definition and neurobiological basis of pain

Question 1

what is pain?

Answer 1

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

Question 2

what is nociception?

Answer 2

the physiological processes triggered by tissue damage
* process of encoding specific somatosensory information in the periphery and its transduction to the brain
* although nociception normally results in pain, this is not mandatory - and vice versa, pain may be experienced without nociception

Question 3

what are nociceptors?

Answer 3

peripheral neurons that respond to noxious stimulation and detect potentially damaging stimuli
* can be specific to a particular type of stimulus (e.g., mechanical, chemical, or temperature) = stimulation-specific nociceptors
* or can respond to a variety of noxious stimulations = polymodal nociceptors - are more abundant

Question 4

what are the 2 types of nociceptive fibers?

Answer 4

Thinly myelinated Aδ fibers: transmit info about acute & localized pain at fast conduction speed

Unmyelinated C fibers: signal more widespread pain with slower conduction speed

Question 5

what is ascending pain pathway?

Answer 5

ascending = injury –> brain
1. nociceptive stimulation
2. nociceptor fibers transmit nociceptive signals to CNS
3. peripheral nociceptor fibers end at the dorsal horn of the spinal cord
4. second-order neurons are activated (go all the way to brain)
5. ascending pain signals are sent to brain via spinothalamic tract - fibers project to the intralaminar and ventroposterior nuclei of the thalamus
6. two supraspinal neuronal systems process nociceptive information (lateral & medial)

Question 6

lateral vs medial pain systems

Answer 6

lateral: mainly encoding sensory discriminative components of pain
* lateral nuclei of the thalamus, S1 & S2
* location, intensity, duration and quality of pain

medial: mainly encoding the affective, motivational components of pain
* medial nuclei of the thalamus, ACC & prefrontal cortex

the IC integrates sensory & affective pain components

Question 7

what is the descending pathway of pain?

Answer 7

descending = starts in the brain - can enhance or inhibit the ascending pain signals
3 different pathways:
1. descending input from ACC –> PFC –> periaqueductal gray (PAG)
2. descending input from the IC via amygdala to the PAG
3. descending pathway from PAG –> rostroventral medulla (RVM) –> dorsal horn

dorsal horn in where descending & ascending pathways interact

Question 8

what are the brain regions in the pain matrix (acute pain network)

Answer 8

1. Primary and secondary somatosensory cortices (S1 & S2)
2. Insular cortex (IC)
3. Anterior cingulate cortex (ACC)
4. Prefrontal cortex (PFC)
5. Thalamus
6. Cerebellum

Question 9

the somatosensory cortices and pain

Answer 9

• receive input from the somatosensory thalamus
• important for the perception of sensory features -e.g. the location and duration of pain

S1: fine-grained representation of pain intensity + first pain
S2: generic response to pain + learning & attention to pain

Question 10

the insular cortex / anterior cingulate cortex and pain

Answer 10

• both components of limbic system = important for the emotional and motivational aspects of pain
• IC: integrates sensory signals with autonomic and emotional responses
• ACC: receives input mainly from medial portions of the thalamus via the IC + sends PFC nociceptive info

posterior IC: processes sensory properties of pain
anterior IC: links pain to subjective emotional experiences

Question 11

the prefrontal cortex and pain

Answer 11

• exhibits the highest activity when a stimulus just becomes painful, with lower activation being associated with higher levels of pain
• may be related to the cognitive aspects of pain perception rather than directly to pain sensation or affect

Question 12

the thalamus and pain

Answer 12

acts as a relay center, transmitting nociceptive signals from the spinal cord to cortical areas

Question 13

the cerebellum and pain

Answer 13

• receives direct input from spinothalamic tract - is one of the subcortical pain-coding structures
• has been implicated in the control of various functions, including motor, sensory, and cognitive
• activity in the cerebellum following painful somatic and visceral stimulation
• plays a role in the modulation of both visceral and somatic nociceptive responses

Question 14

how do we distinguish location and quality of pain?

Answer 14

• despite the similarities in pain experiences and similarities in neural activation patterns, each pain experience is unique - we can differentiate heat from pressure
• evidence that that neural activity in the S1 could underlie identification of the locus of cutaneous pain
• IC also participates in pain localization

Question 15

temporal sequence of cortical activity during pain perception

Answer 15

• earliest pain-induced brain activity originates in the vicinity of S2
• in contrast, tactile stimuli activate this region only after processing in S1

First pain: signals threat and provides precise sensory information for immediate withdrawal - related to activation of S1
Second pain: attracts longer-lasting attention and motivates behavioral responses to limit injury and optimize recovery - related to activation of ACC
both related to activation of S2

Question 16

mechanisms underlying psychological modulation of pain

effect of attention and distraction on pain-evoked activity in the brain

Answer 16

• performing a distracting task modulates pain-evoked activity in the thalamus and other cortical regions like S1, ACC and IC
• cognitive modulation of pain by attention involves early sensory processing in S2 & IC and later processing in the ACC
• perceptual changes in pain related to attention reflect in part a change in cortical processing and in part a decrease in ascending afferent input from the spinal cord bcuz of activation of descending inhibitory controls

Question 17

mechanisms underlying psychological modulation of pain

effect of emotional state on pain-evoked activity

Answer 17

neg emotional states alter pain perception - largest effect on pain unpleasantness rather than the sensory discriminative components of the sensation

emotional states alter pain-evoked cortical activation - most commonly in regions associated with the affective component of pain processing (ACC and IC)

Question 18

mechanisms underlying psychological modulation of pain

effect of expectation on pain-evoked activity

Answer 18

anticipation or expectation of pain can activate pain-related areas in the absence of a physical pain stimulus

PAG, PFC, and ventral striatum are activated during pain expectation
- suggests that such activation may modulate the impending pain evoked activation

Question 19

pain affect without pain sensation in a patient with a postcentral lesion (Ploner, 1999)

Answer 19

clinical examination of patient who suffered from a right-sided stroke → lesion in the right S1 and S2 cortices
numbness of left hand & arm, right side of body was fine

method & results:
* gave patient laser stimulation
* right hand stimulated –> clear sense of location & pain sensation. could describe the pain
* left hand stimulated –> felt an unpleasant feeling somewhere between his fingers and shoulder - was unable to provide quality, intensity or location + longer reaction time

discussion:
* results demonstrate a loss of pain sensation with preserved pain affect
* shows the essential role of S1 & S2 for the sensory discriminative aspects of pain perception
* by contrast, detection of and reaction to painful stimuli as well as pain affect do not require integrity of S1 & S2

conclusion: provides clear evidence for the crucial role of the lateral pain system in the sensory-discriminative pain component and in first pain sensation

Question 20

pain affect encoded in human anterior cingulate but not somatosensory (Rainville, 1997)

Answer 20

method:
* used hypnosis as a cognitive tool to reveal possible cerebral mechanisms of pain affect
* hypnotic suggestions used to alter selectively the unpleasantness of noxious stimuli, without changing the perceived intensity
* PET scans conducted during conditions of alert control, hypnosis control, and hypnotic suggestion
* during each scan, left hand was immersed in neutral and painfully hot water
* after each scan the perceived intensity and unpleasantness
of the stimulation were rated

results:
* painfully hot vs neutral scans support significant pain-related activation in S1, S2, IC, and ACC
* hypnosis induction had no sig effect on pain intensity or unpleasantness → little influence of hypnotic induction on pain-related activation
* hypnotic suggestion: altered both pain affect and activation within some but not all pain-related cortical regions
* no significant pain-evoked activity in S2 → possibly because mental effort or attention demanded by these suggestions may suppress such activation
* ACC: significantly greater activation during increased unpleasant condition than decreased
* S1: lower activation in increased unpleasant condition than decreased → indicates no tendency for increased activation related to increased unpleasantness

conclusion:
* only activation levels within the ACC are consistent with the encoding of the perceived unpleasantness of noxious stimuli
* provides direct evidence of a specific encoding of pain unpleasantness in the ACC
* ACC, IC, S1, and S2 don’t function independently but interact in encoding different aspects of pain
* however, still partial segregation of function between pain affect and sensation