Motor cortex stimulation inhibits thalamic sensory neurons and enhances activity of PAG neurons: possible pathways for antinociception

Pain. 2012 Dec;153(12):2359-2369. doi: 10.1016/j.pain.2012.08.002. Epub 2012 Sep 25.


Motor cortex stimulation is generally suggested as a therapy for patients with chronic and refractory neuropathic pain. However, the mechanisms underlying its analgesic effects are still unknown. In a previous study, we demonstrated that cortical stimulation increases the nociceptive threshold of naive conscious rats with opioid participation. In the present study, we investigated the neurocircuitry involved during the antinociception induced by transdural stimulation of motor cortex in naive rats considering that little is known about the relation between motor cortex and analgesia. The neuronal activation patterns were evaluated in the thalamic nuclei and midbrain periaqueductal gray. Neuronal inactivation in response to motor cortex stimulation was detected in thalamic sites both in terms of immunolabeling (Zif268/Fos) and in the neuronal firing rates in ventral posterolateral nuclei and centromedian-parafascicular thalamic complex. This effect was particularly visible for neurons responsive to nociceptive peripheral stimulation. Furthermore, motor cortex stimulation enhanced neuronal firing rate and Fos immunoreactivity in the ipsilateral periaqueductal gray. We have also observed a decreased Zif268, δ-aminobutyric acid (GABA), and glutamic acid decarboxylase expression within the same region, suggesting an inhibition of GABAergic interneurons of the midbrain periaqueductal gray, consequently activating neurons responsible for the descending pain inhibitory control system. Taken together, the present findings suggest that inhibition of thalamic sensory neurons and disinhibition of the neurons in periaqueductal gray are at least in part responsible for the motor cortex stimulation-induced antinociception.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / physiology*
  • Animals
  • Deep Brain Stimulation / methods*
  • Neural Inhibition / physiology*
  • Nociception / physiology*
  • Nociceptors / physiology*
  • Rats
  • Thalamus / physiology*