Discrete Pattern of Burst Stimulation in the Ventrobasal Thalamus for Anti-Nociception

Abstract

The thalamus has been proposed to play a role in sensory modulation via switching between tonic and burst dual firing of individual neurons. Of the two firing modes, altered burst firing has been repeatedly implicated with pathological pain conditions, which suggests that maintaining a certain form of thalamic burst could be crucial for controlling pain. However, specific elements of burst firing that may contribute to pain control have not yet been actively investigated. Utilizing the deep brain stimulation (DBS) technique, we explored the effects of bursting properties in pain control by electrically stimulating the ventrobasal (VB) thalamus in forms of burst patterned to test different aspects of bursts during the formalin induced nociception in mice. Our results demonstrated that electrical stimulations mimicking specific burst firing properties are important in producing an anti-nociceptive effect and found that the ≤3 ms interval between burst pluses (intra-burst-interval: IntraBI) and ≥3 pulses per burst were required to reliably reduce formalin induced nociceptive responses in mice. Periodicity of IntraBI was also suggested to contribute to anti-nociception to a limited extent.

Thalamic Bursts Down-regulate Cortical Theta and Nociceptive Behavior

“…Our previous characterization of burst patterns in rat models of chronic pain 4, 12, 13, 17 is consistent with clinical observations in pain patients 14, 16, 20 . We also reported that burst inhibition by intrathalamic injection of a T-type calcium channel antagonist attenuates cortical theta and nociceptive behaviors 4 .…”

Thalamic Kv7 channels: pharmacological properties and activity control during noxious signal processing

“…Specifically during burst firing, activation of IM results in a decrease in ISIs within a burst, thereby shaping early phases of activity (Storm, 1989). This is important here, as the dynamic properties of bursting are crucial for interfering with the faithful relay of the information, and therefore should reduce pain responses (Huh et al, 2012;Huh and Cho, 2013a). In particular, it has been shown that formalininduced pain altered the intraburst ISI1 and ISI2 of VB TC neurons in a subtle time-dependent manner which was associated with changes in pain-related behaviour (Huh et al, 2012).…”

Urethane anesthesia depresses activities of thalamocortical neurons and alters its response to nociception in terms of dual firing modes

“…After the 20 min recording following urethane injection, 10 μl of 5% formalin (1:20 dilution of 37% formalin solution in double de-ionized water) was injected into the contralateral paw of the electrode implantation site and neuronal activity was continuously recorded for an additional hrs (awake 10 min + urethane 20 min + formalin injection under urethane 60 min). No saline injection control was done because previous studies showed that saline injection does not induce any long-term behavioral expression of nociception and does not have a prolonged effect as formalin injections do (Huang et al, 2006; Huh and Cho, 2013). Mice were unrestrained and freely moving during all awake recording sessions.…”