Electroacupuncture Zusanli (ST36) on Release of Nitric Oxide in the Gracile Nucleus and Improvement of Sensory Neuropathies in Zucker Diabetic Fatty Rats

Abstract

The purpose of these studies was to examine the effects of electroacupuncture (EA) Zusanli (ST36) on release of nitric oxide (NO) in the gracile nucleus (GN) and determine if functional neuropathic changes were modified by EA ST36-induced NO in the nucleus in Zucker diabetic fatty (ZDF) rats. The foot withdrawal responses to mechanical, thermal and cold stimuli were measured before and after EA stimulation. A microdialysis probe was implanted in the GN and dialysate samples were collected 20 min before, during and after EA ST36. Total nitrate and nitrite (NOx −) concentrations in the samples were quantified by using chemiluminescence. The baseline dialysate NOx − concentrations in the GN were decreased in ZDF rats compared to lean control (LC) rats (P < .05). In ZDF rats, dialysate NOx − releases in the GN were markedly increased during EA ST36, whereas in LC rats, the releases were moderately enhanced at 20–40 min after EA ST36. The withdrawal latencies to mechanical, cold and thermal stimuli were significantly improved 20 min after EA ST36 both in LC and ZDF rats, but not altered by non-acupoint stimulation. The withdrawal latencies to EA ST36 were further potentiated by 3-morpholinyl-sydnoneimine and inhibited by NG-Propyl-l-arginine infused into the GN in ZDF rats (P < .05). These results show that EA ST36 increases NO release in the GN, and NO in the nucleus modifies withdrawal latencies to mechanical, cold, and thermal nociception stimuli. Data suggest that EA ST36 induces NO release in the GN, which contributes to improvement of sensory neuropathies in rats.

Pioglitazone Inhibits the Development of Hyperalgesia and Sensitization of Spinal Nociresponsive Neurons in Type 2 Diabetes

“…Consistent with previous reports, ZDFs developed mechanical 6, 25, 49, 69, 78, 80, 92, 101, 112 , heat 25, 49, 78, 80 , and cold hyperalgesia 80 at 14 to 18 wks of age 25, 69, 101 , results which we replicated in two separate cohorts. In contrast, a comparatively small number of ZDF studies report either mechanical hypoalgesia 89 , heat hypoalgesia 89, 92, 101 , no difference in heat 6 or pressure 73 response thresholds, and/or pressure hyperalgesia prior to hyperglycemia 79 .…”

“…Hyperglycemia develops within 6–10 wks of age 6, 13, 49, 92 in ZDF but not Zucker Lean (ZL fa/+ ) controls, and is followed by behavioral correlates of PDN, including hypersensitivity to mechanical 6, 25, 69, 78, 92, 101, 112 and thermal 25, 49, 78, 80 somatosensory stimulation. However, conflicting studies report either hypoalgesia 89, 92 or hyperalgesia 78, 112 in similarly aged ZDF.…”

Mechanisms of Acupuncture–Electroacupuncture on Persistent Pain

“…164 Electroacupuncture at ST36 induces nitric oxide in the gracile nucleus to attenuate pain in Zucker diabetic fatty rats. 165 In contrast, another study showed that electroacupuncture at ST36 and SP9 inhibits nitric oxide synthase expression in the spinal cord of neuropathic rats. 166 Involvement of nitric oxide in electroacupuncture analgesia needs to be confirmed.…”

Impaired expression of neuronal nitric oxide synthase in the gracile nucleus is involved in neuropathic changes in Zucker Diabetic Fatty rats with and without 2,5-hexanedione intoxication

“…These experiments were performed using inbred male Zucker diabetic fatty (ZDF Gmi™fa/fa) rats (4 months) and age-matched lean, non-diabetic (ZDF Gmi™ +/+ or +/fa) control rats (Genetic Models, Inc., Indianapolis) (Peterson, 1995; Rong, Ma, 2011). The protocol was approved by the Animal Care and Use Committee of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, and was in accord with AAALAC and NIH guidelines.…”

“…Recent studies showed that pain and pressure thresholds are decreased in Zucker Diabetic Fatty (ZDF) rats, a type II diabetic model (Rong, Ma, 2011; Russell, et al, 2008; Zhuang, et al, 1997). Several studies demonstrated that systemic administration of 2,5-hexanedione (2,5-HD) causes neurofilamentous axonal swellings and damages, which prevent proximal-to-distal transport of neurofilaments and other substances, resulting in profound neuropathic changes including hyperalgesia and limb paralysis (Anthony, et al, 1983; LoPachin, et al, 1994).…”