scholarly journals The Role of TMEM16A/ERK/NK-1 Signaling in Dorsal Root Ganglia Neurons in the Development of Neuropathic Pain Induced by Spared Nerve Injury (SNI)

2021 ◽  
Author(s):  
Qinyi Chen ◽  
Liangjingyuan Kong ◽  
Zhenzhen Xu ◽  
Nan Cao ◽  
Xuechun Tang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Dorsal Root ◽  
Electrophysiological Recording ◽  
Erk Pathway ◽  
Spared Nerve Injury ◽  
Positive Interaction ◽  
Nociceptive Neurons ◽  
Nociceptive Responses

AbstractIncreasing evidence suggests that transmembrane protein 16A (TMEM16A) in nociceptive neurons is an important molecular component contributing to peripheral pain transduction. The present study aimed to evaluate the role and mechanism of TMEM16A in chronic nociceptive responses elicited by spared nerve injury (SNI). In this study, SNI was used to induce neuropathic pain. Drugs were administered intrathecally. The expression and cellular localization of TMEM16A, the ERK pathway, and NK-1 in the dorsal root ganglion (DRG) were detected by western blot and immunofluorescence. Behavioral tests were used to evaluate the role of TMEM16A and p-ERK in SNI-induced persistent pain and hypersensitivity. The role of TMEM16A in the hyperexcitability of primary nociceptor neurons was assessed by electrophysiological recording. The results show that TMEM16A, p-ERK, and NK-1 are predominantly expressed in small neurons associated with nociceptive sensation. TMEM16A is colocalized with p-ERK/NK-1 in DRG. TMEM16A, the MEK/ERK pathway, and NK-1 are activated in DRG after SNI. ERK inhibitor or TMEM16A antagonist prevents SNI-induced allodynia. ERK and NK-1 are downstream of TMEM16A activation. Electrophysiological recording showed that CaCC current increases and intrathecal application of T16Ainh-A01, a selective TMEM16A inhibitor, reverses the hyperexcitability of DRG neurons harvested from rats after SNI. We conclude that TMEM16A activation in DRG leads to a positive interaction of the ERK pathway with activation of NK-1 production and is involved in the development of neuropathic pain after SNI. Also, the blockade of TMEM16A or inhibition of the downstream ERK pathway or NK-1 upregulation may prevent the development of neuropathic pain.

scholarly journals Abnormal Reinnervation of Denervated Areas Following Nerve Injury Facilitates Neuropathic Pain

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1007 ◽  
Author(s):  
Hodaya Leibovich ◽  
Nahum Buzaglo ◽  
Shlomo Tsuriel ◽  
Liat Peretz ◽  
Yaki Caspi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Dorsal Root ◽  
Pain Sensitivity ◽  
Spared Nerve Injury ◽  
Drg Neurons ◽  
Nociceptive Neurons ◽  
Peripheral Innervation ◽  
Innervation Patterns

An injury to peripheral nerves leads to skin denervation, which often is followed by increased pain sensitivity of the denervated areas and the development of neuropathic pain. Changes in innervation patterns during the reinnervation process of the denervated skin could contribute to the development of neuropathic pain. Here, we examined the changes in the innervation pattern during reinnervation and correlated them with the symptoms of neuropathic pain. Using a multispectral labeling technique—PainBow, which we developed, we characterized dorsal root ganglion (DRG) neurons innervating distinct areas of the rats’ paw. We then used spared nerve injury, causing partial denervation of the paw, and examined the changes in innervation patterns of the denervated areas during the development of allodynia and hyperalgesia. We found that, differently from normal conditions, during the development of neuropathic pain, these areas were mainly innervated by large, non-nociceptive neurons. Moreover, we found that the development of neuropathic pain is correlated with an overall decrease in the number of DRG neurons innervating these areas. Importantly, treatment with ouabain facilitated reinnervation and alleviated neuropathic pain. Our results suggest that local changes in peripheral innervation following denervation contribute to neuropathic pain development. The reversal of these changes decreases neuropathic pain.

The role of dorsal root ganglia PIM1 in peripheral nerve injury-induced neuropathic pain

2019 ◽  
Vol 709 ◽  
pp. 134375
Author(s):  
Yun Zou ◽  
Yumeng Cao ◽  
Yuqi Liu ◽  
Xinyi Zhang ◽  
Jinbao Li ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Dorsal Root Ganglia ◽  
Peripheral Nerve Injury ◽  
Dorsal Root

scholarly journals The Antiallodynic Action of Pregabalin May Depend on the Suppression of Spinal Neuronal Hyperexcitability in Rats with Spared Nerve Injury

2014 ◽  
Vol 19 (4) ◽  
pp. 205-211 ◽  
Author(s):  
Lei Ding ◽  
Jie Cai ◽  
Xiang-Yang Guo ◽  
Xiu-Li Meng ◽  
Guo-Gang Xing
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Dynamic Range ◽  
Inhibitory Effect ◽  
Electrophysiological Recording ◽  
Spared Nerve Injury ◽  
Withdrawal Threshold ◽  
Wdr Neurons

BACKGROUND: Pregabalin (PGB) is a novel antiepileptic drug and is also used as a first-line medication for the treatment of neuropathic pain. However, the mechanisms of its analgesic effects remain largely unknown.OBJECTIVES: To elucidate the mechanisms underlying the antiallodynic action of PGB in rats with neuropathic pain.METHODS: In a rat model of neuropathic pain induced by spared nerve injury, mechanical allodynia, as a behavioural sign of neuropathic pain, was assessed by measuring 50% paw withdrawal threshold with von Frey filaments. Activities of dorsal horn wide dynamic range (WDR) neurons were examined by extracellular electrophysiological recording in vivo.RESULTS: Spinal administration of PGB exerted a significant antiallodynic effect and a prominent inhibitory effect on the hypersensitivity of dorsal horn WDR neurons in rats with spared nerve injury.CONCLUSION: The antiallodynic action of PGB is likely dependent on the suppression of WDR neuron hyperexcitability in rats with neuropathic pain.

scholarly journals Lack of efficacy of a partial adenosine A1 receptor agonist in neuropathic pain models in mice

2021 ◽  
Author(s):  
Katharina Metzner ◽  
Tilman Gross ◽  
Annika Balzulat ◽  
Gesine Wack ◽  
Ruirui Lu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Partial Agonist ◽  
Pharmacological Intervention ◽  
Spared Nerve Injury ◽  
Drg Neurons ◽  
Behavioral Experiments ◽  
Nociceptive Neurons ◽  
Electrophysiological Properties

AbstractPrevious studies suggest that adenosine A1 receptors (A1R) modulate the processing of pain. The aim of this study was to characterize the distribution of A1R in nociceptive tissues and to evaluate whether targeting A1R with the partial agonist capadenoson may reduce neuropathic pain in mice. The cellular distribution of A1R in dorsal root ganglia (DRG) and the spinal cord was analyzed using fluorescent in situ hybridization. In behavioral experiments, neuropathic pain was induced by spared nerve injury or intraperitoneal injection of paclitaxel, and tactile hypersensitivities were determined using a dynamic plantar aesthesiometer. Whole-cell patch-clamp recordings were performed to assess electrophysiological properties of dissociated DRG neurons. We found A1R to be expressed in populations of DRG neurons and dorsal horn neurons involved in the processing of pain. However, administration of capadenoson at established in vivo doses (0.03–1.0 mg/kg) did not alter mechanical hypersensitivity in the spared nerve injury and paclitaxel models of neuropathic pain, whereas the standard analgesic pregabalin significantly inhibited the pain behavior. Moreover, capadenoson failed to affect potassium currents in DRG neurons, in contrast to a full A1R agonist. Despite expression of A1R in nociceptive neurons, our data do not support the hypothesis that pharmacological intervention with partial A1R agonists might be a valuable approach for the treatment of neuropathic pain.

scholarly journals Role of dorsal root ganglion K2P1.1 in peripheral nerve injury-induced neuropathic pain

2017 ◽  
Vol 13 ◽  
pp. 174480691770113 ◽  
Author(s):  
Qingxiang Mao ◽  
Jingjing Yuan ◽  
Ming Xiong ◽  
Shaogen Wu ◽  
Liyong Chen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Dorsal Root

Role of TRPV4-P2X7 Pathway in Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion

2021 ◽  
Author(s):  
Xiaohua Fan ◽  
Chuanwei Wang ◽  
Junting Han ◽  
Xinli Ding ◽  
Shaocan Tang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Root
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