Pain week 5 Flashcards
Differentiate btwn fast/first pain and slow/second pain.
What fiber type is associated with fast pain?
What fiber type is associated with slow pain?
With pain, there is an initial sharp and easily localizable pain (fast/first pain) which is often followed by diffuse burning or itching pain (slow/second pain).
Fast pain has been associated with the A delta fibers and their central connections while slow pain is associated with C fibers and their central connections.
Externally applied pressure preferentially blocks larger fibers so that myelinated fibers (including A delta) are blocked while C fibers continue to conduct. In this situation, most forms of tactile sensation disappear and a pinprick is felt only as a dull, aching pain that is particularly unpleasant.
Local anesthetics applied to peripheral nerves block C fibers before myelinated fibers. During the period when only C fibers are blocked, a pinprick is felt only as a sharp, brief pain. Fast pain is well localized and has less emotional impact than slow pain.
These two distinct pain sensations appeart to be processed differently at successive levels of the neuraxis.
What activates nociceptors?
What are the types of nociceptors?
Most nociceptors have ____ ____ ____.
Noxious insults activate nociceptors, these include:
- Thermal nociceptors
- Mechanical nociceptors
- Polymodal nociceptors
- Silent nociceptors, esp. in the viscera
- Most nociceptors are free nerve endings – only a few of these have been characterized, such as those with capsaicin receptors
What kind of stimuli do nociceptors preferentially respond to?
Nociceptors respond preferentially to high intensity stimuli that are destructive to tissue.
Note in attached figure that the nociceptor only begins to respond at a certain temperature. After that temperature, it begins firing rapidly.
Describe how pain differs from other sensations as it pertains to adaptation.
What factors is this attributable to?
Why does pain sensation typically last longer than the initial provocation?
Pain differs from most sensations in that repeated stimulation tends to increase sensitivity rather than decrease it (adaptation). This is attributed to release of sensitizing substances (prostaglandins, leukotrienes, substance P) around the free nerve endings of nociceptors and to changes at central synapses. (Sensitization is produced in part by the synthesis and release of prostaglandins, which lower the threshold of the polymodal nociceptors of C fibers). Pain sensation typically lasts longer than the initiating provocatino due to the persistence of these sensitizing substances and the products of tissue destruction.
Attached figure: Note that the response of the nociceptor increases with repeated stimulation despite the fact that there is no change in the original stimulation.
Define the following terms:
hyperalgesia
allodynia
analgesia
Hyperalgesia: increased response to a stimulus that is normally painful
Allodynia: pain resulting from a stimulus that normally does not produce pain
Analgesia: Absence of pain in response to stimulation which would normally be painful
Describe the mechanism of hyperalgesia.
Describe the mechanism of hyperexcitability of dorsal horn neurons underlying centrally mediated hyperalgesia.
HYPERALGESIA has both peripheral and central origins. • Upon repeated application of noxious mechanical stimuli, nearby nociceptors that were previously unresponsive to mechanical stimuli now become responsive, a phenomenon called sensitization.
• Sensitization of nociceptors results from release of various chemicals by the damaged cells in the vicinity of the injury, including bradykinin, histamine, prostaglandins, leukotrienes, acetylcholine , serotonin and Substance P. – These chemicals decrease the threshold for activation or directly activate the nociceptors.
Hyperexcitability of Dorsal Horn Neurons underlies centrally mediated hyperalgesia
- In conditions of severe and persistent injury, C-fibers (which release glutamate) fire repetitively, and activate NMDA receptors
- This produces a long term change in the excitability of dorsal horn neurons, similar to the long term changes in synaptic transmission observed in the hippocampus and other brain regions, see Long Term Potentiation (LTP).
- This central sensitization may contribute to centrally mediated pain in the absence of a peripheral stimulus, e.g. phantom limb pain
Where are the cell bodies of primary pain afferents located?
What ar ethe distal receptive regions of these neurons?
What type of axons connect receptive endings to the cell bodies and terminals in teh spinal cord?
Where in the spinal cord do nociceptive fibers enter the spinal cord?
PRIMARY PAIN AFFERENTS have their cell bodies in the dorsal root ganglia. The distal receptive regions of these cells are ANATOMICALLY UNSPECIALIZED FREE NERVE ENDINGS. The axons connecting the receptive endings to the cell bodies and terminals in the spinal cord are the smallest myelinated axons (A delta) and unmyelinated axons (C fibers). Most of these NOCICEPTIVE fibers enter the spinal cord via the dorsal root, but many of the unmyelinated axons enter via the ventral root. As a practical matter, cutting the dorsal root alone will not reliably alleviate intractable pain.
Describe the difference in the stimuli required for slow pain vs fast pain receptors to respond.
The adequate stimulus for pain is tissue damage, or a stimulus strong enough to cause tissue damage. FAST PAIN transducers may be similar to unspecialized mechanical, thermal or chemical receptors, but require a higher intensity of stimulation. SLOW PAIN may be initiated in a more indirect way, involving release of bradykinins and/or histamine in response to actual tissue damage. Remeber that pain sensation typically lasts longer than the initiating provocation due to persistence of sensitizing substances and the products of tissue destruction. These substances are typically cleared out slowly (which is why pain can last for prolonged periods of time).
What NTs do primary pain afferents use?
State what pain afferents do upon entry into the spinal cord.
How may pain afferents be involved in reflexes?
Generally, how may pain perception be endogenously blocked within the spinal cord? With drugs?
Primary pain afferents appear to use glutamate and various peptides (esp. substance P) as neurotransmitters.
Upon entering the cord, pain afferents enter Lissauer’s tract (the dorsolateral tract of Lissauer in the posterolateral fasciculus), bifurcate into ascending and descending branches and travel several segments before terminating in the dorsal (posterior) horn of the spinal cord. The distribution of pain afferents within Lissauer’s tract over a few segments in the spinal cord before synapsing in the dorsal horn accounts for the discrepancy of a few segments between the loss of pain sensation and loss of vibration & fine touch sensation following spinal cord injury.
Most pain afferents terminate in Rexed laminae I, II, and V (numbers do not matter. just know Rexed laminae are layers of the spinal cord). Some collaterals terminate on interneurons in the spinal grey matter and mediate spinal reflexes to pain, such as the flexor withdrawal reflex.
The dorsal horn neurons contain receptors for glutamate, serotonin, GABA, glycine and a mu opiod receptor. Descending inhibitory fibers act at these synaptic sites to block pain perception. Drugs acting at these presynaptic sites can also suppress the initiation of the pain signal.
Some neurons of the lateral spinothalamic tract branch off during ascension in the CNS and synapse on the reticular formation of the brainstem. Explain the purpose of this.
Fibers initially going along spinothalamic pathway branch off (as soon as get to brainstem in medulla) to region called reticular formation which is involved in waking us up and making us alert. Is most noticeable when have pain that awakes us. Goes up to thalamus and cortex
Other than the primary somatosensory cortex in the postcentral gyrus, what other parts of the cortex are strongly activated by painful stimuli?
- Central representation of pain is not limited to the primary somatosensory cortex
- the insular and the anterior cingulate cortex are very strongly activated by painful stimuli. Anterior cingulate cortex is heavily involved in the emotional response to pain
The main components of the brain network for acute pain are: primary and secondary somatosensory, insular, anterior cingulate, and prefrontal cortices (S1, S2, IC, ACC, PFC) and thalamus (Th).
Hyperalgesic states during clinically relevant pain are especially reflected in brain areas such as the anterior cingulate and prefrontal cortical regions.
In contrast to most somatosensory neurons, some central pain fibers have very large receptive fields. Explain why this is advantageous.
These provide minimal localizing value, but considerable survival value, by facilitating withdrawal reflexes, escape or avoidance behavior. The neurons with the largest receptive fields have their cell bodies in the deeper Rexed layers of the spinal cord.
What fiber type innervates viscera?
Explain why visceral pain may be experienced as referred pain.
What is phantom limb pain? What is the mechanism behind it?
VISCERAL AND REFERRED PAIN
The origin of the source of pain in the viscera is commonly mislocalized. , Viscera are innervated by C-fibers, some of which run in autonomic trunks to the spinal cord, where they SHARE CENTRAL CONNECTIONS with pain fibers, which innervate the surface of the body. (convergence of peripheral and visceral afferents on ascending fibers in lateral spinothalamic tract). Due to these common central connections, the perception of pain (produced by angina or kidney stones, for example) is REFERRED to specific regions of the skin. Angina pectoris is a severe constricting pain in the chest, often radiating from deep in the chest to the left shoulder and down the arm, due to ischemia of the heart muscle caused by coronary disease.
PHANTOM LIMB PAIN
There is often a vivid sensory experience (including pain) of a missing limb. Ectopic action potential generation at the scar of the stump is thought to contribute to this sensation. Peripheral surgery is sometimes effective in treating this sensation, but not always. Reinnervation and reorganization of central processes is thought to account for the occasional failure of such surgery. Long-lasting hypersensitivity (LTP) of central neurons may be the consequence of high levels of activation of pain fibers in the period immediately following injury.
Explain the segmental and descending suprasegmental endogenous pain control mechanisms.
The segmental pathway involves convergence of pain and touch information at the same segment (dermatome) at which the pain originated. According to the Gate control theory, increased activity of large mechanoreceptors (A fibers) diminishes perception of pain, e.g. rubbing the skin rueduces the sting of a mosquito bite, by activating inhibitory enkephalinergic interneurons on projection neurons within the spinal cord.
Descending suprasegmental control from cerebral structures,m including the hypothalamus, projects to the periaqueductal gray matter (PAG, in the rostral midbrain) and then nucles raphe magnus (MRN) and then reticulospinal tract to the dorsal horn interneurons to block afferent pain transmissoin. This may account for several phenomena, including anesthesia produced by such diverse agents as acupuncture, electrical stimulation, and morphine.
Note the importance of serotenergic and enkephalinergic neurons in this system.
What effect can electrical stimulation of the PAG induce?
What receptor type is found in the periaqueductal gray (as it pertains to pain)? Where else is this receptor found?
What role do these receptors play in endogenous and exogenous relief of pain?
- Opiod receptors are found in the dorsal horn and in the periaqueductal grey
- Endogenous opiods (enkephalins) released by interneurons at these sites reduce pain
- Exogenous opiods such as morphine also act at these sites and reduce pain.
- Opiod receptors are also located in regions other than those that mediate pain. The side effects of opiates used as narcotics are explained in terms of the distribution of these receptors
- Opiod receptors present in muscles of the bowel and anal sphincter account for constipation, a common side effect of the action of opiates
- Opiod receptors in the nucleus of the solitary tract in the brainstem account for respiratory depression and cardiovascular changes (GVA nucleus of CNs VII, IX, and X)
