67-68 - Physiology of Pain Flashcards
Define and differentiate between pain and nociception.
Pain
- The perception of nociceptive (noxious) sensory information
- “The unpleasant sensory and emotional experience which we associate with actual or potential tissue damage and/or describe in terms of such damage.”
Nociception
- The sensory response to a noxious stimulus
- Unconscious activity induced by harmful stimulus
Components of pain
Pain is a multifactorial and multisystem phenomenon
Sensory-Discrimination
Perception of exteroceptive and enteroceptive noxious information and the localization of the site of the stimulus - primary and secondary somatosensory cortices
Motivation-Affective
Emotional and sympathetic responses and associated behaviors - frontal cortex, limbic system, brainstem areas
Exteroceptive pain
pain information coming from the outside the body (skin pain)
Enteroceptive pain
pain information coming from inside the body (visceral pain)
When a nociceptive stimuli is experienced, what does the sensory-discriminative component contribute?
- Location
- Intensity
- Modality (hot/cold, stabbing/burning)
When a nociceptive stimuli is experienced, what does the emotional component contribute?
- Negative impact on affect/mood
- Chronic pain accompanied by depression
What do both the sensory-discriminative and emotional components contribute to?
Conscious perception of pain
Describe physiologic pain
- Acute pain
- Critical for survival
- Body’s own warning signal
- Protects the body from potential or further damage and injury
- Felt within ~0.1 sec after initiation of stimulus
- Also known as “fast pain” because the sensation is felt so quickly
- Very adaptive - As tissue injury heals, the pain lessens
Describe the fibers utilized in fast conduction
Fast conduction - Aδ fibers @ 6 - 30 m/sec
- Elicited by either mechanical or thermal pain stimuli
- Sharp, prickling, electric and cutting types of sensation
Describe pathologic pain
- Chronic Pain
- Begins after > 1 sec after the stimulus and then increases slowly
- Usually associated with tissue injury
- Can become maladaptive – T12 injury that should heal in 3 months, patient comes back in 3 months, the bone has health and there is no longer visible pathology on x-ray, but he is still in pain
- Persists even if there is no more tissue damage and injury is healed
- In that case, it does NOT have a physiological function!
Describe the fibers utilized by pathologic pain
Persistent and slow conducting - C-fibers @ 0.5 – 2 m/sec
- Can be elicited by chemical, mechanical and thermal stimuli
- Dull, throbbing, aching, nauseous sensation
- Strong emotional component
4 types of pain
1 - Nociceptive pain
2 - Inflammatory pain
3 - Dysfunctional pain
4 - Neuropathic pain
Nociceptive pain
- Physiologic (“normal”) pain
- Transient, localized
- No real or minimal tissue damage
- Pathologic when chronic
*** Warning – protective function
Inflammatory pain
- Acute and chronic
- Tissue damage
- Inflammatory process
- Hypersensitivity
*** Protective, promotes healing
Dysfunctional pain
- No understanding lesion found, disproportionate to tissue injury
- IBS (irritable bowel syndrome), fibromyalgia
Neuropathic pain
- Damage to the nervous system (CNS or PNS)
- Disproportionate to intensity of nociceptor activation
- Originates with damage to the nervous system
- Pathologic pain, maladaptive
*** NO protective function
Describe the characteristics of somatic pain
Superficial
- discreet localization
- Initial (sharp; A delta fibers= 20 M/sec)
- Delayed (dull, burning; C-fibers= 1 M/sec)
Deep
- diffuse localization
- Connective tissue, bones, joints, muscle; muscle cramps, headache
Describe the characteristics of visceral pain
- Primarily mediated by C-fibers
- Poorly localized, nauseating, frequently accompanied by sweating and changes in BP
- You can localize it, just not very well, not as well as somatic pain
- Often radiates or is referred to a other somatic site following a dermatome pattern
E.g., angina, colic, ulcer, appendicitis, renal stones
Describe the steps in the physiology of processing pain
1 - Transduction (At the location of the painful stimulus)
2 - Transmission (Travels via fibers to the dorsal horn of the spinal cord)
3 - Modulation (Arrives at spinal cord)
4 - Perception (Arrives at brain)
What is involved in pain transduction at the location of the painful stimulus?
Pain neurons or nociceptors
Which free nerve endings are involved in the body and face?
Body - spinal ganglia
Face - trigeminal ganglia
What does high threshold mean in terms of nociceptors?
- This is important so you are not responding to pain all the time
- Need a low threshold for proprioception, for example
- If these activated each time you touched something or sat down, we would have problems and a lot of pain
Are nociceptors fast or slow adaptors?
Slow
What types of stimuli do nociceptors respond to?
1 - Mechanical – only noxious stimulus
2 - Thermal - TRP receptor family
- CMR-1 (52⁰C, TRPV2) - Noxious heat
VR-1 (>42⁰C, TRPV2) - Noxious heat, capsaicin
3 - Chemical
Describe “inflammatory soup” in relation to peripheral nociceptive processing
There are three components
- Nociceptor activation
- Vasodilation
- Inflammation
Inflammatory soup is the release of all the things that nociceptors respond to and that participate in the inflammatory process
Describe direct and indirect nociceptor activation
Direct activation
- Opening of cation channels (e.g., Na+)
- Membrane depolarization
- Generation of action potentials
Indirect sensitization
- Lowered thresholds
What is hyperalgesia
Hyperalgesia is an increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves.
What do we call hyperalgesia when it occurs in the periphery?
Primary hyperalgesia
Describe primary hyperalgesia
- Spreading of action potentials over other areas where membrane is at resting state
- Increased sensitivity occurs because the threshold is lowered
- This leads to an increased ‘receptive field’ size
- Inflammatory mediators and
Substance P induced - Activation of “silent nociceptors”
– Only signal in response to the molecules secreted by other activated nociceptors
– Expand the receptive field for the pain stimulus
Where will we see secondary hyperalgesia?
In the CNS, not the periphery
Describe allodynia
Pain resulting from non-noxious stimulus
Describe hyperalgesia
An increased response to a stimulus that is normally painful (noxious stimulus)
What is the axon reflex?
- When stimulation of the sympathetic nervous system occurs by pain processes
- It is the coupling of sensory and autonomic systems
- The sympathetic nerves get activated and actually contribute to the development of a flare response, leading to the triple response of Lewis
What causes a flare response?
Flare response due to activation of peripheral nerves (e.g. vasodilation)
There is a release of Substance P and movement of action potential along the primary afferents towards the spinal cord
What is the triple response of Lewis?
- Redness
- Edema
- Wheal
After transduction (at the site of the painful stimulus) is transmission (via the fibers of the dorsal horn). What are the two types of nociceptive fibers?
1 - A delta fibers (myelinated)
2 - C fibers (unmyelinated)
A delta fibers
- Responsible for localized, sharp “first pain”
- Respond to intense mechanical (pinching) and thermal stimuli
- Lightly myelinated, medium diameter
C fibers
- Mediate poorly localized, diffuse “second pain”
- Polymodal as in it responds to mechanical, thermal and chemical stimuli
- Unmyelinated, small diameter
What are the four types of fibers associated with nociceptors?
- Cutaneous
- Articular (joint)
- Muscle
- Viscera
Cutaneous fibers
- A delta (mechanical)
- A delta (mechanical + heat)
- C fiber polymodal nociceptor
Articular (joint) fibers
- Approx. 2x as many unmyelinated fibers myelinated fibers
- A delta (small myelinated)
- C-fibers (unmyelinated)
- Respond to mechanical stimulation, inflammation
Muscle fibers
- Similar to joint
- Respond to mechanical, thermal, chemical and ischemia
Viscera fibers
- Predominately C-fibers
- Respond to mechanical distention and chemical stimuli
How does the spinal cord process fibers in the dorsal horn?
Through different lamina (layers) found within the dorsal horn
You need to know
- Lamina I
- Lamina II and III
- Lamina V
Role of lamina I of dorsal horn
A delta fibers
- Fast, acute pain
Role of lamina II and III of dorsal horn
C fibers
- Slow, chronic pain
Role of lamina V of dorsal horn
WDR neurons (wide dynamic range) - Noxious and non-noxious signals
Describe the “wind up” phenomenon of central sensitization
This is a process of increased sensitivity that includes three components
- Secondary hyperalgesia (CNS and PNS)
- Recruitment of adjacent neurons in the spinal cord
- Changing pharmacology
Describe secondary hyperalgesia
“Secondary Hyperalgesia” = PNS and CNS events
Prolonged and increased activation of nociceptors in the periphery and projection
pathways at the spinal cord
Recall that primary hyperalgesia was due to PERIPHERAL sensitization
Describe the changing pharmacology in the “wind up” phenomenon
- Release of neurotransmitters occurs (glutamate, Substance P, BDNF, etc.)
- NMDA (n-methyl-d-aspartic acid) does not get activated right away, but once it is activated, the flood gates are opened…
- Influx of calcium into the post-synaptic cell, depolarization occurs
- Overall the post-synaptic cell with have increased activation and firing
- We call this “wind up” phenomenon
What other components are there of the “wind up” phenomenon?
- Neuronal plasticity
- Memories of pain and pathophysiology
Neuronal plasticity
Modulation of intracellular signaling (cAMP, etc.) and changes in gene expression (c-fos, jun)
Memories of pain or pathophysiology
Lasting effects –> Chronic pain
Need to remember the different function of acute sensitization and chronic sensitization
REMEMBER:
1) Acute sensitization
Protective
2) Chronic sensitization
Maladaptive
No function
What is the last step in pain processing?
Supraspinal perception
What are the two ascending somatosensory pathways?
- Dorsal column (medial lemniscus - DC-ML)
- Anterolateral system (AL)
What does the DC-ML carry?
Discriminative Touch
Proprioception
What does the anterolateral system carry?
Temperature
Pain
“Crude touch”
Two components of the spinothalamic tract
Neospinothalamic
Paleospinothalamic
Describe the neospinothalamic tract
- Fast type A delta fibers for mechanical and acute thermal pain
- Projections form Lamina I, IV and V
- Anterolateral Columns to the Thalamus (Ventral Posterolateral (VPL))
- Contributes to primary sensory cortex ***
What is the role of the primary sensory cortex?
Primary sensory cortex Lateral system - Sensory-discriminative component - ***PRIMARY FUNCTION*** This tract will tell you “I have a sharp pain on my left arm and the level of pain is 5/10 - Location, intensity and modality - “First” pain – sharp, well-localized - Sharp pain in my left arm
Describe the paleospinothalamic tract
- Slow type C-fibers
- Lamina II, III + V
- Anterolateral Columns
- Thalamus
- Dorsomedial nucleus (DM)
- Limbic system
Describe the contribution to the limbic system
Limbic system
- Medial system: Affective-motivation pathways
- Emotional and visceral responses to pain
** PRIMARY FUNCITON **
- The emotional reaction to pain
- The pain that really “gets to you”
- “Second” pain – dull, throbbing, poorly localized
Release of stress hormones, attention, etc.
- You really start focusing and stressing about your pain!!!
- Ouch!! That hurts – I don’t like it
What are two other ascending tracts?
Spinoreticular tract
Spinomesencephalic tract
Spinoreticular tract
Reticular Formation
Motor response to pain
Descending pain control
Spinomesencephalic tract
Midbrain – PAG
Regulation and modulation of pain experience
Descending pain control
Superior colliculus - eye movements and regulation of gaze to the site of injury
Describe the role of the brain in pain perception and the specific role of the amygdala and pre-frontal cortex
Once the pain signal reaches the brain, there are a number of brain areas that are being activated…
This is where the perception of pain is really happening
You need your brain to interpret where you’re hurting
Initially they are just nociceptive signals and physiological responses
Amygdala – major center for fear, plays a role in pain perception
Prefrontal cortex – center for cognitive function and the cognitive perception of pain
Some of the most activated areas in the pain state are the…
Anterior cingulate cortex and the insula
Anterior cingulate cortex (ACC)
Active during 1) perception of pain, 2) imagining pain and 3) observation of pain in others
Attention to pain
Initiation of behavioral reactions to pain
Insula
relay station to the limbic system (learning and pain memory) and to the hypothallmus
Gate control theory example
When you’re in pain, you kiss it, shake your hand, put it in your mouth, rub it, etc.
These things actually work
Describe the gate control theory
Gating mechanism within the spinal cord that closes in response to normal stimulation of the fast conductivity large nerve fibers (Aβ - touch, proprioception)
However, it opens when the slow conduction pain fibers (Aδ and C) transmit a high volume and intensity of sensory signals
The gate can be closed again if these pain signals were countered by renewed stimulation of the large fibers
There are three sites of action in descending pain control. What are they?
1 - Periaqueductal gray - midbrain
2 - Rostral ventral medulla - brainstem
3 - Locus coeruleus - pons in brainstem
What do you need to understand about descending pain control?
- It is a regulatory mechanism used to control the descending pain pathways (occurs in the spinal cord)
- It is complex, but you just need to know that this is an endogenous system that our bodies use to control pain
What types of medications utilize the descending pain control pathway?
Opioids
Describe the periaqueductal gray matter (midbrain)
Activates enkephalin-releasing neurons that project to the raphe nuclei in the brainstem
Describe the rostral ventral medulla (brainstem)
Nucleus raphe magnus
5HT projections to the dorsal horn of the spinal cord
Describe the locus coeruleus (pons and midbrain)
NE projections to the dorsal horn of the spinal cord
Describe pain modulation that occurs in the ventrolateral periaqueductal gray matter (PAG)
- Analgesia (inability to feel pain) blocked by naloxone
- Inhibit A and C fibers
- Decreased BP
- Decreased HR
- Vasodilation
- Immobility
- Inhibition of sympathetics (time to recover)
Describe pain modulation that occurs in the dorsal periaqueductal gray matter (PAG)
- Analgesia (inability to feel pain) is not blocked by naloxones
- Selective inhibition of nociceptive input
- Defense reaction so BP and HR go up
- Vasoconstriction of skin and viscer
- Vasodilation of skeletal muscles
- Pupillary dilation
- Piloerection
- Fight/flight behavior
- Muscle tone increase
- Aversive behavior
- Sympathetics are excited in preparation of fight or flight
How can you therapeutically modulate pain?
Typical Pharmacologic Approaches: Opioid analgesics NSAIDs Glucocorticoids DMARDS
Can either relieve pain or delay or arrest a disease process
Occurs primarily at the site of injury and in the dorsal horn
What are the common pain types?
Chronic pain
Referred pain (visceral – cutaneous)
Projected pain
Neuropathic Pain
What are all the different types of neuropathic pain?
Thalamic Phantom limb pain (amputation) Sympathetic mediated pain (SMP) - Complex Regional Pain Syndrome (CRPS) ** - Reflex sympathetic dystrophy ** - Causalgia ** Fibromyalgia Diabetic neuropathy
Referred (reflective) pain and convergence
Reflective pain - perceived at a location other than the site of the painful stimulus
Convergence -
of somatic and visceral pain fibers on secondary afferents in the dorsal horn (dermatomes)
You will have convergence at the spinal cord – this is why it follows dermatomes
Projected pain
Provides evidence in support of the labeled line theory of sensory processing
Example would be hitting your ‘funny bone’ at the elbow and perceiving the pins and needles sensation (paresthesias) localized to the hand and fingers
Phantom pain and reorganization
Imaginary pain
When you have amputation, but you still feel pain when the limb is no longer there
This is because of some of the reorganizations that occur
Sympathetic mediated pain (SMP)
Two types:
- Complex Regional Pain Syndrome - CRPS (can result in neuroplasticity following recovery)
- Reflex Sympathetic Dystrophy (RSD); Causalgia
Reflex Sympathetic Dystrophy (RSD); Causalgia
- Continuous burning pain long after seemingly trivial injuries
- May develop following a traumatic peripheral injury
hyperpathia - Dystrophic changes
skin, nails, hair, muscles and/or bone - Sympathetic hyperactivity (variable)
temp. changes and hyperhidrosis - Pain enhanced by:
allodynia
sympathetic activation
Treatment
Treatment
sympathectomy or a sympathetic nerve block
other interventions
