6 Mechanisms of Pain Flashcards
1
Q
Pain (p.4)
- Pain
- # of neurons to relay pain information from the periphery to the cortex
- nociceptors
- The purpose of pain
- Persistent or chronic pain
A
- Pain is the perception (i.e. Pain is in the Brain) of noxious or potentially damaging stimuli.
- It takes three neurons to relay pain information from the periphery to the cortex.
- Peripheral sensory neurons (the first neuron in the chain) that are dedicated to detecting pain are called nociceptors.
- The purpose of pain is to get you to alter your behavior or attend to a situation.
-
Persistent or chronic pain
- Pain (often ongoing) that occurs in the presence or absence of observable pathology.
- can be produced by changes anywhere in the pain pathway.
2
Q
Pain (p.4)
- For the GI tract (and most other systems)
- the first neuron
- the second neuron
- the third
- There is an additional pathway for visceral pain
- Nociceptors
- usually/
- respond to/
A
-
For the GI tract (and most other systems)
- the first neuron is the primary afferent neuron located in spinal or inferior vagal ganglion
- the second neuron is in the spinal cord dorsal horn or brainstem (NTS),
- the third is in the thalamus (a hideously complex potato-shaped structure in the diencephalon)
-
There is an additional pathway for visceral pain
- Dorsal Column Pathway that makes an additional stop in the dorsal column nuclei, e.g. nucleus gracilis
-
Nociceptors
- usually unmyelinated and slower (aka C-fiber) or lightly myelinated and faster (A∂ fiber).
- _ respond to_ noxious mechanical stimulation (aka high threshold mechanical stimulation) and/or noxious heat (fire), noxious cold, or chemical (pH) stimuli.
3
Q
Pain
- Adequate stimulus
- This may not be true for gut visceral afferents
- because/
- professional nociceptors
A
-
Adequate stimulus
- there are different types of sensory neurons and each responds to a unique class or type of stimulation.
- For nociceptors, the hallmark is the ability to respond only (fire action potentials) to high threshold mechanical/temperature (e.g. a pinch, fire, ice) or noxious chemical (acid) stimulation.
-
This may not be true for gut visceral afferents
-
because many (perhaps the majority) can detect both noxious and non-noxious stimuli;
- the GI tract is heavily innervated by sensory neurons that can do more than one job.
- But, the GI tract also has professional nociceptors; those neurons that only detect noxious stimuli.
-
because many (perhaps the majority) can detect both noxious and non-noxious stimuli;
4
Q
How could pain information be transmitted in the absence of dedicated pain fibers? (p.8)
- Frequency Coding
- Silent afferents
- the two choices above do not begin to consider/
- Visceral hypersensitivity
- Hypersensitivity (allodynia)
- Hyperalgesia
A
-
Frequency Coding
- low frequency firing pattern is interpreted by the CNS as normal function.
- At high frequency, stimulation is perceived as pain.
-
Silent afferents
- In the bladder there are sensory fibers that do not normally fire even at potentially noxious levels of stimulation.
- Following inflammation, these fibers may be active even during normal micturition and may produce painful sensation.
- These fibers would be a special class of sensory neurons that would be classified as nociceptors.
-
the two choices above do not begin to consider changes that could (and probably do) occur in the spinal cord and brain
- Changes in primary afferents may be the first step in changes that occur throughout the pain pathway
- **Visceral hypersensitivity **and why can it be so debilitating
- Hypersensitivity (allodynia) is when normal sensations, which in the case of visceral input may be only subconscious, become painful
-
Hyperalgesia is when painful stimuli become more painful.
- Example: Irritable Bowl Syndrome (IBS).
5
Q
Visceral Pain Comorbidities
A
-
Depression
- persistent visceral pain can lead to depression, depression can cause pain, and each condition can exacerbate the other.
-
Nausea
- Primarily the domain of vagal afferents
- # 1 reason that chemotherapies are aborted, even more so than vomiting
-
Cachexia
- Weakness, fatigue and muscle loss.
- Can accompany pain,
- negative symptom for any GI disorder, especially GI cancers.
-
Poor sleep hygiene
- Pain can degrade sleep leading to overall decline in quality of life.
6
Q
Sensory Pathways for Visceral Sensation (p.11)
- There are two ways sensory information travels from the viscera of the GI tract to the brain:
- Components of the Vagus nerve include:
- Visceral motor output from the/
- Somatic motor output from the/
- Somatic sensory neurons located in/
- Visceral sensory neurons located in/
A
-
There are two ways sensory information travels from the viscera of the GI tract to the brain:
- Vagal visceral afferents
- Spinal visceral afferent
-
Components of the Vagus nerve include:
- Visceral motor output from the dorsal motor nucleus (DMN) of the vagus.
- Somatic motor output from the nucleus ambiguus.
- Somatic sensory neurons located in superior vagal ganglion that project to trigeminal nucleus
- Visceral sensory neurons located in the inferior vagal ganglion (aka nodose) that project to the nucleus tractus solitarius (nTS)
7
Q
Vagal Visceral Pathways (Cranial Nerve X): Other important (i.e. testable) tidbits about the Vagus
- Vagus means/
- It is 80-85%/
- Vagal visceral sensory fibers probably do not/
- Moreover, visceral sensory information carried in the vagus does NOT/
- How do we know this? (Hint: which patient population could provide insight into this issue?)
- Visceral afferents encode/
- The vagus provides sensory fibers to/
- The sensory component of the vagus nerve/
A
- Vagus means “wanderer”.
- It is 80-85% sensory.
- Vagal visceral sensory fibers probably do not carry “pain” information for the gut (it may transmit pain for organs of the thoracic cavity).
-
Moreover, visceral sensory information carried in the vagus does NOT reach consciousness.
- It may be associated with general feelings like hunger, satiety, nausea, as well as emotional components of visceral pain.
-
How do we know this? (Hint: which patient population could provide insight into this issue?)
- Paraplegics with cervical complete spinal transections still detect pain
- No sensory input from the parasympathetic nervous system
- The only thing that’s intact b/n gut and brain is the vagus nerve
- Visceral afferents encode physical and chemical events (distension, contraction, pH) and relay this information back to the CNS to modulate function.
- The vagus provides sensory fibers to organs from the pharynx to the splenic flexure.
-
The sensory component of the vagus nerve is NOT part of the parasympathetic nervous system.
- The sensory fibers “run with” the parasympathetic preganglionic fibers but belong to a different functional system.
8
Q
Spinal Visceral Sensory – Conscious Pain (greater splanchnic nerve) (p.14)
- Sensory fibers originate/
- Only 1-2% of all spinal sensory neurons innervate
- Sensory fibers must/
- For the sympathetic system, sensory fibers run with/
- For the parasympathetic system, sensory fibers run with/
- You can do sensory nerve blocks by/
A
- Sensory fibers originate in the spinal or dorsal root ganglia.
- Only 1-2% of all spinal sensory neurons innervate viscera.
-
Sensory fibers must “hitch a ride” with components of the sympathetic nervous system and the sacral portion of the parasympathetic system.
- They do not belong to either system!
- For the sympathetic system, sensory fibers run with the greater (T5 to T 8) splanchnic nerve, the lesser (T10 to T11) splanchnic nerve, the least (T12) splanchnic nerve , the lumbar splanchnics (there are usually 4 in humans), and sacral splanchnics.
- For the parasympathetic system, sensory fibers run with pelvic splanchnic nerves that also contain preganglionic parasympathetic fibers.
- You can do sensory nerve blocks by injecting neuroactive agents into prevertebral ganglia or plexus.
9
Q
Comparison of Sources of Sensory Innervation of viscera (p.16)
- Dual innervation for sensory fibers to the gut
- what’s associated with abdominal dysfunction
A
-
Dual innervation for sensory fibers to the gut
- Spinal (“Sympathetic”)
- Craniosacral (“Parasympathetic”)
- Composite sensation of pain, nausea, fear, and discomfort u
10
Q
Referred Pain (p.17-18)
- ?
- Caused by/
- intense visceral sensory input may be perceived as/
- Take home message
A
- the sensation of pain in somatic structures as the result of pain impulses arising in visceral structures.
-
Caused by the sharing of second order sensory neurons in the dorsal horn.
- virtually every second order sensory neuron that receives visceral input can also be stimulated by stimulation of somatic tissues.
- intense visceral sensory input may be perceived as arising from some portion of the abdominal wall instead of the affected organ.
- Take home message: Single visceral (in this case spinal) afferent projects to a large number of spinal neurons making it very likely that synaptic activity generated by this fiber will overlap with somatic sensation.
11
Q
Referred Pain Locations (don’t memorize!)
- The abdomen can be divided into/
- The location of referred pain from different pathologies/
A
- The abdomen can be divided into four quadrants plus the central region.
- The location of referred pain from different pathologies is somewhat reproducible and can be useful for diagnostic purposes.
- Right lower quadrant:
- Acute appendicitis
- Mesenteric lymphadenitis
- Infective distal ileitis
- Crohn’s disease
- In women:
- Ectopic pregnancy
- Ruptured ovarian cyst
- Acute salpingitis
- Renal disorders
- Right ureteric calculus
- Acute pyelonephritis
- Acute cholecystitis
- Acute rheumatic fever
- Pyogenic sacroiliitus
- Right upper quadrant:
- Acute cholecystitis
- Biliary colic
- Acute hepatic distension or inflammation
- Perforated duodenal ulcer
- Central abdominal pain
- Gastroenteritis
- Small intestinal colic
- Acute pancreatitis
- Left upper quadrant
- Perisplenitis
- Splenic infarct
- Left lower quadrant
- Acute diverticulitis
- Pyogenic sacroiliitis
12
Q
Best pain therapy
A
- Address underlying mechanism
- Pharmacotherapies will only work temporarily
13
Q
1 risk factor for pancreatitis & NSAIDs
A
- Pancreatitis: smoking (alcohol not so much)
- NSAIDs: liver toxicity
14
Q
To decrease pancreatic secretions (p.22-23)
- Proton-pump inhibitors
- Oral pancreatic enzymes
- SubQ octreotide
- Nerve block
- Whipple procedure
A
- Proton-pump inhibitors - increases duodenal pH and thus decrease stimulus for pancreatic excretion – unlikely to work but safe.
- Oral pancreatic enzymes – not clear why they work, but it may involve feedback mechanism via a decrease in CCK release.
- SubQ octreotide – (mimics somatostatin) inhibits release of gastrin, CCK, glucagon, VIP, GH and pancreatic polypeptide. Mixed results from at least 3 small studies. Expensive and painful in some patients.
- Nerve block - inject local anesthetics or toxins (alcohol, phenol) to silence sensory neurons.
- Remove most of the pancreas via Whipple procedure.
15
Q
IBS
- Check patients who are coming in with IBS-like symptoms for/
- Treatment for IBS
A
- Check patients who are coming in with IBS-like symptoms for Celiac disease
- Treatment for IBS
- Oxycodone
- Low dose anti-depressants
- TCAs: amitriptyline (Elavil)
- SSRIs: Sertraline (Zoloft), Fluoxetine (Prozac)
- Smooth muscle relaxants: anti-muscarinics (hyoscine, levsin)
- 5-HT4 agonist (Tegasrod, Zelnorm)
- Anticonvulsants: neurotinin (gabapentin)
