Involvement of adenosine A1 receptor in electroacupuncture-mediated inhibition of astrocyte activation during neuropathic pain

Abstract

Neuropathic pain is a chronic pain condition caused by damage or dysfunction of the central or peripheral nervous system. Electroacupuncture (EA) has an antinociceptive effect on neuropathic pain, which is partially due to inhibiting astrocyte activation in the spinal cord. We found that an intrathecal injection of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist, reversed the antinociceptive effects of EA in a chronic constriction injury-induced neuropathic pain model. The expression of GFAP in L4-L6 spinal cord was significantly upgraded, while DPCPX suppressed the effect of the EA-mediating inhibition of astrocyte activation, as well as wiping out the EA-induced suppression of cytokine content (TNF-α). These results indicated that the adenosine A1 receptor is involved in EA actions during neuropathic pain through suppressing astrocyte activation as well as TNF-α upregulation of EA, giving enlightenment to the mechanisms of acupuncture analgesia and development of therapeutic targets for neuropathic pain.

Targeting Adenosine Receptors: A Potential Pharmacological Avenue for Acute and Chronic Pain

“…In this report, the effect of A 1 ARs was related to the inhibition of astrocyte activation. [ 29 ]. Similar results were obtained in a Complete Freund’s adjuvant (CFA)-induced inflammatory pain mouse model, corroborating the involvement of A 1 ARs in electroacupuncture-mediated antinociception [ 30 ].…”

Role of spinal adenosine A1 receptors in the analgesic effect of electroacupuncture in a rat model of neuropathic pain

“…11,12 Traditional Chinese medicine considers that repeated acupuncture at the zusanli acupoint has an analgesic effect, and studies have also shown that single acupuncture at the bilateral zusanli acupoints had an analgesic effect on neuropathic pain in rats. 13 Moreover, the analgesic effects of EA were similar to those of conventional acupuncture used in traditional Chinese medicine, with a frequency of 2/100 Hz resulting in the best analgesic effects Figure 6. Effects of AV-shA1RNA and AV-shCTRL on analgesic effect of electroacupuncture.…”

“…17 Studies in a rat model of neuropathic pain found that astrocytes in the spinal cord segment were in an active state, and that activation of A1Rs on these astrocytes inhibited their activation, thereby reducing the release of inflammatory substances and resulting in an analgesic effect. 13 Numerous studies in different animal models of pain have shown that stimulation of A1Rs in the spinal cord or throughout the body can produce analgesic effects. 18 Delivery of a physiological stimulus that does not cause tissue damage, such as mechanical stimulation, hypoxia, or an electric current, is considered to promote the transport of ATP from many types of cells (including dermal tissue and neurons) to the extracellular environment, 19 where it is metabolized into adenosine.…”

Laser irradiation activates spinal adenosine A1 receptor to alleviate osteoarthritis pain in monosodium iodoacetate injected rats

“…The procedures and dosing of DPCPX were performed as previously described (Zhang et al, 2018). Rats were anesthetized with isoflurane.…”

“…However, there are outstanding controversies regarding the role of spinal A1R in acupuncture or electroacupuncture (EA)-mediated analgesia in the central nervous system. For example, Zhang et al (2018) found that intrathecal injection of 8-cyclopentyl-1,3dipropylxanthine (DPCPX) reversed the analgesic effects of EA at ST36 (Zusanli) and LR3 (Taichong) in a neuropathic pain model via the suppression of both astrocyte activation and tumor necrosis factor-α (TNF-α) upregulation. Conversely, Jiang et al (2018) observed that A1R was unchanged when EA was applied along the spine, bilaterally in the same neuropathic pain model.…”