opiates and their receptors

what are opiates

neuropeptides = bind to receptors within the brain, spinal cord, gi tract, analgesic effect, decrease motility in gut, treat pain but addictive. opiates = natural, opioids = synthetic

synthesis, storage, release

stored in large dense core vesicles, released through exocytosis, penk, pomc, pdym = precursor molecules, 3 major classes - endorphins, enkephalins, dynorphins

opioid receptors

3 classes of receptors, mu, delta and kappa, differ in localization and affinity to opioids, they are all gpcrs and inhibit adenylyl cyclase, and activation of mu receptors = increases k+ conductance = hyperpolarizes the cell, and activation of kappa and delta receptors = closes ca2+ channels blocking cell signaling

mechanisms of action

modulate nocicpetiv signaling by blocking neurotransmitter through inhibiting calcium influx into presynaptic terminal and opening potassium channels to hyperpolarize the cell, acts on mu receptors mostly in brains tem and spinal cord = analgesia and respiratory effects, increase amount of dopamine released with the brain reward system = euphoric feelings

termination of action

metabolized by peptidases

opioids in pain management and analgesia

pain is a protective mechanism = unpleasant sensory and emotional experiences - neospinal thalamic tract, paleospinal thalamic tract and archispinal thalamic tract

opioids in pain management and analgesia

opioids mediate immune cells express opioids receptors, opioids inhibit the ascending transmission of pain signals from nociceptors in dorsal horn of spinal cord, in diencephalon and medulla of brain opioids can bind to mu receptors on gabaergic neurons to inhibit pain signals

opioids induced hyperalgesia

treated for pain with opioids experiences a higher sensitivity to painful stimuli, spinal ltp = abrupt or interrupted use of opioids between DRG nociceptor neurons and spinal cord neurons, LTP = analgesic tolerance, pain experienced during withdrawal and neuropathic pain induced by injury, microglia releases signaling molecules which contributes to this phenomenon

describe the reward pahtway

vta = activates = dopamine released to NA and releases dopamine into prefrontal cortex, vta = cues and reward, euphoria = nucleus accumbens = limbic system involved with reward

opioid tolerance

repeated use of opioids = tolerance to opioids = higher dose, first small number of receptors activated, but then large doses of opioids = overactivated, then body restores balance by moving receptors into inactive storage in vesicles, but some remain and require opioids to remain active, can be severe and perpetuate addiction as the remaining receptors turn off

stress in addiction

critical influencin factor in drug vunerability, hpa axis, avp system and pomc and dynorphin system are involved