ELECTROPHYSIOLOGICAL ANALYSIS ASSESSING THE ANALGESIC NATURE OF THE LATERAL HABENULA (LHb)
Abstract
Local field potential (LFP) is a collective neural signal of all the synaptic activity occurring at a specific area of the brain, thereby offering a unique insight into how the brain functions. The habenula is involved in the pain pathway and decision-making. Located above the thalamus, it has been proposed to function with nucleus accumbens and periacqueductal gray
(PAG) along with other regions in a descending pain modulation pathway. The main purpose of the present study was to determine the contribution of LHb to the nociceptive input and the effect of activation on antinociception. One week after implantation of electrode in the LHb in adult Sprague Dawley male rats (n=16), formalin was injected in the right hind paw, LFP recordings were recorded at baseline and post-formalin. Electrical stimulation was delivered to
the LHb, and LFP were recorded in these freely moving animals. Animals
were also subjected to mechanical and thermal paw withdrawal tests to
assess the change of nociception and LFP responses. LFP were analyzed by
power spectrum analysis. The results showed that: (1) Behaviorally,
significant decrease in paw withdrawal threshold and latency were observed
after formalin injections (p < .05), indicating increase in nociception.
Interestingly, electrical stimulation of LHb has significantly reversed the
phenomena, suggesting an antinociceptive role by LHb. (2) Simultaneously, we observed significant increase for the LFP powers during formalin period (p < .05) in response to mechanical and thermal stimuli, which were reduced by
electrical stimulation of LHb (p < .05). (3) There was a trend of significant
increase for all the frequency bands following formalin injection (p < .05)
comparing to the baseline. The possible explanation is that the increased activity in habenula is due to increased inputs from the lateral hypothalamus and the spinal cord, which are part of the neural circuitry involved in pain transmission. (4) Following LHb electrical stimulation, significant decreases of the LFP power in different frequency bands were also observed (p < .05).
Since LHb projects further into ventral tegmental area (VTA, the substantia
nigra (SNc), dorsal raphe, and PAG, which are important structures in
descending modulation of pain, electrical stimulation of habenula may activate the descending inhibitory system to achieve the analgesic effect. In conclusion, formalin-induced inflammatory nociception increases the LFP recordings in the habenula while electrically stimulating this region induce an antinociceptive effect which was also observed via both behavioral and electrophysiological tests.