miR-183 cluster scales mechanical pain sensitivity by regulating basal and neuropathic pain genes.
نویسندگان
چکیده
Nociception is protective and prevents tissue damage but can also facilitate chronic pain. Whether a general principle governs these two types of pain is unknown. Here, we show that both basal mechanical and neuropathic pain are controlled by the microRNA-183 (miR-183) cluster in mice. This single cluster controls more than 80% of neuropathic pain-regulated genes and scales basal mechanical sensitivity and mechanical allodynia by regulating auxiliary voltage-gated calcium channel subunits α2δ-1 and α2δ-2. Basal sensitivity is controlled in nociceptors, and allodynia involves TrkB+ light-touch mechanoreceptors. These light-touch-sensitive neurons, which normally do not elicit pain, produce pain during neuropathy that is reversed by gabapentin. Thus, a single microRNA cluster continuously scales acute noxious mechanical sensitivity in nociceptive neurons and suppresses neuropathic pain transduction in a specific, light-touch-sensitive neuronal type recruited during mechanical allodynia.
منابع مشابه
MicroRNA-183 Suppresses Neuropathic Pain and Expression of AMPA Receptors by Targeting mTOR/VEGF Signaling Pathway.
BACKGROUND Neuropathic pain is a type of chronic pain that results from dysfunctions of the somatosensory nerve system. This study was aimed to investigate the effect of mTOR/VEGF signaling pathway on neuropathic pain and the regulation mechanisms of miR-183 on AMPA Receptors through mTOR/VEGF signaling pathway. METHODS Chronic compress injury (CCI) model was constructed in the current study,...
متن کاملMicroRNA cluster miR-17-92 regulates multiple functionally related voltage-gated potassium channels in chronic neuropathic pain
miR-17-92 is a microRNA cluster with six distinct members. Here, we show that the miR-17-92 cluster and its individual members modulate chronic neuropathic pain. All cluster members are persistently upregulated in primary sensory neurons after nerve injury. Overexpression of miR-18a, miR-19a, miR-19b and miR-92a cluster members elicits mechanical allodynia in rats, while their blockade alleviat...
متن کاملDownregulation of microRNA-218 relieves neuropathic pain by regulating suppressor of cytokine signaling 3.
Neuropathic pain is an incapacitating disease that affects a large number of people worldwide, but effective therapies have not yet been established. microRNAs (miRs) are short non-coding RNAs that participate in several biological processes and states, including neuropathic pain. Nevertheless, the precise role of miRs in regulating neuropathic pain remains largely unknown. In the present study...
متن کاملScaling pain threshold with microRNAs.
P ain is not something universally enjoyed, especially chronic pain involving nerve damage, referred to as neuropathic pain (1). Pain perception can be modulated in a variety of ways—for example, by focusing attention on the painful stimulus. On page 1168 of this issue, Peng et al. (2) report that pain threshold in dorsal root ganglion neurons (DRG), which relay peripheral sensory information t...
متن کاملMiR-30b Attenuates Neuropathic Pain by Regulating Voltage-Gated Sodium Channel Nav1.3 in Rats
Nav1.3 is a tetrodotoxin-sensitive isoform among voltage-gated sodium channels that are closely associated with neuropathic pain. It can be up-regulated following nerve injury, but its biological function remains uncertain. MicroRNAs (miRNAs) are endogenous non-coding RNAs that can regulate post-transcriptional gene expression by binding with their target mRNAs. Using Target Scan software, we d...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Science
دوره 356 6343 شماره
صفحات -
تاریخ انتشار 2017