Exam 3: Pain Pathophysiology and Pain Pathway

what is pain

• an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage

• cognitive emotional response

• pain produces physical or phsyiologic changes

  • diffuse or localized

what is acute pain

• associated with tissue damage and the threat to some tissue injury

• occurs when a stimulus activates high threshold sensory nerve fibers

• serves a protective role to alter an animals behavior to avoid or minimize damage to tissues

• associated with surgery, trauma, some medical conditions

• disappears with healing

• tends to be self limiting

• physiologic

what is chronic pain

• persists beyond the expected course of healng

• usually associated with chronic inflammation, degenerative disease, or following nerve injury or damage

• no biological purpose

• may be considered as a disease state

• induces biochemical and phenotypical changes in the nervous system, peripheral and central sensitization

• difficult to treat

• pathologic or maladaptive

what is visceral pain

• pain originating from visceral organs

• not evoked from all viscera

• diffuse and poorly located

  • transmitted by A-delta and C fibers that travel along SNS and PSNS pathways

what is somatic pain

• pain arising from tissue ssuch as bones, muscles, skin and joints

• well localized

what is neuropathic pain

• pain initiated or caused by primary lesion or dysfunction within the nervous system

• diabetic neuropathy

• nerve transection (post amputation pain)

generally define the pain pathway

• a series of integrated anatomical structures and physiologic procresses that are dynamic and may change their structures or processes according to pain source, intensity, and or duration

• transduction, transmission, modulation, projection, and perception

what is transduction

• activation/depolarization of nociceptors transforms the mechanical/thermal/chemical information

• nociceptors encode the intensity, duration, location, and quality of the stimuli

what are nociceptors

• represent the free endings of primary sensory neurons A-delta and C fibers

• no spontaneous depolarization, high threshold and only responds to noxious stimuli

• thermoreceptors heat = TRPV-1, cold = TRPM-8

• mechanoreceptors = TRPA-1

• chemoreceptors = ASICS, TRPA-1

what are the sensory nerve fibers

• neurons = sense and conduct sensory information

• glial cells = nourish and support neurons

• cell bodies = dorsal root ganglia (body) or trigeminal ganglia (head)

what are A-delta fibers

• small lightly myelinated

• high and low threshold

• fast conducting

• mediate acute, transient shrapr/pricking, localized pain “first pain”

what are C fibers

• small and non-myelinated

• very high threshold

• slow conducting

• mediate slow, persistent burning or dull pain “second or slow onset pain”

what are A-beta fibers

• large myelinated

• low threshold

• rapid conducting

• normally transmit light touch, non-noxious stimuli

• pathologic pain = transmit noxious stimuli

how is somatic sensory fiber transmission described

• cell bodies of sensory nerve fibers are located in the dorsal root ganglia of the spinal nerves and sensory ganglia of cranial nerves (I, VII, IX, X)

• 1st branch travels to the spinal cord then sunapses with second order neuron

• 2nd branch travels through the formed peripheral nerve to reach the sensory nerve endings (skin, muscle, bones, joints)

how is transmission done through visceral sensory fibers

sensory nerve fibers accompany the SNS and PSNS nerves to innervate viscera

what are the synaptic sites in the spinal cord

• laminae I

• Laminae II (substantia gelatinosa)

• Laminae III

• laminae IV

• laminae V

describe laminae I

• sensory relay juntion for pain and temperature

• nociceptive-specific neurons

• wide dynamic range neurons

• projection neurons

• input from A-delta and C fibers

describe Laminae II aka substantia gelatinosa

• WDR neurons

• lnput from A-delta and c fibers

describe Laminae III

• integrates sensory input with info descending from the brain

• neurons that project info to the brain

describe Laminae IV

input from A-beta, A-delta, and C fibers

describe Laminae V

• WDR neurons

• input from A-beta and sympathetic A-delta and C fibers

• synapse with neurons that project to the brain

what is modulation

• impulses from A-delta and C fibers are modulated by interneurons or descending projections

• used to amplify or inhibit signals

what are the excitatory neurotransmitters released with signals from first order neurons

• glutamate or asparate

• Substance P

what receptors does modulation activate with second order neuron binding

• AMPA receptors , KAI receptors, and NK receptors = signal the location, intensity and duration of perpheral stimuli

• mGluR and NMDA receptors involed in long term potentiation and central sensitization

• pre and post opioid, noradrenergic, serotoninergic, and muscarinic recptors

what is projection

• bundles of second order neurons that originate in the spinal horn laminae convey nociceptive information to the brain

• spinothalamic tract

• spinoreticular tract

• spinomesencephalic

• spinohypothalamic tract

what is perception

• third order neurons transport the signals to cortical and subcortical regions

• somatosensory cortex

• periaqueductal grey region

• reticular formation

• limbic system

• these centers process sensory information that elicit fear, anxiety, and aggression, and activate efferent pathways that mediate autonomic, neuroendocrine, and motor responses

describe the descending inhibitory pathway

• effective target site is the dorsal horn of the spinal cord

• descending projection neuron will synapse the gap between first and second order neurons releasing neurotransmtters

• alleviates propagation of the pain impulse (effective for mild pain)

what neurotransmitters are released in the descending inhibitory pathway

• endogenous opioid such as enkephalines, endorphins, dysnorphins

• serotonin

• norepinephrine

• GABA

• glycine

what is the gate control theory with the ascending analgesic pathway

• inhibitory interneurons normally reduce the output of spontaneously active projection neurons, which relay sensory information to the brain

• activation of the low threshold A-beta fibers, which normally transmit nonpainful stimuli, increase inhibitory interneuron effects on projection neurons

how does pathologic pain change the pain pathway

• pathologic pain is more intense than is needed for protection and continues after the inury has healed

• causes perpheral and central sensitization

• leads to primary and secondary hyperalgesia, allodynia

what is perippheral sensitization

• produced by neurochemicalalterations caused by tissue damage and inflammation at the injruy siite

• release and spread of ATP, ions, prostaglandins, bradikinin, nerve growth factor, cytokines, serotonin, histamine, catecholamines, neuropeptide Y and substance P

• leads to transformation of A-beta fibers , recruitment of more A-delta and C fibers = silent nociceptors , increase number and frequency of nociceptive impulses transmitted to the dorsal horn

what is the result of peripheral sensitization

primary hyperalgesia- increased response to a noxious stimunis at sight of injury

what is central sensitization

• produced by change in the excitability neurons in the spinal cord and or activation of glial cells

• an increased frquency and intensity of nociceptive impulses reaching the dorsal horn activate AMPA, KAI, NMDA receptors that are normally dormant

what causes the activation of NMDA receptors in central sensitization

• flooding of th second order synapse with excitory neurotransmitters

• central activation of the arachidonic acid pathway

what is the process of central sensitization

• disruption of the gate control theory and GABA mediated inhibiton = disinhibition

• activation of non-neuronal cell types such as astrocytes and microglia that congregate at site of injured peripheral nerve termination and release cytokines that release pain

what are the ultimate consequences of central sensitization

• secondary hyperalgesia= exaggerated and prolinged pain response that arises from adjacent but outside the area of injury

• allodynia= pain response to a stimulus that doesnt normally cause pain