our topic today is pain transduction there are four phases of nociception including transduction which is the process of converting painful stimuli into electrical signals this electrical signal or action potential can then travel to the brain by way of first second and third order neurons this is called transmission when the pain signal reaches the somatosensory cortex of the parietal lobe the individual becomes consciously aware they are in pain and this is called perception the central nervous system has mechanisms to augment or blunt pain signals and this is called pain modulation the focus of this video is on no susceptor transduction nociceptors or pain receptors are free nerve endings that are capable of generating an action potential when they reach threshold different types of stimuli can cause activation to pain pathways by depolarizing the nociceptor and bringing it to threshold because many different types of stimuli can activate the nociceptor nociceptors are referred to as poly modal receptors think about different stimuli that can cause pain examples might include anything that can cause tissue damage including mechanical stimuli like trauma exposure to chemicals tissue ischemia from lack of oxygen and temperature extremes these stimuli ultimately lead to the opening of sodium and calcium ion channels and nociceptors to allow the no susceptor to reach threshold and convert the initial stimulus into an electrical signal that can be sent to the brain remember that transduction involves transforming one form of energy into another consider your skin being punctured by a nail this mechanical stimulus bands or stretches the no susceptor membrane and opens mechanically gated ion channels for sodium and calcium these ions rush into the cell depolarizing the nosis remembering also heat above 43 degrees Celsius or 109 degrees Fahrenheit causes painful burning sensations at these temperatures heat sensitive ion channels in the no susceptor membrane open to depolarize the no susceptor furthermore cells that have been damaged release various substances that can depolarize the nose receptor these substances include proteases which convert the extra cellular peptide keynesian into bradykinin bradykinin readily binds two bradykinin receptors which are g-protein coupled receptors located on the nociceptor to cause depolarization ATP can also be released from damaged cells and close ATP since two potassium channels to cause depolarization potassium is high inside cells and is released from damaged cells this elevated extracellular potassium will directly depolarize the no susceptor and bring it closer to threshold lactic acid buildup in the ECF of hard working muscles will acutely increase hydrogen ion concentration in the extracellular fluid surrounding those receptors these ions activate a6 or acid sensing ion channels which open and increase permeability of the no susceptor to sodium and/or calcium ions to polarizing the no susceptor in case of a beasting mast cells are activated and release histamine in serotonin which cause nociceptors to depolarize the smallest C fibers are selectively activated by histamine and bring on the sensation of itch these are called pro receptors prostaglandins are released from enzymatic breakdown and of inflammatory cell membranes and buying two g-protein coupled receptors which increases cyclic GMP inside nociceptors prostaglandins also cause phosphorylation of certain tetrodotoxin resistant sodium channels which action causes these channels to open at lower membrane potentials the sensitizing the nociceptors to make them more readily activated other contributors to transduction in those acceptors include calcitonin gene related peptide abbreviated CG RP in substance P electrical activity of the nociceptors causes the nociceptors to release corresponding amounts of substance P and CG RP which increases the inflammatory response and causes vasodilation release of histamine for mast cells and increased sensitization of neighboring nociceptors an example of this sensitization is the allodynia one experiences on the skin with just light touch after a sunburn the substance and peppers that give them their spiciness is known as capsaicin capsaicin activates ligand-gated ion calcium and sodium channels by binding to Val enoyed receptors or vr1 receptors heat and acid will also open these same channels as does the endogenous compound and nand amide interestingly mice who have had their vr1 receptors knocked out are able to drink capsaicin solutions as if it's pure water the r-1 receptors have not been found in Birds this finding led to the idea to produce capsaicin lays birdseed to keep squirrels from eating the seed it was also found that application of capsaicin desensitizes pain fibers and prevent substance P from being released from peripheral and central nerves for this reason a capsaicin cream has been developed and is used to treat pain associated with shingles arthritis mastectomy and high geminal neuralgia here now is a summary of pain transduction which leads to an action potential being transmitted to the brain or one perceives or becomes consciously aware of the painful sensation thanks for watching