Differential Activation of pERK1/2 and c-Fos Following Injury to Different Regions of Primary Sensory Neuron

Abstract

Nerve injury causes hyperexcitability of the dorsal root ganglion (DRG) and spinal dorsal horn (DH) neurons, which results in neuropathic pain. We have previously demonstrated that partial dorsal rhizotomy (PDR) produced less severe pain-like behavior than chronic constriction injury (CCI) or chronic compression of DRG (CCD) and did not enhance DRG neuronal excitability. However, the mechanisms underlying such discrepancy remain unclear. This study was designed to compare the activation of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) in DRG and DH, and c-Fos in DH following treatments of CCI, CCD, and PDR. We confirmed that thermal hyperalgesia produced by PDR was less severe than that produced by CCI or CCD. We showed that pERK1/2 in DRG and DH was greatly activated by CCI or CCD, whereas PDR produced only transient and mild pERK1/2 activation. CCI, CCD, and PDR induced robust c-Fos expression in DH; nevertheless, c-Fos+ neurons following PDR were much fewer than that following CCI or CCD. Blocking retrograde axonal transport by colchicine proximal to the CCI injury site diminished thermal hyperalgesia and inhibited pERK1/2 and c-Fos activation. These findings demonstrate that less severe pain-like behavior produced by PDR than CCI or CCD attributes to less activation of pERK1/2 and c-Fos. Such neurochemical activation partially relies on retrograde axonal transport of certain “injury signals” from the peripheral injured site to DRG somata.

Spinal HDAC6 mediates nociceptive behaviors induced by chronic constriction injury via neuronal activation and neuroinflammation

“…Previous studies have shown that neurochemical alterations such as c-Fos, p-CREB in the ipsilateral DH induced by CCI result in behavioral changes of NP. 26 , 27 Here we investigated whether HDAC6 is involved in the activation of neurons (c-Fos and p-CREB) caused by CCI. Immunofluorescence results showed that the increased expressions of c-Fos and p-CREB induced by CCI were greatly suppressed by ACY-1215 (25 mg/kg, i.p., once a day from day 1 to 14 after CCI) for 14 consecutive days.…”

Methyl Ferulic Acid Alleviates Neuropathic Pain by Inhibiting Nox4-induced Ferroptosis in Dorsal Root Ganglia Neurons in Rats

“…Thus, it is critically vatal to explore new technologies or develop effective drugs [27]. Neuropathic pain is caused by the retrograde transmission of peripheral "injury signals" from the injured site to the DRG, causing hyperexcitability of DRG neurons, which form synapses with spinal dorsal horn (SDH) neurons and ultimately project to the thalamus and cerebral cortex [28,29]. Researches showed that inhibiting oxidative stress in DRG can diminish neuropathic pain [30,31].…”

Methyl ferulic acid alleviates neuropathic pain by inhibiting Nox4-induced ferroptosis in dorsal root ganglia neurons in rats

“…Thus, it is critically vatal to explore new technologies or develop effective drugs [27]. Neuropathic pain is caused by the retrograde transmission of peripheral "injury signals" from the injured site to the DRG, causing hyperexcitability of DRG neurons, which form synapses with spinal dorsal horn (SDH) neurons and ultimately project to the thalamus and cerebral cortex [28,29]. Researches showed that inhibiting oxidative stress in DRG can diminish neuropathic pain [30,31].…”