Transduction

Transmission

Perception

Modulation 

Nociceptive

Neuropathic

Idiopathic or pyschogenic 

Dysfunction of CNS

Allows for spontaneous excitment

Burning, tingling, shock like 

Bradykinins

Serotonin

H+

Prostaglandins

Histamine

Substance P

Peptide released from C fibers

Vasodilation

Extravasation of plasma proteins

Degraulation of mast cells

Sensitizes nerve 

Neurotrasmitter released from A delta and C fibers 

Fast, sharp pain 

Released from Mast cells, basophils, and plts when subtance P binds to receptors

Produces edema and vasodilation

Released from plts with tissue injury

Direct analgesic effect on nociceptors 

Released from inflammatory response

Increases the production of prostaglandins

Sensitize nociceptors 

Phospholipase A2 on phospholipid bilayer of cell forms arachidonic acid when tissue injury occurs 

Further converts to cyclooxygenase pathway and Lipooxygenase pathway 

Cyclooxygenase Pathway 

(COX)

Converts arachnidonic acid to endoperoxides

Endoperoxides form prostacyclin and prostaglandin 

Potentiates edema and stimulates direct nerve ending respectively 

Arachidonic acid converts to hydroperoxy compounds

Converted to leukotrienes

Recieve mechanical and thermal stimuli

Fast pain

Small myelinated 

Reflex withdrawal response 

Mechanical, Thermal, and Chemical

Slow pain

Dull, burning, throbbing, or aching 

First order neuron enter the dorsal root ganglia and synapse with second order neuron in Rex Laminae I or V (grey matter) 

Second Order Neurons cross to contra lateral spinaothalamic tract (white matter) and then to brain

First order neuron enter the dorsal root ganglia and synapse with Interneuron in Rex Laminae II or III (aka substantia gelatinosa) 

Interneuron Then Synapses with second order neuron in Rexed Laminae V before crossing over and on to the brain 

Tissue injury releases substance P and glutamate to activate free nerve endings

Repeated stimulation causes sensitization 

Mediated by the release of alogens 

Decrease in pain theshold

Increase in frequency repsonse to the painful stimuli

Decrease in response latency

Causes spontaneous firing after stimulus is removed 

Neurogenic Inflammation

Substance P stimulates release of histamine from mast cells which vasodilated vessels

Causes red flush around injury, local tissue edema, and sensitization to noxious stimuli 

Occurs in the spinal cord when there is a prolonged discharge (peripherally)

Cause sensitization to second order neurons which increases frequency of discharge

Causes receptor field expansion and adjacent neurons become sensitive 

Central Modulation: Inhibition 

Spinal Level 

Endogenous enkephalins

Inhibit the relsease of substance P

Block post synaptic response to substance P

Central Modulation: Inhibition 

Supraspinal Level

Affects opioid receptors in the brain

"I hurt but I dont care"

Stimulation of SNS

Catecholamines, cortisol, and angiotensin II released

Increased HR, CO, CMO2, BP

Causes myocardial ischemia and dysrhythmias 

Increase plt adhesiveness 

Decreased fibrinolysis- DVTs

Decreased TV, VC, IC, and FRC 

Reluctant to cough and deep breathe

Causes atelectesis and pneumonia 

Ventilation perfusion mismatch

Aterial hypoxemia 

Increase sympathetic activity

Decreased Gastric emptying

Decreased Intestinal Motility- Ileus

Urinary Retention 

Increased ACTH, cortisol, ADH, growth hormone, and glucagon 

Decreased release of testosterone and insulin

Cause hyperglycemia, Na & H2O retention 

Immune response decreased

Healthy individuals can be immunosuppresed 1-2 weeks post-op 

Usually Lower dose than that for antidepressant effect

Action due to blocking reuptake of serotonin or NE or both 

Blocks voltage gated Na Channels

Supresses spontaneous neuronal discharges

Good for neuropathic pain- diabetic neuropathy and tirgeminal neuralgia 

Blocks Dopaminergic Receptors

Extrapyramidal effects undesirable

Antiinflammatory

Inhibits prostaglandin production by blocking phospholipase A2 activation