Optogenetic Chemogenetics

As mentioned above, opioids are extremely helpful in killing acute and cancer pain. Because opioid receptors are G-protein coupled reactions, the inhibitory G-protein is usually coupled or attached with the receptors (Ghelardini et al., 2015, page 219). The onset of reaction in inhibit the pain is rapid and effective due to multiple inhibitory actions at the terminal site (refer to the previous section of mechanism of action). Besides, the interaction of opioids gradually increases the threshold of pain neuron as well as attenuates the pain subjective evaluation (Ghelardini et al., 2015, page 220).

Although genetic engineering is in the early stages of development, many scientists have found ways to reduce pain and chronic diseases. One gene in particular, PRDM12, has been researched in its mutated form. Many organisms that have PRDM12’s mutated form have not been able to sense pain (Doc. 2). This could result in a fuller life for people with chronic diseases. Another advantage to genetic engineering is curing chronic diseases. With the genetic fixes

Opioid receptors belong to the family of G protein-coupled receptors (GPCRs) with opioids as ligands. Opioid receptors, containing four major subtypes, are widely distributed in the brain, the spinal cord and digestive tract. The OPRM1 gene encodes the μ-opioid receptor (MOR), which involved in mediating acute changes in neuronal excitability by suppressing presynaptic release of GABA. Heteromerization of OPRM1 with OPRD1 results in the modulation of receptor binding and signaling properties. Identification of the compounds that selectively activate OPRM1-OPRD1 heterodimerization shows the importance in the treatment of pain and alleviate unwanted effects associated

Microfluidic chips allow for the manipulation, at small quantities of neuronal cells. Further, these chips allow for precise temporal and spatial control. This model is one that can be useful in the framework of neurodegeneration. Deleglise et al (2013) fabricated a 3 chamber microfluidic chip. The chambers held one of: coritical neuron soma and dendrites, cortical axons, or striatal neurons. The chip was designed to replicate an oriented neuronal connection from the coritcal to the striatal cells. Through the use of a chemically induced axotomy, by adding fluid to the central chamber (housing the cortical axon), showed that their chip could be used to simulate a lesion in the neuronal network. An emphasis was placed on the protection of synapses, and event that in axotomy studies, traumatic injury and in many neurodegenerative disorders precedes the loss of neuronal cell soma and axons. They then showed that zVAD-fmk, a caspase inhibitor and resveratrol did not show synaptic protection, while NAD+ and Y27632, a Rho Kinase inhibitor showed significant synaptic protection, despite the mechanism not being clear. Pointing at potential therapeutic targets for neurodegeneration. This can also be further looked at from the functionality of the chip - it is a useful tool in the evaluation of drugs in the axotomy model they presented.

appears to be a discrepancy between its weak affinity for opioid receptors and its potent

There are two key strategies has emerged out as spinal opioid gene therapy proven to be efficacious to induce analgesia in neuropathic patients. First, several groups have used transgenes encoding endogenous opioid agonists delivered to the DRGs. Goss et al used preproenkephalin, a d-opioid receptor agonist, and endomorphine-2, a μ opioid receptor agonist, delivered by HSV vectors (Goss et al. 2001).

It is more commonly attributed to the PNS with syndromes including: post-herpetic neuralgia, HIV, diabetic neuropathy, among others while the CNS is the source for spinal cord injury pain. Peripheral neuropathic pain is usually localized to site of affected nerves. This pain changes the nociceptor processing by altering the ion channel activity. The Nav1.7 gene mutation of the sodium channel is one alteration. Another family of ion channels affected by neuropathic pain are the transient receptor potential (TRP) channels. They regulate the action potential by gating the transmembrane ion influx. Specifically, the TRPV1 channels on the C fibers. Activation of these unmyelinated nociceptors results in burning and heat hyperalgesia. Neuropathic pain also imbalance of cytokines and chemokines in interactions between the

This article discusses optogenetic inhibition, which is the use of light-activated ion pumps to enable transient activity suppression of genetically targeted neurons by pulses of light. The created silencer ‘Jaws’ results in red light-induced photocurrents three times those of earlier silencers. This red-shifted variant can help solve known issues associated with implants, as it is a non-invasive method. Similar to previously mentioned papers focusing optogenetic excitation, this article will be used to provide more information about ChR variants and provides the basic knowledge to understand neuronal silencing as it is used in studies regarding optogenetics and Parkinson’s disease.

Pathophysiology and pharmacology of pain remain complex despite of the recent advancements in pain molecular and neurobiology (1, 2). Current findings suggest several new drug targets such as transient receptor potential (TRP) channels, voltage-gated potassium, sodium channels, imidazoline receptors, cholecystokinin (CCK) receptors and novel strategies like designer receptor G protein coupled receptors (DREADDs) and optogenetics for the pain management (3-5). Enzymes of the endocannabinoid cascade such as N-Acylphosphatidylethanolamine-selective phospholipase D (NAPE-PLD), Fatty acid amide hydrolase (FAAH), Diacylglycerol lipase (DAGL) α, α, β-Hydrolase domain containing 4, (ABHD-4), ABHD-6, ABHD-12 and Monoacylglycerol lipase (MAGL) and the

There are many advantages and disadvantages of using optogenetics. Some of the benefits of using optogenetics include being able to apply the technique to numerous levels of brain function such as neurons, synapses, local circuits and even behaviour to obtain a visual record and manipulate activity. By targeting the probe or light source to specific cellular compartments or areas of interests, specificity is achieved and researchers are able to establish links when optogenetics is implemented at different levels of the nervous system. Moreover, both the spatial resolution and temporal resolution is very precise with a millisecond scale as opsins are able to rapidly cause changes in targeted neurons by either activating or inhibiting them. Lastly,

In modern neuroscience, accurate optical reporting of electrical activity in defined neuronal populations can be monumental task. The reason for the enormity of this task is due largely in part to the lack of a sufficient, effective and accurate optical reporting procedure for activity of the brain. At this point in time, genetically encoded fluorescent indicators seem to be the answer for accurate and effective optical reporting, largely because they allow monitoring of defined neuronal circuits and do not require any chemical access. Ideally, these indicators would produce large fluorescent responses, allowing imaging on how input signals are processed into output signals by neurons. In addition, these ideal indicators would have

To effectively integrate the applications of optogenetics in a living organism, there needs to be previous genetic manipulation to enable the rat to be receptive to optogenetic technologies. The genetic manipulation involves creating transgenic rats. Transgenic manipulation involves the movement or insertion of a gene in an organism that does not normally possess the gene. The gene of interest is the gene for halorhodopsin, and to produce rats that possess this gene requires injecting a DNA construct into a fresh embryo.

The early evidences of presynaptic modulation of sensory afferents were important for the development of a model to explain how nociception processing happens, the Gate Theory of Pain. In this model, the balance between nociceptive input from large and small sensory fibers determines whether or not T-cells (pain afferent cells that projected to the forebrain) will fire and trigger the Action System, which will promote responses to the painful stimuli. Increase in T-cells excitability can be produced by small fibers (Aδ and C fibers) activation, thus unbalancing the net nociceptive input towards the activation of pain pathways. On the other hand, selective activation of large fibers (Aα and Aβ fibers) reduces excitability of T-cells by reducing

Photodynamic therapy (PDT) is a new form of phototherapy using nontoxic photo sensitive compounds that are targeted to kill malignant and other diseased cells and also microbial cells, including bacteria, fungi and viruses. PDT is widely used in biomedical fields. It is used clinically to treat a wide range of medical conditions, including related macular degeneration and malignant cancers,[1] and is recognised as a treatment strategy which is both minimally invasive and minimally toxic. Photodynamic therapy (PDT) uses a photoresponsive agent and a light source such as laser or another type of light. The photosensitising agent is a chemical that makes the target cells sensitive to light. The photosensitising agent can be applied by injecting

The most promising at the moment is optogenetic defibrillation. Optogenetics is the combined use of genetic and optical techniques for functional sensing and control in biological tissue [41]. Using genetically introduced light-gated ion channels and pumps, optogenetics offers alternatives to traditional method of excitation and suppression. In particular, Channelrodopsin-2 (ChR2), a light sensitive protein, and its variants have widespread application as optical actuators in neuroscience and now are being used in experimental cardiac research.