الفهرس 
Introduction
PainOnly 14 pages are availabe for public view
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Abstract
Chronic pain is one of the most common health problems in the world and a major challenge to clinical practice (Kuner 2010). It is related to prolonged tissue damage or injuries to the peripheral or central nervous system (CNS), resulting from some complex changes in nociceptive pathways. These include changes in the expression of proteins such as ion channels, transmitters, and receptors, as well as plastic changes in neural circuits of the CNS (Saab 2012).
The high prevalence and incidence of global chronic pain, its substantial and growing comorbidities, and its linkage with myriad social and economic determinants collectively provide an important justification for regarding pain as a public health priority.
The most commonly used drugs to treat this type of pain are opioids, and opioid overdose is now a leading cause of death among young Americans. Opioids are the most widely prescribed drugs for pain, with current estimates at nearly one opioid prescription per living American . While opioids are not the only options for moderate to severe pain, other drugs are no more effective. These issues present a devastating problem for patients, health care systems, and society.
54 healthy volunteers who fulfil the inclusion criteria randomly assigned to three groups of 18 participants each, the first group receive active (anodal) stimulation targeting the left primary motor cortex (the current intensity 2 mA for 20 min). The second group also active stimulation targeting the left insular cortex with the same parameters as the previous group. The third group the sham group targeting the lt primary motor cortex ( current intensity 2mA for only 30 seconds then ramped down to zero maintained for 20 minutes).
The device used is a 4x1 multichannel adaptor (CBL-204, Biopac System Inc., Goleta, CA, USA) connected to a conventional tDCS battery-driven constant current stimulator (NeuroConn GmbH, Ilmenau, Germany). Stimulation was delivered using silver/silver chloride sintered ring electrodes (EL-TP-RNG Sintered; Stens Biofeedback Inc., San Rafael, CA, USA).
Participants were evaluated for the primary and secondary sensitisation using the VF brush also the VF filament and the neurotips® for assessment of pinprick hyperalgesia. Also, the pain intensity was subjectively assessed using the NRS(0-100).at baseline after removal of capsaicin cream and after the HD tDCS session.
The main findings of our study was:
1) Active stimulation was tolerable and didn’t generate significant adverse effects.
2) Active stimulation targeting the insula and the motor cortex relative to sham stimulation decreases the pain score resulted from capsaicin application.
3) The time to start to feel significant decrease in pain score is shorter in the active stimulation groups compared to sham group.
4) HD tDCS in the way we have carried this out can reduce the primary and secondary sensitisation more than placebo (sham) stimulation. This will imply that the effect is more than the just subjective reduction in reported pain. There is a definitive reduction in neurophysiological surrogates as well.
5) We were able to stimulate the insula, and the effect of this is at least the same magnitude as the primary motor cortex stimulation which makes this a feasible target for those with more widespread pain.
6) We can measure areas of primary and secondary sensitisation and use it as a surrogate for the biological effect of any intervention. The HD- tDCS method we use can stimulate insula as well as PMC effectively.
7) HD-tDCS can modulate pain as well as primary and secondary sensitisation.
Overall, this dissertation tried to answer some questions about the effects of the HD tDCS when targeting the primary motor cortex or the insular cortex as regard pain, alodynia and hyperalgesia induced by capsaicin pain model.
Evidence so far shows that the insular cortex stimulation is bilateral based on the neuroimaging studies. However, the effect on the primary motor cortex also suggests a bilateral effect in some studies and contralateral effect in other studies.
Future directions:
Stimulation of the brain is a rapidly growing field with an enormous potential for research and therapy. Shortly more studies using tDCS (conventional and HD-tDCS) will be expected to understand better the underlying mechanisms followed by more efficient customised stimulations protocols.
Meta-analysis and controlled large-scale clinical trials will fill in the need for more robust study findings regarding the effect of tDCS in various neurological and psychiatric disorders.
The research will focus on other methods of low-intensity transcranial electrical stimulations that have been less investigated, such as transcranial Alternating Current Stimulation (tACS), transcranial Random Noise Stimulation (tRNS) and transcranial Pulsed Current Stimulation (tPCS).
Modelling studies will be more accurate in estimating the electric field flow induced by tDCS in cortical as well as in deeper subcortical brain areas. Furthermore, methods to fully automate current-flow modelling for individualised treatment with tDCS will further investigated for clinical use.
These simulation studies might require incorporation of individual structural and functional connectivity data to verify whether the current follows anatomical or functional connectivity pathways, once it reaches the cortex.
Future technical developments will focus on producing new designs of electrodes, stimulators, devices resulting in low-cost, light-weight, programmable and portable tDCS devices. Development of new electrodes and new electrode montages will lead to new forms of tDCS protocols, such as simultaneous anodal stimulation on different brain regions (as the cerebellum, spinal cord).
Recording of electrical brain activity from the same electrodes as used for stimulation will allow for a more accurate understanding of activity and connectivity changes involved or induced by tDCS. With the gained knowledge, it is very likely that the application of tDCS will increasingly develop in routine clinical practice for a variety of neurological and psychiatric conditions over the next few years.
The combination between different modalities of NIBS as a combination between tDCS and rTMS. Also, the use of HD tDCS one side in the insula plus the PMC o the other may give a bigger biological effect.
In conclusion, this study demonstrates that anodal HD tDCS targeting the primary motor cortex or the insular cortex induce analgesic response presented by a rapid reduction in the pain scores also associated with the reduction in the neurophysiological surrogates as well.