Electroacupuncture Alleviated Referral Hindpaw Hyperalgesia via Suppressing Spinal Long-Term Potentiation (LTP) in TNBS-Induced Colitis Rats

Abstract

Although referred pain or hypersensitivity has been repeatedly reported in irritable bowel syndrome (IBS) patients and experimental colitis rodents, little is known about the neural mechanisms. Spinal long-term potentiation (LTP) of nociceptive synaptic transmission plays a critical role in the development of somatic hyperalgesia in chronic pain conditions. Herein, we sought to determine whether spinal LTP contributes to the referral hyperalgesia in colitis rats and particularly whether electroacupuncture (EA) is effective to alleviate somatic hyperalgesia via suppressing spinal LTP. Rats in the colitis group (induced by colonic infusion of 2,4,6-trinitrobenzenesulfonic acid, TNBS), instead of the control and vehicle groups, displayed evident focal inflammatory destruction of the distal colon accompanied not only with the sensitized visceromotor response (VMR) to noxious colorectal distension (CRD) but also with referral hindpaw hyperalgesia indicated by reduced mechanical and thermal withdrawal latencies. EA at Zusanli (ST36) and Shangjuxu (ST37) attenuated the severity of colonic inflammation, as well as the visceral hypersensitivity and referral hindpaw hyperalgesia in colitis rats. Intriguingly, the threshold of C-fiber-evoked field potentials (CFEFP) was significantly reduced and the spinal LTP was exaggerated in the colitis group, both of which were restored by EA treatment. Taken together, visceral hypersensitivity and referral hindpaw hyperalgesia coexist in TNBS-induced colitis rats, which might be attributed to the enhanced LTP of nociceptive synaptic transmission in the spinal dorsal horn. EA at ST36 and ST37 could relieve visceral hypersensitivity and, in particular, attenuate referral hindpaw hyperalgesia by suppressing the enhanced spinal LTP.

Electroacupuncture Inhibits the Activity of Astrocytes in Spinal Cord in Rats with Visceral Hypersensitivity by Inhibiting P2Y1 Receptor‐Mediated MAPK/ERK Signaling Pathway

“…(b)), 40 mmHg (P < 0.01, Figure 1(c)), 60 mmHg (P < 0.01, Figure 1(d)), and 80 mmHg (P < 0.05,Figure 1(e)), indicating that inhibiting activation of astrocyte reduced chronic visceral hypersensitivity in IBS model which is consistent with previous reports on the role of glial cells in other inflammatory visceral hypersensitivities[17].…”

“…Intestinal inflammation injury leads to the activation of spinal cord astrocytes which release a large number of neuroactive substances, enhance the sensitivity and reactivity of dorsal horn neurons, and generate central sensitization [15,16]. For example, 2,4,6-trinitrobenzene sulfonic acid (TNBS) can lead to the enhancement of long-term potentiation (LTP) in pain synaptic transmission of the spinal dorsal horn in colitis rats [17]. e purinergic system regulates the activity of the glutamate energy system [18] which affects the NMDA receptor and also plays an important role in the communication of glial cells by regulating glutamate release in glial cells of the spinal cord [19,20].…”

Electroacupuncture and Moxibustion Regulate Hippocampus Glia and Mitochondria Activation in DSS‐Induced Colitis Mice

“…Clinical and experimental studies have shown beneficial role of acupuncture and moxibustion in reducing IBD disease activity and inflammation [20][21][22]. Our previous studies also found that both EA and moxibustion have therapeutic effect on colitis rats [4,11,23]. Herein, we sought to observe whether EA and moxibustion could be able to regulate the astrocyte and microglial and mitochondria activation of hippocampal area in the colitis model, providing new clues for studying the curative effect of EA and moxibustion on the basis of gut-brain axis.…”

Mitochondrial Respiratory Chain and Its Regulatory Elements SIRT1 and SIRT3 Play Important Role in the Initial Process of Energy Conversion after Moxibustion at Local Skin

“…Electroacupuncture at ST36 acupoint can effectively inhibit lipopolysaccharide-induced multiple peritonitis in mice [ 47 ]. ST36 was also chosen to investigate the mechanism of moxibustion analgesic effect in our previous studies [ 23 , 48 , 49 ]. Moxibustion at ST36 acupoint can effectively increase the expression of HSP in cardiac muscle, brain tissue, gastric mucosa, and other distal tissues and organs in healthy rats [ 50 ].…”