Effects Of Inhibition Of Primary Somatosensory Cortex On Laser Induced Brain Responses In Rats

As our basic feeling,pain can help us perceive the noxious stimulus and protect us from harm,which plays an indispensable role in our life.Pain is a distressing experience associated with actual or potential tissue damage with sensory,emotional,cognitive and social components.The definition of pain promulgated by the International Association for the Study of Pain has provided a powerful conceptual anchor for scientific and healthcare professional advances in understanding the nature and treatment of acute and chronic pain.we need to understand the nature of pain from the biopsychosocial perspective.In the past few decades,our understanding of the neural mechanisms of pain has been rapidly improved,however,there is still a lack of understanding of the basic mechanisms of pain processing.Whereas there is a general agreement that functional neuroimaging techniques like electroencephalography(EEG),magnetoencephalography(MEG),functional magnetic resonance imaging(fMRI),and positron emission tomography(PET)reliably detect increased neural activity in S1 in response to the simulation of non-nociceptive in humans.Nevertheless,the role of primary somatosensory cortex(S1)in pain processing has long been in dispute.Human brain imaging studies have not consistently reveal pain-related activation of S1.As a matter of fact,in comparison with the constantly described responses in the thalamus,in the insular cortex,and in the cingulate cortex,responses to nociceptive stimulation in S1 are reported in approximately 75 % of functional neuroimaging studies.A number of studies has adopted non-nociceptive specific stimuli such as electrical or mechanical stimuli,these stimuli not only activate nociceptive A? and C fibers but also the coactivation of non-nociceptive A? fibers.A? fibers is tactile fibers,so it is not possible to exclude that the responses in S1 are entirely explained by the tactile input concomitant to the nociceptive input.Several factors may also contribute to the different results among studies.First,the evidence demonstrating that S1 activation is highly modulated by cognitive factors that alter pain perception,including attention and previous experience.Second,the precise somatotopic organization of S1 may lead to small focal activations,which are degraded by sulcal anatomical variability when averaging data across subjects.Finally,some EEG and MEG studies to localize the cortical sources of the responses evoked by nociceptive stimuli recorded on the scalp,using different source analysis approaches,it could also be the cause of inconsistent S1 detection results.Moreover,in those study who find S1 is activated by nociceptive stimuli,found that the activation of S1 located mainly contralateral to the side of stimulation.The role of S1 ipsilateral to the side of nociceptive stimuli has not been clearly confirmed.The discovery of neurons with bilateral receptive fields in the hand region of primary somatosensory cortex(S1FL)has firmly established in non-human mammals(such as cats,monkeys).This implies the the bilateral S1 representation of somatosensory information presented to the hands.Furthermore,Subjects who have had one cerebral hemisphere injured or surgically removed retain the capacity to be consciously aware of a painful stimulus presented ipsilateral to their remaining hemisphere.Quantitative psychophysical analysis of these subjects reveals that they have almost no disruption of their capacity to experience and evaluate pain intensity.These results suggest the existence of bilateral S1 mechanism engaged in the processing of nociceptive stimuli.Pain research using animal models is a continuing necessity–to understand fundamental mechanisms,identify new analgesic targets,and inform,guide and follow up human studies–if novel analgesics are to be developed for the treatment of chronic pain.To demonstrate the two issues above,we carried out the following two experiments.In Study 1,We used microinjection technique and electrocorticography(ECoG)recording to investigate the role of S1 in pain processing.To ascertain whether S1 responds to nociceptive stimuli,it is crucial to employ somatosensory stimuli that activate A? and C skin nociceptors selectively,without the coactivation of non-nociceptive A? fibers.Without contact with the skin,laser stimulators is suitable to explore the nociceptive system.Infrared lasers are able to circumvent most of the shortcomings encountered by conventional heat stimulators.Consistent with human studies,it is commonly reported that laser evoked ERPs in freely moving rodents also show different components at latencies compatible with the conduction velocity of A?-fibres and C-fibres.However,“A?-ERPs” virtually reflect the activation of the auditory system by laser generated ultrasounds,A?-fibres are virtually never activated by heat in rodents.By using ongoing white noise to abolish the laser evoked ultrasound response,therefore,the LEPs of rat in this study mainly reflects the activation of C-fibres pathway.By surgically implantation ECo G electrodes and placement a single stainless steel guide cannula into the forelimb representative area of left S1(S1FL),GABAA receptor agonist muscimol was then microinjected into S1 FL in freely-moving rodents to inhibit the activity of S1 FL,in order to compare the effects of muscimol injection,saline injection was also performed in the S1 FL of the same rat,after the infusion,laser stimulation applied to the right forepaw of the rats,subsequently observed the changes of laser-evoked cortical responses compared with the saline control condition.The results showed that the inhibition in S1 FL regions reduce the N1 amplitude of C fiber LEPS(C-LEPS).The study confirmed that S1 contralateral to the stimuli is involved in the processing of painful stimuli.In Study 2,We also used microinjection technique and ECo G recording to investigate the role of S1 ipsilateral to the side of nociceptive stimuli.By surgically implantation ECo G electrodes and placement the stainless steel guide cannula into left S1 FL and left primary visual cortex(V1),muscimol and saline were then microinjected into S1 FL and V1 in order in freely-moving rodents,after the infusion,the laser stimuli randomly applied to the left and right forepaw of the rats,subsequently observed the changes of laser-evoked cortical responses compared with the control condition.The results showed that the inhibition in S1 FL regions will reduce the N1 amplitude of C-LEPS of the left and right forepaw.According to the EEG topography,when the inhibition of left S1 FL,then the stimulation applied to the left forepaw,the responses of S1 ipsilateral to the side of nociceptive stimuli will also reduced significantly.These results suggest that painful stimuli can activate both the left-and right-S1,both sides of S1 were involved in the processing of nociceptive stimulus.The two studies will provide strong evidence to solve the two problems above,will help us to understand the central mechanism behind this basic feeling and provide theoretical support for the later research.