Electroacupuncture and Lumbar Transplant of GDNF-Secreting Fibroblasts Synergistically Attenuate Hyperalgesia after Sciatic Nerve Constriction

Abstract

Electroacupuncture (EA) has been shown to induce potent analgesic effects on neuropathic pain in both patients and rodents. Cell therapy to release antinociceptive agents near the pain processing centers of the spinal cord is a promising next step in the development of treatment modalities. This study investigated the effects of the combination of EA and cell therapy by glial cell line-derived neurotrophic factor (GDNF) on neuropathic pain in rats. The hyperalgesic state was induced by chronic constriction injury (CCI) of the sciatic nerve and fibroblasts genetically modified to secrete bioactive GDNF (FBs-GDNF) were used for cell therapy. Fifty-eight rats with neuropathic pain were randomly divided into five groups (CCI+PBS, n = 11; CCI+FBs-GDNF, n = 12; CCI+EA+PBS, n = 11; CCI+EA+FBs-pLNCX2, n = 12; CCI+EA+FBs-GDNF, n = 12). On the 7th day after CCI, the rats received intrathecal transplantation of FBs-GDNF or control fibroblasts (FBs-pLNCX2). In the meantime, EA was administered once every other day from the 7th day after CCI surgery for 21 days. The paw withdrawal latency (PWL) to radiant heat was measured every other day. The results showed that the ipsilateral PWL of the rats from all three EA treatment groups significantly increased starting on the 12th day compared with the PBS control group. Strikingly, the group which received EA treatment and FBs-GDNF transplantation (CCI+EA+FBs-GDNF) showed a significantly decreased thermal hyperalgesia after 2 weeks post CCI surgery compared with the groups which received EA treatment and FBs-pLNCX2 transplantation (CCI+EA+FBs-pLNCX2) or PBS (CCI+EA+PBS) as well as the FBs-GDNF transplantation group without EA treatment (CCI+FBs-GDNF). Our data suggest that EA and cell therapy can synergistically attenuate hyperalgesia in neuropathic pain rats.

Acupuncture in the Postoperative Setting for Breast Cancer Patients: A Feasibility Study

“…Multiple benefits of acupuncture in surgical patients have been demonstrated in the literature (Dong et al, 2013). Acupuncture appears to have an important role as an effective adjunctive therapy for postoperative pain management .…”

Nociceptor plasticity: A closer look

“…Conversely, the role of this channel in visceral pain remains unknown; in fact, Nav 1.7 seems not to be required for visceral pain processing, and a very recent study advocates that pharmacological block of NaV 1.7 alone in the viscera may be insufficient in targeting chronic visceral pain (Hockley et al, ). NaV 1.8 is involved in different adaptive and neuroplasticity‐related mechanisms on which light has been shed with NaV 1.8 gene knock‐out models: different investigations detected a marked hyperalgesia after nociceptive stimulation in mice (Dong, Sun, Lu, Wang, & Wu, ); also, if a Chronic Constriction Injury (CCI) was provoked in mice, mRNA alteration and protein rearrangement were observed in cells (Wang, Wang, et al, ). Moreover, NaV 1.8 channels were over‐expressed in Large Sensorial Cells after L5‐L6 root ligation (Fukuoka & Noguchi, ).…”

Electroacupuncture treatment contributes to the downregulation of neuronal nitric oxide synthase and motoneuron death in injured spinal cords following root avulsion of the brachial plexus

“…It is generally accepted that neurotrophic factors may prevent motoneuron death following PNI (38)(39)(40)(41). In the hippocampus, following cerebral ischemia-reperfusion injury in a mouse model, EA treatment enhanced endogenous BDNF expression, thereby possibly improving the survival environment for intracerebral neurons (42,43).…”