Quan" for 30 min every day and the thermal thresholds were detected after EA at 3, 5, 7, 10, 14 days after operation. On day 14 after nerve injury, the in situ hybridization method was used to investigate the change of NMDA R1 mRNA in L4-L5 DRG. The thermal threshold reduced significantly from day 3 after operation in CCI rats. After multiple EA treatment, the ipsilateral thermal hyperalgesia relieved gradually and the thermal threshold had no difference with control side after day 5 (P > 0.05). From Day 7 after operation, the thermal threshold at each time point were significantly different compared with CCI group respectively (P > 0.05). Moreover the EA had accumulative effect. On Day 14 after operation, the NMDAR1 mRNA positive neurons and the mean optic density in ipsilateral L4-5 DRG were less than that of control side (P < 0.05), mainly in medium and small neurons. After EA treatment, the NMDAR1 mRNA positive neurons in ipsilateral DRG had no considerable difference comparing with those of control side, significantly increased comparing with CCI group (P < 0.05). It's concluded that the NMDA receptors in DRG relate closely with the generation and development of neuropathic pain. The multiple EA treatment can attenuate the thermal hyperlagesia of neuropathic pain rats and regulate the NMDA receptor.

Electroacupuncture Reduces Hyperalgesia after Injections of Acidic Saline in Rats

“…Similar to our findings, consecutive applications of EA for three days in a model of visceral hypersensitivity in mice did not develop tolerance to the analgesic treatment with electroacupuncture [42]. However, some studies have demonstrated the participation of opioid system in the antihyperalgesia of electroacupuncture promoted by the application through the administration of blockers of μ and δ opioid receptors [8, 16, 19–21, 27, 31, 33, 36, 43]. Other studies also confirmed the action of β -endorphin as evidenced, an increase in plasma after application of electroacupuncture in the postoperative ovariectomy in female dogs [24] and rats [27].…”

Acupuncture-Analgesia-Mediated Alleviation of Central Sensitization

“…Several animal studies have shown that EA treatment can attenuate the hyperalgesia of neuropathic pain through the downregulation of NMDAR phosphorylation at the spinal cord level [ 63 – 66 ]. EA decreases in the expression level of the NR-2B subunit of the NMDAR in the dorsal horn [ 51 , 67 – 69 ].…”

“…Animal studies have also revealed that acupuncture causes a reduction in glycine inhibition [ 102 ] and an increase in the activity of the neurotrophin BDNF (causing neuron plasticity) [ 101 ], NMDA, AMPA, and metabotropic glutamate receptors in the postsynaptic neurons [ 103 ]. Acupuncture increases the levels of these neuropeptides, including opioids, serotonin, norepinephrine, and amino acids and reduces the levels of the local inflammatory cytokines and the expression of their receptors [ 59 , 63 ]. In a neuropathic pain rat model, repeated EA had a time-dependent cumulative analgesic effect; this might be associated with its modulatory effects on NK cells, as well as on splenic IL-2, β -Endorphin ( β -EP), and plasma IL-2, IL-1 β , interferon gamma (IFN- γ ), and transforming growth factor beta (TGF- β ) levels [ 104 ].…”