Increased Nerve Growth Factor Signaling in Sensory Neurons of Early Diabetic Rats Is Corrected by Electroacupuncture

Abstract

Diabetic polyneuropathy (DPN), characterized by early hyperalgesia and increased nerve growth factor (NGF), evolves in late irreversible neuropathic symptoms with reduced NGF support to sensory neurons. Electroacupuncture (EA) modulates NGF in the peripheral nervous system, being effective for the treatment of DPN symptoms. We hypothesize that NGF plays an important pathogenic role in DPN development, while EA could be useful in the therapy of DPN by modulating NGF expression/activity. Diabetes was induced in rats by streptozotocin (STZ) injection. One week after STZ, EA was started and continued for three weeks. NGF system and hyperalgesia-related mediators were analyzed in the dorsal root ganglia (DRG) and in their spinal cord and skin innervation territories. Our results show that four weeks long diabetes increased NGF and NGF receptors and deregulated intracellular signaling mediators of DRG neurons hypersensitization; EA in diabetic rats decreased NGF and NGF receptors, normalized c-Jun N-terminal and p38 kinases activation, decreased transient receptor potential vanilloid-1 ion channel, and possibly activated the nuclear factor kappa-light-chain-enhancer of activated B cells (Nf-κB). In conclusion, NGF signaling deregulation might play an important role in the development of DPN. EA represents a supportive tool to control DPN development by modulating NGF signaling in diabetes-targeted neurons.

A Systematic Review of Experimental and Clinical Acupuncture in Chemotherapy-Induced Peripheral Neuropathy

“…Thus, acupuncture can modify the expression of different genes and the expression of genes that control transcriptional factors that are crucial for cell homeostasis [60]. In Figure 1, we summarized the acupuncture mechanisms and mediators in CIPN based on what we know from animal studies of diabetic neuropathy [59, 61] and from human studies of brain imaging during acupuncture [62]. …”

Auricular Acupressure Can Modulate Pain Threshold

“…After this first examination, a seed of Vaccaria was applied on the top of the scaphoid fossa of one earlobe in the region corresponding to the finger-tips and finger-backs in Nogier's somatotopic map ( Figure 2 ; treated group) or on the neck (control group). Vaccaria seed was applied by Dr. Nori, a qualified and trained physician [ 16 , 32 ]. The acupoint was selected by searching the point most sensitive to a probe (tip tweezers) and tender to palpation.…”

“…On the other hand, Chan et al [ 29 ] found an increased concentration of the spinal antinociceptive neurotransmitter substance P in skin tissue samples derived from acupuncture points in anesthetized dogs, thus suggesting that there is a difference in the neurochemical profile between acupuncture points and control points. Concerning the molecular mechanisms involved in the nociceptive signaling pathways modulated by AT, it has been reported that AT by acupuncture-based techniques exerts its therapeutic effects causing a decrease in activity of the p38 signaling pathway in the spinal cord [ 30 ], an increase in NF- κ B activity [ 31 , 32 ], and a negative regulation of nerve growth factor (NGF) [ 32 – 34 ].…”

Effects of electroacupuncture at 2 and 100 Hz on rat type 2 diabetic neuropathic pain and hyperalgesia-related protein expression in the dorsal root ganglion

“…** P<0.01, compared with the normal group; # P<0.05, ## P<0.01, compared with DNP group options are very limited and only marginally effective. EA has become increasingly popular and is used in the treatment of patients with chronic diseases of the nervous system, including DNP (Nori et al, 2013). EA has been demonstrated as a therapy for managing DNP safely and effectively (Nori et al, 2013), although its mechanism of action remains unclear.…”

“…EA has become increasingly popular and is used in the treatment of patients with chronic diseases of the nervous system, including DNP (Nori et al, 2013). EA has been demonstrated as a therapy for managing DNP safely and effectively (Nori et al, 2013), although its mechanism of action remains unclear. The analgesic effect produced by EA depends on proper prescription of specific acupoints and electrical parameters.…”