definition and neurobiological basis of pain Flashcards
what is pain?
an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
what is nociception?
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
what are nociceptors?
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
what are the 2 types of nociceptive fibers?
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
what is ascending pain pathway?
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)
lateral vs medial pain systems
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
what is the descending pathway of pain?
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
what are the brain regions in the pain matrix (acute pain network)
- Primary and secondary somatosensory cortices (S1 & S2)
- Insular cortex (IC)
- Anterior cingulate cortex (ACC)
- Prefrontal cortex (PFC)
- Thalamus
- Cerebellum
the somatosensory cortices and pain
- 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
the insular cortex / anterior cingulate cortex and pain
- 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
the prefrontal cortex and pain
- 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
the thalamus and pain
acts as a relay center, transmitting nociceptive signals from the spinal cord to cortical areas
the cerebellum and pain
- 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
how do we distinguish location and quality of pain?
- 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
temporal sequence of cortical activity during pain perception
- 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
mechanisms underlying psychological modulation of pain
effect of attention and distraction on pain-evoked activity in the brain
- 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
mechanisms underlying psychological modulation of pain
effect of emotional state on pain-evoked activity
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)
mechanisms underlying psychological modulation of pain
effect of expectation on pain-evoked activity
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
pain affect without pain sensation in a patient with a postcentral lesion (Ploner, 1999)
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
pain affect encoded in human anterior cingulate but not somatosensory (Rainville, 1997)
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
