Studies on deep brain stimulation of the ventral posterolateral nucleus for reducing cold allodynia

Abstract

Neuropathic pain is often severe. Neuropathic pain causes patients to feel

indescribable pain in whole life. Neuropathic pain, one of the degenerative

diseases, is caused by direct or indirect nerve injury. To modulate pain in

patients, deep brain stimulation (DBS) is used in clinic, but its mechanism

of action remains unclear. Patients with neuropathic pain can feel pain by

various types of stimulations such as mechanical and cold stimuli. However,

studies of cold allodynia are less than those of tactile allodynia. To study

the effect of DBS for cold allodynia, three experiments were carried on

using experimental animals. First, it was found that conventional behavior

test with DBS study on neuropathic pain could not alter cold allodynia.

Therefore, in second experiment, an altered behavior test method which is

measuring duration of showing pain responses is introduced, and it is

different from conventional test method for measuring neuropathic pain. It 2

is, besides, demonstrated that the new test method is well co-related with

conventional one. Finally, in third experiment, the new test method for

measuring cold allodynia was applied for DBS study, and it is demonstrated

that cold allodynia was decreased by DBS. Besides, further experiment

was carried on for investigating action mechanism of DBS on cold

allodynia.

In this study, the suppression of pain by DBS in the Ventral posterolateral

nucleus (VPL) in neuropathic pain rats was observed. To carry on animal

experiments, a tibial and sural transection model which is one of sciatic

nerve injury models was used, and mechanical and cold allodynia through

von Frey and acetone tests were measured. Especially, a new behavior test

method which is altered from conventional response counting method was

applied in this study. The altered method records the duration of pain

response. After all, to demonstrate how DBS acts in modulating pain,

electrophysiological study was carried on.

First, it is found that the electrical stimulation of the VPL effectively

suppresses mechanical allodynia. However it could not be demonstrated any

changes in cold allodynia using conventional behavior test method. Second,

the new behavior test that records the time of showing withdrawal

behaviors by pain stimulation. DBS in the VPL (VPL DBS) demonstrated

that pain response duration was significantly reduced in mechanical

allodynia. Finally, this new behavior test method was applied for measuring

cold allodynia. It was found that there are differences in the degree of cold

allodynia elicited between a conventional method that measured the number

of pain responses and altered novel method that measured the duration of

pain responses. Cold allodynia after DBS did not differ when conventional

analysis was applied, but the pain response duration was decreased. In

electrophysiological study, it was demonstrated that neuronal activity in the

VPL is suppressed by DBS in VPL. From this study, it could be suggested

that VPL DBS can modulate cold allodynia. Besides, it could be also

suggested that the difference between tactile and cold allodynia in VPL

DBS is resulted from complex pathways on pain processing and pain

signaling.