Physiology of Pain

Question 1

how is pain different from all other senses?

Answer 1

• the sensation is elicited by multiple stimuli, b/c we can’t build a pain R that only reacts to one type of pain
• it pre-empts all other signals–so pain signals will shut down all other signals due to the possible severity with damage to the tissue
• differences result in multiple alterations in the physiological functioning in pain pathways

Question 2

fast pain vs. slow pain

Answer 2

• fast pain
  
  • immediate injury
  • sharp pain
• slow pain
  
  • often characterized as dull or achy
  • often occurs some time after the injury

Question 3

pain by location

Answer 3

• deep pain
• muscle pain
• visceral pain
• somatic/cutaneous pain

Question 4

sensory Rs for pain

Answer 4

• many are bare nerve endings with specialized ion channels that open in response to a specific stimulus (e.g. thermoreceptors–which can also respond to pain)
• nociceptors

Question 5

nociceptors

Answer 5

• senses noxious stimulus
• bare nerve ending
• two types of fibers:
  
  • alpha delta–small, sparsely myelinated; fast and sharp pain
  • C fibers–unmyelinated fibers assoc with dull pain, slow pain–>slow conductors and hard to activate b/c it makes it harder for just anything to stimulate the fiber that way

Question 6

types of nociceptors and the issue they face

Answer 6

• issue: must be able to detect a wide variety of damaging stimuli
• types:
  
  1. sensitive to both thermal and mechanical stimuli–majority
  2. sensitive only to thermal stimuli
  3. sensitive only to mechanical
  4. silent/sleeping–not active under most conditions except when we have already injured something and we cause additional tissue injury

Question 7

channels on the nociceptors

Answer 7

• many mixed modality nociceptors express a mechxnosensitive Na channel (SCN9A or Na1.7)
  
  • mutations in this channel lead to an absence of pain sensation
  • another class produces a paroxysmal pain syndrome so neurons are activated inappropriately without injury so the channels are activated spontaneously without pain

Question 8

ligand gated channels on nociceptors

Answer 8

• they alter the sensitivity of the nociceptors to input
• they include Rs for:
  
  • substance P
  • kinins like bradykinin
  • ATP–not much ATP in ECF so if we detect a higher quantity than normal, then this is an indicator that the cell has been damaged and contents spilled
  • H+
• these chemicals also exist in the SC and influence nociceptive inputs at synapses
• these chemicals bind to their receptors and change the sensitivity of nociceptors by increasing it and activate silent nociceptors
  
  • they are released due to activated nociceptors, damaged tissue, and recruited WBC

Question 9

dorsal columns

Answer 9

proprioceptive and discriminative fine touch

Question 10

spinothalamic tract

Answer 10

fast pain

Question 11

spinoreticulothalamic system

Answer 11

slow pain

Question 12

sensing noxious stimuli in the SC

Answer 12

• at the first synapse for these neurons, it is in the SC
  
  • the alpha delta fibers will be faster transmitting and release EAA from the pre-synaptic terminal and will bind to a non-NMDA R on a 2nd order neuron
  • the C fibers will release substance P to a tachykinin R and EAA to NMDA and non NMDA R at the first synapse
• nociceptors that travel with the spinoreticulothalamic pathway for slow pain synapse on an interneuron in the SC before crossing and ascending in the reticular formation
  
  • this synapse is the site of much modulation of the SC function by local pathways (gate theory) or descending pathways (opioids)

Question 13

sensing noxious stimuli for visceral pain

Answer 13

• visceral afferents travel with autonomic Ns
• visceral nociceptors travel with the autonomic Ns and have additional synapses in the the hypothalamus and medulla–processing occurs lower and produces an autonomic effect vs. a conscious effect

Question 14

central processing of noxious stimuli in the brain

Answer 14

• nociceptive input is distributed widely in the cortex so impossible to develop a lesion that will get rid of pain
  
  • utilizes the thalamus to send info to the mediofrontal cortex, post central gyrus, and insular cortex

Question 15

S1 and 2 with pain

Answer 15

• S1 and S2 receive input from the nociceptors and play a role in the localization of pain
  
  • if we damage one, then change how we experience pain but not pain itself

Question 16

insular cortex and pain

Answer 16

• insular cortex is important in the interpretation of nociceptive inputs
• processes information about the internal state of the body–if everything is okay or not
• contributes to the autonomic response to pain–by activating the hypothalamus
  
  • sweating, high BP/HR, fever, rapid breathing
• integrates all signals related to the pain–asymbolia so someone who has damage to this area has awareness of and feelings of pain but can’t describe it to you

Question 17

lesions and pain

Answer 17

lesions in any one area of the brain does NOT abolish the ability to experience pain BUT the experience is changed

Question 18

nociceptive inputs and the amygdala

Answer 18

• many nociceptive inputs go to the amygdala

- this is important for activating/producing the emotional components inherent in the sensation of pain

Question 19

Gate Theory of Pain

Answer 19

• other somatic input to the brain can help alleviate pain such as rubbing the area around where the pain occurred
• neurons traveling in the spinoreticulothalamic tract synapse on an interneuron w/in the SC before ascending

1. activate an Abeta fiber by normal stimuli (like rubbing the area)–activated by a small amount of stimuli
   
   • has a branch that travels within the dorsal columns to relay the pressure information
   • branch that goes to SC to synapse on interneuron
2. Abeta fiber releases EAA and activates an inhibitory interneuron in the SC
3. the inhibitory interneuron goes to synapse on the neuron that will go up to the brain in the pain pathway and it releases glycine to inhibit the activity of the second order neuron
   
   • this will hyper polarize the neuron so pain actually has to be worse to get the message thru b/c further from threshold
4. reduces sensation of pain

Question 20

descending mechanism to modify painful inputs

Answer 20

• use presynaptic inhibition to reduce activation of the 2nd order nociceptive neuron in the SC
  
  • comes to a point when knowing there is pain is unproductive
  • this is activated later than gate theory

1. neurons in the periaqueductal gray are activated by numerous inputs, including opiate (mu R), EAA (NMDA and non NMDA R), and the cannabinoids (acts on CB-1)
2. axons from the PAG neurons travel to the midline raphe nuclei and release enkephalins (Leu and Met) which activate the raphe neurons
3. axons from the raphe neurons travel to the SC and release serotonin, which activate inhibitory interneurons, causing them to release opiates
   
   • inhibits the neuron relaying pain fun input to the brain
4. opiates released by the interneuron activate mu receptors on the presynaptic terminal of the C fiber
5. produces pre synaptic inhibition that reduces the release of substance P from the nociceptor and reduces pain transmission

Question 21

deep pain

Answer 21

• assoc with periosteum, ligaments–bone pain
• usually dull, achy
• few A delta fibers
• many C fibers
• associated with muscle spasm

Question 22

muscle pain

Answer 22

• cause: usually injury or ischemia during contraction
• both A delta and C fibers present
  
  • get both fast and slow pain associated with muscle
• pts may come in with pain intermittent with exertion b/c usually blood vessels will dilate during exercise due to NO and sympathetics acting thru beta R

Question 23

visceral pain

Answer 23

• poorly localized
• few Rs–almost all are C fibers so can’t localize well b/c so few, which means by the time we feel pain it usually involves a large segment of viscera
• stretch receptors–distension
• often referred pain–pt tells you pain is somewhere other than where it is

Question 24

visceral pain and plasticity

Answer 24

• early in life, many of our experiences enable us to refine the map that is genetically coded in the cortex, and this includes anatomically eliminating synapses as well as strengthening others
  
  • plasticity happens in infants
• with visceral inputs, we can’t refine the map from the viscera the same way we do with cutaneous senses
  
  • previous experience teaches the brain that the shoulder is more likely to experience pain than the heart–w/o map of cortex, the brain does its best guess of where the pain would be from that general vicinity
  • confound this with the fact that the nociceptors may converge on the same interneuron in the SC and the brain is left with best guess–so with the converging, we lose the ability to localize the pain